ALL

Charles Mullighan, MD, MBBS

Credit: St Jude Children’s

Research Hospital

New research indicates that Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) becomes more common with age and is associated with poor prognosis.

The study also showed that Ph-like ALL is characterized by genomic alterations that might make patients receptive to treatment with tyrosine kinase inhibitors (TKIs).

Initial tests in a small number of patients seem to support this theory, but trials are needed to verify and expand upon these results, according to researchers.

Charles Mullighan, MD, MBBS, of the St Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported the results in The New England Journal of Medicine.

Age and prognosis

The researchers performed genomic profiling of 1725 patients with precursor B-cell ALL, detailed genomic analyses of 154 patients with Ph-like ALL, and transcriptome sequencing for 160 patients with non-Ph-like ALL.

The team found the prevalence of Ph-like ALL increased significantly with age, from 10% among children with standard-risk B-ALL (ages 1 to 9) and 13% among those with high-risk ALL (ages 10 to 15) to 21% among adolescents (ages 16 to 20) and 27% among young adults with ALL (ages 21 to 39).

Regardless of their age, patients with Ph-like ALL were less likely than other B-ALL patients to be alive and leukemia-free 5 years after diagnosis.

Overall survival for children, adolescents, and young adults with Ph-like ALL was 62%, compared to 91% for other B-ALL patients of the same age. Leukemia-free survival was about 47% for patients with Ph-like ALL and about 83% for other patients.

Genomic alterations and TKI treatment

The researchers found that 91% of patients with Ph-like ALL had chromosomal rearrangements or other genetic alterations that activate cytokine receptor or kinase signaling.

“We identified several new subgroups of Ph-like ALL that were distinguished by the type of cytokine receptor or kinase gene alteration,” said Kathryn Roberts, PhD, also of St Jude Children’s Research Hospital.

Evidence suggests that several of these subtypes would be vulnerable to TKIs and other targeted therapies. For example, about 12% of patients had rearrangements involving the genes ABL1, ABL2, CSF1R, and PDGFRB, which are known to respond to dasatinib and related TKIs.

Other Ph-like ALL patients had gene rearrangements involving JAK2, EPOR, and other genes that can be targeted by the drug ruxolitinib.

To determine if TKIs are effective in these patients, the researchers administered TKIs to 12 patients with Ph-ALL. Follow-up is not sufficient for all of the patients, but 5 achieved remission following TKI treatment (alone, with chemotherapy, or followed by transplant), and 1 patient has been in remission for more than a year.

“We showed that Ph-like ALL is a common disease that spans the age spectrum, and we identified new genomic alterations that converge on a handful of signaling pathways that are vulnerable to treatment with tyrosine kinase inhibitors,” Dr Mullighan said. “The findings lead the way for clinical trials that could help to transform the outlook for patients, regardless of age.”

A study testing TKI therapy in children with Ph-like ALL is scheduled to begin later this year or early in 2015.

Charles Mullighan, MD, MBBS

Credit: St Jude Children’s

Research Hospital

New research indicates that Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) becomes more common with age and is associated with poor prognosis.

The study also showed that Ph-like ALL is characterized by genomic alterations that might make patients receptive to treatment with tyrosine kinase inhibitors (TKIs).

Initial tests in a small number of patients seem to support this theory, but trials are needed to verify and expand upon these results, according to researchers.

Charles Mullighan, MD, MBBS, of the St Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported the results in The New England Journal of Medicine.

Age and prognosis

The researchers performed genomic profiling of 1725 patients with precursor B-cell ALL, detailed genomic analyses of 154 patients with Ph-like ALL, and transcriptome sequencing for 160 patients with non-Ph-like ALL.

The team found the prevalence of Ph-like ALL increased significantly with age, from 10% among children with standard-risk B-ALL (ages 1 to 9) and 13% among those with high-risk ALL (ages 10 to 15) to 21% among adolescents (ages 16 to 20) and 27% among young adults with ALL (ages 21 to 39).

Regardless of their age, patients with Ph-like ALL were less likely than other B-ALL patients to be alive and leukemia-free 5 years after diagnosis.

Overall survival for children, adolescents, and young adults with Ph-like ALL was 62%, compared to 91% for other B-ALL patients of the same age. Leukemia-free survival was about 47% for patients with Ph-like ALL and about 83% for other patients.

Genomic alterations and TKI treatment

The researchers found that 91% of patients with Ph-like ALL had chromosomal rearrangements or other genetic alterations that activate cytokine receptor or kinase signaling.

“We identified several new subgroups of Ph-like ALL that were distinguished by the type of cytokine receptor or kinase gene alteration,” said Kathryn Roberts, PhD, also of St Jude Children’s Research Hospital.

Evidence suggests that several of these subtypes would be vulnerable to TKIs and other targeted therapies. For example, about 12% of patients had rearrangements involving the genes ABL1, ABL2, CSF1R, and PDGFRB, which are known to respond to dasatinib and related TKIs.

Other Ph-like ALL patients had gene rearrangements involving JAK2, EPOR, and other genes that can be targeted by the drug ruxolitinib.

To determine if TKIs are effective in these patients, the researchers administered TKIs to 12 patients with Ph-ALL. Follow-up is not sufficient for all of the patients, but 5 achieved remission following TKI treatment (alone, with chemotherapy, or followed by transplant), and 1 patient has been in remission for more than a year.

“We showed that Ph-like ALL is a common disease that spans the age spectrum, and we identified new genomic alterations that converge on a handful of signaling pathways that are vulnerable to treatment with tyrosine kinase inhibitors,” Dr Mullighan said. “The findings lead the way for clinical trials that could help to transform the outlook for patients, regardless of age.”

A study testing TKI therapy in children with Ph-like ALL is scheduled to begin later this year or early in 2015.

Charles Mullighan, MD, MBBS

Credit: St Jude Children’s

Research Hospital

New research indicates that Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) becomes more common with age and is associated with poor prognosis.

The study also showed that Ph-like ALL is characterized by genomic alterations that might make patients receptive to treatment with tyrosine kinase inhibitors (TKIs).

Initial tests in a small number of patients seem to support this theory, but trials are needed to verify and expand upon these results, according to researchers.

Charles Mullighan, MD, MBBS, of the St Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported the results in The New England Journal of Medicine.

Age and prognosis

The researchers performed genomic profiling of 1725 patients with precursor B-cell ALL, detailed genomic analyses of 154 patients with Ph-like ALL, and transcriptome sequencing for 160 patients with non-Ph-like ALL.

The team found the prevalence of Ph-like ALL increased significantly with age, from 10% among children with standard-risk B-ALL (ages 1 to 9) and 13% among those with high-risk ALL (ages 10 to 15) to 21% among adolescents (ages 16 to 20) and 27% among young adults with ALL (ages 21 to 39).

Regardless of their age, patients with Ph-like ALL were less likely than other B-ALL patients to be alive and leukemia-free 5 years after diagnosis.

Overall survival for children, adolescents, and young adults with Ph-like ALL was 62%, compared to 91% for other B-ALL patients of the same age. Leukemia-free survival was about 47% for patients with Ph-like ALL and about 83% for other patients.

Genomic alterations and TKI treatment

The researchers found that 91% of patients with Ph-like ALL had chromosomal rearrangements or other genetic alterations that activate cytokine receptor or kinase signaling.

“We identified several new subgroups of Ph-like ALL that were distinguished by the type of cytokine receptor or kinase gene alteration,” said Kathryn Roberts, PhD, also of St Jude Children’s Research Hospital.

Evidence suggests that several of these subtypes would be vulnerable to TKIs and other targeted therapies. For example, about 12% of patients had rearrangements involving the genes ABL1, ABL2, CSF1R, and PDGFRB, which are known to respond to dasatinib and related TKIs.

Other Ph-like ALL patients had gene rearrangements involving JAK2, EPOR, and other genes that can be targeted by the drug ruxolitinib.

To determine if TKIs are effective in these patients, the researchers administered TKIs to 12 patients with Ph-ALL. Follow-up is not sufficient for all of the patients, but 5 achieved remission following TKI treatment (alone, with chemotherapy, or followed by transplant), and 1 patient has been in remission for more than a year.

“We showed that Ph-like ALL is a common disease that spans the age spectrum, and we identified new genomic alterations that converge on a handful of signaling pathways that are vulnerable to treatment with tyrosine kinase inhibitors,” Dr Mullighan said. “The findings lead the way for clinical trials that could help to transform the outlook for patients, regardless of age.”

A study testing TKI therapy in children with Ph-like ALL is scheduled to begin later this year or early in 2015.

ALL cells in the bone marrow

Two genes appear to play a key role in acute lymphoblastic leukemia (ALL), particularly for patients who also have Down syndrome.

Researchers found evidence suggesting that 2 in 3 cases of ALL among patients with Down syndrome may be caused by mutations in RAS or JAK2, but the mutations tend not to occur together.

The group therefore believes that if we can begin to identify which of the genes is mutated in ALL patients, we can tailor therapy accordingly.

“We believe our findings are a breakthrough in understanding the underlying causes of leukemia, and, eventually, we hope to design more tailored and effective treatment for this cancer, with less toxic drugs and less side effects,” said study author Dean Nizetic, MD, PhD, a professor at both Queen Mary University of London in the UK and Lee Kong Chian School of Medicine in Singapore.

He and his colleagues reported their findings in Nature Communications.

