AML

The combination of all-trans­-retinoic acid (ATRA) and arsenic trioxide continues to show advantages over ATRA and chemotherapy as first-line therapy for patients with low- or intermediate-risk acute promyelocytic leukemia (APL), investigators report.

The final analysis of theAPL046 study, a noninferiority trial of ATRA plus arsenic trioxide (ATRA-ATO) vs. ATRA and standard chemotherapy, showed that event-free survival (EFS) and overall survival (OS) were significantly better among patients assigned to ATRA-ATO. Patients in this group also had a significantly lower cumulative incidence of relapse, reported Francesco Lo-Coco, MD, of University Tor Vergata in Rome and colleagues.

“Our results support the use of ATRA-ATO in patients with newly diagnosed APL and point to this strategy as the new standard of care for low- or intermediate-risk patients. Studies exploring the role of ATRA-ATO are warranted in other APL subsets including high-risk, pediatric, and elderly patients,” they wrote (J Clin Oncol. 2016 July 11. doi: 10.1200/JCO.2016.67.1982).

In the trial, 276 patients with newly diagnosed APL were randomly assigned to receive either ATRA-ATO or ATRA plus chemotherapy with idarubicin, mercaptopurine, and methotrexate.

A total of 263 patients were evaluable for response to induction, including 127 assigned to ATRA-ATO and 136 assigned to ATRA-chemotherapy. Following induction, all patients assigned to ATRA-ATO and 127 assigned to chemotherapy (97%) achieved a complete remission (CR).

After a median follow-up of 40.6 months, the rate of EFS, the primary outcome, was 97.3% for ATRA-ATO vs. 80% for ATRA-chemotherapy (P less than .001). The cumulative incidences of relapse were 1.9% and 13.9%, respectively (P = .0013), and overall survival rates at 50 months were 99.2% vs. 92.6% (P = . 0073).

Hematologic toxicities were more frequent among patients assigned to chemotherapy, while liver function abnormalities occurred more often among those assigned to ATO.

One patient assigned to ATRA-ATO died while in CR, from bronchopneumonia caused by the H1N1 (influenza) virus. Five patients assigned to chemotherapy died in CR, from hemorrhagic shock, pulmonary embolism, bronchopneumonia (two patients) and secondary myelodysplastic syndrome.

Of the 17 patients who experienced relapses during follow-up, 2 assigned to ATRA-ATO had relapses at 22 and 27 months. The remaining 15 relapses were among patients assigned to ATRA-chemotherapy, occurring at a median of 14 months.

The authors noted that the superior EFS and cumulative incidence of relapse with ATRA-ATO emerged only after longer follow-up, indicating that the advantage of ATRA-ATO over ATRA-chemotherapy increases over time and that “the inclusion of ATO in the treatment of low- or intermediate-risk APL not only reduces mortality and hematologic toxicity, but also results in improved and sustained antileukemic activity.”

The study was supported by the Gruppo Italiano Malattie Ematologiche dell’Adulto Foundation; the Associazione Italiana Contro le Leucemie, Linfomi e Mieloma, Associazione Italiana per la Ricerca sul Cancro, and the German Federal Ministry of Education and Research. Dr. Lo-Coco disclosed honoraria, consulting, and speakers’ bureau activities with Teva Pharmaceutical, Lundbeck, Novartis, Baxalta, and Pfizer. Several other coauthors disclosed similar relationships.

tor@frontlinemedcom.com

The combination of all-trans­-retinoic acid (ATRA) and arsenic trioxide continues to show advantages over ATRA and chemotherapy as first-line therapy for patients with low- or intermediate-risk acute promyelocytic leukemia (APL), investigators report.

The final analysis of theAPL046 study, a noninferiority trial of ATRA plus arsenic trioxide (ATRA-ATO) vs. ATRA and standard chemotherapy, showed that event-free survival (EFS) and overall survival (OS) were significantly better among patients assigned to ATRA-ATO. Patients in this group also had a significantly lower cumulative incidence of relapse, reported Francesco Lo-Coco, MD, of University Tor Vergata in Rome and colleagues.

“Our results support the use of ATRA-ATO in patients with newly diagnosed APL and point to this strategy as the new standard of care for low- or intermediate-risk patients. Studies exploring the role of ATRA-ATO are warranted in other APL subsets including high-risk, pediatric, and elderly patients,” they wrote (J Clin Oncol. 2016 July 11. doi: 10.1200/JCO.2016.67.1982).

In the trial, 276 patients with newly diagnosed APL were randomly assigned to receive either ATRA-ATO or ATRA plus chemotherapy with idarubicin, mercaptopurine, and methotrexate.

A total of 263 patients were evaluable for response to induction, including 127 assigned to ATRA-ATO and 136 assigned to ATRA-chemotherapy. Following induction, all patients assigned to ATRA-ATO and 127 assigned to chemotherapy (97%) achieved a complete remission (CR).

After a median follow-up of 40.6 months, the rate of EFS, the primary outcome, was 97.3% for ATRA-ATO vs. 80% for ATRA-chemotherapy (P less than .001). The cumulative incidences of relapse were 1.9% and 13.9%, respectively (P = .0013), and overall survival rates at 50 months were 99.2% vs. 92.6% (P = . 0073).

Hematologic toxicities were more frequent among patients assigned to chemotherapy, while liver function abnormalities occurred more often among those assigned to ATO.

One patient assigned to ATRA-ATO died while in CR, from bronchopneumonia caused by the H1N1 (influenza) virus. Five patients assigned to chemotherapy died in CR, from hemorrhagic shock, pulmonary embolism, bronchopneumonia (two patients) and secondary myelodysplastic syndrome.

Of the 17 patients who experienced relapses during follow-up, 2 assigned to ATRA-ATO had relapses at 22 and 27 months. The remaining 15 relapses were among patients assigned to ATRA-chemotherapy, occurring at a median of 14 months.

The authors noted that the superior EFS and cumulative incidence of relapse with ATRA-ATO emerged only after longer follow-up, indicating that the advantage of ATRA-ATO over ATRA-chemotherapy increases over time and that “the inclusion of ATO in the treatment of low- or intermediate-risk APL not only reduces mortality and hematologic toxicity, but also results in improved and sustained antileukemic activity.”

The study was supported by the Gruppo Italiano Malattie Ematologiche dell’Adulto Foundation; the Associazione Italiana Contro le Leucemie, Linfomi e Mieloma, Associazione Italiana per la Ricerca sul Cancro, and the German Federal Ministry of Education and Research. Dr. Lo-Coco disclosed honoraria, consulting, and speakers’ bureau activities with Teva Pharmaceutical, Lundbeck, Novartis, Baxalta, and Pfizer. Several other coauthors disclosed similar relationships.

tor@frontlinemedcom.com

The combination of all-trans­-retinoic acid (ATRA) and arsenic trioxide continues to show advantages over ATRA and chemotherapy as first-line therapy for patients with low- or intermediate-risk acute promyelocytic leukemia (APL), investigators report.

The final analysis of theAPL046 study, a noninferiority trial of ATRA plus arsenic trioxide (ATRA-ATO) vs. ATRA and standard chemotherapy, showed that event-free survival (EFS) and overall survival (OS) were significantly better among patients assigned to ATRA-ATO. Patients in this group also had a significantly lower cumulative incidence of relapse, reported Francesco Lo-Coco, MD, of University Tor Vergata in Rome and colleagues.

“Our results support the use of ATRA-ATO in patients with newly diagnosed APL and point to this strategy as the new standard of care for low- or intermediate-risk patients. Studies exploring the role of ATRA-ATO are warranted in other APL subsets including high-risk, pediatric, and elderly patients,” they wrote (J Clin Oncol. 2016 July 11. doi: 10.1200/JCO.2016.67.1982).

In the trial, 276 patients with newly diagnosed APL were randomly assigned to receive either ATRA-ATO or ATRA plus chemotherapy with idarubicin, mercaptopurine, and methotrexate.

A total of 263 patients were evaluable for response to induction, including 127 assigned to ATRA-ATO and 136 assigned to ATRA-chemotherapy. Following induction, all patients assigned to ATRA-ATO and 127 assigned to chemotherapy (97%) achieved a complete remission (CR).

After a median follow-up of 40.6 months, the rate of EFS, the primary outcome, was 97.3% for ATRA-ATO vs. 80% for ATRA-chemotherapy (P less than .001). The cumulative incidences of relapse were 1.9% and 13.9%, respectively (P = .0013), and overall survival rates at 50 months were 99.2% vs. 92.6% (P = . 0073).

Hematologic toxicities were more frequent among patients assigned to chemotherapy, while liver function abnormalities occurred more often among those assigned to ATO.

One patient assigned to ATRA-ATO died while in CR, from bronchopneumonia caused by the H1N1 (influenza) virus. Five patients assigned to chemotherapy died in CR, from hemorrhagic shock, pulmonary embolism, bronchopneumonia (two patients) and secondary myelodysplastic syndrome.

Of the 17 patients who experienced relapses during follow-up, 2 assigned to ATRA-ATO had relapses at 22 and 27 months. The remaining 15 relapses were among patients assigned to ATRA-chemotherapy, occurring at a median of 14 months.

The authors noted that the superior EFS and cumulative incidence of relapse with ATRA-ATO emerged only after longer follow-up, indicating that the advantage of ATRA-ATO over ATRA-chemotherapy increases over time and that “the inclusion of ATO in the treatment of low- or intermediate-risk APL not only reduces mortality and hematologic toxicity, but also results in improved and sustained antileukemic activity.”

