Haematological malignancies developing in previously healthy individuals who received haematopoietic growth factors

Report from the Research on Adverse Drug Events and Reports (RADAR) project

Charles L. Bennett*, Andrew M. Evens, Leslie A. Andritsos, Lakshmi Balasubramanian, Mark Mai, Matthew J. Fisher, Timothy M. Kuzel, Cara Angelotta, June M McKoy, Julie M. Vose, Philip J. Bierman, David J. Kuter, Steven M. Trifilio, Steven M. Devine, Martin S. Tallman

*Corresponding author for this work

Research output: Contribution to journalReview article

118 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)642-650
Number of pages9
JournalBritish Journal of Haematology
Volume135
Issue number5
DOIs
StatePublished - Dec 1 2006

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Hematologic Neoplasms
Drug-Related Side Effects and Adverse Reactions
Intercellular Signaling Peptides and Proteins
Granulocyte Colony-Stimulating Factor
Research
Tissue Donors
Siblings
Volunteers
Stem Cells
Drug Therapy
Hematopoietic Stem Cell Transplantation
B-Cell Chronic Lymphocytic Leukemia
Hematopoietic Stem Cells
Acute Myeloid Leukemia
Thrombocytopenia
Autoantibodies
polyethylene glycol-recombinant human megakaryocyte growth and development factor
Healthy Volunteers
Leukemia
Clinical Trials

Keywords

  • Granulocyte colony-stimulating factor
  • Haematopoietic growth factors
  • Megakaryocyte growth and development factor
  • Research on Adverse Drug Events and Reports

ASJC Scopus subject areas

  • Hematology

Cite this

Bennett, Charles L. ; Evens, Andrew M. ; Andritsos, Leslie A. ; Balasubramanian, Lakshmi ; Mai, Mark ; Fisher, Matthew J. ; Kuzel, Timothy M. ; Angelotta, Cara ; McKoy, June M ; Vose, Julie M. ; Bierman, Philip J. ; Kuter, David J. ; Trifilio, Steven M. ; Devine, Steven M. ; Tallman, Martin S. / Haematological malignancies developing in previously healthy individuals who received haematopoietic growth factors : Report from the Research on Adverse Drug Events and Reports (RADAR) project. In: British Journal of Haematology. 2006 ; Vol. 135, No. 5. pp. 642-650.
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abstract = "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.",
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author = "Bennett, {Charles L.} and Evens, {Andrew M.} and Andritsos, {Leslie A.} and Lakshmi Balasubramanian and Mark Mai and Fisher, {Matthew J.} and Kuzel, {Timothy M.} and Cara Angelotta and McKoy, {June M} and Vose, {Julie M.} and Bierman, {Philip J.} and Kuter, {David J.} and Trifilio, {Steven M.} and Devine, {Steven M.} and Tallman, {Martin S.}",
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Bennett, CL, Evens, AM, Andritsos, LA, Balasubramanian, L, Mai, M, Fisher, MJ, Kuzel, TM, Angelotta, C, McKoy, JM, Vose, JM, Bierman, PJ, Kuter, DJ, Trifilio, SM, Devine, SM & Tallman, MS 2006, 'Haematological malignancies developing in previously healthy individuals who received haematopoietic growth factors: Report from the Research on Adverse Drug Events and Reports (RADAR) project', British Journal of Haematology, vol. 135, no. 5, pp. 642-650. https://doi.org/10.1111/j.1365-2141.2006.06312.x

Haematological malignancies developing in previously healthy individuals who received haematopoietic growth factors : Report from the Research on Adverse Drug Events and Reports (RADAR) project. / Bennett, Charles L.; Evens, Andrew M.; Andritsos, Leslie A.; Balasubramanian, Lakshmi; Mai, Mark; Fisher, Matthew J.; Kuzel, Timothy M.; Angelotta, Cara; McKoy, June M; Vose, Julie M.; Bierman, Philip J.; Kuter, David J.; Trifilio, Steven M.; Devine, Steven M.; Tallman, Martin S.

In: British Journal of Haematology, Vol. 135, No. 5, 01.12.2006, p. 642-650.

Research output: Contribution to journalReview article

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T1 - Haematological malignancies developing in previously healthy individuals who received haematopoietic growth factors

T2 - Report from the Research on Adverse Drug Events and Reports (RADAR) project

AU - Bennett, Charles L.

AU - Evens, Andrew M.

AU - Andritsos, Leslie A.

AU - Balasubramanian, Lakshmi

AU - Mai, Mark

AU - Fisher, Matthew J.

AU - Kuzel, Timothy M.

AU - Angelotta, Cara

AU - McKoy, June M

AU - Vose, Julie M.

AU - Bierman, Philip J.

AU - Kuter, David J.

AU - Trifilio, Steven M.

AU - Devine, Steven M.

AU - Tallman, Martin S.

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N2 - 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.

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