The researchers conducted full-exome or targeted sequencing in 42 samples from 39 patients with ALL and Down syndrome. The team found similar recurrence rates for driver mutations in RAS (15/42), JAK2 mutations (12/42), and P2RY8-CRLF2 fusions (14/42).

Together, RAS and JAK2 mutations drove two-thirds of the ALL cases, though the mutations were almost completely mutually exclusive (P=0.016).

The researchers also noted that, in two-thirds of patients with relapsed ALL, there was a switch from a primary JAK2- or PTPN11-mutated subclone to a RAS-mutated subclone in relapse.

Moving forward, the team plans to conduct more studies to determine how else RAS and JAK2 might affect children who have ALL, with or without Down syndrome.

ALL cells in the bone marrow

Two genes appear to play a key role in acute lymphoblastic leukemia (ALL), particularly for patients who also have Down syndrome.

Researchers found evidence suggesting that 2 in 3 cases of ALL among patients with Down syndrome may be caused by mutations in RAS or JAK2, but the mutations tend not to occur together.

The group therefore believes that if we can begin to identify which of the genes is mutated in ALL patients, we can tailor therapy accordingly.

“We believe our findings are a breakthrough in understanding the underlying causes of leukemia, and, eventually, we hope to design more tailored and effective treatment for this cancer, with less toxic drugs and less side effects,” said study author Dean Nizetic, MD, PhD, a professor at both Queen Mary University of London in the UK and Lee Kong Chian School of Medicine in Singapore.

He and his colleagues reported their findings in Nature Communications.

The researchers conducted full-exome or targeted sequencing in 42 samples from 39 patients with ALL and Down syndrome. The team found similar recurrence rates for driver mutations in RAS (15/42), JAK2 mutations (12/42), and P2RY8-CRLF2 fusions (14/42).

Together, RAS and JAK2 mutations drove two-thirds of the ALL cases, though the mutations were almost completely mutually exclusive (P=0.016).

The researchers also noted that, in two-thirds of patients with relapsed ALL, there was a switch from a primary JAK2- or PTPN11-mutated subclone to a RAS-mutated subclone in relapse.

Moving forward, the team plans to conduct more studies to determine how else RAS and JAK2 might affect children who have ALL, with or without Down syndrome.

ALL cells in the bone marrow

Two genes appear to play a key role in acute lymphoblastic leukemia (ALL), particularly for patients who also have Down syndrome.

Researchers found evidence suggesting that 2 in 3 cases of ALL among patients with Down syndrome may be caused by mutations in RAS or JAK2, but the mutations tend not to occur together.

The group therefore believes that if we can begin to identify which of the genes is mutated in ALL patients, we can tailor therapy accordingly.

“We believe our findings are a breakthrough in understanding the underlying causes of leukemia, and, eventually, we hope to design more tailored and effective treatment for this cancer, with less toxic drugs and less side effects,” said study author Dean Nizetic, MD, PhD, a professor at both Queen Mary University of London in the UK and Lee Kong Chian School of Medicine in Singapore.

He and his colleagues reported their findings in Nature Communications.

The researchers conducted full-exome or targeted sequencing in 42 samples from 39 patients with ALL and Down syndrome. The team found similar recurrence rates for driver mutations in RAS (15/42), JAK2 mutations (12/42), and P2RY8-CRLF2 fusions (14/42).

Together, RAS and JAK2 mutations drove two-thirds of the ALL cases, though the mutations were almost completely mutually exclusive (P=0.016).

The researchers also noted that, in two-thirds of patients with relapsed ALL, there was a switch from a primary JAK2- or PTPN11-mutated subclone to a RAS-mutated subclone in relapse.

Moving forward, the team plans to conduct more studies to determine how else RAS and JAK2 might affect children who have ALL, with or without Down syndrome.

Photo from Penn Medicine

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for the T-cell therapy CTL019 to treat adults and children with relapsed or refractory acute lymphoblastic leukemia (ALL).

The therapy consists of a patient’s own T cells genetically engineered to produce chimeric antigen receptors (CARs) directed against CD19.

CTL019 is the first personalized cellular therapy for cancer to receive breakthrough designation from the FDA.

Breakthrough designation is intended to expedite the development and review of new medicines that treat serious or life-threatening conditions, if the therapy has demonstrated substantial improvement over available therapies.

The breakthrough designation for CTL019 is based on early trial results in adults and children with ALL.

At ASH 2013, researchers presented results of the first 27 ALL patients (22 children and 5 adults) treated with CTL019. Eighty-nine percent of the patients achieved a complete response to the treatment. Six patients relapsed during follow-up, which ranged from 2 months to 18 months.

There was also a high rate of toxicity, particularly cytokine release syndrome, but this was resolved via treatment with the IL-6 agonist tocilizumab.

The first pediatric ALL patient to receive CTL019 celebrated the second anniversary of her cancer remission in May. And the first adult patient remains in remission 1 year after receiving the therapy.

“Our early findings reveal tremendous promise for a desperate group of patients, many of whom have been able to return to their normal lives at school and work after receiving this new, personalized immunotherapy,” said Carl June, MD, of the University of Pennsylvania.

“Receiving the FDA’s breakthrough designation is an essential step in our work with Novartis to expand this therapy to patients across the world who desperately need new options to help them fight this disease.”

In August 2012, the University of Pennsylvania announced an exclusive global research and licensing agreement with Novartis to further study, develop, and commercialize personalized CAR T-cell therapies for the treatment of cancers.

Trials of CTL019 began in the summer of 2010 in patients with relapsed and refractory chronic lymphocytic leukemia, and they are now underway for patients with ALL, non-Hodgkin lymphoma, and myeloma.

CTL019 cells are a patients’ own T cells genetically engineered to express an anti-CD19 scFv coupled to CD3ζ signaling and 4-1BB co-stimulatory domains. The cells are activated and expanded ex vivo with anti-CD3 and anti-CD28 beads, then infused into patients.

Photo from Penn Medicine

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for the T-cell therapy CTL019 to treat adults and children with relapsed or refractory acute lymphoblastic leukemia (ALL).

The therapy consists of a patient’s own T cells genetically engineered to produce chimeric antigen receptors (CARs) directed against CD19.

CTL019 is the first personalized cellular therapy for cancer to receive breakthrough designation from the FDA.

Breakthrough designation is intended to expedite the development and review of new medicines that treat serious or life-threatening conditions, if the therapy has demonstrated substantial improvement over available therapies.

The breakthrough designation for CTL019 is based on early trial results in adults and children with ALL.

At ASH 2013, researchers presented results of the first 27 ALL patients (22 children and 5 adults) treated with CTL019. Eighty-nine percent of the patients achieved a complete response to the treatment. Six patients relapsed during follow-up, which ranged from 2 months to 18 months.

There was also a high rate of toxicity, particularly cytokine release syndrome, but this was resolved via treatment with the IL-6 agonist tocilizumab.

The first pediatric ALL patient to receive CTL019 celebrated the second anniversary of her cancer remission in May. And the first adult patient remains in remission 1 year after receiving the therapy.

“Our early findings reveal tremendous promise for a desperate group of patients, many of whom have been able to return to their normal lives at school and work after receiving this new, personalized immunotherapy,” said Carl June, MD, of the University of Pennsylvania.

“Receiving the FDA’s breakthrough designation is an essential step in our work with Novartis to expand this therapy to patients across the world who desperately need new options to help them fight this disease.”

In August 2012, the University of Pennsylvania announced an exclusive global research and licensing agreement with Novartis to further study, develop, and commercialize personalized CAR T-cell therapies for the treatment of cancers.

Trials of CTL019 began in the summer of 2010 in patients with relapsed and refractory chronic lymphocytic leukemia, and they are now underway for patients with ALL, non-Hodgkin lymphoma, and myeloma.

CTL019 cells are a patients’ own T cells genetically engineered to express an anti-CD19 scFv coupled to CD3ζ signaling and 4-1BB co-stimulatory domains. The cells are activated and expanded ex vivo with anti-CD3 and anti-CD28 beads, then infused into patients.

Photo from Penn Medicine

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for the T-cell therapy CTL019 to treat adults and children with relapsed or refractory acute lymphoblastic leukemia (ALL).

The therapy consists of a patient’s own T cells genetically engineered to produce chimeric antigen receptors (CARs) directed against CD19.

CTL019 is the first personalized cellular therapy for cancer to receive breakthrough designation from the FDA.

Breakthrough designation is intended to expedite the development and review of new medicines that treat serious or life-threatening conditions, if the therapy has demonstrated substantial improvement over available therapies.

The breakthrough designation for CTL019 is based on early trial results in adults and children with ALL.

At ASH 2013, researchers presented results of the first 27 ALL patients (22 children and 5 adults) treated with CTL019. Eighty-nine percent of the patients achieved a complete response to the treatment. Six patients relapsed during follow-up, which ranged from 2 months to 18 months.

There was also a high rate of toxicity, particularly cytokine release syndrome, but this was resolved via treatment with the IL-6 agonist tocilizumab.

The first pediatric ALL patient to receive CTL019 celebrated the second anniversary of her cancer remission in May. And the first adult patient remains in remission 1 year after receiving the therapy.

“Our early findings reveal tremendous promise for a desperate group of patients, many of whom have been able to return to their normal lives at school and work after receiving this new, personalized immunotherapy,” said Carl June, MD, of the University of Pennsylvania.

“Receiving the FDA’s breakthrough designation is an essential step in our work with Novartis to expand this therapy to patients across the world who desperately need new options to help them fight this disease.”

