Myelodysplastic syndrome and acute myeloid leukemia after receipt of granulocyte colony-stimulating factors in older patients with non-Hodgkin lymphoma

Cancer. 2019 Apr 1;125(7):1143-1154. doi: 10.1002/cncr.31914. Epub 2018 Dec 12.


Background: Granulocyte colony-stimulating factors (G-CSFs), which are used for the prevention of complications from chemotherapy-related neutropenia, are linked to the risk of developing second primary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The objective of this study was to examine the correlation between using a specific G-CSF agent and the risk of MDS/AML among older patients with non-Hodgkin lymphoma (NHL).

Methods: This was a retrospective cohort study of adults aged >65 years who were diagnosed with first primary NHL between 2001 and 2011. With data from the Surveillance, Epidemiology, and End Results-Medicare-linked database, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the risk of MDS/AML associated with the receipt of G-CSF(filgrastim and pegfilgrastim) in Cox proportional-hazards models, which were stratified according to treatment accounting for confounding by indication.

Results: Among 18,245 patients with NHL patients who had a median follow-up of 3.5 years, 56% received chemotherapy and/or immunotherapy, and G-CSF was most commonly used in those who received rituximab plus multiple chemotherapy regimens (77%). Subsequent MDS/AML diagnoses were identified in 666 patients (3.7%). A modest increased risk of MDS/AML was observed with the receipt of G-CSF (HR, 1.28; 95% CI, 1.01-1.62) and a trend was observed with increasing doses (Ptrend < .01). When specific agents were analyzed, an increased risk of MDS/AML was consistently observed with filgrastim (≥10 doses: HR, 1.67; 95% CI, 1.25-2.23), but not with pegfilgrastim (≥10 + doses: HR, 1.11; 95% CI, 0.84-1.45).

Conclusions: A higher of MDS/AML was observed in patients with NHL risk among those who received G-CSF that was specific to the use of filgrastim (≥10 doses), but not pegfilgrastim. Neutropenia prophylaxis is an essential component of highly effective NHL treatment regimens. The differential risk related to the types of G-CSF agents used warrants further study given their increasing use and newly available, US Food and Drug Administration-approved, biosimilar products.

Keywords: acute myeloid leukemia; epidemiology; granulocyte colony-stimulating factors; myelodysplastic syndrome; non-Hodgkin lymphoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Female
  • Filgrastim / therapeutic use*
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Hematologic Agents / therapeutic use*
  • Humans
  • Information Storage and Retrieval
  • Leukemia, Myeloid, Acute / epidemiology*
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Male
  • Medicare
  • Myelodysplastic Syndromes / epidemiology*
  • Neoplasms, Second Primary / epidemiology*
  • Neutropenia / chemically induced
  • Neutropenia / prevention & control*
  • Polyethylene Glycols / therapeutic use*
  • Rituximab / adverse effects
  • SEER Program
  • United States / epidemiology


  • Antineoplastic Agents, Immunological
  • Hematologic Agents
  • Granulocyte Colony-Stimulating Factor
  • pegfilgrastim
  • Polyethylene Glycols
  • Rituximab
  • Filgrastim