Intermediate-Dose versus Low-Dose Cyclophosphamide and Granulocyte Colony-Stimulating Factor for Peripheral Blood Stem Cell Mobilization in Patients with Multiple Myeloma Treated with Novel Induction Therapies

Abstract

Peripheral blood progenitor cell mobilization with intermediate-dose cyclophosphamide (ID-CY) and granulocyte colony-stimulating factor (G-CSF) has been shown to be more efficacious, albeit more toxic, than low-dose cyclophosphamide (LD-CY) mobilization regimens in patients with multiple myeloma treated with conventional therapies. However, the relative importance of cyclophosphamide dose intensity in peripheral blood progenitor cell mobilization after novel induction regimens is not known. Here we report mobilization outcomes of 123 patients who underwent transplantation within 1 year of starting induction chemotherapy with novel agents. We compared consecutive patients undergoing mobilization with ID-CY/G-CSF (3-4 g/m(2)) at one institution (n = 55) with patients receiving LD-CY/G-CSF (1.5 g/m(2)) at a different transplantation center (n = 68). At baseline, the 2 groups were well balanced, except for more frequent previous lenalidomide use in the ID-CY group (P = .04). Compared with LD-CY, ID-CY use was associated with higher median peak PB CD34(+) cell count (35/μL versus 160/μL; P < .001), CD34(+) cell yield on day 1 of collection (2.6 × 10(6)/kg versus 11.7 × 10(6)/kg, P ≤ .001), and total CD34(+) cell yield (7.5 × 10(6)/kg versus 16.6 × 10(6)/kg; P ≤ .001). Six patients in the LD-CY group had mobilization failure, compared with no patients in the ID-CY group. A significantly higher proportion of patients in the LD-CY group (P < .001) were unable to collect ≥5 × 10(6)/kg and ≥10 × 10(6)/kg CD34(+) cells. Neutrophil and platelet engraftment were significantly faster in the ID-CY group, likely because of higher infused CD34(+) cell doses. In conclusion, compared with LD-CY, ID-CY produced a more robust peripheral blood progenitor cell mobilization and significantly reduced the rates of mobilization failure. These data caution against the use of LD-CY-containing mobilization strategies in patients with multiple myeloma undergoing stem cell collection after novel induction regimens.

G-CSF plus preemptive plerixafor vs hyperfractionated CY plus G-CSF for autologous stem cell mobilization in multiple myeloma: effectiveness, safety and cost analysis

“…Retrospective studies comparing different CY doses have shown a higher CD34+ cell yield associated with higher dose of CY but with more considerable toxicity, which limits the use of very high dose CY (7 g/m 2 ) and favor the use of intermediate-to-high dose. 6,8,9 Indeed, fractionation of CY in our study allowed administration of a relatively high dose of CY (5 g/m 2 ) with decreased immediate toxicity, mainly nausea and vomiting, but was still associated with significant hematological toxicity.…”

“…Median time to neutrophil engraftment was 11 days (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) in the CY group compared with 12 days (10-15) in the plerixafor group (P = 0.027). Similarly, median time to platelet engraftment was 12 days (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) in the CY group compared with 12 days (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) in the plerixafor group (P = 0.12).…”

“…The mobilization strategies implemented by most transplant centers consist of G-CSF alone (steady-state strategy) or CY followed by G-CSF (chemo-mobilizing strategy). [5][6][7][8][9][10][11][12][13][14] However, the impact of CY dose on stem cell yield, subsequent engraftment and toxicity remains a matter of controversy. Moreover, the introduction of the new mobilizing agent, plerixafor, an inhibitor of stromal cell-derived factor 1α/C-X-C chemokine receptor type 4, 15,16 makes the choice of mobilization strategy even more controversial.…”

Evaluation of the Feasibility and Efficacy of Autologous Stem Cell Transplantation in Elderly Patients with Multiple Myeloma

“…The standard regimen for stem cell mobilization in younger patients with MM consists of CY followed by granulocyte colony-stimulating factor (G-CSF) administration. Compared to the intermediate dose of CY at 3-4 g/m 2 , a dose reduction to CY to 1.5 g/m 2 may reduce the incidence of febrile neutropenia, although the yield of CD34+ cells harvested would be lower (23). In the current study, 10 elderly patients (one patient older than 70 years) received 4 g/m 2 of CY for stem cell mobilization, while eight elderly patients (five patients older than 70 years) received a decreased dose of CY of 2-3 g/m 2 ( Table 2).…”

The Singapore Myeloma Study Group Consensus Guidelines for the management of patients with multiple myeloma

“…(12,40) Mobilisation chemotherapy and stem cell collection High-dose cyclophosphamide (Cy) at 4-7 g/m 2 with granulocyte colony-stimulating factor (GCSF) has been shown to be effective for haematopoietic progenitor cell mobilisation despite associated haematologic toxicity. (59) Vinorelbine 25 mg/m 2 in combination with Cy 1,500 mg/m 2 (Vino-Cy) was shown to be comparable to Cy mobilisation in a study using historical controls. (12,60) We recommend one of the following mobilisation protocols: A haematopoietic progenitor cell collection adequate for two SCTs should be the target; this is conventionally accepted to be greater than 5 × 10 6 per kg/body weight.…”