In August 2012, the University of Pennsylvania announced an exclusive global research and licensing agreement with Novartis to further study, develop, and commercialize personalized CAR T-cell therapies for the treatment of cancers.

Trials of CTL019 began in the summer of 2010 in patients with relapsed and refractory chronic lymphocytic leukemia, and they are now underway for patients with ALL, non-Hodgkin lymphoma, and myeloma.

CTL019 cells are a patients’ own T cells genetically engineered to express an anti-CD19 scFv coupled to CD3ζ signaling and 4-1BB co-stimulatory domains. The cells are activated and expanded ex vivo with anti-CD3 and anti-CD28 beads, then infused into patients.

The US Food and Drug Administration (FDA) has granted the bispecific antibody blinatumomab breakthrough designation for the treatment of adults with relapsed or refractory B-precursor acute lymphoblastic leukemia (B-ALL).

The decision was based on promising results of a phase 2 trial, which were presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) and the 19th Congress of the European Hematology Association (EHA).

According to the FDA, breakthrough designation is intended to expedite the development and review of drugs for serious or life-threatening conditions.

For a treatment to receive this designation, there must be preliminary clinical evidence suggesting the drug may offer substantial improvement over currently available therapy on at least one clinically significant endpoint.

Trial results

Nicola Gökbuget, MD, of Goethe University in Frankfurt, Germany, and Max Topp, MD, of the University of Wuerzberg in Germany, presented phase 2 results with blinatumomab at the EHA Congress as abstracts S1314 and S722. The trial was sponsored by Amgen, the company developing blinatumomab.

“Blinatumomab is a bispecific antibody which has two parts,” Dr Gökbuget noted. “With one part—the CD3 part—it attracts T cells, and with the other part, it binds to CD19. And CD19 is a target available on the vast majority of B-precursor ALL blast cells.”

To test this mechanism, Dr Gökbuget and her colleagues evaluated blinatumomab monotherapy in 189 patients with relapsed or refractory B-ALL and a median age of 39 (range, 18-79).

The patients received blinatumomab by continuous intravenous infusion—4 weeks on and 2 weeks off—for up to 5 cycles.

Safety

Dr Gökbuget noted that major toxicities were related to cytokine release syndrome—for example, fever and headache—but cytopenias were also common.

“Another side effect observed with this compound—and this is something seen often with other T-cell therapies—was [central nervous system] events,” she added.

The most frequent adverse events (AEs) were pyrexia (59%), headache (35%) and febrile neutropenia (29%). The most frequent grade 3 or higher AEs were febrile neutropenia (26%), anemia (15%), and neutropenia (15%). Two percent of patients had grade 3 or higher cytokine release syndrome.

The most common grade 3 or higher nervous system AEs were headache (4%), encephalopathy (3%), and ataxia (2%). Three patients (2%) had grade 5 AEs considered treatment-related—2 with sepsis and 1 with Candida infection.

Efficacy

The study’s primary endpoint was complete remission (CR) or CR with partial hematologic recovery (CRh) within the first 2 cycles.

An exploratory endpoint was minimal residual disease (MRD) response (<10^-4) within the first 2 cycles. If a patient was MRD-negative, he was classified as having a complete MRD response.

In all, 43% (81/189) of patients achieved a CR/CRh within 2 cycles of therapy. Thirty-three percent (63/189) achieved a CR, and 9% (18/189) achieved a CRh.

Eighty-two percent (60/73) of patients with a CR/CRh who were evaluable for an MRD assessment achieved an MRD response. This included 86% (50/58) of CR patients and 67% (10/15) of CRh patients. Seventy-one percent (51/73) of patients with CR/CRh had a complete MRD response.

The median relapse-free survival was 5.9 months.

“So to conclude, we have observed considerable antileukemic activity for this single-drug therapy,” Dr Gökbuget said. “We have to keep in mind this is a single drug, and, usually, these patients receive many different chemotherapy compounds.”

“Also, although these patients were poorly selected, this is, so far, the largest trial in adult ALL where standardized PCR-based MRD detection was tested in the relapsed setting. So these data will be very important.”

The US Food and Drug Administration (FDA) has granted the bispecific antibody blinatumomab breakthrough designation for the treatment of adults with relapsed or refractory B-precursor acute lymphoblastic leukemia (B-ALL).

The decision was based on promising results of a phase 2 trial, which were presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) and the 19th Congress of the European Hematology Association (EHA).

According to the FDA, breakthrough designation is intended to expedite the development and review of drugs for serious or life-threatening conditions.

For a treatment to receive this designation, there must be preliminary clinical evidence suggesting the drug may offer substantial improvement over currently available therapy on at least one clinically significant endpoint.

Trial results

Nicola Gökbuget, MD, of Goethe University in Frankfurt, Germany, and Max Topp, MD, of the University of Wuerzberg in Germany, presented phase 2 results with blinatumomab at the EHA Congress as abstracts S1314 and S722. The trial was sponsored by Amgen, the company developing blinatumomab.

“Blinatumomab is a bispecific antibody which has two parts,” Dr Gökbuget noted. “With one part—the CD3 part—it attracts T cells, and with the other part, it binds to CD19. And CD19 is a target available on the vast majority of B-precursor ALL blast cells.”

To test this mechanism, Dr Gökbuget and her colleagues evaluated blinatumomab monotherapy in 189 patients with relapsed or refractory B-ALL and a median age of 39 (range, 18-79).

The patients received blinatumomab by continuous intravenous infusion—4 weeks on and 2 weeks off—for up to 5 cycles.

Safety

Dr Gökbuget noted that major toxicities were related to cytokine release syndrome—for example, fever and headache—but cytopenias were also common.

“Another side effect observed with this compound—and this is something seen often with other T-cell therapies—was [central nervous system] events,” she added.

The most frequent adverse events (AEs) were pyrexia (59%), headache (35%) and febrile neutropenia (29%). The most frequent grade 3 or higher AEs were febrile neutropenia (26%), anemia (15%), and neutropenia (15%). Two percent of patients had grade 3 or higher cytokine release syndrome.

The most common grade 3 or higher nervous system AEs were headache (4%), encephalopathy (3%), and ataxia (2%). Three patients (2%) had grade 5 AEs considered treatment-related—2 with sepsis and 1 with Candida infection.

Efficacy

The study’s primary endpoint was complete remission (CR) or CR with partial hematologic recovery (CRh) within the first 2 cycles.

An exploratory endpoint was minimal residual disease (MRD) response (<10^-4) within the first 2 cycles. If a patient was MRD-negative, he was classified as having a complete MRD response.

In all, 43% (81/189) of patients achieved a CR/CRh within 2 cycles of therapy. Thirty-three percent (63/189) achieved a CR, and 9% (18/189) achieved a CRh.

Eighty-two percent (60/73) of patients with a CR/CRh who were evaluable for an MRD assessment achieved an MRD response. This included 86% (50/58) of CR patients and 67% (10/15) of CRh patients. Seventy-one percent (51/73) of patients with CR/CRh had a complete MRD response.

The median relapse-free survival was 5.9 months.

“So to conclude, we have observed considerable antileukemic activity for this single-drug therapy,” Dr Gökbuget said. “We have to keep in mind this is a single drug, and, usually, these patients receive many different chemotherapy compounds.”

“Also, although these patients were poorly selected, this is, so far, the largest trial in adult ALL where standardized PCR-based MRD detection was tested in the relapsed setting. So these data will be very important.”

The US Food and Drug Administration (FDA) has granted the bispecific antibody blinatumomab breakthrough designation for the treatment of adults with relapsed or refractory B-precursor acute lymphoblastic leukemia (B-ALL).

The decision was based on promising results of a phase 2 trial, which were presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) and the 19th Congress of the European Hematology Association (EHA).

According to the FDA, breakthrough designation is intended to expedite the development and review of drugs for serious or life-threatening conditions.

For a treatment to receive this designation, there must be preliminary clinical evidence suggesting the drug may offer substantial improvement over currently available therapy on at least one clinically significant endpoint.

Trial results

Nicola Gökbuget, MD, of Goethe University in Frankfurt, Germany, and Max Topp, MD, of the University of Wuerzberg in Germany, presented phase 2 results with blinatumomab at the EHA Congress as abstracts S1314 and S722. The trial was sponsored by Amgen, the company developing blinatumomab.

“Blinatumomab is a bispecific antibody which has two parts,” Dr Gökbuget noted. “With one part—the CD3 part—it attracts T cells, and with the other part, it binds to CD19. And CD19 is a target available on the vast majority of B-precursor ALL blast cells.”

To test this mechanism, Dr Gökbuget and her colleagues evaluated blinatumomab monotherapy in 189 patients with relapsed or refractory B-ALL and a median age of 39 (range, 18-79).

The patients received blinatumomab by continuous intravenous infusion—4 weeks on and 2 weeks off—for up to 5 cycles.

Safety

Dr Gökbuget noted that major toxicities were related to cytokine release syndrome—for example, fever and headache—but cytopenias were also common.

“Another side effect observed with this compound—and this is something seen often with other T-cell therapies—was [central nervous system] events,” she added.

The most frequent adverse events (AEs) were pyrexia (59%), headache (35%) and febrile neutropenia (29%). The most frequent grade 3 or higher AEs were febrile neutropenia (26%), anemia (15%), and neutropenia (15%). Two percent of patients had grade 3 or higher cytokine release syndrome.

