Haematological malignancies developing in previously healthy individuals who received haematopoietic growth factors: report from the Research on Adverse Drug Events and Reports (RADAR) project

Abstract

Summary Pegylated recombinant human megakaryocyte growth and development factor (PEG‐rHuMGDF) and granulocyte colony‐stimulating factor (G‐CSF) promote haematopoietic progenitor cell maturation. We reviewed the findings for healthy volunteers/donors who developed haematological malignancies following PEG‐rHuMGDF or G‐CSF administration. Information was reviewed for three of 538 volunteers who received PEG‐rHuMGDF in clinical trials and two of 200 donors who underwent G‐CSF mobilised stem cell harvesting procedures for sibling stem cell transplants. Mantle cell, diffuse large B‐cell lymphoma and chronic lymphocytic leukaemia were diagnosed 1–5 years after PEG‐rHuMGDF exposure among three volunteers. For one patient, thrombocytopenia due to autoantibodies to PEG‐rHuMGDF developed shortly after PEG‐rHuMGDF administration and persisted until chemotherapy was administered. All three achieved complete remission, although one patient relapsed. Acute myeloid leukaemia was diagnosed 4 and 5 years after G‐CSF mobilisation in two donors who underwent peripheral blood stem cell donation for sibling allogeneic haematopoietic stem cell transplantation. Following intensive chemotherapy, one died from acute leukaemia and the second is in complete remission. Controversy exists over the appropriateness of administering haematopoietic growth factors to healthy individuals. While a causal relationship with haematological malignancies cannot be demonstrated, long‐term follow‐up among healthy individuals who receive haematopoietic growth factors is needed.

To G or not to G: is this still a question in allogeneic transplantation?

“…The few cases of acute myeloid leukemia reported in healthy donors, 3 are rather consistent with the age-adjusted incidence of leukemia in adults; 4 and in one case, offers some insights into the mechanisms of leukemogenesis. 5 Fortunately, G-CSF, at least in the unrelated donor setting remains listed under the IND protocols, which implies that every donor provides informed consent for the research, including agreement for perpetual annual follow-up.…”

Regeneration, health status and quality of life after rhG-CSF-stimulated stem cell collection in healthy donors: a cross-sectional study

“…Reports on malignancies after rhG-CSF administration in healthy individuals are still anecdotal, and in most cases a genetic risk may be present as donors experienced the same malignant entity as their siblings. 9,11 In a small study, Nagler et al 34 observed epigenetic changes in lymphocytes of healthy individuals after rhG-CSF administration, which were similar to those seen in cancer patients. The compliance of donors for follow-up was rather low in our sibling donor population, probably because of residences being far away from the donation center or because of the death of the relatives for whom they donated.…”

“…Several donors were identified who experienced acute leukemia after rhG-CSF administration. 9,10 Bennett et al 11 reported two malignancies among 200 sibling donors within 5 years. An ongoing monitoring of risks, possibly associated with rhG-CSF administration to healthy donors, should be warranted.…”

Allogeneic peripheral blood stem cell collection as of 2008

“…A few cases of leukemia in PBSC donors have been reported, although these publications have been criticized for selection bias and misleading statistical techniques [19,48,49]. The National Marrow Donor program (NMDP) has recently provided some reassuring data on this issue.…”