How to Manage Neutropenia in Multiple Myeloma Antonio Palumbo, 1 Jon Bladé, 2 Mario Boccadoro, 1 Carmela Palladino, 1 Faith Davies, 3 Meletios Dimopoulos, 4 Anna Dmoszynska, 5 Hermann Einsele, 6 Philippe Moreau, 7 Orhan Sezer, 8 Andrew Spencer, 9 Pieter Sonneveld, 10 Jesus San Miguel 11 Abstract Neutropenia is a hematologic adverse event characterized by an absolute neutrophil count (ANC) lower than 1500 cells/mL. This reduction may be due to decreased neutrophil production, accelerated use, a shift in compartments of neutrophils, or a combination of these factors. Neutropenia is often associated with infections, which are major causes of morbidity and mortality in patients with cancer. In patients with multiple myeloma, the novel agents thalidomide, lenalidomide, and bortezomib have improved outcome, but chemotherapy-related neutropenia should be carefully considered. Chemotherapy-related high-risk factors for severe neutropenia include regimens with an expected neutropenia rate of  50%, such as the 3-drug combinations including lenalidomide plus alkylating agents or doxorubicin, whereas low-risk regimens include combinations of the novel agents with dexamethasone alone. Patient characteristics, disease stage, type of current and previous treatment, and ANC  1000 cells/mL at baseline are additional factors that define the risk of severe neutropenia. Granulocyte-colony stimulating factor (G-CSF) should be used to manage chemotherapy-related neutropenia so that patients may stay on treatment for a longer time and benefit from it. Primary G-CSF prophylaxis should be used when high-risk regimens are administered or when low/intermediate-risk regimens are used and additional risk factors are present. Reactive G-CSF treatment is indicated when patients undergoing low-risk chemotherapy experience grade 3/4 neutropenia. If ANC restores to  1000 cells/mL, therapy can be resumed with no dose modifications. In case of persistence of severe neutropenia, treatment should be delayed until ANC reaches  1000 cells/mL, and dose reductions are necessary. Clinical Lymphoma, Myeloma & Leukemia, Vol. 12, No. 1, 5-11 © 2012 Elsevier Inc. All rights reserved. Keywords: Absolute neutrophil count, Granulocyte colony-stimulating factor, Multiple myeloma, Myelosuppression, Neutropenia Definition and Classification of Neutropenia Neutropenia is a blood disorder related to neutrophilic white cells, which are essential to prevent bacterial and fungal infections. Neu- trophils originate from pluripotential stem cells in the bone mar- row. 1 Two hematopoietic growth factors, namely granulocyte colo- ny-stimulating factor (G-CSF) and granulocyte-macrophage colony- stimulating factor, regulate the production and deployment of neutrophils. 2 Healthy adults have an absolute neutrophil count (ANC) of about 1500-7000 cells/mL (1.5-7.0  10 9 /L). According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V3.0, it is classified as mild (ANC 1 Myeloma Unit, Division of Hematology, University of Torino, AOU San Giovanni Battista, Torino, Italy 2 Department of Hematology, Hospital Clinic, Barcelona, Spain 3 Institute of Cancer Research and Royal Marsden Hospital, London, United Kingdom 4 Department of Clinical Therapeutics, University of Athens School of Medicine, Alexandra General Hospital, Athens, Greece 5 Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland 6 Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany 7 Hematology Department, University Hospital Hôtel-Dieu, Nantes, France 8 Department of Hematology and Oncology, University Medical Center, Hamburg, Germany 9 Malignant Hematology and Stem Cell Transplantation Service, Alfred Hospital, Melbourne, Australia 10 Department of Hematology, University Hospital Rotterdam, Rotterdam, Netherlands 11 Servicio de Hematología, Hospital Universitario de Salamanca, and CIC, IBMCC (USAL-CSIC), Salamanca, Spain Submitted: Aug 4, 2011; Revised: Oct 14, 2011; Accepted: Nov 9, 2011 Address for correspondence: Antonio Palumbo, Myeloma Unit, Division of Hematology, University of Torino, AOU San Giovanni Battista, Torino, Italy Fax: +39 01 1696 3737; e-mail contact: appalumbo@yahoo.com Review Clinical Lymphoma, Myeloma & Leukemia February 2012 5 2152-2650/$ - see frontmatter © 2012 Elsevier Inc. All rights reserved. doi: 10.1016/j.clml.2011.11.001