The study was supported by the Gruppo Italiano Malattie Ematologiche dell’Adulto Foundation; the Associazione Italiana Contro le Leucemie, Linfomi e Mieloma, Associazione Italiana per la Ricerca sul Cancro, and the German Federal Ministry of Education and Research. Dr. Lo-Coco disclosed honoraria, consulting, and speakers’ bureau activities with Teva Pharmaceutical, Lundbeck, Novartis, Baxalta, and Pfizer. Several other coauthors disclosed similar relationships.

tor@frontlinemedcom.com

Hematopoietic stem cells

in the bone marrow

Whole-genome profiling of open chromatin is a reliable way to identify the cells of origin in acute myeloid leukemia (AML), according to research published in Nature Communications.

“Knowing the cell of origin of cancer cells can provide insight into tumor subtypes and possibly diagnostic and therapeutic benefit,” said study author Jennifer Trowbridge, PhD, of the Jackson Laboratory for Mammalian Genetics in Bar Harbor, Maine.

“But existing methods to identify cell of origin from bulk tumor cell samples have been unsuccessful.”

Dr Trowbridge and her colleagues hypothesized that analyzing open chromatin in bulk tumor cells might provide a better method for identifying cancer cells of origin because of the cell-type specificity of chromatin structure.

The researchers worked with a mouse model of AML driven by expression of MLL-AF9, a fusion oncogene formed by a chromosome translocation between chromosomes 9 and 11.

The team began with 5 distinct, normal cell types found in the bone marrow in both mice and humans: long-term hematopoietic stem cells (HSCs), short-term HSCs, multipotent progenitors, common myeloid progenitors, and granulocyte macrophage progenitors.

The AML that developed from these different cells of origin had different penetrance and aggressiveness when engrafted in mice. The stem cell-derived lines proved the most aggressive and the committed progenitor lines the least aggressive.

These patterns were also reflected in the frequency of leukemia-initiating cells in each cell line, with HSCs having the highest frequency and committed progenitors having the lowest.

The researchers then set out to profile the open chromatin in these distinct AML samples and compare them to open chromatin patterns in normal cells using computational models.

The team identified open chromatin signatures and gene expression patterns in AML samples that may allow stem-cell-derived AML to be distinguished from progenitor-cell-of-origin AML.

These results support findings in human data suggesting the stage of a progenitor cell when it transforms to leukemia impacts clinical progression, with earlier-stage cell-of-origin cancers being more aggressive.

The researchers noted that, with further study of open chromatin in normal human stem and progenitor cell types as well as AML patient cohorts, this profiling approach could reveal precise regions with prognostic significance based on cell of origin; in other words, a valuable cancer biomarker.

Hematopoietic stem cells

in the bone marrow

Whole-genome profiling of open chromatin is a reliable way to identify the cells of origin in acute myeloid leukemia (AML), according to research published in Nature Communications.

“Knowing the cell of origin of cancer cells can provide insight into tumor subtypes and possibly diagnostic and therapeutic benefit,” said study author Jennifer Trowbridge, PhD, of the Jackson Laboratory for Mammalian Genetics in Bar Harbor, Maine.

“But existing methods to identify cell of origin from bulk tumor cell samples have been unsuccessful.”

Dr Trowbridge and her colleagues hypothesized that analyzing open chromatin in bulk tumor cells might provide a better method for identifying cancer cells of origin because of the cell-type specificity of chromatin structure.

The researchers worked with a mouse model of AML driven by expression of MLL-AF9, a fusion oncogene formed by a chromosome translocation between chromosomes 9 and 11.

The team began with 5 distinct, normal cell types found in the bone marrow in both mice and humans: long-term hematopoietic stem cells (HSCs), short-term HSCs, multipotent progenitors, common myeloid progenitors, and granulocyte macrophage progenitors.

The AML that developed from these different cells of origin had different penetrance and aggressiveness when engrafted in mice. The stem cell-derived lines proved the most aggressive and the committed progenitor lines the least aggressive.

These patterns were also reflected in the frequency of leukemia-initiating cells in each cell line, with HSCs having the highest frequency and committed progenitors having the lowest.

The researchers then set out to profile the open chromatin in these distinct AML samples and compare them to open chromatin patterns in normal cells using computational models.

The team identified open chromatin signatures and gene expression patterns in AML samples that may allow stem-cell-derived AML to be distinguished from progenitor-cell-of-origin AML.

These results support findings in human data suggesting the stage of a progenitor cell when it transforms to leukemia impacts clinical progression, with earlier-stage cell-of-origin cancers being more aggressive.

The researchers noted that, with further study of open chromatin in normal human stem and progenitor cell types as well as AML patient cohorts, this profiling approach could reveal precise regions with prognostic significance based on cell of origin; in other words, a valuable cancer biomarker.

Hematopoietic stem cells

in the bone marrow

Whole-genome profiling of open chromatin is a reliable way to identify the cells of origin in acute myeloid leukemia (AML), according to research published in Nature Communications.

“Knowing the cell of origin of cancer cells can provide insight into tumor subtypes and possibly diagnostic and therapeutic benefit,” said study author Jennifer Trowbridge, PhD, of the Jackson Laboratory for Mammalian Genetics in Bar Harbor, Maine.

“But existing methods to identify cell of origin from bulk tumor cell samples have been unsuccessful.”

Dr Trowbridge and her colleagues hypothesized that analyzing open chromatin in bulk tumor cells might provide a better method for identifying cancer cells of origin because of the cell-type specificity of chromatin structure.

The researchers worked with a mouse model of AML driven by expression of MLL-AF9, a fusion oncogene formed by a chromosome translocation between chromosomes 9 and 11.

The team began with 5 distinct, normal cell types found in the bone marrow in both mice and humans: long-term hematopoietic stem cells (HSCs), short-term HSCs, multipotent progenitors, common myeloid progenitors, and granulocyte macrophage progenitors.

The AML that developed from these different cells of origin had different penetrance and aggressiveness when engrafted in mice. The stem cell-derived lines proved the most aggressive and the committed progenitor lines the least aggressive.

These patterns were also reflected in the frequency of leukemia-initiating cells in each cell line, with HSCs having the highest frequency and committed progenitors having the lowest.

The researchers then set out to profile the open chromatin in these distinct AML samples and compare them to open chromatin patterns in normal cells using computational models.

The team identified open chromatin signatures and gene expression patterns in AML samples that may allow stem-cell-derived AML to be distinguished from progenitor-cell-of-origin AML.

These results support findings in human data suggesting the stage of a progenitor cell when it transforms to leukemia impacts clinical progression, with earlier-stage cell-of-origin cancers being more aggressive.

The researchers noted that, with further study of open chromatin in normal human stem and progenitor cell types as well as AML patient cohorts, this profiling approach could reveal precise regions with prognostic significance based on cell of origin; in other words, a valuable cancer biomarker.

Repeat infusions of mesenchymal stromal stem cells appear to inhibit the development of chronic graft-versus-host disease (cGVHD) in patients who have undergone an allogeneic stem cell transplant.

The 2-year cumulative incidence of cGVHD among those randomized to receive repeated infusions of umbilical cord–derived mesenchymal stromal cells (MSCs) was half that of controls treated with a saline placebo, based on results from a randomized phase II, double blind trial in 124 patients with hematologic malignancies who underwent an HLA-haploidentical allogeneic hematopoietic stem cell transplantation (HSCT).

“Our goal was to minimize the incidence of cGVHD, reduce the severity of cGVHD, and demonstrate the safety of MSC infusions. We performed repeated infusions of MSCs once a month for a total of four rounds for each patient. Over the median 47-month posttransplantation period, the incidence of cGVHD was lower in the MSCs group than in the non-MSCs control group,” Lei Gao, MD, of the Third Military Medical University in Chongqing, China, and colleagues wrote in the Journal of Clinical Oncology (2016 Jul 11. doi: 10.1200/JCO.2015.65.3642).

Although cGVHD is associated with a reduced risk of leukemia relapse, it is still the leading cause of nonrelapse deaths after HSCT. The incidence of cGVHD is higher among recipients of HLA-haploidentical HSCT, in which the donor and recipient have identical HLA alleles on only one copy of chromosome, than among HLA-matched recipients, who have identical alleles on both copies.

The researchers randomly assigned 124 patients who had undergo HLA-haploidentical HSCT to receive either placebo or MSCs at a dose of 3 x 10⁷ cells/100 mL per month for four cycles beginning 4 months after HSCT

Of the 124 randomized patients, 12 discontinued the study due to cGVHD or disease progression.

The 2-year cumulative incidence of cGVHD among patients treated with MSCs was 27%, compared with 49% for placebo-treated controls (P = .021). Seven patients in the control group but none in the MSC-treated group developed typical lung cGVHD (P = .047).

The investigators also observed increases in memory B lymphocytes and regulatory T cells, and in the ratio of type 1 to type 2 T-helper cells, as well as a decrease in natural killer cells.

The finding that the MSC infusions increased the number of regulatory T cells while decreasing the incidence of cGVHD suggests that regulatory T cells play an inhibitory role, the investigators said.

The study was supported by the Chinese Academy of Sciences. Chinese National Natural Science Foundation, and other Chinese government grants. The authors reported having no relationships to disclose.

Repeat infusions of mesenchymal stromal stem cells appear to inhibit the development of chronic graft-versus-host disease (cGVHD) in patients who have undergone an allogeneic stem cell transplant.

The 2-year cumulative incidence of cGVHD among those randomized to receive repeated infusions of umbilical cord–derived mesenchymal stromal cells (MSCs) was half that of controls treated with a saline placebo, based on results from a randomized phase II, double blind trial in 124 patients with hematologic malignancies who underwent an HLA-haploidentical allogeneic hematopoietic stem cell transplantation (HSCT).

“Our goal was to minimize the incidence of cGVHD, reduce the severity of cGVHD, and demonstrate the safety of MSC infusions. We performed repeated infusions of MSCs once a month for a total of four rounds for each patient. Over the median 47-month posttransplantation period, the incidence of cGVHD was lower in the MSCs group than in the non-MSCs control group,” Lei Gao, MD, of the Third Military Medical University in Chongqing, China, and colleagues wrote in the Journal of Clinical Oncology (2016 Jul 11. doi: 10.1200/JCO.2015.65.3642).

Although cGVHD is associated with a reduced risk of leukemia relapse, it is still the leading cause of nonrelapse deaths after HSCT. The incidence of cGVHD is higher among recipients of HLA-haploidentical HSCT, in which the donor and recipient have identical HLA alleles on only one copy of chromosome, than among HLA-matched recipients, who have identical alleles on both copies.

The researchers randomly assigned 124 patients who had undergo HLA-haploidentical HSCT to receive either placebo or MSCs at a dose of 3 x 10⁷ cells/100 mL per month for four cycles beginning 4 months after HSCT

Of the 124 randomized patients, 12 discontinued the study due to cGVHD or disease progression.

The 2-year cumulative incidence of cGVHD among patients treated with MSCs was 27%, compared with 49% for placebo-treated controls (P = .021). Seven patients in the control group but none in the MSC-treated group developed typical lung cGVHD (P = .047).

The investigators also observed increases in memory B lymphocytes and regulatory T cells, and in the ratio of type 1 to type 2 T-helper cells, as well as a decrease in natural killer cells.

The finding that the MSC infusions increased the number of regulatory T cells while decreasing the incidence of cGVHD suggests that regulatory T cells play an inhibitory role, the investigators said.

The study was supported by the Chinese Academy of Sciences. Chinese National Natural Science Foundation, and other Chinese government grants. The authors reported having no relationships to disclose.

Repeat infusions of mesenchymal stromal stem cells appear to inhibit the development of chronic graft-versus-host disease (cGVHD) in patients who have undergone an allogeneic stem cell transplant.

The 2-year cumulative incidence of cGVHD among those randomized to receive repeated infusions of umbilical cord–derived mesenchymal stromal cells (MSCs) was half that of controls treated with a saline placebo, based on results from a randomized phase II, double blind trial in 124 patients with hematologic malignancies who underwent an HLA-haploidentical allogeneic hematopoietic stem cell transplantation (HSCT).

“Our goal was to minimize the incidence of cGVHD, reduce the severity of cGVHD, and demonstrate the safety of MSC infusions. We performed repeated infusions of MSCs once a month for a total of four rounds for each patient. Over the median 47-month posttransplantation period, the incidence of cGVHD was lower in the MSCs group than in the non-MSCs control group,” Lei Gao, MD, of the Third Military Medical University in Chongqing, China, and colleagues wrote in the Journal of Clinical Oncology (2016 Jul 11. doi: 10.1200/JCO.2015.65.3642).

Although cGVHD is associated with a reduced risk of leukemia relapse, it is still the leading cause of nonrelapse deaths after HSCT. The incidence of cGVHD is higher among recipients of HLA-haploidentical HSCT, in which the donor and recipient have identical HLA alleles on only one copy of chromosome, than among HLA-matched recipients, who have identical alleles on both copies.

The researchers randomly assigned 124 patients who had undergo HLA-haploidentical HSCT to receive either placebo or MSCs at a dose of 3 x 10⁷ cells/100 mL per month for four cycles beginning 4 months after HSCT

Of the 124 randomized patients, 12 discontinued the study due to cGVHD or disease progression.

The 2-year cumulative incidence of cGVHD among patients treated with MSCs was 27%, compared with 49% for placebo-treated controls (P = .021). Seven patients in the control group but none in the MSC-treated group developed typical lung cGVHD (P = .047).

The investigators also observed increases in memory B lymphocytes and regulatory T cells, and in the ratio of type 1 to type 2 T-helper cells, as well as a decrease in natural killer cells.

The finding that the MSC infusions increased the number of regulatory T cells while decreasing the incidence of cGVHD suggests that regulatory T cells play an inhibitory role, the investigators said.

The study was supported by the Chinese Academy of Sciences. Chinese National Natural Science Foundation, and other Chinese government grants. The authors reported having no relationships to disclose.

Among children with de novo acute myeloid leukemia, shorter telomere length at the end of induction chemotherapy predicted delayed bone marrow recovery in later courses, according to a study of 115 patients published online in the Journal of Clinical Oncology.

“This association was not related to differences in host factors, telomere maintenance gene variants, AML disease characteristics, or therapeutic exposures,” wrote Robert Gerbing of Children’s Oncology Group (Monrovia, Calif.), and his associates. “If validated in a larger cohort, prospective ascertainment of telomere length at end of AML induction may permit individualized risk assessment for severe myelosuppression and toxicities with subsequent therapy, as well as clarify the influence of age and cytogenetic or molecular disease characteristics.”

Acute myeloid leukemia comprises about one in five childhood leukemias and requires intensive treatment that has led to mortality in up to 19% of patients, the researchers noted (Blood 2008 Feb 1;111[3]:1044-53).

“Prolonged, profound neutropenia is a well recognized risk factor for sepsis and invasive fungal infections, both major contributors to treatment-related mortality,” they added. In nonleukemic hematopoietic cells, telomere length is a “quantifiable host factor that may indicate potential risk for impaired bone marrow recovery after chemotherapy,” they wrote (J Clin Oncol. 2016 Jun 27. doi: 10.1200/JCO.2016.67.3467).

To test this hypothesis, the researchers analyzed paired diagnostic and remission bone marrow samples for 115 children with de novo AML enrolled in a Children’s Oncology Group protocol (AAML0531) that involved five chemotherapy courses. After each course, 62 patients reached absolute neutrophil count (ANC) recovery (500 cells/mcL) within the expected time frame, meaning that the recovery time was always less than one standard deviation of the group average. The remaining 53 patients had significantly delayed ANC recovery, meaning that they exceeded the group average by at least one standard deviation after at least two courses of chemotherapy.

The study size was adequate to detect a 0.2-unit difference in average telomere length between the two groups, the investigators noted. To measure telomere length, they estimated telomere content based on quantitative polymerase chain reaction (PCR) of bone marrow samples taken after induction chemotherapy. Then they compared patients who fell within the lowest quartile of telomere content to those in quartiles 2 through 4.

Telomere content was not associated with days to ANC recovery after the first three chemotherapy courses. After the fourth and fifth courses (intensifications two and three), patients had longer ANC recovery times than during the first three courses (mean, 45.2 days for intensification two and 43.7 days for intensification three). But patients with the shortest telomeres (that is, the patients in telomere content quartile 1) had significantly longer average ANC recovery times compared with patients in telomere content quartiles 2 through 4, both for intensifications two (P less than .001) and three (P = .002).

“Analysis of individual quartiles confirmed the association between less telomere content in quartile 1 and delays in ANC recovery,” the investigators noted. After they accounted for age at diagnosis, short telomere length remained a significant predictor of delayed ANC recovery after the fourth (P = .002) and fifth (P = .009) courses. Finally, DNA sequencing revealed evidence of telomere biology disorders, the investigators said.

The work was supported by an Alex’s Lemonade Stand Young Investigators Award, by a St. Baldrick’s Foundation Scholar Award, and by the National Institutes of Health. Mr. Gerbing and senior author Maria Gramatges, MD, had no disclosures. Two coinvestigators disclosed ties to Pfizer, Novartis, Dexcom, and several other pharmaceutical companies.

Among children with de novo acute myeloid leukemia, shorter telomere length at the end of induction chemotherapy predicted delayed bone marrow recovery in later courses, according to a study of 115 patients published online in the Journal of Clinical Oncology.

“This association was not related to differences in host factors, telomere maintenance gene variants, AML disease characteristics, or therapeutic exposures,” wrote Robert Gerbing of Children’s Oncology Group (Monrovia, Calif.), and his associates. “If validated in a larger cohort, prospective ascertainment of telomere length at end of AML induction may permit individualized risk assessment for severe myelosuppression and toxicities with subsequent therapy, as well as clarify the influence of age and cytogenetic or molecular disease characteristics.”

Acute myeloid leukemia comprises about one in five childhood leukemias and requires intensive treatment that has led to mortality in up to 19% of patients, the researchers noted (Blood 2008 Feb 1;111[3]:1044-53).

“Prolonged, profound neutropenia is a well recognized risk factor for sepsis and invasive fungal infections, both major contributors to treatment-related mortality,” they added. In nonleukemic hematopoietic cells, telomere length is a “quantifiable host factor that may indicate potential risk for impaired bone marrow recovery after chemotherapy,” they wrote (J Clin Oncol. 2016 Jun 27. doi: 10.1200/JCO.2016.67.3467).

To test this hypothesis, the researchers analyzed paired diagnostic and remission bone marrow samples for 115 children with de novo AML enrolled in a Children’s Oncology Group protocol (AAML0531) that involved five chemotherapy courses. After each course, 62 patients reached absolute neutrophil count (ANC) recovery (500 cells/mcL) within the expected time frame, meaning that the recovery time was always less than one standard deviation of the group average. The remaining 53 patients had significantly delayed ANC recovery, meaning that they exceeded the group average by at least one standard deviation after at least two courses of chemotherapy.

