Optimal conditioning regimen for haplo‐identical stem cell transplantation in adult patients with acquired severe aplastic anemia: Prospective de‐escalation study of TBI and ATG dose

Abstract

This prospective study explored an optimal conditioning regimen to ensure engraftment with minimal toxicity in adult patients with severe aplastic anemia (SAA) who received haplo-identical stem cell transplantation from a related mismatched donor (Haplo-SCT). We explored a safe and sufficient dose of rabbit ATG (Thymoglobulin) in combination with 800 cGy total body irradiation (TBI) and fludarabine (Flu, 30 mg/m /day) for 5 days using step-by-step dose de-escalation. The dose of ATG was de-escalated from 10 mg/kg (group 1), to 7.5 mg/kg (group 2), to 5 mg/kg (group 3), and the TBI dose was reduced to 600 cGy (group 4) beginning in October 2014. If one patient developed transplant-related mortality (TRM) with engraftment in a group, we moved to the next lower dose group. Thirty-four patients were enrolled in groups 1-3 (n = 10) and 4 (n = 24). All patients achieved primary engraftment. The incidence of acute GVHD (grade ≥ 2) and chronic GVHD (≥ moderate) was 29.4% and 14.7%, respectively. With a median follow-up of 56.6 and 21.8 months in groups 1-3 and group 4, respectively, the 2-year probability of overall survival (91.7% in group 4 vs 70% in groups 1-3, P = 0.155) and GVHD-free survival (78.4% in group 4 vs 50% in groups 1-3, P = 0.115) was shown tended to be better in group 4. This study explored an optimal conditioning with step-by-step de-escalation dosage of ATG and TBI to reduce TRM with sustained graft function. TBI-600 cGy/Flu/intermediate-dose ATG resulted in feasible outcomes of Haplo-SCT for adult patients with SAA.

Mesenchymal stromal cells as prophylaxis for graft-versus-host disease in haplo-identical hematopoietic stem cell transplantation recipients with severe aplastic anemia?—a systematic review and meta-analysis

“…As a result, 32 records were excluded, and 29 studies met the inclusion criteria. The included studies were divided into two groups (MSCs [31][32][33][34][35][36][37][38]; no MSCs [22,24,25,[39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56]) based on whether they applied the MSCs or not. The selection process is illustrated in Fig.…”

“…Therefore, it is of great importance to clarify key factors related to the outcomes of SAA with haplo-HSCT. For example, some meta-analyses compared different donor sources in haplo-HSCT, evaluating whether peripheral blood (PB) or BM as graft source produces a more satisfactory outcome in SAA patients [23], while others sought the optimal conditioning regimen for haplo-HSCT in patients with SAA [24][25][26]. In addition, several meta-analyses have approved the efficacy of MSCs in haplo-HSCT recipients with hematological conditions, mostly in hematological malignancies [27,28].…”

Mesenchymal Stromal Cells as Prophylaxis for Graft-versus-host Disease in Haplo-identical Hematopoietic Stem Cell Transplantation Recipients With Severe Aplastic Anemia? - A Systematic Review and Meta-analysis

“…As a result, 32 records were excluded, and 29 studies met the inclusion criteria. The included studies were divided into two groups (MSCs [31][32][33][34][35][36][37][38] ; no MSCs 22,25,[39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57] ) based on whether they applied the MSCs or not. The selection process is illustrated in Fig.…”

“…Therefore, it's of great importance to clarify key factors related to the outcomes of SAA with haplo-HSCT. For example, some meta-analyses compared different donor sources in haplo-HSCT, evaluating whether PB or BM as graft source produces a more satisfactory outcome in SAA patients 23 , others sought the optimal conditioning regimen for haplo-HSCT in patients with SAA [24][25][26] . In addition, several meta-analyses have approved the e cacy of MSCs in haplo-Data extraction from the eligible studies was carried out independently by 2 authors.…”

Acquired severe aplastic anaemia: how medical therapy evolved in the 20th and 21st centuries

“…Most protocols include ATG, but its need, timing and dosing along with the ideal total body irradiation (TBI) dose to prevent rejection and reduce transplant-related complications are not yet elucidated. TBI doses of 400-600 cGy may be required to allow for successful engraftment, 24,[93][94][95][96][97][98] especially in less treated patients. Thus, haploidentical HSCT in SAA should be performed in clinical protocols.…”