Work

Transplant Characteristics and Outcomes of Philadelphia (Ph)-like Acute Lymphoblastic Leukemia (ALL)

Year: 2020

Type: article

Abstract: Background Ph-like ALL is a recently recognized high risk B-ALL subgroup, defined by a gene expression profile similar to Ph (+) ALL that activates tyrosine kinase or cytokine receptor signaling. Several studies have described inferior outcomes with conventional chemotherapy and although small series suggest that it is responsive to targeted therapies, stem cell transplant (SCT) remains the only potentially curative option. However, the SCT outcomes of Ph-like ALL are not well defined and it remains unknown whether SCT is able to overcome the adverse prognosis associated with it. Methods We retrospectively identified 77 adult patients with Ph (-) B-ALL that received a SCT at Memorial Sloan Kettering, 2008-2018, and reviewed their cytogenetic and molecular reports at diagnosis. Testing for Ph-like ALL is employed in an algorithmically driven approach at our institution including cytogenetics, chromosomal microarray and next generation sequencing (NGS). Ph-like ALL was defined by the presence of abnormalities including ABL -class fusions that phenocopy BCR-ABL ( ABL1, ABL2, CSF1R and PDGFRB ) or alterations of CRFL2, JAK2 and EPOR that activate JAK/STAT signaling. We then analyzed the SCT outcomes of Ph-like patients and compared them to Ph (-) patients. Results A Ph-like signature was identified in 13 of 77 (16.9%) patients by NGS (n=7), cytogenetics (n=1), both NGS/cytogenetics (n=2) or microarray (n=3). Median age of all 13 patients was 42.7 (range 23.9-67.7) years and 6 (46.2%) patients were adolescents/young adults (<40 years). Ph-like abnormalities included mutations of NRAS (n=3), JAK2 (n=2), NF1 (n=2), FLT3 ITD (n=1), and IL7R (n=1), fusions involving CRFL2 (n=3) or PDGFRB (n=1) and ABL1 rearrangements (n=1). Three patients had concomitant IKZF1 mutations. Most patients received myeloablative conditioning (n=8, 61.5%) and the most common donor type was matched unrelated (n=7, 53.8%) (Fig 1). At a median follow up of 17.3 (range 0.5-109.3) months, overall survival (OS) was comparable between the Ph-like and Ph (-) groups with one-year OS rates of 74% and 70% (p=0.534) respectively (Fig 2A). Causes of death in Ph-like patients were relapse (n=2) and infectious complications (n=1). One-year cumulative incidence of relapse was 32.7% in Ph-like vs 17.3% in Ph (-) patients, however it did not reach statistical significance (p=0.94, Fig 3). Among the 4 Ph-like patients who relapsed, 1 had refractory disease prior to SCT, 2 were in second remission and 1 in first remission. One-year disease free survival was also comparable between the 2 groups (67% for Ph-like vs 65% for Ph (-), p=0.719) (Fig 2B). Finally, acute GVHD rates by day 100 were 69.2% in Ph-like (n=9) vs 53.1% (n=34) in Ph (-) patients (p=0.3). Conclusions Our findings suggest that SCT overcomes the adverse prognosis associated with the Ph-like signature and should be incorporated in the treatment of patients with this disease entity.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2019.12.624