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.
Highlights
Severe aplastic anemia (SAA) is a rare multi-lineage bone marrow failure and life-threatening disorder, with a high annual incidence of nearly 8% of all malignant and nonmalignant hematological disorders in China [1, 2]
Despite promising evidence for haploidentical family donors (HFD)-Hematopoietic stem cell transplantation (HSCT) in acquired SAA in the last decade, several obstacles remain, such as standardized conditioning regimen, methods to regulate the donor T-cells and decrease graft-versus-host disease (GVHD), stem cell source, donor selection, and management of graft failure (GF) or poor graft function, which need to be resolved for widespread use [23, 24]
Patients with SAA grafted from HFD, who were administered a reduced-intensity fludarabine-based conditioning regimen, with third party cells infusion, showed an encouraging 2-year survival of 91.0%, without decrease in the engraftment potency and increase in incidence of GVHD
Summary
Severe aplastic anemia (SAA) is a rare multi-lineage bone marrow failure and life-threatening disorder, with a high annual incidence of nearly 8% of all malignant and nonmalignant hematological disorders in China [1, 2]. A total of 77 patients with SAA from two research centers, who received HFDHSCT 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.
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