The study size was adequate to detect a 0.2-unit difference in average telomere length between the two groups, the investigators noted. To measure telomere length, they estimated telomere content based on quantitative polymerase chain reaction (PCR) of bone marrow samples taken after induction chemotherapy. Then they compared patients who fell within the lowest quartile of telomere content to those in quartiles 2 through 4.

Telomere content was not associated with days to ANC recovery after the first three chemotherapy courses. After the fourth and fifth courses (intensifications two and three), patients had longer ANC recovery times than during the first three courses (mean, 45.2 days for intensification two and 43.7 days for intensification three). But patients with the shortest telomeres (that is, the patients in telomere content quartile 1) had significantly longer average ANC recovery times compared with patients in telomere content quartiles 2 through 4, both for intensifications two (P less than .001) and three (P = .002).

“Analysis of individual quartiles confirmed the association between less telomere content in quartile 1 and delays in ANC recovery,” the investigators noted. After they accounted for age at diagnosis, short telomere length remained a significant predictor of delayed ANC recovery after the fourth (P = .002) and fifth (P = .009) courses. Finally, DNA sequencing revealed evidence of telomere biology disorders, the investigators said.

The work was supported by an Alex’s Lemonade Stand Young Investigators Award, by a St. Baldrick’s Foundation Scholar Award, and by the National Institutes of Health. Mr. Gerbing and senior author Maria Gramatges, MD, had no disclosures. Two coinvestigators disclosed ties to Pfizer, Novartis, Dexcom, and several other pharmaceutical companies.

Among children with de novo acute myeloid leukemia, shorter telomere length at the end of induction chemotherapy predicted delayed bone marrow recovery in later courses, according to a study of 115 patients published online in the Journal of Clinical Oncology.

“This association was not related to differences in host factors, telomere maintenance gene variants, AML disease characteristics, or therapeutic exposures,” wrote Robert Gerbing of Children’s Oncology Group (Monrovia, Calif.), and his associates. “If validated in a larger cohort, prospective ascertainment of telomere length at end of AML induction may permit individualized risk assessment for severe myelosuppression and toxicities with subsequent therapy, as well as clarify the influence of age and cytogenetic or molecular disease characteristics.”

Acute myeloid leukemia comprises about one in five childhood leukemias and requires intensive treatment that has led to mortality in up to 19% of patients, the researchers noted (Blood 2008 Feb 1;111[3]:1044-53).

“Prolonged, profound neutropenia is a well recognized risk factor for sepsis and invasive fungal infections, both major contributors to treatment-related mortality,” they added. In nonleukemic hematopoietic cells, telomere length is a “quantifiable host factor that may indicate potential risk for impaired bone marrow recovery after chemotherapy,” they wrote (J Clin Oncol. 2016 Jun 27. doi: 10.1200/JCO.2016.67.3467).

To test this hypothesis, the researchers analyzed paired diagnostic and remission bone marrow samples for 115 children with de novo AML enrolled in a Children’s Oncology Group protocol (AAML0531) that involved five chemotherapy courses. After each course, 62 patients reached absolute neutrophil count (ANC) recovery (500 cells/mcL) within the expected time frame, meaning that the recovery time was always less than one standard deviation of the group average. The remaining 53 patients had significantly delayed ANC recovery, meaning that they exceeded the group average by at least one standard deviation after at least two courses of chemotherapy.

The study size was adequate to detect a 0.2-unit difference in average telomere length between the two groups, the investigators noted. To measure telomere length, they estimated telomere content based on quantitative polymerase chain reaction (PCR) of bone marrow samples taken after induction chemotherapy. Then they compared patients who fell within the lowest quartile of telomere content to those in quartiles 2 through 4.

Telomere content was not associated with days to ANC recovery after the first three chemotherapy courses. After the fourth and fifth courses (intensifications two and three), patients had longer ANC recovery times than during the first three courses (mean, 45.2 days for intensification two and 43.7 days for intensification three). But patients with the shortest telomeres (that is, the patients in telomere content quartile 1) had significantly longer average ANC recovery times compared with patients in telomere content quartiles 2 through 4, both for intensifications two (P less than .001) and three (P = .002).

“Analysis of individual quartiles confirmed the association between less telomere content in quartile 1 and delays in ANC recovery,” the investigators noted. After they accounted for age at diagnosis, short telomere length remained a significant predictor of delayed ANC recovery after the fourth (P = .002) and fifth (P = .009) courses. Finally, DNA sequencing revealed evidence of telomere biology disorders, the investigators said.

The work was supported by an Alex’s Lemonade Stand Young Investigators Award, by a St. Baldrick’s Foundation Scholar Award, and by the National Institutes of Health. Mr. Gerbing and senior author Maria Gramatges, MD, had no disclosures. Two coinvestigators disclosed ties to Pfizer, Novartis, Dexcom, and several other pharmaceutical companies.

Drug release in a cancer cell

Image from PNAS

A study published in Cell has shown that patient-derived cancer cell lines harbor most of the same genetic changes found in patients’ tumors and could therefore be used to learn how cancers are likely to respond to new drugs.

Researchers believe this discovery could help advance personalized cancer medicine by leading to results that help doctors predict the best available drugs or the most suitable clinical trials for each individual patient.

“We need better ways to figure out which groups of patients are more likely to respond to a new drug before we run complex and expensive clinical trials,” said study author Ultan McDermott, MD, PhD, of the Wellcome Trust Sanger Institute in Cambridge, UK.

“Our research shows that cancer cell lines do capture the molecular alterations found in tumors and so can be predictive of how a tumor will respond to a drug. This means the cell lines could tell us much more about how a tumor is likely to respond to a new drug before we try to test it in patients. We hope this information will ultimately help in the design of clinical trials that target those patients with the greatest likelihood of benefiting from treatment.”

The researchers said this is the first systematic, large-scale study to combine molecular data from patients, cancer cell lines, and drug sensitivity.

For the study, the team looked at genetic mutations known to cause cancer in more than 11,000 patient samples of 29 different cancer types, including acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, diffuse large B-cell lymphoma, and multiple myeloma.

The researchers built a catalogue of the genetic changes that cause cancer in patients and mapped these alterations onto 1000 cancer cell lines. Next, they tested the cell lines for sensitivity to 265 different cancer drugs to understand which of these changes affect sensitivity.

This revealed that the majority of molecular abnormalities found in patients’ cancers are also found in cancer cells in the laboratory.

The work also showed that many of the molecular abnormalities detected in the thousands of patient samples can, both individually and in combination, have a strong effect on whether a particular drug affects a cancer cell’s survival.

The results suggest cancer cell lines could be better exploited to learn which drugs offer the most effective treatment to which patients.

“If a cell line has the same genetic features as a patient’s tumor, and that cell line responded to a specific drug, we can focus new research on this finding,” said study author Francesco Iorio, PhD, of the European Bioinformatics Institute in Cambridge, UK.

“This could ultimately help assign cancer patients into more precise groups based on how likely they are to respond to therapy. This resource can really help cancer research. Most importantly, it can be used to create tools for doctors to select a clinical trial which is most promising for their cancer patient. That is still a way off, but we are heading in the right direction.”

Drug release in a cancer cell

Image from PNAS

A study published in Cell has shown that patient-derived cancer cell lines harbor most of the same genetic changes found in patients’ tumors and could therefore be used to learn how cancers are likely to respond to new drugs.

Researchers believe this discovery could help advance personalized cancer medicine by leading to results that help doctors predict the best available drugs or the most suitable clinical trials for each individual patient.

“We need better ways to figure out which groups of patients are more likely to respond to a new drug before we run complex and expensive clinical trials,” said study author Ultan McDermott, MD, PhD, of the Wellcome Trust Sanger Institute in Cambridge, UK.

“Our research shows that cancer cell lines do capture the molecular alterations found in tumors and so can be predictive of how a tumor will respond to a drug. This means the cell lines could tell us much more about how a tumor is likely to respond to a new drug before we try to test it in patients. We hope this information will ultimately help in the design of clinical trials that target those patients with the greatest likelihood of benefiting from treatment.”

The researchers said this is the first systematic, large-scale study to combine molecular data from patients, cancer cell lines, and drug sensitivity.

For the study, the team looked at genetic mutations known to cause cancer in more than 11,000 patient samples of 29 different cancer types, including acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, diffuse large B-cell lymphoma, and multiple myeloma.

The researchers built a catalogue of the genetic changes that cause cancer in patients and mapped these alterations onto 1000 cancer cell lines. Next, they tested the cell lines for sensitivity to 265 different cancer drugs to understand which of these changes affect sensitivity.

This revealed that the majority of molecular abnormalities found in patients’ cancers are also found in cancer cells in the laboratory.

The work also showed that many of the molecular abnormalities detected in the thousands of patient samples can, both individually and in combination, have a strong effect on whether a particular drug affects a cancer cell’s survival.

The results suggest cancer cell lines could be better exploited to learn which drugs offer the most effective treatment to which patients.

“If a cell line has the same genetic features as a patient’s tumor, and that cell line responded to a specific drug, we can focus new research on this finding,” said study author Francesco Iorio, PhD, of the European Bioinformatics Institute in Cambridge, UK.

