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A new study has linked the immunosuppressive drug mycophenolate mofetil (MMF) to an increased risk of central nervous system (CNS) lymphoma in solid organ transplant recipients.
However, the research also suggests that calcineurin inhibitors (CNIs), when given alone or in combination with MMF, may protect transplant recipients from CNS lymphoma.
Researchers reported these findings in Oncotarget.
“MMF remains one of the best current medications for immunosuppression that we have,” said study author Amy Duffield, MD, PhD, of The Johns Hopkins Medical Institutions in Baltimore, Maryland.
“But a better understanding of its association with CNS lymphoproliferative disease will be crucial to further improving patients’ transplant regimens based on all of the risks these patients face.”
Dr Duffield and her colleagues noted that lymphomas and leukemias are known to be complications of solid organ transplants, but these malignancies rarely start in the CNS.
Still, in recent years, clinicians have begun to notice a rise in primary CNS lymphoproliferative disorders among transplant recipients. The current study is thought to be the first large enough to identify a link between MMF and these tumors.
For this work, Dr Duffield and her colleagues analyzed information on 177 patients with post-transplant lymphoproliferative disorder (PTLD) who were seen at Johns Hopkins Hospital between 1986 and 2014.
In that group, 29 patients—mostly kidney transplant recipients—were diagnosed with primary CNS lymphoproliferative disorders. The researchers said these were predominantly classified as monomorphic PTLD (72%), and most of the classifiable lymphomas were large B-cell lymphomas.
There were no cases of primary CNS PTLD diagnosed between 1986 and 1997, but the diagnosis increased markedly in the next decades.
The proportion of primary CNS PTLD cases compared to other PTLDs was 4.4-fold higher in the period from 2005 to 2014 than in the period from 1995 to 2004 (P<0.0001), even though the total number of PTLD cases remained relatively stable over time.
The researchers had prescription records on 16 of the patients who developed primary CNS lymphoproliferative disease.
Fifteen of the 16 patients had been taking MMF in the year prior to, or at the time of, their PTLD diagnosis. On the other hand, 37 of the 102 patients with PTLD outside the CNS had taken MMF (P<0.001).
The researchers also found that patients who took CNIs, either alone or in combination with MMF, seemed to be protected from developing primary CNS disease.
Primary CNS lymphoproliferative disease accounted for 66.7% of PTLDs among patients who took MMF but not a CNI (n=6), 23.9% of PTLDs among patients who took both an MMF and a CNI (n=46), and 1.7% of PTLDs among patients who took just a CNI (n=60).
The researchers found similar trends in a set of 6966 patients with PTLD. Those patients’ records were gleaned from an organ transplant database managed by the Organ Procurement and Transplantation Network and the United Network for Organ Sharing.
“More research needs to be done to confirm our results,” said Genevieve Crane, MD, PhD, of The Johns Hopkins Medical Institutions.
“But our work suggests that, at least in some patients, the combination of MMF and CNIs may be protective against CNS lymphoproliferative disease in a way that had not previously been appreciated.” 
A new study has linked the immunosuppressive drug mycophenolate mofetil (MMF) to an increased risk of central nervous system (CNS) lymphoma in solid organ transplant recipients.
However, the research also suggests that calcineurin inhibitors (CNIs), when given alone or in combination with MMF, may protect transplant recipients from CNS lymphoma.
Researchers reported these findings in Oncotarget.
“MMF remains one of the best current medications for immunosuppression that we have,” said study author Amy Duffield, MD, PhD, of The Johns Hopkins Medical Institutions in Baltimore, Maryland.
“But a better understanding of its association with CNS lymphoproliferative disease will be crucial to further improving patients’ transplant regimens based on all of the risks these patients face.”
Dr Duffield and her colleagues noted that lymphomas and leukemias are known to be complications of solid organ transplants, but these malignancies rarely start in the CNS.
Still, in recent years, clinicians have begun to notice a rise in primary CNS lymphoproliferative disorders among transplant recipients. The current study is thought to be the first large enough to identify a link between MMF and these tumors.
For this work, Dr Duffield and her colleagues analyzed information on 177 patients with post-transplant lymphoproliferative disorder (PTLD) who were seen at Johns Hopkins Hospital between 1986 and 2014.
In that group, 29 patients—mostly kidney transplant recipients—were diagnosed with primary CNS lymphoproliferative disorders. The researchers said these were predominantly classified as monomorphic PTLD (72%), and most of the classifiable lymphomas were large B-cell lymphomas.
