Co-Transplantation of Haploidentical Stem Cells and a Dose of Unrelated Cord Blood in Pediatric Patients with Thalassemia Major

Abstract

Allogeneic stem cell transplantation is a cure for patients suffering from thalassemia major (TM). Historically, patients were limited by the selection of donors, while the advancement of haploidentical stem cell transplantation (haplo-SCT) has greatly expanded the donor pool. However, the outcomes of haplo-SCT in TM recipients vary between different programs. In this study, we retrospectively studied 73 pediatric TM patients (median age, 7 years; range, 3 to 14 years) who underwent haplo-cord transplantation. Both the estimated overall survival and transfusion-free survival were 95.26% (CI 95.77% to 96.23%). Neither primary nor secondary graft failures were observed. The median follow-up period was 811 days (range, 370 to 1433 days). Median neutrophil and platelet engraftment times were 22 days (range, 8 to 48 days) and 20 days (range, 8 to 99 days), respectively. Acute graft-versus-host disease (aGVHD) was observed in 52% of patients and of these, 25% developed grade III to IV aGVHD. Cord blood engraftment was associated with delayed immune recovery and increased aGVHD severity. Viral DNAemia occurred in a relatively high proportion of patients but only 7% of patients developed CMV disease, while another 7% of patients had post-transplantation lymphoproliferative disorder. Long-term complication outcomes were good. Only one patient developed extensive chronic GVHD. No surviving patients were reliant on blood transfusion by the time this manuscript was submitted. This is one of the largest studies on the outcomes of pediatric TM patients who received stem cell transplantations from alternative donors. The haplo-cord program is safe and practical for TM patients that do not have matched donors.

Haploidentical transplant for paediatric patients with severe thalassaemia using post‐transplant cyclophosphamide and methotrexate: A prospectively registered multicentre trial from the Bone Marrow Failure Working Group of Hunan Province, China

“…Therefore, we used MTX at these adjacent time‐points in addition to PTCy to cover the ‘leaking’ T‐cell reactivity. The combination of PTCy and LD‐MTX was also reported in two other studies 16,49 . However, the rates of aGVHD were high, at 42% and 25% in Grades II–IV 16 and Grades III–IV 49 respectively.…”

“…However, because of the benign nature of thalassaemia, further modifications are required to reduce the incidence of both aGVHD and cGVHD. Another study reported an estimated OS and EFS of 95.26%, with no graft failures observed for 73 thalassaemia paediatric patients who underwent co‐transplantation of haploidentical peripheral grafts and a single dose of unrelated cord blood (given six days after transplant), 16 However, the rates of overall and severe aGVHD were high, at 52% and 25% respectively. In this study, the OS and EFS were excellent at 98.1% and 90.7% respectively.…”

“…We used ATG in the conditioning regimen because it was recognized to successfully help the engraftment of allogeneic stem cells and to prevent cGVHD in patients with thalassaemia having matched or mismatched donors 7,13,39,40,44,45 . Moreover, the strategy of PTCy was adopted in recent studies of haploidentical transplantation in patients with thalassaemia 15–17,41,46 . In this study, we used a modified PTCy regimen that included two short‐term cytotoxic drugs post transplant, that is PTCy and LD‐MTX, and one long‐term calcineurin inhibitor to induce the dual immune tolerance.…”

“…Early transplant outcomes from HID for TD‐TM have been disappointing in terms of high rates of failure, high risks of GVHD, and low rates of thalassaemia‐free survival 4,12 . Several studies exploring novel strategies were conducted in an attempt to improve the outcomes of HID transplantation in TD‐TM 13–18 . However, the promising outcomes of these strategies need to be verified in further prospectively designed trials.…”

“…4,12 Several studies exploring novel strategies were conducted in an attempt to improve the outcomes of HID transplantation in TD-TM. [13][14][15][16][17][18] However, the promising outcomes of these strategies need to be verified in further prospectively designed trials.…”