Pre-Transplant MRD Negativity Predicts Favorable Outcomes of CAR-T Therapy Followed By Haploidentical HSCT for Relapsed/Refractory Acute Lymphoblastic Leukemia: A Multi-Center Retrospective Study

Patients with relapsed/refractory acute lymphoblastic leukemia (R/R ALL) usually have a very poor prognosis and an expected survival of less than 6 months.The complete remission (CR) rates in the setting of the first salvage chemotherapy are about 30% to 46% and these rates drop sharply to 18% to 25% after the second salvage chemotherapy. Chimeric antigen receptor T cells (CAR-T) can induce high CR rates of 70-95% (MRD negative CR rates of 60-90%) among patients with R/R ALL. Howeve, relapse after CAR-T treatment is supposed a main obstacle for long-term outcome. Some reports have described relapse rates of 20-70% when the follow-up was long enough. It remains controversial whether these patients should receive allo-HSCT after CAR-T treatment or not. We designed a multi-center retrospective study to assess the efficacy and safety profiles of CAR-T therapy followed by haplo-HSCT. A total of 31 patients treated with CAR-T therapy followed by haplo-HSCT were included. Eleven patients who progressed to MRD positive or relapse subsequently underwent haplo-HSCT (MRD positive or relapse group) and the rest 20 patients with MRD negativity received haplo-HSCT (MRD negative group). The median time from CAR-T infusion to haplo-HSCT was 83 (range 62-114) days. After a median follow-up period of 288 (range 189-554) days post-transplantation, the 100-day cumulative incidence (CI) of grade III~IV aGVHD was 0% and 10.5% in the MRD positive or relapse group and MRD negative group, respectively (P>0.05)(Figure 1a). One and 2-year CIs of cGVHD requiring systemic steroid therapy were 52.3% and 31.1% (P>0.05), 52.3% and 39.7% (P>0.05) in the MRD positive or relapse group and MRD negative group, respectively(Figure 1b).The 1-year cumulative incidence of CMV viremia was 90.9%, 68.4% and 77.8% in the MRD positive or relapse group, MRD negative group and the whole population respectively (P>0.05). The 2-year cumulative incidence of CMV viremia was 90.9%, 78.9% and 85.2% in the MRD positive or relapse group, MRD negative group and the whole population respectively (P>0.05). The 1-year cumulative incidence of EBV viremia was 90.9%, 79.6% and 84.2% in the MRD positive or relapse group, MRD negative group and the whole population, respectively (P>0.05). And the 2-year cumulative incidence of EBV viremia was 90.9%, 89.8% and 89.5% in the MRD negative or relapse group, MRD negative group and the whole population, respectively (P>0.05). Onset of CMV and EBV viremia occurred in 33.5 (26.3