Improved outcome of haploidentical transplantation in severe aplastic anemia using reduced-intensity fludarabine-based conditioning

Abstract

Significant improvements in hematopoietic stem cell transplantation (HSCT) with haploidentical family donors (HFD) have confirmed its therapeutic role in severe aplastic anemia (SAA) and led to the evolution of treatment algorithms. However, the optimal conditioning regimen for HFD-HSCT remains undefined, especially the dosage of cyclophosphamide (Cy).A total of 77 patients with SAA from two research centers, who received HFD-HSCT with reduced-intensity fludarabine + cyclophosphamide + thymoglobulin ± busulfan conditioning regimen plus third-party cells infusion were included in this study, of which 67 pairs had 4-5 loci mismatched. We were particularly interested in whether the dosage of Cy significantly impacted graft failure (GF) and overall survival (OS).All patients showed sustained hematopoietic engraftment without any increase in severe aGVHD and transplantation-related mortality (TRM). The incidences of grade II-IV aGVHD, grade III-IV aGVHD and extensive cGVHD were 18%, 10% and 7%, respectively. The probabilities of 1-year and 5-year OS were 93.1% and 87.9%, respectively. Furthermore, patient age <15 years, MNC cells >8×108/kg and donor age <45 years were associated with better survival (P=0.043, P=0.023, and P=0.037, respectively) and engraftment (P=0.019, P=0.008, and P=0.001, respectively).Our findings indicated that SAA patients lack MSD benefited the most if HFD-HSCT was performed with reduced-intensity fludarabine-based conditioning regimen. Improved outcomes with HFD-HSCT may lead to a salvaged therapy and an expanded direct role for SAA in the future.

A modified conditioning regimen based on low‐dose cyclophosphamide and fludarabine for haploidentical hematopoietic stem cell transplant in severe aplastic anemia patients at risk of severe cardiotoxicity

“…16,17 Recently, this combination has also been used in haplo-HSCT for SAA. [18][19][20][21][22][23] The optimal combination of Flu and Cy in conditioning haplo-HSCT for SAA is undefined.…”

Alternative Immune-Mediated-Based Methods in the Aplastic Anemia Treatment

“…This study showed that co-transplantation of MSCs resulted in fast engraftment of absolute neutrophil count and platelets and 100% donor chimerism [87]. In turn, Yamei and co-workers (2014) demonstrate prolonged survival (follow up of 78 months) in 80.9% patients after cotransplantation of the culture-expanded third party donor-derived UC-MSCs in 21 young people with SAA undergoing haplo-HSCT [103]. Even so, the patients did not show infusion toxicity.…”

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.…”