Low non-relapse mortality and good haematological and renal responses after autologous haematopoietic stem cell transplantation in multiple myeloma patients with renal insufficiency at transplant: A prospective Société Francophone de Greffe de Moelle-Thérapie Cellulaire observational study.

High-dose melphalan followed by autologous haematopoietic stem cell transplantation is widely used in newly diagnosed multiple myeloma (MM) patients as upfront therapy. However, the safety and efficacy of transplantation in patients with renal insufficiency (RI) are controversial. We followed a multicentre (16 SFGM-TC centres) prospective cohort of 50 newly diagnosed MM patients with a serum creatinine clearance of <40 mL/min at transplantation. Patients received a recommended dose of melphalan of 140 mg/m2. The primary end-point was the non-relapse mortality at Day 100. One death occurred during the first 100 days post-transplant. The median time to neutrophil engraftment was 12 days and to platelet engraftment was 13 days. The haematological response improved in 69% of patients, with best responses from partial response (PR) to very good partial response (VGPR) (10%), from PR to complete response (CR)/stringent complete response (sCR) (16%), from VGPR to CR/sCR (39%) and from CR to sCR (2%). At 2 years, the overall survival was 84%, the progression-free survival was 70% and the cumulative incidence of relapse was 20%. The renal response improved in 59% of patients, with the best renal responses post-transplant being minimal (9%), partial (2%) and complete (48%). Autologous transplantation was safe and effective in myeloma patients with RI at transplant.

Efficacy and safety of autologous transplant with non-cryopreserved peripheral blood stem cells in myeloma and lymphoma in Algeria. 10 years' experience.

INTRODUCTION: The storage of harvested stem cells, in standard refrigerators at +4°C, is a simple and inexpensive alternative to cryopreservation for most patients living in countries with limited resources. We present the 10 years' experience of our single center from Oran in Algeria using non-cryopreserved stem cells after conditioning with high dose chemotherapy, in a large group of myeloma and lymphoma patients. METHODS: From May 2009 to December 2019, autologous stem cell transplantation (ASCT) was carried out in our center, of which 420 with multiple myeloma (MM) and 154 patients with lymphoma. The source of stem cells in all patients consisted of mobilized autologous peripheral blood stem cells (PBSCs). A median of one cytapherisis was performed (range, 1-3) and the products of the aphaeresis were stored in a conventional blood bank refrigerator at +4°C, in 300-mL transfer packs (Baxter Healthcare) composed of impermeable gas, polyvinyl chloride plastic film. The viability of the harvested cells is assessed by flow cytometry using 7'AAD (7 Amino-Actinomycine D) and was determined by a trypan blue dye exclusion test. The chemotherapy conditioning regimen (Mel200, BEAM, CBV, EAM, BeEAM) started once a minimum of 2×106 CD34+cell/kg in MM or 3x106 CD34+cell/kg in lymphoma was obtained. RESULTS: In MM patients, the median age at ASCT was 54 years (range; 27-73). The median harvested CD34+ cell count was 3,2x106/kg (range; 1, 22 to 13, 22) and the viability in all cases being >90%. All patients had engraftment on the median of day 9 (range; 7 to 24) and platelet transfusion independence on the median of day 13 (range; 9 to 39). There was no graft failure. Transplant related mortality (TRM) at 100 days was 3,5%. The overall response to transplant was 99% (complete remission (CR) =64,5%; very good partial remission (VGPR) =34%, partial remission (PR) =1,5%). The estimated overall survival (OS) at 5 years was 68% and the median post-transplant progression-free survival (PFS) was 47 months. On December 31th 2021, 41% patient relapsed and 28% died after disease progression. 305 (75%) patients are alive and 237 (59%) without disease activity after a median follow-up of 52 months (range; 13 to 149). In lymphoma patients, 98 Hodgkin`s lymphoma (HL) and 56 non-Hodgkin´s lymphoma (NHL), were auto grafted. The median age at ASCT was 28 years (range; 16-55) and 33 years (17-61) respectively. After mobilization a median of 4,25x106/kg (NHL) and 4,14x106/kg (HL) of CD34+ was infused and the median viability of the cells after 7 days of refrigeration (trypan blue exclusion) was 82%. The median time to achieve 0,5 G/L neutrophil or more was 14 days (9-44) and 15 days (11-27) in HL and NHL, median time to achieve 20 G/L platelets or more at a median of 16 days (10-37) and 17 days (15-28) in HL and NHL. The OS at 5 years was 76% and 67% for patients with HL and NHL respectively. Transplant related mortality at 100 days was 5% in HL and 12,5% in NHL. CONCLUSION: This study demonstrates the feasibility of intensified therapy followed by autologous non-cryopreserved PBSCs infusion in MM and lymphoma patients. This method of ASCT is cheaper, and may potentially enable the widespread use of ASCT activities in other hematology centers in Algeria and in developing countries.