Nonmyeloablative Peripheral Blood Haploidentical Stem Cell Transplantation for Refractory Severe Aplastic Anemia

Abstract

New transplant approaches are urgently needed for patients with refractory severe aplastic anemia (SAA) who lack a matched sibling or unrelated donor (UD) or who have failed UD or cord blood transplant. Patients with refractory SAA are at risk of later clonal evolution to myelodysplastic syndrome and acute leukemia. We report our pilot findings with haploidentical hematopoietic stem cell transplantation (haploHSCT) using uniform reduced-intensity conditioning with postgraft high-dose cyclophosphamide in 8 patients with refractory SAA or patients who rejected a prior UD or cord blood transplant. Six of 8 patients engrafted. Graft failure was associated with donor-directed HLA antibodies, despite intensive pre-HSCT desensitization with plasma exchange and rituximab. There was only 1 case of grade II skin graft-versus-host disease. We show that haploHSCT can successfully rescue refractory SAA patients who lack donor-directed HLA antibodies but not in the presence of donor-directed HLA antibodies. This novel protocol for haploHSCT for SAA has been adopted by the European Group for Blood and Marrow Transplantation Severe Aplastic Anaemia Working Party for a future noninterventional, observational study to further evaluate its efficacy.

Haploidentical BMT and post-transplant Cy for severe aplastic anemia: a multicenter retrospective study

“…33 More recently, Clay et al 25 reported the UK experience on eight patients with SAA who underwent allogeneic PB transplantation from haploidentical donors and received posttransplant Cy with the same conditioning regimen described in our series. 25 In that series, four patients had already failed unrelated donor and/or cord blood transplants, and four had refractory acquired SAA. Another difference from our series is that all patients received PBSC grafts, which have been reported to be associated with decreased survival in patients with SAA.…”

“…34 Nevertheless, the results are similar to our series, with successful engraftment in most patients and low rates of GVHD. 25 In the UK cohort, two patients did not engraft because of anti-HLA Abs, and infection was the most common cause of death. In our series, despite the prior history of multiple transfusions, no patient had developed significant anti-HLA Abs, and this might be one of the reasons for our high rate (94%) of primary engraftment.…”

“…[11][12][13][14][15][16][17][18]20,21 Recently, the use of post-transplant cyclophosphamide (Cy) has permitted transplantation across major HLA barriers for patients receiving BM from a haploidentical donor. [22][23][24][25][26] The use of posttransplant Cy has several advantages compared with traditional methods of ex vivo T-cell depletion, which include lower complexity and cost, and improved immune reconstitution permitting a more widespread adoption of this transplant procedure. 27 Several studies have confirmed the efficacy and safety of this approach, but most reports have focused on patients with hematologic malignancies.…”

Unmanipulated haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide in a patient with paroxysmal nocturnal hemoglobinuria and secondary aplastic anemia

“…[7][8][9] As far as we know, our case is the first that shows a patient with PNH and secondary aplastic anemia who achieved a prolonged disease-free state with haploidentical reduced intensity transplantation. In PNH patients who require an allogeneic transplant but do not have a fully matched related or unrelated donor, a haploidentical reduced intensity transplant may be an acceptable option.…”

Pre-transplant sirolimus might improve the outcome of haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide for patients with severe aplastic anemia

“…[2][3][4][5][6] Simultaneously, another group reported poor survival in eight heavily pre-treated patients with SAA, employing non-ablative conditioning and PTCY. 7 All patients in our study were heavily pre-transfused and were at high risk of graft failure as well as TRM. PTCY resulted in prompt and sustained engraftment in our cohort.…”