Indications for Allogeneic HCT in Adults with Acute Lymphoblastic Leukemia in First Complete Remission

Acute lymphoblastic leukemia (ALL) in adults is associated with poor outcomes as compared to children when treated with chemotherapy, leading to a considerably inferior cure rate. Historically, consolidation with allogeneic hematopoietic cell transplant (alloHCT) was routinely recommended for eligible adults with ALL in first complete remission (CR1) if a donor was available, since randomized studies showed superiority over continuing chemotherapy. With the increasing use of pediatric-inspired frontline regimens in young adults with ALL and the availability of novel salvage agents for relapsed/refractory B-cell ALL that have high potential in inducing a second CR, the role of early alloHCT in the treatment paradigm for ALL needs to be reevaluated, and the decision should be individualized for each patient. Simultaneously, alloHCT has evolved considerably lately, and historical randomized studies that have proven the benefit of alloHCT in adults with ALL in CR1 did not included the increasing use of reduced intensity conditioning and haploidentical transplants, and therefore, data may not entirely apply. Nowadays, detectable minimal residual disease (MRD) is the most prognostic determinant of ALL outcome and should be a major consideration in the decision to perform alloHcT in CR1. Nonetheless, other biological and clinical factors remain relevant and can support the complex decision-making. Such factors include high-risk leukemia genetics, the type of administered chemotherapy regimen and the ability of the patient to tolerate all key components of the regimen, and the availability of effective salvage therapies that allow alloHCT to be performed in CR2 in case of relapse after chemotherapy.