“This could ultimately help assign cancer patients into more precise groups based on how likely they are to respond to therapy. This resource can really help cancer research. Most importantly, it can be used to create tools for doctors to select a clinical trial which is most promising for their cancer patient. That is still a way off, but we are heading in the right direction.”

Drug release in a cancer cell

Image from PNAS

A study published in Cell has shown that patient-derived cancer cell lines harbor most of the same genetic changes found in patients’ tumors and could therefore be used to learn how cancers are likely to respond to new drugs.

Researchers believe this discovery could help advance personalized cancer medicine by leading to results that help doctors predict the best available drugs or the most suitable clinical trials for each individual patient.

“We need better ways to figure out which groups of patients are more likely to respond to a new drug before we run complex and expensive clinical trials,” said study author Ultan McDermott, MD, PhD, of the Wellcome Trust Sanger Institute in Cambridge, UK.

“Our research shows that cancer cell lines do capture the molecular alterations found in tumors and so can be predictive of how a tumor will respond to a drug. This means the cell lines could tell us much more about how a tumor is likely to respond to a new drug before we try to test it in patients. We hope this information will ultimately help in the design of clinical trials that target those patients with the greatest likelihood of benefiting from treatment.”

The researchers said this is the first systematic, large-scale study to combine molecular data from patients, cancer cell lines, and drug sensitivity.

For the study, the team looked at genetic mutations known to cause cancer in more than 11,000 patient samples of 29 different cancer types, including acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, diffuse large B-cell lymphoma, and multiple myeloma.

The researchers built a catalogue of the genetic changes that cause cancer in patients and mapped these alterations onto 1000 cancer cell lines. Next, they tested the cell lines for sensitivity to 265 different cancer drugs to understand which of these changes affect sensitivity.

This revealed that the majority of molecular abnormalities found in patients’ cancers are also found in cancer cells in the laboratory.

The work also showed that many of the molecular abnormalities detected in the thousands of patient samples can, both individually and in combination, have a strong effect on whether a particular drug affects a cancer cell’s survival.

The results suggest cancer cell lines could be better exploited to learn which drugs offer the most effective treatment to which patients.

“If a cell line has the same genetic features as a patient’s tumor, and that cell line responded to a specific drug, we can focus new research on this finding,” said study author Francesco Iorio, PhD, of the European Bioinformatics Institute in Cambridge, UK.

“This could ultimately help assign cancer patients into more precise groups based on how likely they are to respond to therapy. This resource can really help cancer research. Most importantly, it can be used to create tools for doctors to select a clinical trial which is most promising for their cancer patient. That is still a way off, but we are heading in the right direction.”

AML cells

Research published in Nature Communications suggests that mutations in the ZBTB7A gene are associated with t(8;21)-rearranged acute myeloid leukemia (AML).

Investigators believe these mutations may be one of the “missing links” in RUNX1/RUNX1T1-driven leukemogenesis.

The team analyzed samples from 56 patients with t(8;21)-rearranged AML and identified recurring ZBTB7A mutations in 23% of those samples.

This included missense and truncating mutations that resulted in alteration or loss of the C-terminal zinc-finger domain of ZBTB7A.

The investigators noted that the transcription factor ZBTB7A is important for hematopoietic lineage fate decisions and for the regulation of glycolysis.

So the team was not surprised to find that ZBTB7A mutations boosted the energy metabolism in leukemia cells.

“In healthy cells, the active ZBTB7A gene acts like a parking brake on metabolism,” said study author Philipp Greif, MD, of Ludwig-Maximilians-Universität München in Munich, Germany.

“If the gene is defective, cancer cells get more energy to use for proliferation.”

Dr Greif and his colleagues also found they could reduce the growth rate of AML cells by increasing levels of active ZBTB7A.

And the team observed an indication of ZBTB7A’s growth-inhibiting effects in the clinic. Leukemia patients with higher levels of ZBTB7A expression had significantly better chances of survival than patients in whom the gene was hardly active or not active at all.

Now, the investigators plan to explore whether ZBTB7A expression can be used to customize therapies for individual patients. They also believe their discovery is a promising starting point for developing new approaches to treat AML.

“It might be possible to use specially modified glucose molecules to block the energy production process in AML cells,” said study author Luise Hartmann, of Ludwig-Maximilians-Universität München.

“Initial clinical trials in other cancers have already shown that these agents are well-tolerated by patients.”

AML cells

Research published in Nature Communications suggests that mutations in the ZBTB7A gene are associated with t(8;21)-rearranged acute myeloid leukemia (AML).

Investigators believe these mutations may be one of the “missing links” in RUNX1/RUNX1T1-driven leukemogenesis.

The team analyzed samples from 56 patients with t(8;21)-rearranged AML and identified recurring ZBTB7A mutations in 23% of those samples.

This included missense and truncating mutations that resulted in alteration or loss of the C-terminal zinc-finger domain of ZBTB7A.

The investigators noted that the transcription factor ZBTB7A is important for hematopoietic lineage fate decisions and for the regulation of glycolysis.

So the team was not surprised to find that ZBTB7A mutations boosted the energy metabolism in leukemia cells.

“In healthy cells, the active ZBTB7A gene acts like a parking brake on metabolism,” said study author Philipp Greif, MD, of Ludwig-Maximilians-Universität München in Munich, Germany.

“If the gene is defective, cancer cells get more energy to use for proliferation.”

Dr Greif and his colleagues also found they could reduce the growth rate of AML cells by increasing levels of active ZBTB7A.

And the team observed an indication of ZBTB7A’s growth-inhibiting effects in the clinic. Leukemia patients with higher levels of ZBTB7A expression had significantly better chances of survival than patients in whom the gene was hardly active or not active at all.

Now, the investigators plan to explore whether ZBTB7A expression can be used to customize therapies for individual patients. They also believe their discovery is a promising starting point for developing new approaches to treat AML.

“It might be possible to use specially modified glucose molecules to block the energy production process in AML cells,” said study author Luise Hartmann, of Ludwig-Maximilians-Universität München.

“Initial clinical trials in other cancers have already shown that these agents are well-tolerated by patients.”

AML cells

Research published in Nature Communications suggests that mutations in the ZBTB7A gene are associated with t(8;21)-rearranged acute myeloid leukemia (AML).

Investigators believe these mutations may be one of the “missing links” in RUNX1/RUNX1T1-driven leukemogenesis.

The team analyzed samples from 56 patients with t(8;21)-rearranged AML and identified recurring ZBTB7A mutations in 23% of those samples.

This included missense and truncating mutations that resulted in alteration or loss of the C-terminal zinc-finger domain of ZBTB7A.

The investigators noted that the transcription factor ZBTB7A is important for hematopoietic lineage fate decisions and for the regulation of glycolysis.

So the team was not surprised to find that ZBTB7A mutations boosted the energy metabolism in leukemia cells.

“In healthy cells, the active ZBTB7A gene acts like a parking brake on metabolism,” said study author Philipp Greif, MD, of Ludwig-Maximilians-Universität München in Munich, Germany.

“If the gene is defective, cancer cells get more energy to use for proliferation.”

Dr Greif and his colleagues also found they could reduce the growth rate of AML cells by increasing levels of active ZBTB7A.

And the team observed an indication of ZBTB7A’s growth-inhibiting effects in the clinic. Leukemia patients with higher levels of ZBTB7A expression had significantly better chances of survival than patients in whom the gene was hardly active or not active at all.

Now, the investigators plan to explore whether ZBTB7A expression can be used to customize therapies for individual patients. They also believe their discovery is a promising starting point for developing new approaches to treat AML.

“It might be possible to use specially modified glucose molecules to block the energy production process in AML cells,” said study author Luise Hartmann, of Ludwig-Maximilians-Universität München.

“Initial clinical trials in other cancers have already shown that these agents are well-tolerated by patients.”

Micrograph showing AML

New research suggests that E proteins and their antagonists, Id proteins, can play key roles in acute myeloid leukemia (AML).

The study showed that overexpression of the Id2 protein or knockdown of the E2-2 protein can suppress both mixed-lineage leukemia (MLL)-rearranged AML and t(8;21) AML.

These findings, published in Cancer Cell, suggest the Id2/E-protein axis may be a promising therapeutic target for AML.

“There is a particularly urgent need for new, targeted, drug-based therapies for AML, and with every discovery of what’s driving the cancer, we take a step closer to achieving that,” said study author Ricky Johnstone, PhD, of Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia.

“What we found in this case was the suppression of Id2 protein plays an important, and previously unrecognized, role in allowing MLL re-arranged AML cancer cells to take hold and spread. Drugs that influence levels of this protein, or stop it being suppressed by the cancer, could provide a much-needed new avenue to combatting this disease.”

The researchers first found that Id2 regulates leukemia stem cell (LSC) potential. Specifically, low Id2 expression is associated with LSC enrichment, and Id2 overexpression hinders leukemia development.

Further investigation revealed that the fusion protein MLL-AF9 suppresses Id2 and activates E2-2 expression, while E2-2 depletion phenocopies Id2 overexpression in MLL-AF9-AML cells.

The team also found that Id2’s tumor-suppressive function is conserved in t(8;21) AML. And low expression of Id2 and its associated gene signature are associated with poor prognosis in patients with MLL-rearranged AML or t(8;21) AML.

Micrograph showing AML

New research suggests that E proteins and their antagonists, Id proteins, can play key roles in acute myeloid leukemia (AML).

The study showed that overexpression of the Id2 protein or knockdown of the E2-2 protein can suppress both mixed-lineage leukemia (MLL)-rearranged AML and t(8;21) AML.

