Allogeneic hematopoietic cell transplantation (allo-HCT) has been used to treat advanced acute lymphoblastic leukemia (ALL) in adults over the past 3 decades.¹ A recent retrospective study has shown that the survival rates improved in adult ALL patients in the past 30 years, and the non-relapse mortality (NRM) tended to improve in all stages. Furthermore, relapse rate (RR) greatly improved among patients in the first complete remission (CR1) with Philadelphia chromosome-positive (Ph+).¹

Adult ALL is a rare malignant hematologic cancer that has become a challenge in treatment. The disease affects children more often, with only 40% of the cases found in adults, but with more deadly outcomes.^1,2 Usually, patients in advanced stages of the disease are treated with allo-HCT.¹ Over the past 3 decades, there have been advances in managing the complications of allo-HCT, including infections, graft-versus-host disease (GVHD), and toxicities associated therein.¹ In addition, tyrosine kinase inhibitors (TKIs) and pediatric-inspired intensive chemotherapy have been adopted for adult ALL patients who are Ph+.¹

In a retrospective study, Nishiwaki et al. examined 8,467 adult ALL patients, who were ≥16-year-old and had received their first allo-HCT between 1990 and 2019 from a registry database.¹ The investigators assessed the 5-year overall survival (OS), NRM, and RR in 3 decadal intervals for transplantations received in 3 different stages of the disease, i.e., in CR1, in subsequent CR, and not in CR (non-CR).¹ To identify the risk factors of the outcomes, they also analyzed the treatment outcomes of ALL patients with and without Ph.¹

Overall, the participants were able to observe an improved 5-year OS (CR1: 48.2%-70.2%; subsequent CR: 25.6%-44.1%; and non-CR: 10.0%-22.7%) and NRM (CR1: 26.3%-16.8%; subsequent CR: 42.5%-25.6%; and non-CR: 36.9%-22.1%) in all 3 stages of the disease, but they only observed a decrease in RR in CR1 (26.4%-15.9%), especially among Ph+ patients (39.9%-14.6%), but not in the other disease stages regardless of Ph.¹ The improvements were seen in every decade.¹ In addition, they also observed increasing survival improvements over the 3 decades in Ph+ ALL patients but not with high-risk chromosomal abnormalities [t(4; 11), t(8; 14), t(14; 18), or haplodiploidy].¹

Although there were limitations with this study, such as the incorporation of other new advancements in treatment and missing karyotypes in the study from 1990 to 1999, the study served to justify allo-HCT as a survival-prolonging treatment for ALL in adults over the past 30 years.¹ Moreover, it identified the Ph+ ALL patient in CR1 as most likely to be benefited from the treatment.¹ The key to the greater benefits for the Ph+ ALL patients seems to be the introduction of TKIs specifically targeting the Philadelphia chromosome.^1,3 Remarkably, TKIs have transformed the disease from one that used to have a poorer prognosis than the Ph-negative (Ph-) ALL counterparts, to one where remission is readily attained with the treatment.³ As allo-HCT is the only treatment available that gives adult ALL patients the possibility of a cure, continuous advancements in this regard, such as developing other targeted strategies and immunotherapies, may help further improve its outcomes for ALL patients.^1,3,4