The Comparison of Results of Autologous Transplantation Using Non-Cryopreserved and Cryopreserved Hematopoietic Stem Cells (HSC)
Authors: Voloshin Sergei , Garifullin Andrey , Linnikov Sergey , Kuzyaeva Anastasiya , Shuvaev Vasily , Balashova Valentina , Rysev Georgiy , Chechetkin Alexander , Chebukina Zanna 
Published: February 2021

Background: Bone marrow (peripheral blood stem cells (PBSCs)) autologous transplantation is the standard care for transplant-eligible patients with multiple myeloma. This treatment option is somewhat limited due to the high consumption of economic resources and the access to Cryobank. We performed a retrospective analysis of multiple myeloma patients who underwent autologous transplantation using non-cryopreserved and сryopreserved grafts at our institution from March 2016 to April 2020.
Aim: Compare the results of autologous transplantation using non-cryopreserved and cryopreserved hematopoietic stem cells (HSC).
Methods: 78 patients with MM were included in the study (male/female ratio 1.3:1).
All patients got the standard immunochemotherapy programs. They had remission (≥partial response) till the auto-HSCT. Patients were divided in two groups depending on the technique of HSC storage: non-CRYO (n=35) and CRYO (n=43). Cryopreservation is a standard method of storage of HSC suspension. In our work we used the native HSC suspension which was saved from +4 °C to +6 °C during 72 - 120 hours.
An effectivity and safety were evaluated in such parameters as the number of CD34+ and 7AAD- cells, colony-forming ability (CFA). All of these were made after apheresis and before reinfusion of HSC. Also, we compared the duration of hematopoiesis's recovery, the number of platelet transfusions, the length of hospitalization after auto-HSCT.
Additionally, the effectiveness of therapy was assessed according to the IMWG response criteria and the level of residual tumor load before SCT and on day +100.
Results :
There were no differences in the total number of CD34 + cells x 106/kg, or in the level of 7AAD- cells, or in the total CFA. However, there was a significant difference in the percentage of loss of CD34+ cells from the moment of apheresis to the moment of reinfusion. We suppose it was caused adverse effects by temperature changes in CRYO group. In both groups, there were no severe infusion reactions on day 0. The adverse events (nausea, vomiting, tachycardia, increased total bilirubin and indicator liver enzymes) were absent in the non-CRYO group. But 29/43 (67.4%) patients had such symptoms in the CRYO group on day 0.
The results are presented in the comparison table (image 1) of the evaluated parameters.
All patients had full recovery of hematopoiesis till discharge from the hospital. Neutrophil recovery was achieved at 11th day (range 9-14) and platelets at 12th day (range 8-19) in the non-CRYO group, and 10th day (range 8-14) and 12th day (range 8 -20) in the CRYO group, respectively.
The frequency of achieving a partial response before autoHSCT was 37% (13/35), a very good partial response - 40% (14/35), a complete response - 23% (8/35) in the non-CRYO group and 72% (31/43), 14% (6/43) and 14% (6/43) in the CRIO group, respectively. HSCT was improved the efficiency of treatment as well as the frequency of complete and MRD-negative responses in both groups. Partial response after autoHSCT was achieved in 23% (8/35) patients, very good partial response in 40% (14/35), complete response in 37% (13/35) in the non-CRYO group compared to the CRYO group (47% (20/43), 21% (9/43) and 32% (14/43), respectively).
The MRD status was assessed before and after autoHSCT in 48 patients. The frequency of MRD-negative response before autoHSCT was 8.7% (2/23), after transplantation - 21.7% (5/23) in the non-CRYO group and 4% (1/25) and 12% (3/25) in the CRYO group, respectively.
AutoHSCT was increased the "depth" of the response in 25 patients. However, there were no significant differences between the same-type categories in the non-CRYO and CRYO groups (p&gt;.05).
AutoHSCT led to decrease of tumor load (TL). The average TL value was 0.55% before HSCT and 0.018% after HSCT (p=.036) in the non-CRYO group and 2.05 and 0.37 (p=.003) in the CRYO group, respectively. The mean TL after HSCT in the non-CRYO (0.018%) was smaller than mean TL in the CRYO (0.37%) groups (p &lt;.05).
Conclusion: The method of storage of PBSCs without cryopreserved is equal to traditional method controlled freezing with Dimethyl sulfoxide and can be used in hospitals which have no a Cryobank in their composition.
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Disclosures
Shuvaev: Novartis: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau.