Unrelated Cord Blood Following Haploidentical HSCT with Post-Transplant Cyclophosphamide Improves Results of Alternative Donor Transplant in Thalassemia Major

Background:

Hematopoietic stem cell transplantation (HSCT) is cure for thalassemia major (TM). However, a suitable donor (HLA matched sibling and unrelated donor) for HSCT is less than 50%. Alternative donors were recently used in TM HSCT. Some study have found that thalassemia-free survival (TFS) was approximately 70% in haploidentical HSCT (h-HSCT) or unrelated cord blood (UCB) transplant for TM patients. So, it is necessary to find out a better h-HSCT for TM patients. In our early practice in leukemic HSCT we found that outcomes were improved by adding UCB to post-transplant cyclophosphamide (PT/Cy) h-HSCT. The latter associated with high mortality related transplant (32%). Henceforth, we used this termed haplocord transplant in TM.

Aim:

To develop a high TFS h-HSCT protocol for TM patients.

Patients and methods

First 10 patients with median age 8 (5-17) old years received NF-13-PT/Cy-TM protocol (fig. 1), in which, UCB was added on day 6 after PT/CY h-HSCT. Following 9 patients with age 9 (4-15) old years received NF-14-PT/Cy-TM protocol (fig. 2), in which three doses Thymoglobuline were added to NF-13-PT/Cy-TM protocol. Cyclophosphamide on day 3 and day 4 after transplant were both GVHD prophylaxis for h-HSCT and conditioning for UCB transplant. The HLA (at HLA-A, -B, -C and ¨CDRB1) for the pair of recipient and donor was 2-loci and more mismatched in h-HSCT and 2-loci and less mismatched in UCB.

Results

The results of haplocord transplants for all patients were showed in table 1. For first 10 patients, final cord blood engrafted in 4 patients; final haploidentical donor engrafted in 3 patients, 2 patients had a primary rejection. One had a secondary rejection and gave up therapy and died of infection. One patient died of grade IV acute GVHD. TFS is 6/10. For second group patients, final cord blood engrafted in 4 patients; final haploidentical donor engrafted in 3 patients, mixed donor engrafted in 2. No patient rejected his graft; All 9 patients live with transfusion independence.

Summary

Our data showed that UCB followed PT/Cy h-HSCT using NF-14-PT/Cy-TM protocol improved the results of alternative donor transplant in thalassemia major.

Registered in Clinical Trials: NCT02126046,

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