These findings, published in Cancer Cell, suggest the Id2/E-protein axis may be a promising therapeutic target for AML.

“There is a particularly urgent need for new, targeted, drug-based therapies for AML, and with every discovery of what’s driving the cancer, we take a step closer to achieving that,” said study author Ricky Johnstone, PhD, of Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia.

“What we found in this case was the suppression of Id2 protein plays an important, and previously unrecognized, role in allowing MLL re-arranged AML cancer cells to take hold and spread. Drugs that influence levels of this protein, or stop it being suppressed by the cancer, could provide a much-needed new avenue to combatting this disease.”

The researchers first found that Id2 regulates leukemia stem cell (LSC) potential. Specifically, low Id2 expression is associated with LSC enrichment, and Id2 overexpression hinders leukemia development.

Further investigation revealed that the fusion protein MLL-AF9 suppresses Id2 and activates E2-2 expression, while E2-2 depletion phenocopies Id2 overexpression in MLL-AF9-AML cells.

The team also found that Id2’s tumor-suppressive function is conserved in t(8;21) AML. And low expression of Id2 and its associated gene signature are associated with poor prognosis in patients with MLL-rearranged AML or t(8;21) AML.

Micrograph showing AML

New research suggests that E proteins and their antagonists, Id proteins, can play key roles in acute myeloid leukemia (AML).

The study showed that overexpression of the Id2 protein or knockdown of the E2-2 protein can suppress both mixed-lineage leukemia (MLL)-rearranged AML and t(8;21) AML.

These findings, published in Cancer Cell, suggest the Id2/E-protein axis may be a promising therapeutic target for AML.

“There is a particularly urgent need for new, targeted, drug-based therapies for AML, and with every discovery of what’s driving the cancer, we take a step closer to achieving that,” said study author Ricky Johnstone, PhD, of Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia.

“What we found in this case was the suppression of Id2 protein plays an important, and previously unrecognized, role in allowing MLL re-arranged AML cancer cells to take hold and spread. Drugs that influence levels of this protein, or stop it being suppressed by the cancer, could provide a much-needed new avenue to combatting this disease.”

The researchers first found that Id2 regulates leukemia stem cell (LSC) potential. Specifically, low Id2 expression is associated with LSC enrichment, and Id2 overexpression hinders leukemia development.

Further investigation revealed that the fusion protein MLL-AF9 suppresses Id2 and activates E2-2 expression, while E2-2 depletion phenocopies Id2 overexpression in MLL-AF9-AML cells.

The team also found that Id2’s tumor-suppressive function is conserved in t(8;21) AML. And low expression of Id2 and its associated gene signature are associated with poor prognosis in patients with MLL-rearranged AML or t(8;21) AML.

Neutrophil engulfing bacteria

Image by Volker Brinkmann

Researchers say they have discovered a way to predict which children with acute myeloid leukemia (AML) are at the highest risk of delayed neutrophil recovery.

The team examined the role of telomeres in neutrophil recovery and found that the length of a patient’s telomeres can indicate the rate of recovery following chemotherapy.

The group reported their findings in the Journal of Clinical Oncology.

“We were interested in telomere length as a marker of blood count recovery because defects in telomere maintenance are known risks for bone marrow failure and aplastic anemia,” said study author Maria Monica Gramatges, MD, PhD, of Baylor College of Medicine in Houston, Texas.

“We know that up to 15% to 20% of children can take 2 months or longer to recover their blood counts after a course of AML chemotherapy. Our goal was to understand if these children had an underlying genetic predisposition associated with an impaired capacity for recovery.”

Dr Gramatges and her colleagues hypothesized that short telomere length could be associated with a delay in neutrophil recovery.

So they obtained bone marrow samples from AML patients who recovered as expected (within 30 days) after each chemotherapy course (n=62), and from AML patients who experienced significant delays in recovery after chemotherapy (n=53).

The team then measured telomere length on each subject and categorized the group by quartile, from shortest to longest.

Subjects in the quartile with the shortest telomere lengths took the longest to recover, especially during the last 2 courses of chemotherapy. In an adjusted analysis, lower telomere content was significantly associated with prolonged neutropenia after the fourth (P=0.002) and fifth courses of chemotherapy (P=0.009).

The researchers said these results support the hypothesis that telomeres are an indicator of capacity for neutrophil recovery following chemotherapy.

Dr Gramatges hopes the results of this study will be helpful in further understanding which children are at a higher risk for prolonged myelosuppression and how to target those children with modified treatments, improved supportive care, and closer monitoring in order to prevent potential complications such as severe infections.

“A significant proportion of children with AML suffer from treatment-related toxicities, with some succumbing to complications of the therapies we give, rather than from the actual cancer itself,” Dr Gramatges said.

“We hope this research will help us identify those who are at a higher risk for delayed recovery and use this knowledge to reduce the morbidity and mortality associated with AML treatment.”

Neutrophil engulfing bacteria

Image by Volker Brinkmann

Researchers say they have discovered a way to predict which children with acute myeloid leukemia (AML) are at the highest risk of delayed neutrophil recovery.

The team examined the role of telomeres in neutrophil recovery and found that the length of a patient’s telomeres can indicate the rate of recovery following chemotherapy.

The group reported their findings in the Journal of Clinical Oncology.

“We were interested in telomere length as a marker of blood count recovery because defects in telomere maintenance are known risks for bone marrow failure and aplastic anemia,” said study author Maria Monica Gramatges, MD, PhD, of Baylor College of Medicine in Houston, Texas.

“We know that up to 15% to 20% of children can take 2 months or longer to recover their blood counts after a course of AML chemotherapy. Our goal was to understand if these children had an underlying genetic predisposition associated with an impaired capacity for recovery.”

Dr Gramatges and her colleagues hypothesized that short telomere length could be associated with a delay in neutrophil recovery.

So they obtained bone marrow samples from AML patients who recovered as expected (within 30 days) after each chemotherapy course (n=62), and from AML patients who experienced significant delays in recovery after chemotherapy (n=53).

The team then measured telomere length on each subject and categorized the group by quartile, from shortest to longest.

Subjects in the quartile with the shortest telomere lengths took the longest to recover, especially during the last 2 courses of chemotherapy. In an adjusted analysis, lower telomere content was significantly associated with prolonged neutropenia after the fourth (P=0.002) and fifth courses of chemotherapy (P=0.009).

The researchers said these results support the hypothesis that telomeres are an indicator of capacity for neutrophil recovery following chemotherapy.

Dr Gramatges hopes the results of this study will be helpful in further understanding which children are at a higher risk for prolonged myelosuppression and how to target those children with modified treatments, improved supportive care, and closer monitoring in order to prevent potential complications such as severe infections.

“A significant proportion of children with AML suffer from treatment-related toxicities, with some succumbing to complications of the therapies we give, rather than from the actual cancer itself,” Dr Gramatges said.

“We hope this research will help us identify those who are at a higher risk for delayed recovery and use this knowledge to reduce the morbidity and mortality associated with AML treatment.”

Neutrophil engulfing bacteria

Image by Volker Brinkmann

Researchers say they have discovered a way to predict which children with acute myeloid leukemia (AML) are at the highest risk of delayed neutrophil recovery.

The team examined the role of telomeres in neutrophil recovery and found that the length of a patient’s telomeres can indicate the rate of recovery following chemotherapy.

The group reported their findings in the Journal of Clinical Oncology.

“We were interested in telomere length as a marker of blood count recovery because defects in telomere maintenance are known risks for bone marrow failure and aplastic anemia,” said study author Maria Monica Gramatges, MD, PhD, of Baylor College of Medicine in Houston, Texas.

“We know that up to 15% to 20% of children can take 2 months or longer to recover their blood counts after a course of AML chemotherapy. Our goal was to understand if these children had an underlying genetic predisposition associated with an impaired capacity for recovery.”

Dr Gramatges and her colleagues hypothesized that short telomere length could be associated with a delay in neutrophil recovery.

So they obtained bone marrow samples from AML patients who recovered as expected (within 30 days) after each chemotherapy course (n=62), and from AML patients who experienced significant delays in recovery after chemotherapy (n=53).

The team then measured telomere length on each subject and categorized the group by quartile, from shortest to longest.

Subjects in the quartile with the shortest telomere lengths took the longest to recover, especially during the last 2 courses of chemotherapy. In an adjusted analysis, lower telomere content was significantly associated with prolonged neutropenia after the fourth (P=0.002) and fifth courses of chemotherapy (P=0.009).

The researchers said these results support the hypothesis that telomeres are an indicator of capacity for neutrophil recovery following chemotherapy.

Dr Gramatges hopes the results of this study will be helpful in further understanding which children are at a higher risk for prolonged myelosuppression and how to target those children with modified treatments, improved supportive care, and closer monitoring in order to prevent potential complications such as severe infections.

“A significant proportion of children with AML suffer from treatment-related toxicities, with some succumbing to complications of the therapies we give, rather than from the actual cancer itself,” Dr Gramatges said.

“We hope this research will help us identify those who are at a higher risk for delayed recovery and use this knowledge to reduce the morbidity and mortality associated with AML treatment.”

Patient receiving chemotherapy

Photo by Rhoda Baer

The risk of death from acute myeloid leukemia (AML) may be influenced by where a patient lives, according to a study published in Cancer.

Three regions in North Carolina were found to be associated with a higher risk of death, when compared to the rest of the state.

Patients had a significantly higher risk of death if they lived in northeastern North Carolina (from Wilson to Roanoke Rapids), in a region around Greenville, and a region around Wake County, including Durham County.

