Normal karyotype CALLA-positive adult pre-B ALL: dismal outcome with chemotherapy for patients with loss/gain of ABL1 and/or BCR FISH signals

Clin Lymphoma Myeloma Leuk. 2013 Jun;13(3):281-6. doi: 10.1016/j.clml.2012.09.007. Epub 2012 Oct 24.

Abstract

Background: Diagnostic karyotype and molecular studies represent the most powerful prognostic indicators in acute myeloid leukemia and provide the framework for risk stratification. Risk stratification in ALL has also a vital role in predicting outcome and identifying patients at higher risk of relapse with multiagent chemotherapy, but the role of diagnostic karyotype and molecular markers in adult ALL is limited to few well recognized cytogenetic abnormalities.

Patients and methods: We report a case series of 6 adult ALL patients with a characteristic molecular abnormality that have done poorly with chemotherapy. Between April 2004 and November 2009, 72 adult ALL patients (Pre-B-cell 61; T-cell 11) were referred to and treated at the Leukemia/BMT Program of BC in Vancouver, Canada. FISH for BCR-ABL fusion was positive in 12 of 61 Pre-B cell ALL patients. An additional 6 patients were negative for this typical fusion but had FISH abnormalities related to BCR and/or ABL1.

Results: In this report, we describe the clinical and hematopathologic characteristics of these 6 patients and their poor outcome. We review the literature where only 2 similar cases with normal karyotype Pre-B ALL and associated FISH BCR/ABL1 numerical abnormalities were found.

Conclusion: We recommend screening all adult pre-B ALL patients with normal karyotype for this clonal abnormality and suggest classifying these ALL patients into the high-risk category.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chromosome Aberrations*
  • Cohort Studies
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Male
  • Middle Aged
  • Neprilysin / biosynthesis
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Prognosis
  • Treatment Outcome
  • Young Adult

Substances

  • Fusion Proteins, bcr-abl
  • Neprilysin