Allogeneic hematopoietic stem cell transplantation overcome the poor prognosis of patients with IKZF1plus CD20-a very high-risk subtype in B-cell acute lymphoblastic leukemia.

Genetic deletions of IKZF1 (IKZF1) and IKZF1 plus other mutations (IKZF1) have been identified in B-cell acute lymphoblastic leukemia (B-ALL) with a poor prognosis. Herein, we investigated the combination of IKZF1 and CD20 immunotypes in adult patients with B-ALL in the PDT-ALL-2016 cohort. This study cohort consisted of 161 patients with B-ALL with detailed information on IKZF1 and CD20 expression. The independent cohort included 196 patients from the TARGET dataset. IKZF1 was detected in 36.0% of patients with 3-year event-free survival (EFS) of 37.1 ± 6.7% and overall survival (OS) of 51.5 ± 7.3%, compared to IKZF1 wild-type (IKZF1) with an EFS 55.3 ± 5.1% (P = 0.011) and OS 74.4 ± 4.5% (P = 0.013), respectively. CD20-positive (CD20) was associated with inferior EFS compared to the CD20-negative (CD20) group (P = 0.020). Furthermore, IKZF1 coupled with CD20+, IKZF1/CD20, comprised 12.4% of patients with a 3-year EFS of 25.0 ± 9.7%, compared with IKZF1/CD20 (P ≤ 0.001) and IKZF1/CD20 (P = 0.047) groups. Multivariable analyses demonstrated the independence of IKZF1/CD20, with the highest predicted hazard ratio for EFS and OS. Furthermore, the prognostic panel of IKZF1/CD20 was confirmed in the TARGET cohort. Notably, neither the IKZF1, CD20, or IKZF1/CD20 groups were identified to have poor outcomes in the cohort of allogeneic hematopoietic stem cell transplantation (n = 81).Collectively, our data define IKZF1/CD20 as a very high-risk subtype in B-ALL, and allo-HSCT could abrogate the poor outcome of both IKZF1 and IKZF1/CD20 subsets.