CAR T-cell treatment can result in long-term remissions of relapsed/refractory B-acute lymphoblastic leukemia (ALL). Case reports, on the other hand, showed that leukemia cytogenetics mediated divergent outcomes. From April 2012 to April 2019, researchers looked for children and young adults with relapsed/refractory CD19+ ALL/lymphoblastic lymphoma who had been treated in one of five CD19-directed CAR T-cells (CTL019 or humanized CART19) clinical studies or with commercial tisagenlecleucel. Patients were classified hierarchically based on their leukemia cytogenetics: KMT2A (MLL) rearrangements, Philadelphia chromosome (Ph+), Ph-like, hypodiploidy, or TCF3/HLF were considered high-risk lesions; hyperdiploidy or ETV6/RUNX1 were considered favorable; and iAMP21, IKZF1 deletion, or TCF3/PBX1 were considered intermediate. 

Of 231 individuals aged 1 to 29, 74 (32%) were classified as high risk, 28 (12%) as intermediate, 43 (19%) as favorable, and 86 (37%) as uninformative. Overall, 94% of patients were in full remission, with no differences between strata. There was no difference in relapse-free survival (RFS; P=.8112), with the high-risk group having a 2-year RFS of 63% (95% CI, 52-77). There was no difference in overall survival (OS) (P=.5488), with the high-risk group having a 2-year OS of 70% (95% CI, 60-82). Patients with KMT2A-rearranged infant ALL (n = 13) had a 2-year RFS of 67% (95% CI, 45-99) and an OS of 62% (95% CI, 40-95), with multivariable analysis revealing no increased risk of relapse (hazard ratio, 0.70; 95% CI, 0.21-2.90; P =.7040), but a 3.6-fold increased risk of all-cause death (95% CI, 1.04-12.75; P=.0434). Across cytogenetic categories, CTL019/huCART19/tisagenlecleucel is efficacious in attaining long-term remissions. At two years, relapsed/refractory patients with high-risk cytogenetics, such as KMT2A-rearranged neonatal ALL, showed significant RFS and OS rates.