Salvage HLA-haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide for graft failure in non-malignant disorders

Abstract

Graft failure requires urgent salvage HSCT, but there is no universally accepted approach for this situation. We investigated T-cell replete haploidentical HSCT with post-transplantation cyclophosphamide following serotherapy-based, radiation-free, reduced intensity conditioning in children with non-malignant disorders who had rejected their primary graft. Twelve patients with primary or secondary graft failure received T-cell replete bone marrow grafts from haploidentical donors and post-transplantation cyclophosphamide. The recommended conditioning regimen comprised rituximab 375 mg/m2, alemtuzumab 0.4 mg/kg, fludarabine 150 mg/m2, treosulfan 20–24 g/m2 and cyclophosphamide 29 mg/kg. After a median follow-up of 26 months (7–95), eleven of twelve patients (92%) are alive and well with complete donor chimerism in ten. Neutrophil and platelet engraftment were observed in all patients after a median of 18 days (15–61) and 39 days (15–191), respectively. Acute GVHD grade I was observed in 1/12 patients (8%) and mild chronic GVHD in 1/12 patients (8%). Viral reactivations and disease were frequent complications at 75% and 42%, respectively, but no death from infectious causes occurred. In summary, this retrospective analysis demonstrates that a post-transplantation cyclophosphamide-based HLA-haploidentical salvage HSCT after irradiation-free conditioning results in excellent engraftment and overall survival in children with non-malignant diseases.

Second haploidentical bone marrow transplantation with antithymocyte antibody-containing conditioning regimen for graft failure in eight patients with severe aplastic anemia

“…In hematological malignancies, a second haploidentical BMT with reduced-intensity Flu/Cy conditioning or the Baltimore conditioning protocol (PT/Cy) yielded a one-year OS of 56.6% to 66%, with a relapse rate of 23.1% 23 , 24 . However, as a nonmalignant disorder, second transplantation for GF in SAA had a much lower risk of disease relapse; for instance, PT/Cy-based haploidentical transplantation achieved successful engraftment, with a 2-year OS of 91.6% for graft failure in patients with nonmalignant disorders 25 . In this study, a second haploidentical BMT with ATG-containing conditioning achieved a 5-year OS of 75% for SAA patients with GF, indicating that a second haploidentical BMT is a rescue option for urgent cases of graft failure in patients with SAA, with either PT/CY-based or ATG-containing conditioning regimens.…”

Prospects and Potential for Chimerism Analysis after Allogeneic Hematopoietic Stem Cell Transplantation

“…In general, OS after the second allo-HSCT for graft failure is poor due to high rates of treatment-related mortality associated with infections [ 76 ]. However, recent studies have shown acceptable OS after salvage second allo-HSCT, including CBT or allo-HSCT from haploidentical related donors [ 78 , 79 , 80 , 81 , 82 , 83 ]. No treatments other than salvage second allo-HSCT are established for graft failure with graft rejection, although some investigational drugs, such as an interferon-gamma inhibitor, have been tried [ 76 ].…”

Graft failure after allogeneic hematopoietic stem cell transplantation in pediatric patients with acute leukemia: autologous reconstitution or second transplant?

“…However, failure to establish persistent engraftment after HSCT remains a significant factor contributing to morbidity and mortality. Graft failure (GF) is a rare but significant complication following allogeneic HSCT, with varying incidences depending on the type of donor [ 1 – 3 ].…”