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.

Fig. 1. Flow chart of the patients included in this study.

BCP B-cell precursor, ALL acute lymphoblastic leukemia, Ph Philadelphia chromosome, KMT2Ar KMT2A rearrangements, NOS not otherwise specified.

Fig. 2. Outcomes of all patients according to disease subtype.

a Cumulative incidence of relapse. b Cumulative incidence of non-relapse mortality. c Disease-free survival. d Overall survival.

Fig. 3. Genetic alterations identified in patients.

Data are shown for 57 patients with Ph-like ALL divided into patients with ABL-class fusions (ABL1, ABL2, and PDGFRB), CRLF2 rearrangements, JAK2 rearrangements, other JAK–STAT–activating mutations (JAK2, IL7R, EPOR, FLT3, TYK2 and JAK1), alterations in the RAS pathway (KRAS, NRAS, and PTPN11), and 40 patients with no kinase alteration.

Fig. 4. Outcomes between different genetic subgroups in Ph-like ALL.

a Overall survival. b Cumulative incidence of relapse.