Upfront therapy comprising human leukocyte antigen (HLA)-haploidentical bone marrow transplantation (BMT) with post-transplantation cyclophosphamide (PTCy) was associated with an overall survival (OS) of greater than 90% at up to three years in pediatric and adult patients with severe aplastic anemia (SAA), with minimal graft-versus-host-disease (GVHD), according to study findings published in Blood.
The study also demonstrated that the use of haploidentical donors may expand accessibility to BMT across diverse populations, as 35% of the study’s patient cohort were from underrepresented racial and ethnic backgrounds.
Historically, patients with aplastic anemia had to be young and have a matched sibling donor to have success with transplant, said lead author Amy DeZern, MD, of Johns Hopkins University in Baltimore. “This study is quite paradigm-changing in that you can use an upfront half-matched donor from many potential familial relationships with excellent outcomes,” she noted.
The research study conducted by Dr. DeZern and colleagues was a prospective, single-arm, phase II trial that examined the feasibility and safety of initial reduced-intensity conditioning HLA-haploidentical BMT and PTCy-based GVHD prophylaxis in patients with SAA. Patients received cyclophosphamide, total body irradiation at 200 or 400 cGy, as well as oral mycophenolate mofetil and tacrolimus.
Suitable donors were defined as available HLA-haploidentical relatives of the patient. These relatives could be a biological parent, sibling/half sibling, child, aunt/uncle, first cousin, or extended relative.
The studied treatment strategy allows most patients with aplastic anemia to have a donor and access to a highly successful transplant platform and avoids the long period before hematopoietic recovery with immunosuppressive therapy, as well as the longer-term period with low count infections, Dr. DeZern noted. Further, the approach may potentially avoid avascular necrosis and other long-term, significantly dangerous outcomes like clonal evolution.
In the study, a total of 27 patients (median age = 25 years; range = 3-63 years) were treated on trial. For all patients, the median follow-up period was 40.9 months, with a minimum follow-up of six months and a maximal follow-up of 73.8 months.
Approximately half (52%) of patients who received transplants were male. Around 37% of the cohort self-reported as non-white, which included patients who self-identified as Black (21%), Asian/Pacific Islander (11%), mixed or other race (3%), and Hispanic (3%).
The rates of acute and chronic GVHD were both under 10%, and there were no cases of grade 3-4 acute or moderate/severe chronic GVHD. At day 100, the cumulative incidence of grade 2-4 acute GVHD was 7%, while at two years, the cumulative incidence of chronic GVHD was 4%. There were no incidences of secondary malignancies throughout the study.
In the entire study cohort, the OS was 92% (95% CI 83-100) at one year, two years, and three years. The first seven patients who received the lower dose total body irradiation of 200 cGY were more likely to experience graft failure (3 of 7 patients) compared with the 20 patients who received the higher dose of 400 cGY (0 of 20 patients; p=0.01).
“This platform can be extended to donor sources other than haploidentical,” Dr. DeZern explained, “and it may make a uniform approach to all patients with aplastic anemia, regardless of who they are and who they have surrounding them.” She added that this regimen is “hopefully doing away with immunosuppressive therapy in the majority of patients.”
The authors noted they were unable to obtain information on the transfusions prior to the six-week preconditioning period. Additionally, the researchers stated there were inconsistencies with the time from diagnosis to BMT due to referral patterns.
A future research initiative on the HLA-haploidentical BMT with PTCy approach will be conducted through the Bone Marrow Transplant Clinical Trials Network and will evaluate this platform in the treatment of haplo-donor as well as unrelated donors in a multicenter study, Dr. DeZern noted.
“This is a nontoxic, highly successful platform that ultimately is probably less expensive than immunosuppressive therapy for several years for an individual patient and returns a human being back to their baseline functional status more efficiently,” she concluded.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
DeZern A, Zahurak ML, Symons HJ, et al. Alternative donor BMT with post-transplant cyclophosphamide as initial therapy for acquired severe aplastic anemia [published online ahead of print, 2023 Apr 21]. Blood. doi: 10.1182/blood.2023020435.
