Co-Transplantation of Mesenchymal Stem Cells Further Improves the Prognosis of Allo-HSCT in the Treatment of High Risk and Refractory/Relapse Hematologic Malignancies: A Single-Center Retrospective Study of 175 Patients

BACKGROUD:

Mesenchymal stem cells (MSCs) are known to have immunomodulatory, anti-inflammatory and pro-angiogenic properties and thus have the potential to improve the likelihood of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of hematologic malignancies.

OBJECTIVE:

To explore the efficacy and safety of allo-HSCT by co-transplantation with MSCs in hematologic malignancies patients.

METHODS:

We conducted a single-center retrospective study to comparing the incidence and severity of acute GVHD, recurrence rate and overall survival (OS) of high risk and refractory/relapse hematologic malignancies patients undergoing allo-HSCT with or without co-injection of MSCs. A total of 175 patients (113males/62 females) at Fujian Medical University Union Hospital from January 2016 to June 2019 were analyzed. The median age of the patients is 22 (range 1-65 years). Patients received salvaged conditioning regimens FA5-BuCy as previous reported for high risk and refractory/relapse hematologic malignancies, registered on http://ClinicalTrials.gov (NCT02328950), among whom 31(17.7%)were MSD-HSCT, 21(12%) MUD-HSCT and 123(70.3%)haplo-HSCT. All patients received ATG, cyclosporine A with short course methotrexate for prevention of GVHD. 85 patients transplanted with donor HSCs only, and 90 patients transplanted with HSCs and MSCs .MSCs infusion dose was 1-2×10⁶/kg, at -1~+1 days following HSCs infusion.

RESULTS:

The two groups were well matched demographically. All patients achieved successful engraftment within one month post-HSCT. There was no difference in time to leukocyte and platelet engraftment in the two groups. The incidence of aGVHD (36.5 % versus 26.7 %, P =0.163) was similar in the HSC versus MSC groups. With a median follow-up time of 373 days (range:29-1265days), the 2-yr OS was much better in MSC co-injection groups (77.6% versus 48.4%, P =0.005). Moreover, there was no significant difference in the 2-yr cumulative recurrence rate between the two groups (25.1% vs 16.2%, P = 0.4).

CONCLUSION:

FA5-BUCY as an intensive conditioning regimen facilitates the outcome of advanced diseases with allo-HSCT, and co-transplantation with MSCs could further improve the survival of hematologic malignancies patients who did not reach remission.