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?

Abstract

BackgroundCyclophosphamide plus thalidomide as induction for multiple myeloma patients eligible for autologous stem cell transplantation may be a limiting factor for cell mobilization. The minimum acceptable mobilized peripheral blood stem cell count to prevent deleterious effects during transplantation is 2.0 × 106 CD34+ cells/kg. Combining other treatments to granulocyte-colony stimulating factor, such as cyclophosphamide, could overcome the mobilization limitation. The objective of this study was to assess the number of CD34+ cells mobilized using granulocyte-colony stimulating factor with and without cyclophosphamide after induction with cyclophosphamide, thalidomide and dexamethasone.MethodsA retrospective study was performed of a cohort of multiple myeloma patients submitted to autologous stem cell transplantations at two Brazilian centers between May 2009 and July 2013. The oral cyclophosphamide and thalidomide induction doses used were 1500 mg/month and 100–200 mg/day, respectively. Mobilization doses were 10–15 mcg/kg granulocyte-colony stimulating factor with 2–4 g/m2 cyclophosphamide, or 15–20 mcg/kg granulocyte-colony stimulating factor alone for 5 days. Collection of >2.0 × 106 CD34+ cells/kg was considered sufficient.ResultsEighty-eight patients were analyzed; only 18 received cyclophosphamide. The median age was 58 years old (range: 51–62) for the granulocyte-colony stimulating factor group and 56.5 years old (range: 54–60) for granulocyte-colony stimulating factor plus cyclophosphamide group. Fifty-two patients were male. Eighty cases (90.9%) were Durie-Salmon Staging System III-A/B and 38 (44.7%) and 20 cases (23.5%) were International Staging System 2 and 3, respectively. The group that received cyclophosphamide collected a higher median number of progenitor cells [3.8 (range: 3.1–4.4) vs. 3.2 (range: 2.3–3.8)] (p-value = 0.008). No correlation was observed between better responses or number of induction cycles and the number of cells collected.ConclusionThe number of cells mobilized with granulocyte-colony stimulating factor plus cyclophosphamide was higher. However, in both groups, the median number of CD34+ cells was sufficient to perform a single autologous stem cell transplantation; no deleterious effects were reported during harvesting.

Comparison of the efficiency, safety, and survival outcomes in two stem cell mobilization regimens with cyclophosphamide plus G-CSF or G-CSF alone in multiple myeloma: a meta-analysis

“…The protocols with CTX plus G-CSF, which have been applied more than 25 years [10] while being efficient, are noted to be associated with serious treatment-related adverse effects, like neutropenic fever and hematuria [11,12].To reduce the chemotherapeutic toxicity during mobilization, the strategy with G-CSF alone has been introduced [12]. Indeed, several types of research with small sample sizes have compared the effects of the two mobilization regimens but the conclusions still have controversies between studies [13][14][15][16]. Whether a contradiction in these data was owing to insufficient sample size or genuine heterogeneity remains unknown.…”

Cryopreserved versus non-cryopreserved peripheral blood stem cells for autologous transplantation after high-dose Melphalan in multiple myeloma: comparative analysis

“…An inconvenience of non-CRYO is the lack of PBSC for future ASCT in the small number of patients whom could benefit from it [6]. In Brazil, we deal with limitations for the storage of frozen PBSC, as in other countries where liquid nitrogen at −196°C is not offered by the public health system [10]. In the ideal scenario, mobilization regimens with improved results, such as addition of Plerixafor to G-CSF may be preferred [11].…”

Hematopoietic stem cell mobilization for autologous transplantation in multiple myeloma patients previously exposed to cyclophosphamide, thalidomide, and dexamethasone: is granulocyte-colony stimulating factor alone enough?

“…This concern has been especially pertinent to patients previously exposed to cyclophosphamide or lenalidomide during induction, as these drugs appear to hamper HSC mobilization. In the article that accompanies this comment, Crusoe et al demonstrate the feasibility of using G-CSF alone to mobilize progenitor cells in MM patients induced with a cyclophosphamide, thalidomide and dexamethasone regimen 5 . The number of CD34 + cells mobilized was assessed after using G-CSF with or without cyclophosphamide.…”

“…The retrospective study of Crusoe et al included eighty-eight MM patients who underwent aHSCT at two Brazilian centers 5 . Collection of >2.0 × 10 6  CD34 +  cells/kg was considered sufficient.…”