The most common grade 3 or higher nervous system AEs were headache (4%), encephalopathy (3%), and ataxia (2%). Three patients (2%) had grade 5 AEs considered treatment-related—2 with sepsis and 1 with Candida infection.

Efficacy

The study’s primary endpoint was complete remission (CR) or CR with partial hematologic recovery (CRh) within the first 2 cycles.

An exploratory endpoint was minimal residual disease (MRD) response (<10^-4) within the first 2 cycles. If a patient was MRD-negative, he was classified as having a complete MRD response.

In all, 43% (81/189) of patients achieved a CR/CRh within 2 cycles of therapy. Thirty-three percent (63/189) achieved a CR, and 9% (18/189) achieved a CRh.

Eighty-two percent (60/73) of patients with a CR/CRh who were evaluable for an MRD assessment achieved an MRD response. This included 86% (50/58) of CR patients and 67% (10/15) of CRh patients. Seventy-one percent (51/73) of patients with CR/CRh had a complete MRD response.

The median relapse-free survival was 5.9 months.

“So to conclude, we have observed considerable antileukemic activity for this single-drug therapy,” Dr Gökbuget said. “We have to keep in mind this is a single drug, and, usually, these patients receive many different chemotherapy compounds.”

“Also, although these patients were poorly selected, this is, so far, the largest trial in adult ALL where standardized PCR-based MRD detection was tested in the relapsed setting. So these data will be very important.”

Leukemia patient

Credit: Bill Branson

Children recently diagnosed with standard-risk acute lymphoblastic leukemia (ALL) are likely to have few long-term complications into adulthood, investigators have reported in The Lancet Oncology.

The team said this is because current therapies are less harsh than their predecessors.

Newer protocols have eliminated radiation and restricted the use of chemotherapeutics that may cause subsequent malignancies and other chronic health conditions.

Previous research had only assessed the very long-term outcomes of children treated with older protocols, leaving physicians to piece together information from this outdated data and anecdotal evidence.

“This is one of the first studies to show that, in addition to their excellent probability of survival, long-term survivors of standard-risk childhood ALL are at low risk for complications of their therapy once they enter adulthood,” said study author Paul Nathan, MD, of The Hospital for Sick Children in Toronto, Canada.

He and his colleagues used longitudinal data from the Childhood Cancer Survivor Study, a North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986.

The team analyzed 556 patients from this study who were older than 1 year of age and younger than 10 at the time of diagnosis and who had received treatment consistent with current therapies for standard-risk ALL.

Patients were followed from 5 years following diagnosis to a median of 18 years. The survivor group was compared with a group of their siblings who had not had cancer, as well as the general population.

Twenty-eight patients in the survivor group died. Sixteen of these deaths were from causes other than relapse.

Survivors were at a slightly increased risk of death due to non-relapse causes, when compared to controls. However, no individual cause was increased.

Six survivors developed another malignancy. The risk for most chronic health disorders did not differ between survivors and siblings. But survivors appeared to have a moderately increased risk for osteoporosis or osteopenia, short stature, and cataracts.

Survivors and their siblings had similar socioeconomic outcomes, including education, rates of marriage, independent living, and household income.

While these results suggest the prognosis is favorable, Dr Nathan noted that ALL survivors should receive ongoing care from a knowledgeable primary-care practitioner.

“Among kids with standard-risk ALL, we expect most to survive,” Dr Nathan said. “Now we can say with more certainty that they will probably do well in the long-term as well. This information will be very useful for oncologists counselling newly diagnosed patients and their families and will be quite reassuring to parents.”

Leukemia patient

Credit: Bill Branson

Children recently diagnosed with standard-risk acute lymphoblastic leukemia (ALL) are likely to have few long-term complications into adulthood, investigators have reported in The Lancet Oncology.

The team said this is because current therapies are less harsh than their predecessors.

Newer protocols have eliminated radiation and restricted the use of chemotherapeutics that may cause subsequent malignancies and other chronic health conditions.

Previous research had only assessed the very long-term outcomes of children treated with older protocols, leaving physicians to piece together information from this outdated data and anecdotal evidence.

“This is one of the first studies to show that, in addition to their excellent probability of survival, long-term survivors of standard-risk childhood ALL are at low risk for complications of their therapy once they enter adulthood,” said study author Paul Nathan, MD, of The Hospital for Sick Children in Toronto, Canada.

He and his colleagues used longitudinal data from the Childhood Cancer Survivor Study, a North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986.

The team analyzed 556 patients from this study who were older than 1 year of age and younger than 10 at the time of diagnosis and who had received treatment consistent with current therapies for standard-risk ALL.

Patients were followed from 5 years following diagnosis to a median of 18 years. The survivor group was compared with a group of their siblings who had not had cancer, as well as the general population.

Twenty-eight patients in the survivor group died. Sixteen of these deaths were from causes other than relapse.

Survivors were at a slightly increased risk of death due to non-relapse causes, when compared to controls. However, no individual cause was increased.

Six survivors developed another malignancy. The risk for most chronic health disorders did not differ between survivors and siblings. But survivors appeared to have a moderately increased risk for osteoporosis or osteopenia, short stature, and cataracts.

Survivors and their siblings had similar socioeconomic outcomes, including education, rates of marriage, independent living, and household income.

While these results suggest the prognosis is favorable, Dr Nathan noted that ALL survivors should receive ongoing care from a knowledgeable primary-care practitioner.

“Among kids with standard-risk ALL, we expect most to survive,” Dr Nathan said. “Now we can say with more certainty that they will probably do well in the long-term as well. This information will be very useful for oncologists counselling newly diagnosed patients and their families and will be quite reassuring to parents.”

Leukemia patient

Credit: Bill Branson

Children recently diagnosed with standard-risk acute lymphoblastic leukemia (ALL) are likely to have few long-term complications into adulthood, investigators have reported in The Lancet Oncology.

The team said this is because current therapies are less harsh than their predecessors.

Newer protocols have eliminated radiation and restricted the use of chemotherapeutics that may cause subsequent malignancies and other chronic health conditions.

Previous research had only assessed the very long-term outcomes of children treated with older protocols, leaving physicians to piece together information from this outdated data and anecdotal evidence.

“This is one of the first studies to show that, in addition to their excellent probability of survival, long-term survivors of standard-risk childhood ALL are at low risk for complications of their therapy once they enter adulthood,” said study author Paul Nathan, MD, of The Hospital for Sick Children in Toronto, Canada.

He and his colleagues used longitudinal data from the Childhood Cancer Survivor Study, a North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986.

The team analyzed 556 patients from this study who were older than 1 year of age and younger than 10 at the time of diagnosis and who had received treatment consistent with current therapies for standard-risk ALL.

Patients were followed from 5 years following diagnosis to a median of 18 years. The survivor group was compared with a group of their siblings who had not had cancer, as well as the general population.

Twenty-eight patients in the survivor group died. Sixteen of these deaths were from causes other than relapse.

Survivors were at a slightly increased risk of death due to non-relapse causes, when compared to controls. However, no individual cause was increased.

Six survivors developed another malignancy. The risk for most chronic health disorders did not differ between survivors and siblings. But survivors appeared to have a moderately increased risk for osteoporosis or osteopenia, short stature, and cataracts.

Survivors and their siblings had similar socioeconomic outcomes, including education, rates of marriage, independent living, and household income.

While these results suggest the prognosis is favorable, Dr Nathan noted that ALL survivors should receive ongoing care from a knowledgeable primary-care practitioner.

“Among kids with standard-risk ALL, we expect most to survive,” Dr Nathan said. “Now we can say with more certainty that they will probably do well in the long-term as well. This information will be very useful for oncologists counselling newly diagnosed patients and their families and will be quite reassuring to parents.”

Investigators Grace Liu

and Ross Dickins, PhD

Credit: Walter and Eliza Hall

Institute of Medical Research

Results of preclinical research suggest B-progenitor acute lymphoblastic leukemia (B-ALL) can be “reversed” by coaxing leukemic cells back into normal development.

Researchers found that switching off the gene Pax5 could induce B-ALL in mice, but restoring Pax5 function could prompt disease remission.

Grace Liu, of the Walter and Eliza Hall Institute of Medical Research in Victoria, Australia, and her colleagues detailed this research in Genes & Development.

“Pax5 is essential for normal development of [B cells],” Liu said. “When Pax5 function is compromised, developing B cells can get trapped in an immature state and become cancerous.”

The researchers used transgenic RNAi to suppress endogenous Pax5 expression in the hematopoietic compartment of mice, and this induced B-ALL.

“Along with other genetic changes, deactivating Pax5 drives normal blood cells to turn into leukemia cells, which has been shown before,” Liu said. “However, we showed, for the first time, that reactivating Pax5 enabled the cells to resume their normal development and lose their cancer-like qualities, effectively curing the leukemia.”

The team found that restoring endogenous Pax5 expression triggered immunophenotypic maturation and durable disease remission.

Even brief Pax5 restoration disabled B-ALL cells’ leukemia-initiating capacity in mice. And the researchers observed similar results in human B-ALL cell lines.

“This work shows how inactivating the tumor suppressor gene Pax5 contributes to B-ALL development and how leukemia cells become addicted to low Pax5 levels to continue proliferating,” said study author Ross Dickins, PhD, also of the Walter and Eliza Hall Institute of Medical Research.

“Even though the B-ALL cells have multiple genetic mutations, simply reactivating Pax5 causes tumor cells to resume normal development and lose their cancerous properties.”