There were no cases of primary CNS PTLD diagnosed between 1986 and 1997, but the diagnosis increased markedly in the next decades.
The proportion of primary CNS PTLD cases compared to other PTLDs was 4.4-fold higher in the period from 2005 to 2014 than in the period from 1995 to 2004 (P<0.0001), even though the total number of PTLD cases remained relatively stable over time.
The researchers had prescription records on 16 of the patients who developed primary CNS lymphoproliferative disease.
Fifteen of the 16 patients had been taking MMF in the year prior to, or at the time of, their PTLD diagnosis. On the other hand, 37 of the 102 patients with PTLD outside the CNS had taken MMF (P<0.001).
The researchers also found that patients who took CNIs, either alone or in combination with MMF, seemed to be protected from developing primary CNS disease.
Primary CNS lymphoproliferative disease accounted for 66.7% of PTLDs among patients who took MMF but not a CNI (n=6), 23.9% of PTLDs among patients who took both an MMF and a CNI (n=46), and 1.7% of PTLDs among patients who took just a CNI (n=60).
The researchers found similar trends in a set of 6966 patients with PTLD. Those patients’ records were gleaned from an organ transplant database managed by the Organ Procurement and Transplantation Network and the United Network for Organ Sharing.
“More research needs to be done to confirm our results,” said Genevieve Crane, MD, PhD, of The Johns Hopkins Medical Institutions.
“But our work suggests that, at least in some patients, the combination of MMF and CNIs may be protective against CNS lymphoproliferative disease in a way that had not previously been appreciated.”
A new study has linked the immunosuppressive drug mycophenolate mofetil (MMF) to an increased risk of central nervous system (CNS) lymphoma in solid organ transplant recipients.
However, the research also suggests that calcineurin inhibitors (CNIs), when given alone or in combination with MMF, may protect transplant recipients from CNS lymphoma.
Researchers reported these findings in Oncotarget.
“MMF remains one of the best current medications for immunosuppression that we have,” said study author Amy Duffield, MD, PhD, of The Johns Hopkins Medical Institutions in Baltimore, Maryland.
“But a better understanding of its association with CNS lymphoproliferative disease will be crucial to further improving patients’ transplant regimens based on all of the risks these patients face.”
Dr Duffield and her colleagues noted that lymphomas and leukemias are known to be complications of solid organ transplants, but these malignancies rarely start in the CNS.
Still, in recent years, clinicians have begun to notice a rise in primary CNS lymphoproliferative disorders among transplant recipients. The current study is thought to be the first large enough to identify a link between MMF and these tumors.
For this work, Dr Duffield and her colleagues analyzed information on 177 patients with post-transplant lymphoproliferative disorder (PTLD) who were seen at Johns Hopkins Hospital between 1986 and 2014.
In that group, 29 patients—mostly kidney transplant recipients—were diagnosed with primary CNS lymphoproliferative disorders. The researchers said these were predominantly classified as monomorphic PTLD (72%), and most of the classifiable lymphomas were large B-cell lymphomas.
There were no cases of primary CNS PTLD diagnosed between 1986 and 1997, but the diagnosis increased markedly in the next decades.
The proportion of primary CNS PTLD cases compared to other PTLDs was 4.4-fold higher in the period from 2005 to 2014 than in the period from 1995 to 2004 (P<0.0001), even though the total number of PTLD cases remained relatively stable over time.
The researchers had prescription records on 16 of the patients who developed primary CNS lymphoproliferative disease.
Fifteen of the 16 patients had been taking MMF in the year prior to, or at the time of, their PTLD diagnosis. On the other hand, 37 of the 102 patients with PTLD outside the CNS had taken MMF (P<0.001).
The researchers also found that patients who took CNIs, either alone or in combination with MMF, seemed to be protected from developing primary CNS disease.
Primary CNS lymphoproliferative disease accounted for 66.7% of PTLDs among patients who took MMF but not a CNI (n=6), 23.9% of PTLDs among patients who took both an MMF and a CNI (n=46), and 1.7% of PTLDs among patients who took just a CNI (n=60).
The researchers found similar trends in a set of 6966 patients with PTLD. Those patients’ records were gleaned from an organ transplant database managed by the Organ Procurement and Transplantation Network and the United Network for Organ Sharing.
“More research needs to be done to confirm our results,” said Genevieve Crane, MD, PhD, of The Johns Hopkins Medical Institutions.
“But our work suggests that, at least in some patients, the combination of MMF and CNIs may be protective against CNS lymphoproliferative disease in a way that had not previously been appreciated.”