Augmented immunosuppression and PTCY‐based haploidentical hematopoietic stem cell transplantation for thalassemia major

Abstract

Alternate donor HSCT for thalassemia major from a matched unrelated donor or haploidentical family donor is a feasible therapeutic option in children with no matched family donor. Aggressive pretransplant immunosuppression, reduced toxicity conditioning, and PTCY result in excellent thalassemia‐free survival. We describe here our experience in this cohort. We performed a retrospective analysis of the data on children who underwent a haploidentical HSCT for thalassemia major with PTCY at our center from August 2017 to August 2019. All children received pretransplant immune suppression for 6 weeks with fludarabine and dexamethasone, hypertransfusion and chelation with intravenous desferrioxamine. Conditioning included thiotepa, fludarabine, rabbit ATG, and cyclophosphamide, and GvHD prophylaxis included PTCY with tacrolimus. Twenty children were included and nineteen children engrafted. Acute hypertension occurred in five children, bacterial infection in eight children and viral respiratory infection in three children. Three children suffered from graft rejection. Reactivation of viruses namely CMV, adenovirus, and BK virus was seen in 60% of children. Grades 1‐2 acute GvHD of the skin in four children (20%) and limited chronic GvHD of the skin in four children (20%). Immune cytopenia was documented in three children (15%). Haploidentical HSCT offers a therapeutic option for children with thalassemia major with no suitably matched family or unrelated donors. Our reduced toxicity regimen with PTCY offers a DFS of 75% and OS of 95% with low transplant‐related mortality of 5%.

Features of cytomegalovirus infection and evaluation of cytomegalovirus-specific T cells therapy in children’s patients following allogeneic hematopoietic stem cell transplantation: A retrospective single-center study

“…This study included a relatively large cohort of TM patients; thus, it is a representative study regarding CMV infection in TM. Accordingly, a recent study showed that 15 out of 20 (75%) CMV reactivation was found in PTCY-based haploidentical HSCT for TM ( Vellaichamy Swaminathan et al., 2021 ). Regarding matched sibling donor HSCT using in vivo T-cell depletion myeloablative conditioning, the rate of CMV reactivation was 36.2% ( Qin et al., 2019 ).…”

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

“…It was reported that lower Bu levels correlated with a greater likelihood of graft rejection 29 . Moreover, even with two times pre‐transplant immune suppression therapy, a reduced intensive conditioning without Bu, including rabbit ATG, thiotepa, Flu, low doses of CTX, and 200 centi‐Grey total body irradiation (TBI), produced an unacceptably high GF rate of 20% 17 . We did not include other agents, such as treosulfan 30,31 or thiotepa, 32,33 in the conditioning regimen due to availability and medical insurance issues.…”

“…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.…”