Clinical characteristics and outcome of children with biphenotypic acute leukemia

Abstract

BackgroundKnowledge concerning the clinical and biological presentation, as well as the outcome of treatment, of biphenotypic acute leukemia in children is limited. Design and MethodsThis retrospective review analyzes the clinical features and outcome of children with biphenotypic acute leukemia diagnosed and treated over an 8-year period. According to the EGIL scoring system 24 (3.7%) of 633 patients with acute leukemia were classified as having biphenotypic acute leukemia. The diagnostic work-up and results were reviewed specifically for this study in the light of the newly published WHO criteria for the diagnosis of leukemia of ambiguous lineage. Based on these criteria, 11 (1.7%) patients were categorized according to the new nomenclature as having mixed phenotype acute leukemia. The majority of the patients (58.3%) had a B-lymphoid/myeloid phenotype, followed by the T-lymphoid/myeloid phenotype. The most frequent chromosomal abnormality involved the 14q32 locus. Patients received therapy based on a treatment regimen for acute lymphocytic leukemia regimen, which included myeloid-effective agents. ResultsAt a median follow up of 4 years (range, 6 month -7 years) the overall survival rate was 75.7% and the event-free survival rate was 73.5%. The survival of those patients who underwent hematopoietic stem cell transplantation in first complete remission was not different from that of the patients who were treated with chemotherapy alone (overall survival: 70.1% versus 81.1%, respectively, p=0.39; event-free survival: 70.1% versus 76.2%, respectively, p=0.75). The outcome of the 11 patients who were retrospectively classified as having mixed phenotype acute leukemia according to the new WHO criteria was excellent, with no relapses or deaths occurring among these patients. ConclusionsAn acute lymphocytic leukemia type of induction therapy, using agents that are active against lymphoid and myeloid leukemias, appears to be more effective in achieving and maintaining complete remissions regardless of whether the patients are classified according to EGIL criteria or the new WHO criteria. Hematopoietic stem cell transplantation may not be necessary for all patients in first complete remission.Key words: biphenotypic acute leukemia, diagnosis, therapy, immunophenotyping, stem cell transplant.Citation: Al-Seraihy AS, Owaidah TM, Ayas M, El-Solh H, Al-Mahr M, Al-Ahmari A, and Belgaumi AF. Clinical characteristics and outcome of children with biphenotypic acute leukemia. Haematologica 2009; 94:1682-1690. doi:10.3324/haematol.2009

Mixed-phenotype acute leukemia: historical overview and a new definition

“…34 Evaluation of clinical outcome by classification schemes showed that pediatric patients with MPAL diagnosed using the 2008 WHO criteria had a better outcome as compared with the rest of biphenotypic cases classified using EGIL criteria. 33 Specifically, these 11 MPAL patients were alive and did not have relapse of their disease and only a subset (six patients) were transplanted after achieving remission. 33 Those patients who were initially diagnosed with biphenotypic leukemia using EGIL criteria but did not conform to the 2008 WHO criteria for MPAL did poorly, with an overall survival of 54%.…”

“…Al-Seraihy et al 33 retrospectively evaluated 633 children under 14 years of age with acute leukemia and found that 24 (3.8%) of these cases were classified as biphenotypic acute leukemia using EGIL criteria, while 11 (1.7%) were categorized as MPAL using the new 2008 WHO criteria. A retrospective meta-analysis of major recent studies of biphenotypic acute leukemia using the 2008 WHO criteria is summarized in Table 4.…”

“…39 However, the incidence of the Philadelphia chromosome was noted to be significantly lower in pediatric biphenotypic cases, estimated at 3% in one study. 33 Rubnitz et al 38 found that most of their pediatric cases had abnormal karyotypes (29/33 in total), with the most common being abnormalities of chromosomes 5 or 7 followed by 12p abnormalities. In addition, these authors also used a gene-expression database to compare biphenotypic acute leukemia with AML and ALL.…”

“…Although most studies found the frequency of MPAL with t(9;22) to be 28-35%, pediatric studies report it to be much lower at 3%. 33 Many of these cases show a dimorphic population of blasts, with most showing B and myeloid lineage. This translocation in leukemias with a mixed phenotype was associated with a worse prognosis in some studies.…”

“…33 Those patients who were initially diagnosed with biphenotypic leukemia using EGIL criteria but did not conform to the 2008 WHO criteria for MPAL did poorly, with an overall survival of 54%. 33 Although fewer patients will be classified as MPAL using the 2008 WHO criteria (Table 4), the clinical outcome of these patients has not been evaluated in larger studies.…”