Dr Dickins added that forcing B-ALL cells to resume their normal development could provide a new strategy for treating leukemia. However, genes lost in tumor cells are not traditionally considered suitable drug targets.

“It is very difficult to develop drugs that restore the function of genes that are lost during cancer development,” Dr Dickins said. “However, by understanding the mechanisms by which Pax5 loss causes leukemia, we can begin to look at ways of developing drugs that could have the same effect as restoring Pax5 function.”

Investigators Grace Liu

and Ross Dickins, PhD

Credit: Walter and Eliza Hall

Institute of Medical Research

Results of preclinical research suggest B-progenitor acute lymphoblastic leukemia (B-ALL) can be “reversed” by coaxing leukemic cells back into normal development.

Researchers found that switching off the gene Pax5 could induce B-ALL in mice, but restoring Pax5 function could prompt disease remission.

Grace Liu, of the Walter and Eliza Hall Institute of Medical Research in Victoria, Australia, and her colleagues detailed this research in Genes & Development.

“Pax5 is essential for normal development of [B cells],” Liu said. “When Pax5 function is compromised, developing B cells can get trapped in an immature state and become cancerous.”

The researchers used transgenic RNAi to suppress endogenous Pax5 expression in the hematopoietic compartment of mice, and this induced B-ALL.

“Along with other genetic changes, deactivating Pax5 drives normal blood cells to turn into leukemia cells, which has been shown before,” Liu said. “However, we showed, for the first time, that reactivating Pax5 enabled the cells to resume their normal development and lose their cancer-like qualities, effectively curing the leukemia.”

The team found that restoring endogenous Pax5 expression triggered immunophenotypic maturation and durable disease remission.

Even brief Pax5 restoration disabled B-ALL cells’ leukemia-initiating capacity in mice. And the researchers observed similar results in human B-ALL cell lines.

“This work shows how inactivating the tumor suppressor gene Pax5 contributes to B-ALL development and how leukemia cells become addicted to low Pax5 levels to continue proliferating,” said study author Ross Dickins, PhD, also of the Walter and Eliza Hall Institute of Medical Research.

“Even though the B-ALL cells have multiple genetic mutations, simply reactivating Pax5 causes tumor cells to resume normal development and lose their cancerous properties.”

Dr Dickins added that forcing B-ALL cells to resume their normal development could provide a new strategy for treating leukemia. However, genes lost in tumor cells are not traditionally considered suitable drug targets.

“It is very difficult to develop drugs that restore the function of genes that are lost during cancer development,” Dr Dickins said. “However, by understanding the mechanisms by which Pax5 loss causes leukemia, we can begin to look at ways of developing drugs that could have the same effect as restoring Pax5 function.”

Investigators Grace Liu

and Ross Dickins, PhD

Credit: Walter and Eliza Hall

Institute of Medical Research

Results of preclinical research suggest B-progenitor acute lymphoblastic leukemia (B-ALL) can be “reversed” by coaxing leukemic cells back into normal development.

Researchers found that switching off the gene Pax5 could induce B-ALL in mice, but restoring Pax5 function could prompt disease remission.

Grace Liu, of the Walter and Eliza Hall Institute of Medical Research in Victoria, Australia, and her colleagues detailed this research in Genes & Development.

“Pax5 is essential for normal development of [B cells],” Liu said. “When Pax5 function is compromised, developing B cells can get trapped in an immature state and become cancerous.”

The researchers used transgenic RNAi to suppress endogenous Pax5 expression in the hematopoietic compartment of mice, and this induced B-ALL.

“Along with other genetic changes, deactivating Pax5 drives normal blood cells to turn into leukemia cells, which has been shown before,” Liu said. “However, we showed, for the first time, that reactivating Pax5 enabled the cells to resume their normal development and lose their cancer-like qualities, effectively curing the leukemia.”

The team found that restoring endogenous Pax5 expression triggered immunophenotypic maturation and durable disease remission.

Even brief Pax5 restoration disabled B-ALL cells’ leukemia-initiating capacity in mice. And the researchers observed similar results in human B-ALL cell lines.

“This work shows how inactivating the tumor suppressor gene Pax5 contributes to B-ALL development and how leukemia cells become addicted to low Pax5 levels to continue proliferating,” said study author Ross Dickins, PhD, also of the Walter and Eliza Hall Institute of Medical Research.

“Even though the B-ALL cells have multiple genetic mutations, simply reactivating Pax5 causes tumor cells to resume normal development and lose their cancerous properties.”

Dr Dickins added that forcing B-ALL cells to resume their normal development could provide a new strategy for treating leukemia. However, genes lost in tumor cells are not traditionally considered suitable drug targets.

“It is very difficult to develop drugs that restore the function of genes that are lost during cancer development,” Dr Dickins said. “However, by understanding the mechanisms by which Pax5 loss causes leukemia, we can begin to look at ways of developing drugs that could have the same effect as restoring Pax5 function.”

Lab mice

Credit: Aaron Logan

Researchers say they’ve uncovered a genetic defect in acute lymphoblastic leukemia (ALL) cells that promotes their invasion of the brain.

The team believes the findings, recently published in Genes & Development, could lead to the development of therapies that specifically prevent ALL spread to the central nervous system (CNS).

Currently, curing children with ALL often requires injections of chemotherapy directly into the CNS to limit leukemia growth.

But these therapies can cause long-term health issues.

“If we can find therapies to prevent leukemia spread to the brain, instead of injecting chemotherapy into the brain, that would be huge,” said study author Cynthia Guidos, PhD, of The Hospital for Sick Children (SickKids) in Toronto, Canada.

“Our findings suggest that drugs targeting the functions controlled by a gene called Flt3 could help block leukemic cell growth in the CNS and may be less toxic than current treatments.”

Using a mouse model, the researchers found that CNS-invading leukemias expressed higher levels of Flt3 than leukemias that did not spread to the CNS.

And the CNS-invading leukemias expressed a defective version of Flt3 that cannot be turned off, suggesting that Flt3 allows the leukemic cells to invade the CNS.

The researchers transferred the defective Flt3 gene into mouse leukemia cells that don’t usually invade the brain. And this endowed them with the ability to spread to the CNS.

The team also showed that a Flt3 inhibitor halted growth of the CNS leukemia cells in vitro.

Dr Guidos said the next step for this research will be to investigate whether Flt3 also plays an important role in promoting CNS invasion of human ALL.

She and her colleagues plan to use frozen cells from the SickKids leukemia cell bank, which contains frozen samples from more than 100 patients, to do just that.

Lab mice

Credit: Aaron Logan

Researchers say they’ve uncovered a genetic defect in acute lymphoblastic leukemia (ALL) cells that promotes their invasion of the brain.

The team believes the findings, recently published in Genes & Development, could lead to the development of therapies that specifically prevent ALL spread to the central nervous system (CNS).

Currently, curing children with ALL often requires injections of chemotherapy directly into the CNS to limit leukemia growth.

But these therapies can cause long-term health issues.

“If we can find therapies to prevent leukemia spread to the brain, instead of injecting chemotherapy into the brain, that would be huge,” said study author Cynthia Guidos, PhD, of The Hospital for Sick Children (SickKids) in Toronto, Canada.

“Our findings suggest that drugs targeting the functions controlled by a gene called Flt3 could help block leukemic cell growth in the CNS and may be less toxic than current treatments.”

Using a mouse model, the researchers found that CNS-invading leukemias expressed higher levels of Flt3 than leukemias that did not spread to the CNS.

And the CNS-invading leukemias expressed a defective version of Flt3 that cannot be turned off, suggesting that Flt3 allows the leukemic cells to invade the CNS.

The researchers transferred the defective Flt3 gene into mouse leukemia cells that don’t usually invade the brain. And this endowed them with the ability to spread to the CNS.

The team also showed that a Flt3 inhibitor halted growth of the CNS leukemia cells in vitro.

Dr Guidos said the next step for this research will be to investigate whether Flt3 also plays an important role in promoting CNS invasion of human ALL.

She and her colleagues plan to use frozen cells from the SickKids leukemia cell bank, which contains frozen samples from more than 100 patients, to do just that.

Lab mice

Credit: Aaron Logan

Researchers say they’ve uncovered a genetic defect in acute lymphoblastic leukemia (ALL) cells that promotes their invasion of the brain.

The team believes the findings, recently published in Genes & Development, could lead to the development of therapies that specifically prevent ALL spread to the central nervous system (CNS).

Currently, curing children with ALL often requires injections of chemotherapy directly into the CNS to limit leukemia growth.

But these therapies can cause long-term health issues.

“If we can find therapies to prevent leukemia spread to the brain, instead of injecting chemotherapy into the brain, that would be huge,” said study author Cynthia Guidos, PhD, of The Hospital for Sick Children (SickKids) in Toronto, Canada.

“Our findings suggest that drugs targeting the functions controlled by a gene called Flt3 could help block leukemic cell growth in the CNS and may be less toxic than current treatments.”

Using a mouse model, the researchers found that CNS-invading leukemias expressed higher levels of Flt3 than leukemias that did not spread to the CNS.

And the CNS-invading leukemias expressed a defective version of Flt3 that cannot be turned off, suggesting that Flt3 allows the leukemic cells to invade the CNS.

The researchers transferred the defective Flt3 gene into mouse leukemia cells that don’t usually invade the brain. And this endowed them with the ability to spread to the CNS.

