Cyclophosphamide‐based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma

Abstract

High-dose cyclophosphamide (Cy) is frequently employed for peripheral blood mobilization of hematopoietic stem cells before high-dose chemotherapy with autologous stem cell transplantation (ASCT) in multiple myeloma (MM). The benefit of mobilization with Cy over filgrastim (granulocyte colony-stimulating factor; G-CSF) alone is unclear. Between 2000 and 2008, 167 patients with newly diagnosed MM underwent single ASCT after melphalan conditioning at our institution. Seventy-three patients were mobilized with G-CSF alone, and 94 patients with Cy plus G-CSF (Cy+G-CSF). We retrospectively analyzed Cy’s impact on both toxicity and efficacy. Mobilization efficiency was augmented by Cy; a mean total of 12 versus 5.8 × 106 CD34+ cells/kg were collected from patients mobilized with Cy+G-CSF versus G-CSF, respectively, (P <0.01), over a mean of 1.6 versus 2.2 days of peripheral blood apheresis (p = 0.001). Mobilization-related toxicity was also, however, augmented by Cy; 14% of Cy+G-CSF patients were hospitalized because of complications versus none receiving G-CSF (P <0.0001). Toxicity, including death, related to ASCT was similar between cohorts. Regarding long-term outcomes, multivariate analysis revealed no difference for Cy+G-CSF versus G-CSF (hazard ratio 0.8 for event-free survival [95% confidence interval {CI} 0.57–1.25] and 0.96 for overall survival [95% CI 0.61–1.54]). In summary, we show that mobilization with Cy increases toxicity without positively impacting long-term outcomes in MM. Our findings place into question Cy’s benefit as a routine component of stem cell mobilization regimens in MM. Randomized trials are needed to elucidate the risks and benefits of Cy more definitively.

Is it feasible to use granulocyte-colony stimulating factor alone to mobilize progenitor cells in multiple myeloma patients induced with a cyclophosphamide, thalidomide and dexamethasone regimen?

“…In the current study, no difference in the number of days of apheresis was observed between the groups ( p -value = 0.07). No studies exist that support an increase in induction time preceding mobilization to enhance successful cell collection 22 . In the present study, no association was found between better response and improved survival.…”

“…The cyclophosphamide used in mobilization, in addition to its ability to promote release of progenitor cells from the bone marrow for peripheral collection, has a reputation of reducing the disease further (debulking) during the collection of progenitor cells. Retrospective studies have failed to confirm this effect and have shown no advantage in terms of survival 22 . Similarly, in the present study, no advantages of cyclophosphamide use were found in terms of mobilization, improved response or survival.…”

Poor peripheral blood stem cell mobilization affects long‐term outcomes in multiple myeloma patients undergoing autologous stem cell transplantation

“…Furthermore, it is not known if plerixafor mobilized and transplanted patients have improved PFS and OS. Both plerixafor + G‐CSF or cyclophosphamide + G‐CSF mobilization were reported to be effective mobilization methods to overcome poor mobilization in MM patients …”

High‐dose cyclophosphamide for hard‐to‐treat patients with relapsed or refractory B‐cell non‐Hodgkin's lymphoma, a phase II result

“…The dose‐limiting toxicity of HD‐CPM is cardiac, with fatal myopericarditis occurring at doses greater than 180 mg/kg, administered over 4 days . Intensive cyclophosphamide therapy is commonly used for mobilizing stem cells for autologous transplantation . High‐dose cyclophosphamide is also used for its immunosuppressive and antitumor effects cytoreductive in allogeneic bone marrow transplantation and aplastic anemia .…”