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A randomized evaluation of vinorelbine versus gemcitabine chemotherapy mobilization of stem cells in myeloma patients

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Numerous studies have established bortezomib-based tripleinduction regimens followed by high-dose melphalan chemotherapy with autologous stem cell transplantation (ASCT) as first-line treatment in fit myeloma patients [1–3]. Cyclophosphamide with G-CSF or… Click to show full abstract

Numerous studies have established bortezomib-based tripleinduction regimens followed by high-dose melphalan chemotherapy with autologous stem cell transplantation (ASCT) as first-line treatment in fit myeloma patients [1–3]. Cyclophosphamide with G-CSF or G-CSF alone are most frequently used for CD34+ mobilization before ASCT in myeloma patients [3–6], but up to 20% of patients poorly mobilize following cytokines alone or together with chemotherapy [7]. The additional use of the CXCR4 antagonist plerixafor represents a rescue strategy for sufficient CD34+ mobilization. Since two decades, alternatively, Swiss centers use a non-myelosuppressive CD34+ mobilization regimen combining vinorelbine chemotherapy with G–CSF, which is safe and effective in daily routine [8–10], and the rescue use of plerixafor was also investigated in this setting [10]. This non-myelosuppressive mobilization is associated with less side effects. However, with the predominant use of bortezomib during induction, more myeloma patients present with pre-existing neuropathy at CD34+ collection. A main side effect of vinorelbine, again, is neurotoxicity and, thereby, it can aggravate pre-existing neuropathy [11]. Gemcitabine has been studied as part of combination chemotherapy regimens predominantly in relapsing lymphoma patients, for re-induction and for CD34+ mobilization. Gemcitabine alone or combinations with gemcitabine were reported to be safe and reliable for sufficient autologous CD34+ mobilization [12]. Thus, gemcitabine monotherapy has evolved as an alternative to vinorelbine mobilization, even more so as gemcitabine is not neurotoxic. Previously, we have reported that gemcitabine combined with G-CSF for CD34+ mobilization is safe and effective in myeloma patients [13]. Consequently, we conducted a phase-II study comparing a mobilization strategy with vinorelbine and G-CSF to gemcitabine and G-CSF in myeloma patients in first remission after induction. We included all 136 myeloma patients seen at the University Hospital of Bern, Switzerland, for CD34+ mobilization after first-line induction between 12/2013 and 04/2017 (Patient characteristics in Supplemental Table S1). The study (registered as NCT# 02791373) had approval by the local ethics committee of Bern, Switzerland (decision number #247/12). All patients gave written informed consent. Eligible patients with symptomatic myeloma had standard first-line induction and were considered fit for consecutive melphalan-based HDCT/ASCT. Induction comprised regimens including thalidomide, bortezomib, or lenalidomide (<5 cycles), alone or in combination, plus dexamethasone. The following preconditions had to be fulfilled: age 18–75 years, ECOG <3, polyneuropathy 50 × 10/L without transfusion within These authors contributed equally: Ulrike Bacher, Thomas Pabst

Keywords: cd34 mobilization; gemcitabine; vinorelbine; myeloma patients; mobilization

Journal Title: Bone Marrow Transplantation
Year Published: 2020

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