The team also showed that a Flt3 inhibitor halted growth of the CNS leukemia cells in vitro.

Dr Guidos said the next step for this research will be to investigate whether Flt3 also plays an important role in promoting CNS invasion of human ALL.

She and her colleagues plan to use frozen cells from the SickKids leukemia cell bank, which contains frozen samples from more than 100 patients, to do just that.

Pediatric ALL patient

Credit: Bill Branson

Forgetting to take medication is the number one reason for non-adherence to maintenance therapy in children with acute lymphoblastic leukemia (ALL), according to a new study by the Children’s Oncology Group.

And neglecting to take maintenance medication 10% of the time increases the patient’s risk of relapse threefold.

In a study of 298 children receiving 6-mercaptopurine (6MP) as part of maintenance therapy, African Americans and Asians had significantly lower adherence rates than non-Hispanic whites, at 46%, 28%, and 14%, respectively.

Researchers discovered a number of other race-specific characteristics to explain the disparity, including low maternal education, households with a single parent and multiple children, low-income households, and households in which mothers were not the full-time caregivers.

The investigators had studied adherence in Hispanic children in an earlier study and they were not included here.

“While we don’t yet know why children of different races have significantly different survival rates for ALL,” said senior study author Smita Bhatia, MD, MPH, of City of Hope in Duarte, California, “we know that their adherence to their maintenance medication is a critical factor in their survival.”

And so the researchers explored potential sociodemographic differences that impact adherence to 6MP and reported their findings in Blood.

They enrolled 298 children, with a median age of 6 years at study entry (range, 2-20 years). All were in first continuous remission and receiving maintenance therapy that included 6MP.

One-hundred fifty-nine patients were non-Hispanic whites (the referent group), 71 were Asians, and 68 African Americans.

The researchers recorded adherence for up to 5 months per patient using an electronic monitoring device (MEMS®TrackCapTM) that recorded the date and time the pill bottle was opened. These data were downloaded at the end of the adherence-monitoring period.

They also measured erythrocyte TGN levels of the patients on a monthly basis to determine the association between bottle opening and taking the 6MP. Erythrocyte TGN levels reflect 6MP exposure.

Demographics

The researchers found that disease characteristics were comparable across the racial groups, but sociodemographic characteristics varied significantly.

African American families (64%) reported annual household incomes of less than $50,000 compared with 44% of non-Hispanic white and 33% of Asian families.

African American parents had significantly less formal education than non-Hispanic white and Asian parents. Sixty-six percent of African American fathers and 61% of African American mothers reported having less than a college degree.

This compared with 48% and 31% of non-Hispanic white and Asian fathers, respectively, and 46% and 32% of non-Hispanic white and Asian mothers, respectively.

More African American households (37%) were headed by single parents, compared with non-Hispanic white (9%) and Asian (4%) households.

And only 27% of African American children had their mothers as full-time caregivers, compared with 38% of non-Hispanic white children and 52% of Asian children.

Overall adherence

The investigators found that adherence for the entire population declined over the course of the 5 months, from 94.8% to 91.3% (P<0.0001).

Adherence rates were significantly lower in Asians and African Americans than in non-Hispanic whites, and in patients from low-income households.

Adherence rates were significantly higher in patients from single-parent/single-child households (96.9%) and in households where the mothers were full-time caregivers (94.8%).

Adherence by race

In Asian households, adherence was significantly higher with mothers as full-time caregivers (95.6%) compared with all other configurations of caregivers. And adherence rates in households with income of $50,000 or more were also higher (93.9%) than in households with income under $50,000 (84.2%).

In African American households, those with low maternal education had significantly lower adherence rates, 74.6%, than in those households in which mothers held a college degree, 94.6%. And adherence rates were higher in households with single parents and a single child (94.2%) compared with those households with a single parent and multiple children (80.5%) or even from nuclear families (85.5%).

In non-Hispanic white households, paternal education higher than a postgraduate degree resulted in adherence of 97.2%, compared with households in which the father did not have a postgraduate degree, (95.3%). Again, adherence rates were higher in households with single parents and a single child (97.8%) compared with those from single parents with multiple children (94.0%) or from nuclear families (95.6%).

For all racial groups, forgetfulness was the most common reason for missing doses—non-Hispanic whites, 79%; Asians, 90%; and African Americans, 75%.

“Our data demonstrate that one in four children in remission from ALL does not take the medicine needed to remain cancer free,” said Dr Bhatia, “and in an overwhelming majority, the primary reason why is that they forget to take their pills each day,” said Dr. Bhatia.

“These results are the basis for further studies that will examine how physicians can successfully intervene, using technology, for example, to ensure that children do not experience an increased risk of relapse because they did not take their oral chemotherapy.”

Pediatric ALL patient

Credit: Bill Branson

Forgetting to take medication is the number one reason for non-adherence to maintenance therapy in children with acute lymphoblastic leukemia (ALL), according to a new study by the Children’s Oncology Group.

And neglecting to take maintenance medication 10% of the time increases the patient’s risk of relapse threefold.

In a study of 298 children receiving 6-mercaptopurine (6MP) as part of maintenance therapy, African Americans and Asians had significantly lower adherence rates than non-Hispanic whites, at 46%, 28%, and 14%, respectively.

Researchers discovered a number of other race-specific characteristics to explain the disparity, including low maternal education, households with a single parent and multiple children, low-income households, and households in which mothers were not the full-time caregivers.

The investigators had studied adherence in Hispanic children in an earlier study and they were not included here.

“While we don’t yet know why children of different races have significantly different survival rates for ALL,” said senior study author Smita Bhatia, MD, MPH, of City of Hope in Duarte, California, “we know that their adherence to their maintenance medication is a critical factor in their survival.”

And so the researchers explored potential sociodemographic differences that impact adherence to 6MP and reported their findings in Blood.

They enrolled 298 children, with a median age of 6 years at study entry (range, 2-20 years). All were in first continuous remission and receiving maintenance therapy that included 6MP.

One-hundred fifty-nine patients were non-Hispanic whites (the referent group), 71 were Asians, and 68 African Americans.

The researchers recorded adherence for up to 5 months per patient using an electronic monitoring device (MEMS®TrackCapTM) that recorded the date and time the pill bottle was opened. These data were downloaded at the end of the adherence-monitoring period.

They also measured erythrocyte TGN levels of the patients on a monthly basis to determine the association between bottle opening and taking the 6MP. Erythrocyte TGN levels reflect 6MP exposure.

Demographics

The researchers found that disease characteristics were comparable across the racial groups, but sociodemographic characteristics varied significantly.

African American families (64%) reported annual household incomes of less than $50,000 compared with 44% of non-Hispanic white and 33% of Asian families.

African American parents had significantly less formal education than non-Hispanic white and Asian parents. Sixty-six percent of African American fathers and 61% of African American mothers reported having less than a college degree.

This compared with 48% and 31% of non-Hispanic white and Asian fathers, respectively, and 46% and 32% of non-Hispanic white and Asian mothers, respectively.

More African American households (37%) were headed by single parents, compared with non-Hispanic white (9%) and Asian (4%) households.

And only 27% of African American children had their mothers as full-time caregivers, compared with 38% of non-Hispanic white children and 52% of Asian children.

Overall adherence

The investigators found that adherence for the entire population declined over the course of the 5 months, from 94.8% to 91.3% (P<0.0001).

Adherence rates were significantly lower in Asians and African Americans than in non-Hispanic whites, and in patients from low-income households.

Adherence rates were significantly higher in patients from single-parent/single-child households (96.9%) and in households where the mothers were full-time caregivers (94.8%).

Adherence by race

In Asian households, adherence was significantly higher with mothers as full-time caregivers (95.6%) compared with all other configurations of caregivers. And adherence rates in households with income of $50,000 or more were also higher (93.9%) than in households with income under $50,000 (84.2%).

In African American households, those with low maternal education had significantly lower adherence rates, 74.6%, than in those households in which mothers held a college degree, 94.6%. And adherence rates were higher in households with single parents and a single child (94.2%) compared with those households with a single parent and multiple children (80.5%) or even from nuclear families (85.5%).

In non-Hispanic white households, paternal education higher than a postgraduate degree resulted in adherence of 97.2%, compared with households in which the father did not have a postgraduate degree, (95.3%). Again, adherence rates were higher in households with single parents and a single child (97.8%) compared with those from single parents with multiple children (94.0%) or from nuclear families (95.6%).

For all racial groups, forgetfulness was the most common reason for missing doses—non-Hispanic whites, 79%; Asians, 90%; and African Americans, 75%.

“Our data demonstrate that one in four children in remission from ALL does not take the medicine needed to remain cancer free,” said Dr Bhatia, “and in an overwhelming majority, the primary reason why is that they forget to take their pills each day,” said Dr. Bhatia.

“These results are the basis for further studies that will examine how physicians can successfully intervene, using technology, for example, to ensure that children do not experience an increased risk of relapse because they did not take their oral chemotherapy.”

Pediatric ALL patient

Credit: Bill Branson

Forgetting to take medication is the number one reason for non-adherence to maintenance therapy in children with acute lymphoblastic leukemia (ALL), according to a new study by the Children’s Oncology Group.

And neglecting to take maintenance medication 10% of the time increases the patient’s risk of relapse threefold.

In a study of 298 children receiving 6-mercaptopurine (6MP) as part of maintenance therapy, African Americans and Asians had significantly lower adherence rates than non-Hispanic whites, at 46%, 28%, and 14%, respectively.

