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

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Multiple myeloma (MM) is the most frequent indication for autologous stem cell transplantation (ASCT) [1]. Melphalan 200 mg/m is the gold standard conditioning regimen and peripheral blood stem cells (PBSC)… Click to show full abstract

Multiple myeloma (MM) is the most frequent indication for autologous stem cell transplantation (ASCT) [1]. Melphalan 200 mg/m is the gold standard conditioning regimen and peripheral blood stem cells (PBSC) is the major source of cells [1, 2]. Conventionally, PBSC are cryopreserved after harvesting (CRYO), allowing time for recovery from chemo-mobilization or administration of further cycles of chemotherapy, if needed [2]. Dimethyl sulfoxide (DMSO), a cryoprotectant, is used to prevent freezing damage to living cells [2, 3]. Although generally safe, DMSO can be associated with mild adverse reactions and more severe effects, such as cardiovascular, neurological, respiratory, renal, and hepatic disfunction [3]. Cryopreservation requires expensive equipment and trained personnel, which may not be available in developing countries [2, 4–6]. Storage of PBSC in its natural liquid state is not standard practice, but previous studies showed ASCT can be safely performed using non-cryopreserved PBSC (non-CRYO) [2, 4–6]. The American Association of Blood Bank asserts stem cells remain viable up to 3–5 days when stored in liquid state in blood bank refrigerators at 1–6 °C [7]. Short-term storage of non-CRYO is feasible and cost-saving [2, 4–6]. We herein reported our experience on ASCT for MM using both methods of storage and compared outcomes and costs. We retrospectively analyzed charts of all patients with MM who underwent ASCT at Hospital das Clinicas da Universidade de Sao Paulo between January of 2014 and October of 2016, excluding the period between January and July of 2015, due to internal issues in the stem cell laboratory. In August of 2015, we started to perform ASCT using non-CRYO. After the good results, it became our method of choice; CRYO was then reserved for selected cases (delay due to clinical condition or logistic matters). Follow-up was carried for 30 days post-ASCT. A total of 108 ASCTs were included in two groups: 63 in CRYO and 45 in non-CRYO. Patients in CRYO were mobilized with granulocyte colony-stimulating factor (GCSF) alone, Cyclophosphamide+G-CSF, or G-CSF+ Plerixafor. In non-CRYO, all patients were mobilized with G-CSF alone. A minimum yield of 2 × 10CD34+ cells/kg was mandatory to undergo ASCT. For cryopreservation, 10% DMSO was added and the product stored in mechanical freezer at −80 °C. Non-CRYO cells were stored in blood bank refrigerator at 4 °C for a maximum of 48 h. All patients were conditioned with Melphalan (200 mg/m or 140 mg/m, if chronic renal failure or heart failure). In CRYO, Diphenydramine, Hydrocortisone, and Dipyrone were given prior to infusion to avoid inflammatory reaction to DMSO. Patients in non-CRYO were not premedicated. On day +5 post-ASCT, all patients were started on a daily dose of 300 mcg of G-CSF until neutrophil recovery. All patients signed written consent prior to ASCT. The study was approved by the Research Ethics Committee of Hospital das Clinicas da Universidade de Sao Paulo. Primary endpoint was neutrophil engraftment (NE), defined as time from infusion to the first of three consecutive days with absolute neutrophil count of at least 500/mm; graft failure was defined as no neutrophil recovery until 28 days of transplantation. Secondary endpoints included early transplantation-related mortality (TRM), infection, infusion-related complications, and costs. Early TRM was defined as death related to ASCT on the first 30 days. Infection was evaluated from infusion until NE and required clinical findings with documented microbiological exam or medical image. Neutropenic fever, established as axillary temperature of 37.8 °C or higher with * V. Rocha [email protected]

Keywords: stem cells; transplantation; blood; non cryo

Journal Title: Bone Marrow Transplantation
Year Published: 2018

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