Effective Treatment of Biphenotypic Acute Leukemia in Children with Chemotherapy Alone.

Abstract

Biphenotypic acute leukemia (BAL) is now a well-defined entity. However, the outcome of this rare type of acute leukemia is variable and the treatment strategies are controversial. This is a retrospective review analyzing the clinical features and the outcome of BAL cases diagnosed and treated at our institution between January 1999 and December 2004. The diagnosis was based on morphological and cytochemical evaluation, supported with extensive immunophenotyping. The European Group for Immunophenotyping in Leukemia (EGIL) scoring system was utilized to diagnose the BAL. 17 patients (4.1% of 411 ALL patients) were classified as BAL. Of these 15 were B-lymphoid/myeloid and two were T/B-lymphoid. Median age at diagnosis was 7.23 years (range 1.3–14.4 years). Nine patients were male, four had WBC count >100 × 109/L, and 6 (35.3%) had CNS disease. Cytogenetic analysis was available in 14 cases of which three (21.4 %) had a normal karyotype. The most frequent abnormalities were MLL gene rearrangement (n=4; 28.6%) followed by abnormality at the 14q32 locus (n=3; 21.4%; two patients with add(14)(q32) and one t(8:14)(q21:q32)). All patients were treated uniformly, on a modified St Jude TXIII-B high-risk protocol, with agents known to be effective against both lymphoid and myeloid leukemia. They received a 6-drug induction with prednisone, vincristine, daunomycin, asparaginase, etoposide and cytosine arabinoside, followed by consolidation using high-dose methotrexate (2gm/m2) and mercaptopurine. Post remission all patients were eligible for allogeneic bone marrow transplantation (BMT) if a full matched related donor was available. If none was available, patients received continuation therapy consisting of weekly administration of non cross-resistant drug pairs for 120 weeks. All patient achieved remission post induction. Five patients underwent BMT in first remission (CR1), and 12 were treated with chemotherapy (CTX) alone. Two patients in the CTX arm relapsed. Both relapses were extramedullary (isolated CNS in one and lacrimal duct in the other). These patients were reinduced and underwent BMT in CR2. There were no relapses in the BMT arm. No serious acute therapy-related toxicity or infections were noted in the CTX arm. One patient died of BMT- related complications in CR1. With a median follow-up of 2.6 years, the actuarial OS and EFS at 4 years are 71.6 % and 79.5%, respectively. OS and EFS comparing BMT with CTX are 82% v. 74.1% (p=0.5) and 80% v. 79.5% (p=0.84), respectively. We conclude that this chemotherapy protocol is effective and safe in treating BAL. BMT in CR1 may not be needed for these patients.