A Comparison of Toxicity and Mobilization Efficacy Following Two Different Doses of Cyclophosphamide for Mobilization of Hematopoietic Stem Cells in Multiple Myeloma Patients.

Cyclophosphamide (Cy) (2-7 g/m²) has been shown to be an effective regimen for hematopoietic stem cell (HSC) mobilization in multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT). However, the optimal dose to be used, which maximizes HSC collection yields while minimizing febrile neutropenia and other toxicities, remains controversial. Two historical cohorts of MM patients who received G-CSF and Cy at dose of either 4g/m² (Cy4) or 2g/m² (Cy2) were compared.

A total of 72 patients undergoing first mobilization with Cy and G-CSF at a single institution between June 2006 and December 2008 were retrospectively analyzed. The initial Cy4 patient cohort (n=35) was mobilized with Cy 4gm/m² starting on Day 1 followed by G-CSF 10ug/kg/day starting on Day 7 and continuing until completion of apheresis. Beginning in Feb 2008, the Cy dose was reduced to 2gm/m² and the G-CSF start date was moved to day 4 (Cy2 n=37). Apheresis was initiated at physician discretion based on patient specific factors. Minimal and optimal yield was defined as collection of ≥2 × 10⁶ and ≥6-10 × 10⁶ CD34+ cells/kg respectively. Prophylactic antibiotics were given for ANC <500 to reduce risk of febrile neutropenia.

Minimal cell dose required for ASCT (≥2 × 10⁶ CD34+ cells/kg) was achieved in 97% vs. 86.5% of Cy4 and Cy2 patients, respectively. Of the 5 patients failing to mobilize on Cy2, four of these subsequently mobilized adequately following G-CSF and plerixafor. Median number of apheresis collections required was significantly lower in the Cy4 patients (1 vs.3, p=0.0065). The proportion of patients collecting the minimal and optimal cell dose in 2 or fewer days of apheresis was 94% vs. 86.5% (p= 0.4304) and 77% vs. 35% (p=0.0004), in the Cy4 and Cy2 patients respectively. However, mobilization with Cy4 was associated with a significantly higher incidence of hospital admissions due to febrile neutropenia (40% vs. 5%, p=0.0005), which is what prompted the change from Cy4 to Cy2.

Although Cy4 and Cy2 are both effective HSC mobilizing regimens, mobilization efficacy and toxicity vary greatly. Cy4 results in higher HSC yields requiring fewer apheresis procedures, but this benefit is offset by increased morbidity and hospital utilization. Based on the suboptimal results with Cy 4g/m² and Cy 2g/m² mobilization, newer mobilization strategies are clearly needed for MM patients. We are currently exploring a chemotherapy-free approach utilizing G-CSF +/- plerixafor, with the aim of optimizing HSC yields while minimizing toxicity and costs (apheresis collections, hospital utilization, etc.). In our current algorithm, all MM patients receive G-CSF at a dose of 10ug/kg/day, with a day 4 peripheral CD34+ cell count determining requirement for plerixafor on the evening prior to apheresis collection(s).

Off Label Use: Cyclophosphamide is being used as off label use for hematopoietic stem cell mobilization.