A novel protocol for haploidentical hematopoietic SCT without in vitro T-cell depletion in the treatment of severe acquired aplastic anemia

Abstract

Mismatched related donors of hematopoietic SCT (HSCT) for severe aplastic anemia (SAA) present challenges mainly associated with graft failure and GVHD. The greater the HLA disparity, the poorer the OS. About 19 consecutive SAA/very SAA (VSAA) patients who received HSCT from haploidentical family donors in our center are reported in this study, 18/19 pairs had 2-3 loci mismatched. All 19 cases failed to respond to previous therapy and were heavily transfused before transplantation. The conditioning regimen before HSCT included BU, CY and thymoglobulin. The recipients received CsA, mycophenolate mofetil (MMF) and short-term MTX for GVHD prophylaxis. The source of stem cell grafts was a combination of G-CSF-primed BM and G-CSF-mobilized peripheral blood stem cells. All patients achieved 100% donor myeloid engraftment; the median time for myeloid engraftment was 12 days (ranging from 10-29 days) and for platelets was 18 days (ranging from 8-180 days) with a cumulative platelet engraftment incidence of 84.21 ± 10.53%. The cumulative incidence was 42.1 ± 11.3% for grade II-IV acute GVHD and 56.2 ± 12.4% for chronic GVHD. The OS was 64.6 ± 12.4% with a median 746-day (90-1970) follow-up for surviving patients. These limited retrospective analysis data suggest that HLA-haploidentical HSCT for SAA patients without an HLA-identical sibling donor might be feasible. Further research to increase OS by decreasing GVHD while maintaining stable engraftment will be needed in the future.

Good outcome of haploidentical hematopoietic SCT as a salvage therapy in children and adolescents with acquired severe aplastic anemia

“…19 (2) Mixtures of G-PB and G-BM have successfully introduced T-cell hyporesponsiveness, polarization of T cells from Th1 to Th2 and protected from aGVHD. 20 (4) Higher-dose stem cell numbers may be given via a combination of G-BM and G-PBSC than via BM or PB alone to overcome the harmful effect of ATG on hematopoiesis. 2 (5) G-BM also may add BM-derived MSCs to grafts, which may reduce severe GVHD and enhance engraftment.…”

“…The probability of graft failure (GF) at 100 days was 25% and the OS at 5 years was 30% in 20 patients as reported by the Center for International Blood and Marrow Transplant Research (CIBMTR) SAA Working Party, 3 while all 19 patients achieved donor myeloid engraftment and the OS was 64% in the Xu et al report. 4 Successful unmanipulated SCT from haploidentical 3-loci-mismatched parents in two children with SAA was performed in our preliminary clinical trial. 5 In this report, we describe the favorable outcome of another cohort of consecutive 17 children and adolescents with SAA who underwent haploidentical HSCT in our center.…”

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

“…18 However, past reports of haploidentical HSCT as therapy in SAA have encountered important limitations with graft failure and risk of severe graft-versus host disease (GVHD). [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.…”

Outcome of patients activating an unrelated donor search for severe acquired aplastic anemia

“…As illustrated in around one third of patients in our cohort, the search for an HLA-matched VUD may be unsuccessful. Thus, the usefulness of alternative HSCT procedures using haplo-identical donors [30][31][32] or cordblood cells [33] in these patients also needs to be further explored in the near future. research article…”