The increased risk remained even when the researchers controlled for other factors.

“The geographic survival disparities we found could not be explained by other sociodemographic variables or proximity to experienced treating facilities,” said study author Ashley Freeman, MD, of the University of North Carolina (UNC) in Chapel Hill.

“This raises the possibility that more complex features of the local healthcare infrastructure, including provider referral and practice patterns, are affecting patient outcomes.”

To study death rates from AML across North Carolina, Dr Freeman and her colleagues analyzed data on 553 adults who were diagnosed with AML between 2003 and 2009 and received inpatient chemotherapy within 30 days of diagnosis.

The team used the UNC Lineberger Integrated Cancer Information and Surveillance System, a database that links insurance claims information to a state information database called the NC Cancer Registry.

The researchers assessed the risk of death in 9 regions defined by the North Carolina Area Health Education Centers (AHEC) Program, a program established in 1972 to address physician shortages and the uneven distribution of healthcare services in North Carolina.

“We looked at geographic disparities because we are trying to improve outcomes for all citizens in North Carolina, consistent with the mission of our cancer center,” said William A. Wood, MD, of UNC.

“We are also trying to find situations in which disparities shouldn’t exist but do for arbitrary reasons—such as where a patient happens to live—so that we can figure out how to improve equity across the state.”

The researchers determined that a region around Greensboro had the lowest risk of death for AML.

Compared to the Greensboro region, the risk of death was 4 times higher in an area of northeastern North Carolina that included Roanoke Rapids, Rocky Mount, and Wilson—the highest in the state.

Compared to the Greensboro region, the risk of death was more than 2 times greater in the eastern region of the state around Greenville, and it was nearly twice as high in the region around Wake County.

“There are areas of the state where there is an elevated mortality, and we need to better understand the factors that are driving that—whether they’re environmental, patient, or provider-related,” said Anne-Marie Meyer, PhD, of UNC.

Nearly half of patients in the study received their care at hospitals not affiliated with one of the state’s 3 National Cancer Institute (NCI) comprehensive cancer centers.

The researchers did not find a significant link between the risk of death and the distance from patients’ homes to their treating facility or the nearest NCI-designated center.

And there was no significant difference in the risk of death at 1 year between patients who received treatment at an NCI-designated cancer center and those who did not. However, patients with a more serious prognosis were more likely to be treated at an NCI-designated cancer center.

The researchers did identify regional differences in healthcare resources. “Area L,” which is the name for the region in northeastern North Carolina that spans from Wilson to Roanoke Rapids, for example, has some of the lowest proportion of general practitioner physicians and radiation oncologists, as well as the highest burden of disease.

However, it is not clear why the disparities continued even after the researchers controlled for regional factors like poverty and education. The team believes other factors could be involved, such as the providers’ experience with treating rare or complex diseases or how supportive care is delivered.

Although there was not a significant association between survival and treatment at an NCI-designated center, there may be other features of treatment facilities, such as patient volume and academic affiliation, that are important for patient outcomes.

The researchers said their next step is to identify those factors and develop programs to try to close the gaps.

“The message here is that acute myeloid leukemia is representative of diseases that are uncommon, involve high-complexity care, and have high risk for morbidity and mortality,” Dr Wood said.

“If we can figure out how to coordinate and improve delivery of effective interventions for this disease throughout the state of North Carolina, then we may be able to develop a model for improving outcomes in many other diseases throughout the state as well.”

Patient receiving chemotherapy

Photo by Rhoda Baer

The risk of death from acute myeloid leukemia (AML) may be influenced by where a patient lives, according to a study published in Cancer.

Three regions in North Carolina were found to be associated with a higher risk of death, when compared to the rest of the state.

Patients had a significantly higher risk of death if they lived in northeastern North Carolina (from Wilson to Roanoke Rapids), in a region around Greenville, and a region around Wake County, including Durham County.

The increased risk remained even when the researchers controlled for other factors.

“The geographic survival disparities we found could not be explained by other sociodemographic variables or proximity to experienced treating facilities,” said study author Ashley Freeman, MD, of the University of North Carolina (UNC) in Chapel Hill.

“This raises the possibility that more complex features of the local healthcare infrastructure, including provider referral and practice patterns, are affecting patient outcomes.”

To study death rates from AML across North Carolina, Dr Freeman and her colleagues analyzed data on 553 adults who were diagnosed with AML between 2003 and 2009 and received inpatient chemotherapy within 30 days of diagnosis.

The team used the UNC Lineberger Integrated Cancer Information and Surveillance System, a database that links insurance claims information to a state information database called the NC Cancer Registry.

The researchers assessed the risk of death in 9 regions defined by the North Carolina Area Health Education Centers (AHEC) Program, a program established in 1972 to address physician shortages and the uneven distribution of healthcare services in North Carolina.

“We looked at geographic disparities because we are trying to improve outcomes for all citizens in North Carolina, consistent with the mission of our cancer center,” said William A. Wood, MD, of UNC.

“We are also trying to find situations in which disparities shouldn’t exist but do for arbitrary reasons—such as where a patient happens to live—so that we can figure out how to improve equity across the state.”

The researchers determined that a region around Greensboro had the lowest risk of death for AML.

Compared to the Greensboro region, the risk of death was 4 times higher in an area of northeastern North Carolina that included Roanoke Rapids, Rocky Mount, and Wilson—the highest in the state.

Compared to the Greensboro region, the risk of death was more than 2 times greater in the eastern region of the state around Greenville, and it was nearly twice as high in the region around Wake County.

“There are areas of the state where there is an elevated mortality, and we need to better understand the factors that are driving that—whether they’re environmental, patient, or provider-related,” said Anne-Marie Meyer, PhD, of UNC.

Nearly half of patients in the study received their care at hospitals not affiliated with one of the state’s 3 National Cancer Institute (NCI) comprehensive cancer centers.

The researchers did not find a significant link between the risk of death and the distance from patients’ homes to their treating facility or the nearest NCI-designated center.

And there was no significant difference in the risk of death at 1 year between patients who received treatment at an NCI-designated cancer center and those who did not. However, patients with a more serious prognosis were more likely to be treated at an NCI-designated cancer center.

The researchers did identify regional differences in healthcare resources. “Area L,” which is the name for the region in northeastern North Carolina that spans from Wilson to Roanoke Rapids, for example, has some of the lowest proportion of general practitioner physicians and radiation oncologists, as well as the highest burden of disease.

However, it is not clear why the disparities continued even after the researchers controlled for regional factors like poverty and education. The team believes other factors could be involved, such as the providers’ experience with treating rare or complex diseases or how supportive care is delivered.

Although there was not a significant association between survival and treatment at an NCI-designated center, there may be other features of treatment facilities, such as patient volume and academic affiliation, that are important for patient outcomes.

The researchers said their next step is to identify those factors and develop programs to try to close the gaps.

“The message here is that acute myeloid leukemia is representative of diseases that are uncommon, involve high-complexity care, and have high risk for morbidity and mortality,” Dr Wood said.

“If we can figure out how to coordinate and improve delivery of effective interventions for this disease throughout the state of North Carolina, then we may be able to develop a model for improving outcomes in many other diseases throughout the state as well.”

Patient receiving chemotherapy

Photo by Rhoda Baer

The risk of death from acute myeloid leukemia (AML) may be influenced by where a patient lives, according to a study published in Cancer.

Three regions in North Carolina were found to be associated with a higher risk of death, when compared to the rest of the state.

Patients had a significantly higher risk of death if they lived in northeastern North Carolina (from Wilson to Roanoke Rapids), in a region around Greenville, and a region around Wake County, including Durham County.

The increased risk remained even when the researchers controlled for other factors.

“The geographic survival disparities we found could not be explained by other sociodemographic variables or proximity to experienced treating facilities,” said study author Ashley Freeman, MD, of the University of North Carolina (UNC) in Chapel Hill.

“This raises the possibility that more complex features of the local healthcare infrastructure, including provider referral and practice patterns, are affecting patient outcomes.”

To study death rates from AML across North Carolina, Dr Freeman and her colleagues analyzed data on 553 adults who were diagnosed with AML between 2003 and 2009 and received inpatient chemotherapy within 30 days of diagnosis.

The team used the UNC Lineberger Integrated Cancer Information and Surveillance System, a database that links insurance claims information to a state information database called the NC Cancer Registry.

The researchers assessed the risk of death in 9 regions defined by the North Carolina Area Health Education Centers (AHEC) Program, a program established in 1972 to address physician shortages and the uneven distribution of healthcare services in North Carolina.

“We looked at geographic disparities because we are trying to improve outcomes for all citizens in North Carolina, consistent with the mission of our cancer center,” said William A. Wood, MD, of UNC.

“We are also trying to find situations in which disparities shouldn’t exist but do for arbitrary reasons—such as where a patient happens to live—so that we can figure out how to improve equity across the state.”

The researchers determined that a region around Greensboro had the lowest risk of death for AML.

Compared to the Greensboro region, the risk of death was 4 times higher in an area of northeastern North Carolina that included Roanoke Rapids, Rocky Mount, and Wilson—the highest in the state.

Compared to the Greensboro region, the risk of death was more than 2 times greater in the eastern region of the state around Greenville, and it was nearly twice as high in the region around Wake County.

“There are areas of the state where there is an elevated mortality, and we need to better understand the factors that are driving that—whether they’re environmental, patient, or provider-related,” said Anne-Marie Meyer, PhD, of UNC.