Researchers discovered a number of other race-specific characteristics to explain the disparity, including low maternal education, households with a single parent and multiple children, low-income households, and households in which mothers were not the full-time caregivers.

The investigators had studied adherence in Hispanic children in an earlier study and they were not included here.

“While we don’t yet know why children of different races have significantly different survival rates for ALL,” said senior study author Smita Bhatia, MD, MPH, of City of Hope in Duarte, California, “we know that their adherence to their maintenance medication is a critical factor in their survival.”

And so the researchers explored potential sociodemographic differences that impact adherence to 6MP and reported their findings in Blood.

They enrolled 298 children, with a median age of 6 years at study entry (range, 2-20 years). All were in first continuous remission and receiving maintenance therapy that included 6MP.

One-hundred fifty-nine patients were non-Hispanic whites (the referent group), 71 were Asians, and 68 African Americans.

The researchers recorded adherence for up to 5 months per patient using an electronic monitoring device (MEMS®TrackCapTM) that recorded the date and time the pill bottle was opened. These data were downloaded at the end of the adherence-monitoring period.

They also measured erythrocyte TGN levels of the patients on a monthly basis to determine the association between bottle opening and taking the 6MP. Erythrocyte TGN levels reflect 6MP exposure.

Demographics

The researchers found that disease characteristics were comparable across the racial groups, but sociodemographic characteristics varied significantly.

African American families (64%) reported annual household incomes of less than $50,000 compared with 44% of non-Hispanic white and 33% of Asian families.

African American parents had significantly less formal education than non-Hispanic white and Asian parents. Sixty-six percent of African American fathers and 61% of African American mothers reported having less than a college degree.

This compared with 48% and 31% of non-Hispanic white and Asian fathers, respectively, and 46% and 32% of non-Hispanic white and Asian mothers, respectively.

More African American households (37%) were headed by single parents, compared with non-Hispanic white (9%) and Asian (4%) households.

And only 27% of African American children had their mothers as full-time caregivers, compared with 38% of non-Hispanic white children and 52% of Asian children.

Overall adherence

The investigators found that adherence for the entire population declined over the course of the 5 months, from 94.8% to 91.3% (P<0.0001).

Adherence rates were significantly lower in Asians and African Americans than in non-Hispanic whites, and in patients from low-income households.

Adherence rates were significantly higher in patients from single-parent/single-child households (96.9%) and in households where the mothers were full-time caregivers (94.8%).

Adherence by race

In Asian households, adherence was significantly higher with mothers as full-time caregivers (95.6%) compared with all other configurations of caregivers. And adherence rates in households with income of $50,000 or more were also higher (93.9%) than in households with income under $50,000 (84.2%).

In African American households, those with low maternal education had significantly lower adherence rates, 74.6%, than in those households in which mothers held a college degree, 94.6%. And adherence rates were higher in households with single parents and a single child (94.2%) compared with those households with a single parent and multiple children (80.5%) or even from nuclear families (85.5%).

In non-Hispanic white households, paternal education higher than a postgraduate degree resulted in adherence of 97.2%, compared with households in which the father did not have a postgraduate degree, (95.3%). Again, adherence rates were higher in households with single parents and a single child (97.8%) compared with those from single parents with multiple children (94.0%) or from nuclear families (95.6%).

For all racial groups, forgetfulness was the most common reason for missing doses—non-Hispanic whites, 79%; Asians, 90%; and African Americans, 75%.

“Our data demonstrate that one in four children in remission from ALL does not take the medicine needed to remain cancer free,” said Dr Bhatia, “and in an overwhelming majority, the primary reason why is that they forget to take their pills each day,” said Dr. Bhatia.

“These results are the basis for further studies that will examine how physicians can successfully intervene, using technology, for example, to ensure that children do not experience an increased risk of relapse because they did not take their oral chemotherapy.”

Monoclonal antibodies

Credit: Linda Bartlett

Preclinical research suggests the B-cell activating receptor (BAFF-R) may be a promising therapeutic target for treatment-resistant leukemia.

A monoclonal antibody (mAb) that targets BAFF-R overcame resistance to nilotinib and enhanced the efficacy of both nilotinib and vincristine in vitro.

The mAb, called B-1239, also demonstrated antileukemic effects in mouse models, when given alone. But it did not appear to improve upon the effects of nilotinib when given in combination.

Nora Heisterkamp, PhD, of Children’s Hospital Los Angeles in California, and her colleagues reported these findings in Molecular Cancer Therapeutics.

In a previous study, the researchers had shown that BAFF-R is expressed on pre-B ALL cells but not on their normal counterparts.

“We’ve now demonstrated that BAFF-R is a strong potential therapeutic target for treating chemotherapy-resistant leukemia cells, without damaging healthy cells,” Dr Heisterkamp said.

She and her colleagues began this research by generating pre-B ALL cells from the bone marrow of wild-type mice and BAFF-R-null mice with a retroviral vector carrying the BCR/ABL oncogene. They found that wild-type pre-B-ALL cells expressed high levels of BAFF-R.

The team then treated both wild-type and BAFF-R-deficient leukemic cells with nilotinib. The wild-type cells developed resistance to nilotinib in 9 to 10 days, but the BAFF-R-deficient cells were eradicated by treatment.

The researchers next tested the effects of B-1239, a human codon-optimized anti-BAFF-R mAb. B-1239 bound to BAFF-R on both Ph-positive and Ph-negative ALL cells in vitro, and the mAb inhibited BAFF-R in a dose-dependent manner.

In pre-B-ALL cells, B-1239 alone had little effect on cell viability or proliferation. However, when combined with vincristine or nilotinib, B-1239 reduced cell count and viability more than either agent alone.

The researchers also found that B-1239 stimulated natural killer cell-mediated cytotoxicity in patient-derived ALL cells. And the mAb stimulated phagocytosis by macrophages.

Finally, Dr Heisterkamp and her colleagues tested B-1239 in mice transplanted with TXL2 cells. Mice received human IgG, B-1239 alone, nilotinib alone, or nilotinib and B-1239.

At 12 days after the last treatment, leukemia cell numbers in the circulation of control mice and B-1239-treated mice were comparable.

However, B-1239-treated mice showed significant inhibition of ALL cell growth in the bone marrow and spleen, when compared to control mice. mAb-treated mice also had significantly lower spleen weights than controls.

Nilotinib alone also significantly reduced the ALL cell burden in the peripheral blood, spleen, and bone marrow, when compared to controls. But there was no significant difference in these measures between mice that received nilotinib alone or nilotinib plus B-1239.

Nevertheless, Dr Heisterkamp and her colleagues said they will continue to evaluate the use of B-1239 for the treatment of ALL.

Monoclonal antibodies

Credit: Linda Bartlett

Preclinical research suggests the B-cell activating receptor (BAFF-R) may be a promising therapeutic target for treatment-resistant leukemia.

A monoclonal antibody (mAb) that targets BAFF-R overcame resistance to nilotinib and enhanced the efficacy of both nilotinib and vincristine in vitro.

The mAb, called B-1239, also demonstrated antileukemic effects in mouse models, when given alone. But it did not appear to improve upon the effects of nilotinib when given in combination.

Nora Heisterkamp, PhD, of Children’s Hospital Los Angeles in California, and her colleagues reported these findings in Molecular Cancer Therapeutics.

In a previous study, the researchers had shown that BAFF-R is expressed on pre-B ALL cells but not on their normal counterparts.

“We’ve now demonstrated that BAFF-R is a strong potential therapeutic target for treating chemotherapy-resistant leukemia cells, without damaging healthy cells,” Dr Heisterkamp said.

She and her colleagues began this research by generating pre-B ALL cells from the bone marrow of wild-type mice and BAFF-R-null mice with a retroviral vector carrying the BCR/ABL oncogene. They found that wild-type pre-B-ALL cells expressed high levels of BAFF-R.

The team then treated both wild-type and BAFF-R-deficient leukemic cells with nilotinib. The wild-type cells developed resistance to nilotinib in 9 to 10 days, but the BAFF-R-deficient cells were eradicated by treatment.

The researchers next tested the effects of B-1239, a human codon-optimized anti-BAFF-R mAb. B-1239 bound to BAFF-R on both Ph-positive and Ph-negative ALL cells in vitro, and the mAb inhibited BAFF-R in a dose-dependent manner.

In pre-B-ALL cells, B-1239 alone had little effect on cell viability or proliferation. However, when combined with vincristine or nilotinib, B-1239 reduced cell count and viability more than either agent alone.

The researchers also found that B-1239 stimulated natural killer cell-mediated cytotoxicity in patient-derived ALL cells. And the mAb stimulated phagocytosis by macrophages.

Finally, Dr Heisterkamp and her colleagues tested B-1239 in mice transplanted with TXL2 cells. Mice received human IgG, B-1239 alone, nilotinib alone, or nilotinib and B-1239.

At 12 days after the last treatment, leukemia cell numbers in the circulation of control mice and B-1239-treated mice were comparable.

However, B-1239-treated mice showed significant inhibition of ALL cell growth in the bone marrow and spleen, when compared to control mice. mAb-treated mice also had significantly lower spleen weights than controls.

Nilotinib alone also significantly reduced the ALL cell burden in the peripheral blood, spleen, and bone marrow, when compared to controls. But there was no significant difference in these measures between mice that received nilotinib alone or nilotinib plus B-1239.

