Intermediate- Versus Low-Dose Cyclophosphamide and Granulocyte Colony Stimulating Factor for Peripheral Blood Progenitor Cell Mobilization in Patients with Multiple Myeloma Treated with Novel Induction Chemotherapies – A Multicenter Analysis

Peripheral blood progenitor cell (PBPC) mobilization with intermediate-dose cyclophosphamide (3–4 gm/m²) (ID-CY) and G-CSF has been shown to be less toxic than high-dose CY (≥7 gm/m²) -based, and more efficacious than low-dose CY (LD-CY) (1–2 gm/m²) -based mobilization regimens in multiple myeloma (MM) patients following conventional induction regimens. However the relative importance of CY dose intensity in PBPC mobilization following novel induction regimens is not known. Herein we report comparative efficacy of PBPC mobilization in MM patients following novel induction chemotherapies, relative to CY dose intensity.

This multicenter outcomes study includes 123 patients who underwent a planned, single autograft within 1-year of starting induction chemotherapy with novel chemotherapy agents (thalidomide, lenalidomide, bortezomib), from 2003–2010. Consecutive patients undergoing mobilization with ID-CY/G-CSF (3–4 gm/m²) (n=55) at one institution were compared against consecutive patients receiving LD-CY/G-CSF (1.5 gm/m²) (n=68) at a different transplant center. At baseline the two groups were compared for parameters predicting mobilization failure. In order to assess efficiency of PBPC mobilization, we evaluated peak peripheral blood (PB) CD34+ cell counts, CD34+ cell yield on day1 of collection, total CD34+ cell collection, and total number of apheresis sessions. Mobilization failure was defined as failure to collect ≥2 ×10⁶cells/kg body weight. All patients with normal renal function received uniform conditioning with Mel200 (MEL140 if serum creatinine was >2 mg/dl). SPSS version 13.0 was used for statistical analysis.

At baseline, the ID-CY and LD-CY cohorts were well balanced respectively in terms of mean age (57-yrs vs. 59-yrs, p=0.3), gender (males; 66% vs. 58%, p=0.4), high-risk cytogenetics (p=0.6), prior radiation (34% vs. 18%, p=0.06), disease stage (p=0.5), number of prior therapies (p=0.5) and remission status (p=0.2). No difference was observed in the types of novel therapies received prior to transplant (p=0.2), except 22% of the patients received lenalidomide in LD-CY vs. 40% in the ID-CY group (p=0.04). Compared to LD-CY, ID-CY use was associated with higher median peak PB CD34+ cell count (35/ul vs. 160/ul, p<0.001), CD34+ yield on day 1 of collection (2.6 ×10⁶/kg vs. 11.6 ×10⁶/kg, p=<0.001), total CD34+ cell yield (7.7 ×10⁶/kg vs. 24.9 ×10⁶/kg, p=<0.001), and a trend towards fewer apheresis sessions (p=0.052). Three patients in the LD-CY group had mobilization failure, while no patient in the ID-CY group had mobilization failure. Significantly higher proportion of patients (27% vs. 3.6%, p=<0.001) were unable to collect >5×10⁶/kg CD34+ cells in LD-CY group. Neutrophil engraftment was significantly faster (15.4 days vs. 9.9 days) in the ID-CY patients, likely because of higher infused CD34+ cell dose. Conclusion: In conclusion, compared with LD-CY, ID-CY produced a more robust PBPC mobilization, in all parameters analyzed. These data caution against the use of LD-CY containing mobilization strategy in MM patients undergoing stem cell collection following novel induction regimens.

No relevant conflicts of interest to declare.