Diagnosing and treating mixed phenotype acute leukemia: a multicenter 10-year experience in México

Abstract

Mixed phenotype acute leukemia (MPAL) in adults represents nearly 2 to 5 % of all acute leukemia cases. There are two large studies throughout the world and only case reports and small series have been reported in Latin America. This study retrospectively analyses the clinical characteristics and survival of 27 patients with MPAL evaluated in three medical institutions of Mexico. All cases meet World Health Organization 2008 criteria; 70.3 % of patients had B lymphoid/myeloid lineage MPAL. Induction chemotherapy protocols included 7 + 3 hyper-CVAD, high-density schedules, and pediatric-like regimens such as New York II and total XI. Complete remission was achieved in 23/27 patients (85.2 %). Only one patient died due to chemotherapy-induced aplasia during remission induction (5.2 %). In 68 % of cases, we were able to administer maintenance therapy as a regimen in lymphoblastic leukemia. At the time of analysis, 70.4 % of the patients in the entire cohort had died mainly as result of disease progression (73.6 %). Disease-free survival was 13 months (95 % CI, 9.6-16.3 months) and overall survival was 14.8 months (95 % CI 13.4-16.27). Survival rates are low and standardized therapy for the management of this type of leukemia is still lacking. This is the largest series reported in Mexico and to the best of our knowledge in Latin America.

Mixed-phenotype acute leukemia: state-of-the-art of the diagnosis, classification and treatment

“…The reason is probably due to biology and differentiation potential into mixed-lineage leukemic cells in leukemogenesis of childhood ALL or AML more common in the elderly population. In most MPAL case series male patients predominated similarly to AML or ALL in large population-based studies 3,6,14,21,27,32 . Future research of genetic and hormonal characteristics, environment exposures are likely to provide insight into the observed sex differences.…”

“…A British study of 100 patients with MPAL suggested that the incidence was higher in adults than in children 6 . Finally, MPAL was found to be more prevalent in males 3,6,14 . Selected characteristics of samples of patients with MPAL meeting the 2008 WHO criteria as reported in the literature are summarized in Table 4.…”

“…Differentiation of malignant transformed cells ceases at the level of leukemic blasts and their subsequent uncontrolled proliferation and accumulation in organs, in particular bone marrow, leading to clinical manifestations of the disease 1 . The diagnosis and classification of AL require a multidisciplinary approach integrating morphology, immunophenotyping, cytogenetics and molecular biology in the presence of ≥ 20% of blasts in bone marrow aspirates 2,3 . Based on the above mentioned examinations, most AL cases may be classified as either acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL).…”

How I treat mixed-phenotype acute leukemia

“…30 Whatever classification is used, there appears to be a uniformly poor outcome in MPAL (or BAL) that is inferior to the outcome in more typical AML or ALL. Based on adult and mixed pediatric/adult series, patients with EGIL-defined BAL have complete remission (CR) rates of 30% to 80.6%, 33 45 baseline creatinine and uric acid levels, 47 extra medullary involvement at diagnosis, 44 immunophenotype (T-myeloid being worse), 41 failing to respond to induction therapy, 37,44,48 type of induction therapy (favoring non-AML), 29,44,48 and type of postremission therapy (favoring transplant 27,33 and more intensive conditioning 48 ).…”

Survival of patients with mixed phenotype acute leukemias: A large population-based study

“…Later, the WHO classification and definitions were universally accepted [4,6] (see Table 1 for definitions). Until now, only smaller case series of mixed phenotype acute leukemias (MPAL) were published [7][8][9][10][11][12][14][15][16][17][18]. In the present study we investigated the incidence and outcome of MPAL and compared these with acute lymphoid, acute myeloid and other not well characterized acute leukemias in a large database.…”