Haploidentical Stem Cell Transplantation With a Novel Conditioning Regimen in Older Patients: A Prospective Single-Arm Phase 2 Study

Abstract

Objective: Haploidentical stem cell transplantation (haplo-SCT) has demonstrated encouraging results in younger patients. There is also an increasing need for haplo-SCT in older patients. However, the high risk of treatment-related mortality (TRM) in older patients is still a major concern. We aimed to investigate a novel conditioning regimen (Bu/Flu/Cy/ATG) followed by haplo-SCT in older patients.Method: This prospective, single-arm clinical trial was performed at Peking University Institute of Hematology, China. Patients were enrolled if they were (1) diagnosed with acute leukemia or MDS; (2) without MSD and MUD, and with HID available; and (3) age ≥55 years. The Bu/Flu/Cy/ATG regimen consisted of the following agents: Ara-C (2 g/m2/day, injected i.v.) on days-10 and−9; BU (9.6 mg/kg, injected i.v. in 12 doses) on days-8,−7, and−6; Flu (30 mg/m2/day, injected i.v.) from day−6 to day−2; Cy (1 g/m2/day, injected i.v.) on days−5 and−4; semustine (250 mg/m2, orally) on day-3 and antithymocyte globulin (ATG) [2.5 mg/kg/day, rabbit, SangStat (Lyon, France)] on days−5,−4,−3, and−2. The primary endpoint was 1-year TRM.Results: From April 1, 2018 to April 10, 2020, a total of 50 patients were enrolled. All patients achieved neutrophil engraftment with complete donor chimerism. The cumulative incidence of grade 2-4 aGVHD at day-100 was 22.0%. The cumulative incidences of CMV viremia and EBV viremia on day 100 were 68.0 and 20.0%, respectively. The cumulative incidence of TRM at 1-year was 23.3%. and the cumulative incidence of relapse (CIR) at 1 year after transplantation was 16.5%. The overall survival (OS) and leukemia-free survival (LFS) at 1 year were 63.5 and 60.2%, respectively. The outcomes were also comparable with patients who received Bu/Cy/ATG regimen using a propensity score matching method.Conclusions: In conclusion, this study suggested that a novel conditioning regimen followed by haploidentical HSCT might be a promising option for older patients. The study was registered as a clinical trial.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03412409.

Current Trends in Transplantation of Patients with Hematological Malignancies

“…for 2 days), and ATG (2.5 mg/kg/day, i.v. for 4 days) were comparable to those of matched patients who received a Bu/Cy/ATG regimen (Sun et al, 2021). For individuals with refractory leukemia, an intensive conditioning regimen may help to lower the high malignancy burden and improve prognosis.…”

“…In China, the (mBu/Cy)-based regimen is the most common, accounting for up to 59 percent of allo-HSCT cases while TBI-based regimens are used in 12% of allo-HSCT cases, with TBI + Cy accounting for two-thirds of them. (Sun et al, 2021). More older patients (age 55 and above) and patients with a high risk of comorbidity (such as HCT-CI 3) can undergo allo-HSCT with acceptable NRM thanks to a reduced intensity regimen (RIC) that replaces (or partially replaces) cyclophosphamide with fludarabine (Xhang et al, 2021).…”

The consensus from The Chinese Society of Hematology on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation: 2021 update

“…for 2 days) and ATG (2.5 mg/kg/day, i.v. for 4 days), the 1-year NRM, DFS and OS were 23.3, 60.2 and 63.5%, respectively, and were comparable with those of matched patients who received a Bu/Cy/ATG regimen (Table 3 ) [ 69 ].…”

“…The optimal conditioning regimen for a patient should be selected based on the type and status of the disease, comorbidities, underlying conditions, and donor type. For example, a standard-intensity conditioning regimen is used in younger patients (younger than 55 years old), and RIC regimens are used in patients older than 55 years or patients with poor organ function (HCT-CI ≥ 3) [ 69 ].…”

Haploidentical Stem Cell Transplantation for Acute Myeloid Leukemia: Current Therapies, Challenges and Future Prospective

“…In the past two decades, advances in the establishment of algorithms for best haploidentical donor selection (40)(41)(42), optimization of conditioning regimens (43)(44)(45), shifts from TCD grafts to unmanipulated bone marrow and/or peripheral blood harvests (3,5,21,46,47), enhancement of hematopoietic recovery through endothelial cell-directed N-acetyl-L-cysteine intervention and/or donor-specific antibody desensization (34,48,49), biomarker-directed graft-versus-host disease (GVHD) prophylaxis (50)(51)(52), minimal/measurable residual disease (MRD)-directed relapse intervention (7,53), and approaches for enhancing immunologic recovery (54)(55)(56) have successfully improved the outcomes of patients with hematological malignancies, especially those with AML receiving haplo-SCT. Unfortunately, for subjects with AML who underwent haploidentical allografts, relapse and infections remain the causes of death that restrict further improvement in clinical outcomes (57,58).…”