Comparison of Cryopreserved Versus Non-Cryopreserved Strategies for Autologous Stemcell Transplantation in Multiple Myeloma in Two Centers in Uruguay

Introduction: Autologous hematopoietic stem cell transplantation (ASCT) is a standard treatment for many hematologic malignancies. Multiple Myeloma (MM) is the main indication for ASCT in adults in Latin America and worldwide. The classic methodology for performing ASCT includes cryopreservation of the stem cell product during the period from collection to infusion. Recent studies have demonstrated the feasibility of performing ASCT in MM by maintaining the stem cell product at 4°c while the patient receives the conditioning regimen.

Objective: The primary objective was to compare time to neutrophil and platelet engraftment in patients who received the first ASCT for MM with or without cryopreservation. Secondary objectives included the incidence of graft failure, early mortality and toxicity.

Methods: Observational, descriptive, retrospective study comparing two strategies for ASCT in MM with or without stem cell cryopreservation. Patients older than 18 years, diagnosed with MM who received a first ASCT at two centers in Uruguay from October 15, 2018, to December 23, 2023 were included. All the patients had a peripheral blood stem cell (PBSC) collection. They were matched 1:2 in terms of age, gender, MM subtype, stage of the disease, ISS risk score, number of prior treatment lines, induction regimen, melphalan dose, mobilization regimen, number of CD34+ cells collected and infused (one patient from Maciel Hospital without cryopreservation and 2 patients from the Hospital Británico with cryopreserved stem cells).

Results: Sixty-nine patients were analyzed, 23 from Hospital Maciel and 46 from Hospital Británico. Forty patients (58%) were female and 29 (42%) were male. The median age at transplant was 60 years old (range 31-72). Most of the patients (89.8%) were in Durie Salmon stage III. Fifty-two patients had no renal failure (stage A). According to the International Staging System, 21 patients (30.4%) were stage II and 18 (26%) were stage I.

The pre transplant response was classified as complete response (CR) in 19 patients (27.5%); very good partial response in 22 patients (31.9%); partial response in 25 patients (36.2%) and stringent CR in 3 patients (4.3%).

Sixty patients (87%) were collected in one apheresis. The median number of harvested stem cells was 9 x 10(6)/kg (range 2.7 - 32.32), and the median of stem cells infused was 5.44 x 10(6)/kg, (range 2.7 - 10.82). Most of the patients (n=62; 89.9%) received a melphalan dose of 200 mg/m2. Seven patients (10.1%) received 140 mg/m2, due to renal impairment. No patient required renal replacement therapy.

According to the EBMT-ASTCT-CIBMTR-APBMT consensus definitions, the time to neutrophil engraftment was 10 days (6-12) at Hospital Maciel and 9 days (7-12) at Hospital Británico (p=0.38). The time to platelet engraftment was 20 days (17-25) in Hospital Maciel and 19 days (15-30) in Hospital Británico (p=0.14).

The median length of hospital stay was 21 days (range 18 - 34) for Hospital Maciel, and 24 days (range 19 - 41) for Hospital Británico (p= 0.78). No graft failure was observed in either group.

Discussion: Multiple Myeloma is the main indication for ASCT in adults, and it is of utmost importance to develop strategies to make the procedure more accessible and affordable while preserving safety and efficacy. The classic methodology to preserve stem cell viability after collection is with cryopreservation, usually with the cryoprotective agent DMSO, but the feasibility of short-term storage of the progenitor cells at 4°C. has also been established. In this paired analysis comparing two contemporary cohorts, one with cryopreservation (Hospital Británico) and the other without (Hospital Maciel) we demonstrated that hematologic reconstitution did not differ significantly, and that both strategies achieved similar time to neutrophil and platelet engraftment. No graft failure was observed, confirming the efficacy of both strategies. Although there were no major complications associated with the infusion of cryopreserved cells, the absence of DMSO in fresh infusions may prevent the toxicity associated with this cryoprotectant.

Conclusion: Cryopreserved and non-cryopreserved ASCT appear to achieve similar outcomes in terms of engraftment. Non-cryopreservation could be a strategy to improve affordability and accessibility to ASCT in MM, particularly in resource-limited areas.