Abstract
Twenty patients with relapsed B-ALL after HSCT were treated with CAR T cell therapy and were evaluated for efficacy and safety. Twelve patients previously received haploidentical transplantation, while 8 patients received HLA-matched transplantation. The median relapse time was 12 months (range, 4 to 72). Thirteen patients received autologous CAR T cells, and 7 patients received allogeneic CAR T cells, which were derived from transplant donors. The median infusion dose was 2.9×106/kg (range, 0.33 to 12×106/kg). Nineteen patients were evaluated for efficacy, among which 17 patients (89.5%) achieved MRD negative. The CR rates in the HLA-matched transplantation group and haploidentical transplantation group were 100% (7/7) and 83.3% (10/12), respectively. The median follow-up time was 9.80 months (range, 2.40 to 64.97). Ten patients (50%) died of relapse, 3 patients (15%) died of infection, and 1 patient (5%) died of aGVHD. Fifteen patients (75%) developed CRS, including 3 (20%) grade 1 CRS, 6 (40%) grade 2 CRS, and 6 (40%) grade 3 CRS. Ten patients (50%) developed aGVHD, including 1 (10%) grade I aGVHD, 6 (60%) grade II aGVHD, and 3 (30%) grade III aGVHD. The log rank test showed that CAR T cell origin was correlated with aGVHD occurrence in the haploidentical transplantation group (P = 0.005). The authors’ study indicated that the initial efficacy and safety of CAR T cell therapy for patients with post-transplant relapse were satisfactory. However, aGVHD was a concern in patients with a history of haploidentical transplantation occupied with allogeneic CAR T cells, which warrants clinical attention.
Highlights
The prognosis of relapsed acute lymphoblastic leukemia (ALL) after hematopoietic stem cell transplantation (HSCT) is dismal
None of the patients had been treated with cellimmunotherapy, except one patient who received the first chimeric antigen receptor (CAR) T cell therapy before allo-HSCT
The 20 patients were evaluated for efficacy and safety
Summary
The prognosis of relapsed acute lymphoblastic leukemia (ALL) after hematopoietic stem cell transplantation (HSCT) is dismal. A retrospective study of 465 cases of relapsed ALL after 1st HSCT showed that the median survival time was only 5.5 months. A study of 232 pediatric patients showed that the 3-year overall survival (OS) after relapse was 13% [2]. For post-transplant relapses, donor lymphocyte infusion (DLI), second transplantation, intense chemotherapy and cytokine treatment have been tried as salvage regimens without significant clinical benefits. The success of DLI varies from 0 to 57.1% with mere increase in median survival by 6 months [3, 4]. Second transplantation resulted in an OS of only 14% at 2 years among 245 patients [6]. Failure of the above regimens highlights the need for novel alternative and more effective therapies
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