Hematopoietic Cell Transplantation for Philadelphia Chromosome Negative Adult Acute Lymphoblastic Leukemia in the Modern Era of Immune Therapy.

purpose of reviewThis review will discuss the data and controversies related to HCT in the front-line and relapsed/refractory setting in the context of newly available targeted immunotherapies. RECENT

findingsRecent studies in adult Ph-negative ALL support the use of measurable residual disease (MRD) response to front-line therapy to guide consolidation. As such, most MRD-negative patients do not require front-line HCT. Blinatumomab benefits patients with B-ALL with MRD+ complete response (CR) and can be used as a bridge to HCT; whether HCT is still required in this setting is an area of ongoing inquiry. Blinatumomab and inotuzumab result in high rates of MRD negative CR in adults with relapsed/refractory ALL and allow more patients with relapsed disease to receive HCT. Chimeric antigen receptor T cell (CAR-T) therapies may serve as a bridge to HCT or as a stand-alone therapy for relapsed/refractory patients; data suggests there may be greater benefit to consolidating CAR-T with HCT in HCT-naïve adults. The decision to incorporate consolidative allogeneic HCT into front-line therapy should be primarily guided by MRD status and the ALL regimen utilized. Targeted immunotherapies result in high MRD-negative CR rates, allowing more adults with relapsed/refractory ALL to be successfully bridged to HCT; early incorporation of these therapies may also prove valuable in reducing the need for HCT in the front-line setting by increasing MRD negative CR rates.