Upfront haploidentical transplant for acquired severe aplastic anemia: registry-based comparison with matched related transplant

Abstract

BackgroundHaploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) is an alternative treatment method for severe aplastic anemia (SAA) patients lacking suitable identical donors and those who are refractory to immunosuppressive therapy (IST). The current study evaluated the feasibility of upfront haploidentical HSCT in SAA patients.MethodsWe conducted a multicenter study based on a registry database. One hundred fifty-eight SAA patients who underwent upfront transplantation between June 2012 and September 2015 were enrolled.ResultsEighty-nine patients had haploidentical donors (HIDs), and 69 had matched related donors (MRDs) for HSCT. The median times for myeloid engraftment in the HID and MRD cohorts were 12 (range, 9–20) and 11 (range, 8–19) days, with a cumulative incidence of 97.8 and 97.1% (P = 0.528), respectively. HID recipients had an increased cumulative incidence of grades II–IV acute graft-versus-host disease (aGVHD) (30.3 vs. 1.5%, P < 0.001), grades III–IV aGVHD (10.1 vs. 1.5%, P = 0.026), and chronic GVHD (cGVHD) (30.6 vs. 4.4%, P < 0.001) at 1 year but similar extensive cGVHD (3.4 vs. 0%, P = 0.426). The three-year estimated overall survival (OS) rates were 86.1 and 91.3% (P = 0.358), while the three-year estimated failure-free survival (FFS) rates were 85.0 and 89.8% (P = 0.413) in the HID and MRD cohorts, respectively. In multivariate analysis, survival outcome for the entire population was significantly adversely associated with increased transfusions and poor performance status pre-SCT. We did not observe differences in primary engraftment and survival outcomes by donor type.ConclusionsHaploidentical SCT as upfront therapy was an effective and safe option for SAA patients, with favorable outcomes in experienced centers.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0398-y) contains supplementary material, which is available to authorized users.

Diagnosis and Treatment of Aplastic Anemia

“…In a prospective multicenter study of 101 AA patients receiving haploidentical transplants in China, 94% of patients achieved successful engraftment with 3-year overall and failure free survival of 89% and 86%, respectively [27]. A registry-based comparison of upfront haploidentical and MSD transplantation in 158 consecutive SAA patients in China have shown similar high rates of engraftment and OS, but significantly higher rates of grade III–IV acute GVHD (10% versus 1.5%) and chronic GVHD (31% versus 4.4%) for haploidentical transplants [28]. A more recent study of 16 patients receiving haploidentical or unrelated donor transplants with post-transplant cyclophosphamide showed encouraging results with 100% engraftment and no instances of grade 3 or higher GVHD [29].…”

A review of hematopoietic cell transplantation in China: data and trends during 2008–2016

“…HID HCT has been considered a potential option in patients with SAA in the absence of an identical sibling donor or URD. 6,27,28 The feasibility of HID transplantation was evaluated for treating SAA patients following the failure of previous immunosuppressant therapy in a prospective multicenter clinical trial registered as ChiCTR-ONC-12002107 at http://www.chictr.org.cn/enIndex.aspx. 27 HID HCT, as an upfront therapy, was an effective and safe option for SAA patients with favorable outcomes in experienced centers in a registry-based comparison study.…”

“…27 HID HCT, as an upfront therapy, was an effective and safe option for SAA patients with favorable outcomes in experienced centers in a registry-based comparison study. 28 The consideration of cost effectiveness between these two highly expensive treatments, immunosuppressive therapy and HCT, may have a great effect on the future trends.…”

“…The conclusion that HID HCT can give similar clinical outcomes with MRD and URD is supported by a series of comparative studies listed in Table 2. 18,21,27,28,[31][32][33][34][35][36][37] The use of HID continues to increase due to its convenience and ready availability without delay. A dramatic increase in the number of HID HCTs performed was observed in 2013, but only a slower increase in MRD, URD and CBT.…”

Aplastic anemia is related to alterations in T cell receptor signaling

“…Aplastic anemia (AA) is a disease characterized by bone marrow hematopoietic dysfunction and peripheral blood pancytopenia (1). The severity of AA is defined according the blood count parameters and bone marrow findings.…”