David P. Steensma
The appropriate role of iron chelation therapy in the management of patients with myelodysplastic syndromes (MDS) is currently controversial. Some investigators interpret data to indicate that careful attention to iron parameters, with early initiation of iron chelation in patients with evidence suggesting transfusion-associated iron overload, is an important component of high-quality MDS patient care. Other physicians are more skeptical, noting that chelation can be cumbersome or costly, has associated risks, and has not yet been shown to reduce morbidity or mortality in the MDS setting. This article reviews the extent to which iron chelation therapy might be either an important clinical intervention in MDS or a distraction from more pressing clinical concerns.
Anat Gafter-Gvili, David P. Steensma and Michael Auerbach
Coadministration of intravenous (IV) iron improves responses to erythropoiesis-stimulating agents (ESAs) in the treatment of cancer-associated (CAA) and chemotherapy-induced anemia (CIA). Twelve prospective studies have demonstrated synergy between parenteral iron and ESAs, with variable degrees of improved hemoglobin (Hgb) response rates, shorter times to target Hgb levels, and a lower ESA dose required for equivalent Hgb responses. Clinically significant adverse events (AEs) with currently available IV iron products are uncommon. Pretreatment serum hepcidin levels may predict response magnitude. Safety concerns among many oncologists are driven by reports of serious AEs from older IV iron formulations that are no longer available, and misinterpretation of the nature and frequency of minor infusion reactions. Premedication with antihistamines is of unproven benefit and can cause symptoms that mimic anaphylaxis, prompting intervention with vasopressors and converting self-limited reactions into hemodynamically significant AEs. Payer rules proscribing the administration of ESAs and IV iron on the same day also have limited the clinical adoption of IV iron and ESA coadministration. At a time when financial resources are scarce, the ability to reduce use of costly ESAs is beneficial. Despite a favorable risk/benefit ratio for IV iron in CAA and CIA, current IV iron recommendations in guidelines from ASCO/ASH, NCCN, and ESMO are inconsistent. The authors believe more routine use of IV iron for CAA and CIA is appropriate in view of existing evidence, and suggest reconsideration of the current ASCO/ASH guidelines, which state “there is insufficient evidence to consider the use of intravenous iron as a standard of care.”
Jeffrey Crawford, Jeffrey Allen, James Armitage, Douglas W. Blayney, Spero R. Cataland, Mark L. Heaney, Sally Htoy, Susan Hudock, Dwight D. Kloth, David J. Kuter, Gary H. Lyman, Brandon McMahon, David P. Steensma, Saroj Vadhan-Raj, Peter Westervelt and Michael Westmoreland
Jeffrey Crawford, James Armitage, Lodovico Balducci, Pamela Sue Becker, Douglas W. Blayney, Spero R. Cataland, Mark L. Heaney, Susan Hudock, Dwight D. Kloth, David J. Kuter, Gary H. Lyman, Brandon McMahon, Hope S. Rugo, Ayman A. Saad, Lee S. Schwartzberg, Sepideh Shayani, David P. Steensma, Mahsa Talbott, Saroj Vadhan-Raj, Peter Westervelt, Michael Westmoreland, Mary Dwyer and Maria Ho
Febrile neutropenia, a common side effect of myelosuppressive chemotherapy in patients with cancer, can result in prolonged hospitalization and broad-spectrum antibiotic use, often prompting treatment delays or dose reductions of drug regimens. Prophylactic use of myeloid growth factors (mainly the colony-stimulating factors filgrastim and pegfilgrastim) in patients of heightened risk can reduce the severity and duration of febrile neutropenia. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Myeloid Growth Factors provide recommendations on the use of these agents mainly in the oncology setting based on clinical evidence and expert consensus. This version includes revisions surrounding the issue of timing of pegfilgrastim administration. It also includes new sections on tbo-filgrastim, a recently approved agent that is biologically similar to filgrastim, and the role of myeloid growth factors in the hematopoietic cell transplant setting