Haploidentical hematopoietic stem cell transplantation in aplastic anemia: a systematic review and meta-analysis of clinical outcome on behalf of the severe aplastic anemia working party of the European group for blood and marrow transplantation (SAAWP of EBMT)

Abstract

Aplastic anemia (AA) is a serious hematological disorder, which is solely cured by hematopoietic stem cell transplantation (HSCT). Haploidentical HSCT is an emerging modality with encouraging outcomes in several blood conditions. The present study aims to comprehensively assess the feasibility and safety of haploidentical HSCT in patients with severe and very severe AA. It is a systematic review and meta-analysis of studies related to haploidentical stem cell transplantation in idiopathic AA investigating rates of successful engraftment, acute graft-versus-host disease (aGvHD), chronic GvHD (cGvHD), transplant-related mortality (TRM), and posttransplantation viral infections (including cytomegalovirus [CMV]) in patients with AA. The effects of reduced-intensity conditioning (RIC) and nonmyeloablative conditioning (NMA), as well as various GvHD prophylaxis regimens on these outcomes were evaluated. In total 15 studies were identified, (577 patients, 58.9% males), successful engraftment was observed in 97.3% of patients (95% CI, 95.9-98.7) while grades II-IV aGvHD and cGvHD were reported in 26.6% and 25.0%, respectively. The pooled incidence of TRM was 6.7% per year (95% CI, 4.0-9.4). RIC regimens were associated with higher proportions of successful engraftment (97.7% vs 91.7%, P = 0.03) and aGvHD (29.5% vs 18.7%, P = 0.008) when compared with NMA regimens with no differences in cGvHD or mortality incidence. When compared with methotrexate-containing regimens and other regimens, posttransplant cyclophosphamidecontaining regimens reduced the rates of aGvHD (28.6%, 27.8%, and 12.8%, respectively, P = 0.02), CMV viremia (55.7%, 38.6%, and 10.4%, respectively, P < 0.001), and CMV disease in initially viremic patients (2.1%, 33.0%, and 0%, respectively, P < 0.001). We have concluded that Haploidentical HSCT was associated with promising outcomes in terms of successful engraftment and reduced complications. Future prospective trials are needed to identify the preferred conditioning regimen, GvHD prophylaxis, and graft source in the setting of haploidentical transplant for AA.

A mini-review on aplastic anemia, illustrated by a case report on bone marrow hot pockets mimicking sclerotic bone metastases

“…Relapses occur in 30-60% but usually respond to a second round of immunosuppressive therapy with ATG [1,3]. Alternatives to repeating IST are MUD bone marrow transplant (in patients under 30 years of age), experimental transplantation (meaning cord blood, MMUD or haplo -in patients under 20 years of age) [12] or adding Eltrombopag to IST [1,2,13]. Eltrombopag, the synthetic mimetic of TPO, shows durable effect in up to 50% of patients and can also be added to first line IST, increasing response rate up to 80% (and complete response to 50%) [1,13,14].…”

History of hematopoietic cell transplantation: challenges and progress

“…121,122 Moreover, recent papers reported outstanding survival figures for AA patients given HLA-haploidentical grafts. 123,124 Taken together, these findings suggested that upfront marrow transplantation should be considered for all patients with AA who have a suitable donor rather than waiting until failure of immunosuppressive therapy.…”

Considerations in Preparative Regimen Selection to Minimize Rejection in Pediatric Hematopoietic Transplantation in Non-Malignant Diseases

“…A well-established alkylating agent, cyclophosphamide has maintained its role in HSCT due to its highly immunosuppressive properties and the relative resistance of hematopoietic stem cells to this agent even the highest doses (8,10,11). Recent studies have utilized cyclophosphamide post graft infusion to improve the outcomes of haploidentical transplant procedures (12)(13)(14). The success of this strategy has probably entrenched this agent as a major element of transplant therapy.…”