Acute megakaryoblastic leukemia: experience of GIMEMA trials

Abstract

The objective of the study was to evaluate the incidence, characteristics, treatment and outcome of acute megakaryoblastic leukemia (AMeL) in patients enrolled in GIMEMA trials. Between 1982 and 1999, 3603 new consecutive cases of AML aged over 15 years were admitted to GIMEMA trials. Of them, 24 were AMeL. The incidence of AMeL among AML patients enrolled in GIMEMA trials was 0.6% (24/3603). Diagnosis was based on morphological criteria. Out of 11 cytogenetic studies performed two presented chromosome 3 abnormalities. Twelve patients (50%) reached a CR, five (21%) died in induction and seven (27%) were unresponsive. The median duration of CR was 35 weeks (range 10-441). Seven patients underwent transplantation procedures (1 BMT, 4 aBMT, 2 aPBSCT). Four patients died in CR due to chemotherapy-related complications. Comparing the CR rate between AMeL and the other cases of AML enrolled in GIMEMA trials, no differences were observed. These results were mirrored for different age groups. The median survival was 40 weeks. At present, after a followup of a minimum of 2 years, only two patients are alive in CR, all the others having died. A 5-year Kaplan-Meier curve shows a disease-free survival of 17% and an actuarial overall survival of 10%. AMeL is a rare form of AML. The CR duration and the overall survival in this group of patients are very poor, even if similar to those observed in other AML. Furthermore, a high number of deaths in CR were observed. On the basis of these data, a specific therapeutic approach, possibly with innovative treatments, should be evaluated.

Infiltração cutânea na leucemia megacariocítica aguda com expressão de CD56

“…20 A imunofenotipagem, com a identificação de glicoproteínas de membrana CD41, CD42 e/ou CD61, é considerada o método de escolha para o diagnóstico de leucemia megacariocítica aguda. 6,10,22,23 As células mononucleares da medula óssea, analisadas por Citometria de Fluxo, revelaram o seguinte imunofenótipo: 94% CD45+ (marcador Panleucocitário); 93% HLA-DR+ (marcador de células apresentadoras de antígeno-macrófagos, linfócitos B ativados e ainda mieloblastos); 81% CD56+ (marcador células NK) e 69% CD61+ (marcador de plaquetas e megacarioblastos). Adicionalmente foi identificada uma pequena subpopulação com fenótipo mielóide imaturo HLA-DR/CD13+ (23%), mieloperoxidase positiva (11,5%) e CD33+ (5%).…”

“…1,2,3 Representa 3% a 5% dos casos de LMA e exibe uma curva de incidência de distribuição com um pico bimodal, ou seja, um pico em crianças menores de três anos e outro em idosos. 1,3,5,6,7 A utilização apenas de critérios morfológicos e citoquímicos não é suficiente para um diagnóstico correto, pois são células morfologicamente indistinguíveis, com reações citoquímicas Sudan Black (SB) e mieloperoxidase negativas. 1,2 Assim, a utilização de técnicas de imunofenotipagem é essencial para o diagnóstico diferencial, mostrando uma população de células leucêmicas com ausência da maioria dos marcadores linfóides e mielóides de superfície.…”

“…Verifica-se que há expressão para os antígenos da linhagem megacariocítica: CD41a (complexo glicoprotéico IIb/IIIa), CD42b (glicoproteína Ib) e/ou CD61 (glicoproteína IIIa) ou antígeno relacionado ao fator VIII, permitindo uma classificação correta em 98% dos casos. 2,4,[6][7][8][9][10] O CD56 é uma molécula de adesão de célula neural (NCAM), encontrada nas células natural killer (NK) e subpopulações de células T. 2,11 Na LMA está presente em 15% a 20% dos casos, sendo freqüentemente associado às leucemias de linhagem monocítica, a trissomia 8, a t(8;21), t(15;17) e ao rearranjo 11q23. 2 A expressão aberrante de CD56 pode predispor à infiltração leucêmica extramedular.…”

Erythroid and megakaryocytic transformation

“…Another class of aggressive megakaryocytic leukemias is adult AMKL. This is a rare malignancy that comprises nearly 1% of adult AML cases (Tallman et al, 2000;Pagano et al, 2002). Similar to the other subtypes of AMKL, this leukemia is characterized by the excessive production of primitive megakaryoblasts within the bone marrow and extensive myelofibrosis.…”

“…There are three main groups of patients who develop distinct forms of AMKL: children with Down syndrome (DS) (DS-AMKL); infants without DS (non-DS pediatric AMKL); and adults. AMKL comprises approximately 5-7% of AML in children without DS (Barnard et al, 2006) and 1% of adult AML (Tallman et al, 2000;Pagano et al, 2002). In the context of DS, however, megakaryocytic disorders are relatively common, occurring in as many as 10% of newborns.…”