Nearly half of patients in the study received their care at hospitals not affiliated with one of the state’s 3 National Cancer Institute (NCI) comprehensive cancer centers.

The researchers did not find a significant link between the risk of death and the distance from patients’ homes to their treating facility or the nearest NCI-designated center.

And there was no significant difference in the risk of death at 1 year between patients who received treatment at an NCI-designated cancer center and those who did not. However, patients with a more serious prognosis were more likely to be treated at an NCI-designated cancer center.

The researchers did identify regional differences in healthcare resources. “Area L,” which is the name for the region in northeastern North Carolina that spans from Wilson to Roanoke Rapids, for example, has some of the lowest proportion of general practitioner physicians and radiation oncologists, as well as the highest burden of disease.

However, it is not clear why the disparities continued even after the researchers controlled for regional factors like poverty and education. The team believes other factors could be involved, such as the providers’ experience with treating rare or complex diseases or how supportive care is delivered.

Although there was not a significant association between survival and treatment at an NCI-designated center, there may be other features of treatment facilities, such as patient volume and academic affiliation, that are important for patient outcomes.

The researchers said their next step is to identify those factors and develop programs to try to close the gaps.

“The message here is that acute myeloid leukemia is representative of diseases that are uncommon, involve high-complexity care, and have high risk for morbidity and mortality,” Dr Wood said.

“If we can figure out how to coordinate and improve delivery of effective interventions for this disease throughout the state of North Carolina, then we may be able to develop a model for improving outcomes in many other diseases throughout the state as well.”

CMV infection

Small studies have suggested that early cytomegalovirus (CMV) reactivation may protect against leukemia relapse and even death after hematopoietic stem cell transplant.

However, a new study, based on data from about 9500 patients, suggests otherwise.

Results showed no association between CMV reactivation and relapse but suggested CMV reactivation increases the risk of non-relapse mortality.

Researchers reported these findings in Blood.

“The original purpose of the study was to confirm that CMV infection may prevent leukemia relapse, prevent death, and become a major therapeutic tool for improving patient survival rates,” said study author Pierre Teira, MD, of the University of Montreal in Quebec, Canada.

“However, we found the exact opposite. Our results clearly show that . . . the virus not only does not prevent leukemia relapse [it] also remains a major factor associated with the risk of death. Monitoring of CMV after transplantation remains a priority for patients.”

For this study, Dr Teira and his colleagues analyzed data from 9469 patients who received a transplant between 2003 and 2010.

The patients had acute myeloid leukemia (AML, n=5310), acute lymphoblastic leukemia (ALL, n=1883), chronic myeloid leukemia (CML, n=1079), or myelodysplastic syndromes (MDS, n=1197).

The median time to initial CMV reactivation was 41 days (range, 1-362 days).

The researchers found no significant association between CMV reactivation and disease relapse for AML (P=0.60), ALL (P=0.08), CML (P=0.94), or MDS (P=0.58).

However, CMV reactivation was associated with a significantly higher risk of nonrelapse mortality for AML (P<0.0001), ALL (P<0.0001), CML (P=0.0004), and MDS (P=0.0002).

Therefore, CMV reactivation was associated with significantly lower overall survival for AML (P<0.0001), ALL (P<0.0001), CML (P=0.0005), and MDS (P=0.003).

“Deaths due to uncontrolled CMV reactivation are virtually zero in this study, so uncontrolled CMV reactivation is not what reduces survival rates after transplantation,” Dr Teira noted. “The link between this common virus and increased risk of death remains a biological mystery.”

One possible explanation is that CMV decreases the ability of the patient’s immune system to fight against other types of infection. This is supported by the fact that death rates from infections other than CMV are higher in patients infected with CMV or patients whose donors were.

For researchers, the next step is therefore to verify whether the latest generation of anti-CMV treatments can prevent both reactivation of the virus and weakening of the patient’s immune system against other types of infection in the presence of CMV infection.

“CMV has a complex impact on the outcomes for transplant patients, and, each year, more than 30,000 patients around the world receive bone marrow transplants from donors,” Dr Teira said.

“It is therefore essential for future research to better understand the role played by CMV after bone marrow transplantation and improve the chances of success of the transplant. This will help to better choose the right donor for the right patient.”

CMV infection

Small studies have suggested that early cytomegalovirus (CMV) reactivation may protect against leukemia relapse and even death after hematopoietic stem cell transplant.

However, a new study, based on data from about 9500 patients, suggests otherwise.

Results showed no association between CMV reactivation and relapse but suggested CMV reactivation increases the risk of non-relapse mortality.

Researchers reported these findings in Blood.

“The original purpose of the study was to confirm that CMV infection may prevent leukemia relapse, prevent death, and become a major therapeutic tool for improving patient survival rates,” said study author Pierre Teira, MD, of the University of Montreal in Quebec, Canada.

“However, we found the exact opposite. Our results clearly show that . . . the virus not only does not prevent leukemia relapse [it] also remains a major factor associated with the risk of death. Monitoring of CMV after transplantation remains a priority for patients.”

For this study, Dr Teira and his colleagues analyzed data from 9469 patients who received a transplant between 2003 and 2010.

The patients had acute myeloid leukemia (AML, n=5310), acute lymphoblastic leukemia (ALL, n=1883), chronic myeloid leukemia (CML, n=1079), or myelodysplastic syndromes (MDS, n=1197).

The median time to initial CMV reactivation was 41 days (range, 1-362 days).

The researchers found no significant association between CMV reactivation and disease relapse for AML (P=0.60), ALL (P=0.08), CML (P=0.94), or MDS (P=0.58).

However, CMV reactivation was associated with a significantly higher risk of nonrelapse mortality for AML (P<0.0001), ALL (P<0.0001), CML (P=0.0004), and MDS (P=0.0002).

Therefore, CMV reactivation was associated with significantly lower overall survival for AML (P<0.0001), ALL (P<0.0001), CML (P=0.0005), and MDS (P=0.003).

“Deaths due to uncontrolled CMV reactivation are virtually zero in this study, so uncontrolled CMV reactivation is not what reduces survival rates after transplantation,” Dr Teira noted. “The link between this common virus and increased risk of death remains a biological mystery.”

One possible explanation is that CMV decreases the ability of the patient’s immune system to fight against other types of infection. This is supported by the fact that death rates from infections other than CMV are higher in patients infected with CMV or patients whose donors were.

For researchers, the next step is therefore to verify whether the latest generation of anti-CMV treatments can prevent both reactivation of the virus and weakening of the patient’s immune system against other types of infection in the presence of CMV infection.

“CMV has a complex impact on the outcomes for transplant patients, and, each year, more than 30,000 patients around the world receive bone marrow transplants from donors,” Dr Teira said.

“It is therefore essential for future research to better understand the role played by CMV after bone marrow transplantation and improve the chances of success of the transplant. This will help to better choose the right donor for the right patient.”

CMV infection

Small studies have suggested that early cytomegalovirus (CMV) reactivation may protect against leukemia relapse and even death after hematopoietic stem cell transplant.

However, a new study, based on data from about 9500 patients, suggests otherwise.

Results showed no association between CMV reactivation and relapse but suggested CMV reactivation increases the risk of non-relapse mortality.

Researchers reported these findings in Blood.

“The original purpose of the study was to confirm that CMV infection may prevent leukemia relapse, prevent death, and become a major therapeutic tool for improving patient survival rates,” said study author Pierre Teira, MD, of the University of Montreal in Quebec, Canada.

“However, we found the exact opposite. Our results clearly show that . . . the virus not only does not prevent leukemia relapse [it] also remains a major factor associated with the risk of death. Monitoring of CMV after transplantation remains a priority for patients.”

For this study, Dr Teira and his colleagues analyzed data from 9469 patients who received a transplant between 2003 and 2010.

The patients had acute myeloid leukemia (AML, n=5310), acute lymphoblastic leukemia (ALL, n=1883), chronic myeloid leukemia (CML, n=1079), or myelodysplastic syndromes (MDS, n=1197).

The median time to initial CMV reactivation was 41 days (range, 1-362 days).

The researchers found no significant association between CMV reactivation and disease relapse for AML (P=0.60), ALL (P=0.08), CML (P=0.94), or MDS (P=0.58).

However, CMV reactivation was associated with a significantly higher risk of nonrelapse mortality for AML (P<0.0001), ALL (P<0.0001), CML (P=0.0004), and MDS (P=0.0002).

Therefore, CMV reactivation was associated with significantly lower overall survival for AML (P<0.0001), ALL (P<0.0001), CML (P=0.0005), and MDS (P=0.003).

“Deaths due to uncontrolled CMV reactivation are virtually zero in this study, so uncontrolled CMV reactivation is not what reduces survival rates after transplantation,” Dr Teira noted. “The link between this common virus and increased risk of death remains a biological mystery.”

One possible explanation is that CMV decreases the ability of the patient’s immune system to fight against other types of infection. This is supported by the fact that death rates from infections other than CMV are higher in patients infected with CMV or patients whose donors were.

For researchers, the next step is therefore to verify whether the latest generation of anti-CMV treatments can prevent both reactivation of the virus and weakening of the patient’s immune system against other types of infection in the presence of CMV infection.

“CMV has a complex impact on the outcomes for transplant patients, and, each year, more than 30,000 patients around the world receive bone marrow transplants from donors,” Dr Teira said.

“It is therefore essential for future research to better understand the role played by CMV after bone marrow transplantation and improve the chances of success of the transplant. This will help to better choose the right donor for the right patient.”