1.
Upfront Alternative Donor Transplant Versus Immunosuppressive Therapy in Patients with Severe Aplastic Anemia Who Lack Fully HLA Matched Related Donor: Systematic Review and Meta-Analysis of Retrospective Studies. on Behalf of the Severe Aplastic Anemia Working Party of European Group for Blood and Marrow Transplantation (SAAWP of EBMT)
Alotaibi, H., Aljurf, M., de Latour, R., Alfayez, M., Bacigalupo, A., Fakih, R. E., Schrezenmeier, H., Ahmed, S. O., Gluckman, E., Iqbal, S., et al
Transplantation and cellular therapy. 2021
Abstract
Idiopathic aplastic anemia is a rare and life-threatening disorder with hematopoietic stem cell transplant (HSCT) from matched sibling donor (MSD) being the standard treatment strategy for young patients. The use of alternative donor transplant (ADT) from a matched unrelated donor (MUD) or HLA haploidentical donor (HID) is not commonly used in the frontline setting. The aim of this systematic review/meta-analysis is to compare ADT as an upfront, rather than delayed, treatment strategy in the absence of a MSD to immunosuppressive therapy (IST) in severe aplastic anemia (SAA). We searched PUBMED/MEDLINE and EMBASE (1998-2019) for studies that compared the outcomes of ADT with IST as upfront therapy in patients with SAA. We included studies with five patients or more in each arm. Studies that included patients with inherited forms of bone marrow failure syndromes were excluded. The primary outcome was the 5- year overall survival rate. Five studies met the inclusion criteria and were included in this meta-analysis. The pooled 5-year odd ratio (OR) for OS was statistically significant at 0.44 [95% CI 0.23-0.85] in favor of upfront ADT. Additionally, the survival was compared between upfront versus salvage ADT in six studies. The pooled 5-year OR for OS was statistically significant at 0.31 [95% CI 0.15-0.64] in favor of upfront ADT. Although this analysis has some limitations including the retrospective nature of the included studies, the lack of ethnic diversity, the predominantly pediatric population and the relatively suboptimal IST regimen used in some of the studies, it indicated that upfront ADT is a potential alternative treatment option in young and pediatric SAA patients who lack an HLA identical sibling donor, particularly when optimal IST is not available.
2.
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)
ElGohary, G., El Fakih, R., de Latour, R., Risitano, A., Marsh, J., Schrezenmeier, H., Gluckman, E., Hochsmann, B., Pierri, F., Halkes, C., et al
Bone marrow transplantation. 2020
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 cyclophosphamide-containing 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.