Nevertheless, Dr Heisterkamp and her colleagues said they will continue to evaluate the use of B-1239 for the treatment of ALL.

Monoclonal antibodies

Credit: Linda Bartlett

Preclinical research suggests the B-cell activating receptor (BAFF-R) may be a promising therapeutic target for treatment-resistant leukemia.

A monoclonal antibody (mAb) that targets BAFF-R overcame resistance to nilotinib and enhanced the efficacy of both nilotinib and vincristine in vitro.

The mAb, called B-1239, also demonstrated antileukemic effects in mouse models, when given alone. But it did not appear to improve upon the effects of nilotinib when given in combination.

Nora Heisterkamp, PhD, of Children’s Hospital Los Angeles in California, and her colleagues reported these findings in Molecular Cancer Therapeutics.

In a previous study, the researchers had shown that BAFF-R is expressed on pre-B ALL cells but not on their normal counterparts.

“We’ve now demonstrated that BAFF-R is a strong potential therapeutic target for treating chemotherapy-resistant leukemia cells, without damaging healthy cells,” Dr Heisterkamp said.

She and her colleagues began this research by generating pre-B ALL cells from the bone marrow of wild-type mice and BAFF-R-null mice with a retroviral vector carrying the BCR/ABL oncogene. They found that wild-type pre-B-ALL cells expressed high levels of BAFF-R.

The team then treated both wild-type and BAFF-R-deficient leukemic cells with nilotinib. The wild-type cells developed resistance to nilotinib in 9 to 10 days, but the BAFF-R-deficient cells were eradicated by treatment.

The researchers next tested the effects of B-1239, a human codon-optimized anti-BAFF-R mAb. B-1239 bound to BAFF-R on both Ph-positive and Ph-negative ALL cells in vitro, and the mAb inhibited BAFF-R in a dose-dependent manner.

In pre-B-ALL cells, B-1239 alone had little effect on cell viability or proliferation. However, when combined with vincristine or nilotinib, B-1239 reduced cell count and viability more than either agent alone.

The researchers also found that B-1239 stimulated natural killer cell-mediated cytotoxicity in patient-derived ALL cells. And the mAb stimulated phagocytosis by macrophages.

Finally, Dr Heisterkamp and her colleagues tested B-1239 in mice transplanted with TXL2 cells. Mice received human IgG, B-1239 alone, nilotinib alone, or nilotinib and B-1239.

At 12 days after the last treatment, leukemia cell numbers in the circulation of control mice and B-1239-treated mice were comparable.

However, B-1239-treated mice showed significant inhibition of ALL cell growth in the bone marrow and spleen, when compared to control mice. mAb-treated mice also had significantly lower spleen weights than controls.

Nilotinib alone also significantly reduced the ALL cell burden in the peripheral blood, spleen, and bone marrow, when compared to controls. But there was no significant difference in these measures between mice that received nilotinib alone or nilotinib plus B-1239.

Nevertheless, Dr Heisterkamp and her colleagues said they will continue to evaluate the use of B-1239 for the treatment of ALL.

Blood samples

Credit: Graham Colm

A method of measuring minimal residual disease (MRD) can predict transplant outcomes in adults with acute lymphoblastic leukemia (ALL), according to a study published in Biology of Blood and Marrow Transplantation.

Researchers used the test, called LymphoSIGHT, to evaluate MRD in patient blood samples.

The test successfully predicted both relapse and survival and detected evidence of disease a median of 3 months prior to relapse.

This research was conducted by Aaron C. Logan, MD, PhD, of the University of California, San Francisco, and his colleagues. It was sponsored by Sequenta, Inc., makers of the LymphoSIGHT test.

The researchers used LymphoSIGHT to analyze 237 blood samples from 29 adults who underwent allogeneic hematopoietic stem cell transplant (HSCT) to treat ALL.

The LymphoSIGHT test consists of a 2-step process. First, cancer cell DNA sequences are identified in a diagnostic sample. Follow-up samples are then screened for these sequences to detect MRD.

The results, which are generated in 7 days using Sequenta’s CLIA-certified laboratory, are provided in a report that shows a patient’s MRD status and level, as well as MRD trends over time.

The researchers found the test could quantify MRD in 93% of patients. MRD positivity was defined as more than 1 leukemia cell per 1 million white blood cells.

Patients who were MRD-positive before HSCT conditioning were significantly more likely than MRD-negative patients to relapse after transplant (hazard ratio=7.7, P=0.003).

And patients who were MRD-positive in the first 90 days after transplant had a significantly higher risk of relapse than patients who were MRD-negative (hazard ratio=14; P<0.0001).

Patients who were MRD-positive at any point after HSCT (17 of 25 evaluable patients) all relapsed and died from their disease. Their median survival was 359 days (range, 85-1991 days). The median lead-time from MRD detection to clinical relapse was 89 days (range, 0-207 days).

Of the 8 patients who remained MRD-negative, 6 were still alive at a median of 1853 days post-HSCT (range, 1641-2732). Two patients died from complications of graft-vs-host disease, without evidence of leukemia recurrence.

The researchers said these results suggest the LymphoSIGHT test can help physicians understand treatment responses and patient prognoses, as well as guide treatment decisions.

Blood samples

Credit: Graham Colm

A method of measuring minimal residual disease (MRD) can predict transplant outcomes in adults with acute lymphoblastic leukemia (ALL), according to a study published in Biology of Blood and Marrow Transplantation.

Researchers used the test, called LymphoSIGHT, to evaluate MRD in patient blood samples.

The test successfully predicted both relapse and survival and detected evidence of disease a median of 3 months prior to relapse.

This research was conducted by Aaron C. Logan, MD, PhD, of the University of California, San Francisco, and his colleagues. It was sponsored by Sequenta, Inc., makers of the LymphoSIGHT test.

The researchers used LymphoSIGHT to analyze 237 blood samples from 29 adults who underwent allogeneic hematopoietic stem cell transplant (HSCT) to treat ALL.

The LymphoSIGHT test consists of a 2-step process. First, cancer cell DNA sequences are identified in a diagnostic sample. Follow-up samples are then screened for these sequences to detect MRD.

The results, which are generated in 7 days using Sequenta’s CLIA-certified laboratory, are provided in a report that shows a patient’s MRD status and level, as well as MRD trends over time.

The researchers found the test could quantify MRD in 93% of patients. MRD positivity was defined as more than 1 leukemia cell per 1 million white blood cells.

Patients who were MRD-positive before HSCT conditioning were significantly more likely than MRD-negative patients to relapse after transplant (hazard ratio=7.7, P=0.003).

And patients who were MRD-positive in the first 90 days after transplant had a significantly higher risk of relapse than patients who were MRD-negative (hazard ratio=14; P<0.0001).

Patients who were MRD-positive at any point after HSCT (17 of 25 evaluable patients) all relapsed and died from their disease. Their median survival was 359 days (range, 85-1991 days). The median lead-time from MRD detection to clinical relapse was 89 days (range, 0-207 days).

Of the 8 patients who remained MRD-negative, 6 were still alive at a median of 1853 days post-HSCT (range, 1641-2732). Two patients died from complications of graft-vs-host disease, without evidence of leukemia recurrence.

The researchers said these results suggest the LymphoSIGHT test can help physicians understand treatment responses and patient prognoses, as well as guide treatment decisions.

Blood samples

Credit: Graham Colm

A method of measuring minimal residual disease (MRD) can predict transplant outcomes in adults with acute lymphoblastic leukemia (ALL), according to a study published in Biology of Blood and Marrow Transplantation.

Researchers used the test, called LymphoSIGHT, to evaluate MRD in patient blood samples.

The test successfully predicted both relapse and survival and detected evidence of disease a median of 3 months prior to relapse.

This research was conducted by Aaron C. Logan, MD, PhD, of the University of California, San Francisco, and his colleagues. It was sponsored by Sequenta, Inc., makers of the LymphoSIGHT test.

The researchers used LymphoSIGHT to analyze 237 blood samples from 29 adults who underwent allogeneic hematopoietic stem cell transplant (HSCT) to treat ALL.

The LymphoSIGHT test consists of a 2-step process. First, cancer cell DNA sequences are identified in a diagnostic sample. Follow-up samples are then screened for these sequences to detect MRD.

The results, which are generated in 7 days using Sequenta’s CLIA-certified laboratory, are provided in a report that shows a patient’s MRD status and level, as well as MRD trends over time.

The researchers found the test could quantify MRD in 93% of patients. MRD positivity was defined as more than 1 leukemia cell per 1 million white blood cells.

Patients who were MRD-positive before HSCT conditioning were significantly more likely than MRD-negative patients to relapse after transplant (hazard ratio=7.7, P=0.003).

And patients who were MRD-positive in the first 90 days after transplant had a significantly higher risk of relapse than patients who were MRD-negative (hazard ratio=14; P<0.0001).

Patients who were MRD-positive at any point after HSCT (17 of 25 evaluable patients) all relapsed and died from their disease. Their median survival was 359 days (range, 85-1991 days). The median lead-time from MRD detection to clinical relapse was 89 days (range, 0-207 days).

Of the 8 patients who remained MRD-negative, 6 were still alive at a median of 1853 days post-HSCT (range, 1641-2732). Two patients died from complications of graft-vs-host disease, without evidence of leukemia recurrence.

The researchers said these results suggest the LymphoSIGHT test can help physicians understand treatment responses and patient prognoses, as well as guide treatment decisions.