Vinorelbine-Based Hematopoietic Stem-Cell Mobilization: A More Effective, Low-Cost Alternative to Conventional Chemotherapy
Authors: Duarte Bruno Kosa Lino , Colella Marcos Paulo , Souza Fernando Vieira Pericole , Yamaguti-Hayakawa Gabriela G , Marques Jose Francisco Comenalli , Vigorito Afonso Celso , De Paula Erich Vinicius , Ozelo Margareth C 
Published: October 2019

Abstract
INTRODUCTION: Autologous stem cell transplantation (ASCT) is the cornerstone of the treatment of several hematological malignancies, including multiple myeloma (MM) and aggressive and relapsed/refractory lymphomas. The mobilization of peripheral blood stem-cells (PBSC) for ASCT, however, is not always possible, with failure rates around 20%. Although the introduction of drugs such as plerixafor has greatly improved on this issue, they are still expensive and inaccessible in lower-income countries. The use of chemomobilization with drugs such as cyclophosphamide, etoposide, and others are a more affordable option, but they still lead to severe neutropenia, and in some settings to longer inpatient stays, with the associated costs.
Vinorelbine is a vinca alkaloid which has already been reported to be effective in PBSC mobilization in combination with granulocyte growth-factor (G-CSF). We tested whether vinorelbine-based strategy for PBSC mobilization would be more effective and less resource-consuming than mobilization with conventional chemotherapy in combination with GCSF.
METHODS: This is a retrospective, single-center analysis of the 74 patients with plasma cell disorders and lymphomas who underwent PBSC mobilization in our institution from January 2016 until May 2018.
Until March 2017 PBSC mobilization at our institution was done with cyclophosphamide 2 gm/sqm plus G-CSF, for plasma-cell disorders, or with conventional chemotherapy regimens, such as ICE (ifosfamide, carboplatin and etoposide) and DHAP (dexamethasone, cytarabine and cisplatin) plus G-CSF for lymphomas. Peripheral CD34+ cells were counted daily after white blood cells reached > 1000 cells/μl, and leukapheresis was performed on the first day of peripheral CD34+ cell count > 10/μl, with a target of at least 2x106CD34+ cells/kg. Due to local limitations and the unpredictability of the day of PBSC harvesting, the whole procedure-from chemotherapy administration to apheresis-was done in the inpatient setting. From March 2017 onwards, in an effort to reduce costs and increase efficacy, a vinorelbine-based protocol for mobilization with a 35 gm/sqm dose on day one, GCSF 12-16 mcg/kg/day from day 4 onwards and PBSC harvesting on day 8, or latter, when peripheral CD34+ cell count was higher than 10/μl was implemented for all patients, irrespective of their diagnosis.
RESULTS: Patients' characteristics are summarized in Table 1. Seventy-four patients underwent mobilization, 38 (51.3%) with vinorelbine and 36 (47.3%) with conventional chemotherapy, with an 81.1% success rate. Patients had a median age of 54 years, with a median of one previous treatment line, which included radiotherapy in 22.4% of patients. Plasma-cell disorders were the most frequent diagnosis (59.5%). Due to a shortage of melphalan, only 52.7% of patients have proceeded to ASCT so far. Vinorelbine-based PBSC mobilization resulted in higher success rates (92.1% vs. 69.4%, p=0.017), lower length of hospital stay (median of 3 vs. 16 days, p<0.001), more predictable day of the first leukapheresis (median 7 days after chemotherapy, range 7-9 vs. 10 days, range 9-18) and a higher count of peripheral CD34+cells prior to leukapheresis (median 47.74 vs. 27.24 cells/μl, p=0.08) than mobilization with conventional chemotherapy-regimens (Figure 2). Patients in both groups were comparable regarding all variables depicted in Table 1, except for failure in a previous PBSC mobilization attempt (18.4% in the vinorelbine group vs. 2.8% in the conventional chemotherapy group, p=0.056). Two (5.3%) patients in the conventional chemotherapy group developed febrile neutropenia (FN), one of whom died. No episodes of FN or death were observed in the vinorelbine group. Progression-free survival and time for neutrophils engraftment after ASCT did not differ between groups (Figure 2). Direct costs of both strategies were roughly the same.
CONCLUSIONS: Vinorelbine is a safe, effective and less costly strategy for PBSC mobilization in patients undergoing ASCT. It is associated with less toxicity and mobilization failures, shorter hospital length of stay and yields higher CD34+ blood cell counts, all of which decrease the indirect costs associated with PBSC, without loss of efficacy.
Vinorelbine is a low-cost effective alternative to PBSC mobilization that can be useful in resource-constrained settings, where access to costly drugs, such as plerixafor, is limited.

Disclosures
De Paula: Hematology and Transfusion Medicine Center, University of Campinas: Employment. Ozelo:Pfizer: Honoraria, Research Funding, Speakers Bureau; Shire: Honoraria, Research Funding, Speakers Bureau; Grifols: Honoraria; Novo Nordisk: Honoraria, Research Funding, Speakers Bureau; Bioverativ: Honoraria, Research Funding; BioMarin: Honoraria, Speakers Bureau.