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Non-inferior long-term outcomes of adults with Philadelphia chromosome-like acute lymphoblastic leukemia.

ABSTRACT: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is associated with inferior outcomes in the chemotherapy setting. We hypothesized that allogeneic hematopoietic cell transplantation (allo-HCT)-based post-remission therapy would improve outcomes of this entity. We examined the frequency and long-term outcomes of adults with Ph-like ALL, particularly focusing on allo-HCT outcomes for Ph-like ALL versus non-Ph-like ALL. Ph-like ALL was determined by anchored multiplex PCR-based targeted next-generation sequencing. Of the 344 patients, 57 (16.6%) had Ph-like ALL, 197 (57.3%) had Ph-positive ALL, and 90 (26.1%) had B-other ALL. To further evaluate the prognosis of Ph-like ALL, outcome analyses were restricted to 147 patients, excluding Ph-positive ALL. The actual allo-HCT rates in complete remission were 87.7% for Ph-like ALL, 71.4% for B-other standard-risk ALL, and 70.4% for B-other poor-risk ALL. Patients with Ph-like ALL had a higher 5-year overall survival (60.6% vs 27.1%; P = 0.008) than B-other poor-risk ALL subgroup, while no difference was observed compared with B-other standard-risk ALL subgroup. Similar results were noted in a separate analysis for patients receiving allo-HCT in complete remission. In multivariate analyses, B-other poor-risk ALL was associated with poorer outcomes. Our data showed that allo-HCT-based post-remission therapy may have contributed to non-inferior outcomes of adult Ph-like ALL.

SUBMITTER: Cho H

PROVIDER: S-EPMC8338554 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose Philadelphia chromosome (Ph) -like acute lymphoblastic leukemia (ALL) is a high-risk subtype of childhood ALL characterized by kinase-activating alterations that are amenable to treatment with tyrosine kinase inhibitors. We sought to define the prevalence and genomic landscape of Ph-like ALL in adults and assess response to conventional chemotherapy. Patients and Methods The frequency of Ph-like ALL was assessed by gene expression profiling of 798 patients with B-cell ALL age 21 to 86 years. Event-free survival and overall survival were determined for Ph-like ALL versus non-Ph-like ALL patients. Detailed genomic analysis was performed on 180 of 194 patients with Ph-like ALL. Results Patients with Ph-like ALL accounted for more than 20% of adults with ALL, including 27.9% of young adults (age 21 to 39 years), 20.4% of adults (age 40 to 59 years), and 24.0% of older adults (age 60 to 86 years). Overall, patients with Ph-like ALL had an inferior 5-year event-free survival compared with patients with non-Ph-like ALL (22.5% [95% CI, 14.9% to 29.3%; n = 155] v 49.3% [95% CI, 42.8% to 56.2%; n = 247], respectively; P < .001). We identified kinase-activating alterations in 88% of patients with Ph-like ALL, including CRLF2 rearrangements (51%), ABL class fusions (9.8%), JAK2 or EPOR rearrangements (12.4%), other JAK-STAT sequence mutations (7.2%), other kinase alterations (4.1%), and Ras pathway mutations (3.6%). Eleven new kinase rearrangements were identified, including four involving new kinase or cytokine receptor genes and seven involving new partners for previously identified genes. Conclusion Ph-like ALL is a highly prevalent subtype of ALL in adults and is associated with poor outcome. The diverse range of kinase-activating alterations in Ph-like ALL has important therapeutic implications. Trials comparing the addition of tyrosine kinase inhibitors to conventional therapy are required to evaluate the clinical utility of these agents in the treatment of Ph-like ALL.

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Non-inferior long-term outcomes of adults with Philadelphia chromosome-like acute lymphoblastic leukemia.

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