RARS with fibrosis and del(20q) transformed into ALL.

Transformation of myelodysplastic syndrome (MDS) into acute myelogenous leukemia occurs in approximately 30 % of cases, while progression into acute lymphoblastic leukemia (ALL) is rare. We report on a 67-year-old man with the diagnosis of MDS, subtype refractory anemia with ring sideroblasts (RARS), karyotype 20q- , JAK-2 negative and grade III fibrosis on the bone marrow biopsy, who evolved into ALL 33 months after the diagnosis of MDS. RARS is one of the subtypes of MDS with most indolent course. Deletion of the long arm of chromosome 20 (20q-) is considered as good prognosis by the International Prognostic Scoring System, an important scoring system for predicting survival and evolution of MDS. Primary MDS with bone marrow fibrosis may represent a distinct clinicopathological and is supposed to have an unfavorable prognosis. The combined analysis of these features makes this rare report still more challenging and illustrates that biology of MDS is yet to be discovered.

Acute promyelocytic leukemia associated with the PLZF-RARA fusion gene: two additional cases with clinical and laboratorial peculiar presentations.

Acute promyelocytic leukemia (APL) is characterized by the presence of the t(15;17) and PML-RARa rearrangement, with good response to treatment with retinoids. However, few cases of variant APL involving alternative chromosomal aberrations have been reported, including t(11;17)(q23;q21) (Wells et al. in Nat Genet 17:109-113, 1; Arnould et al. in Hum Mol Genet 8:1741-1749, 2) t(5;17)(q35;q12-21), t(11;17)(q13;q21) (Grimwade et al in Blood 96:1297-1308, 3) and der(17) (Rego et al. in Blood (ASH Annual Meeting Abstracts)114:Abstract 6, 4), whereby RARa is fused to the PLZF, NPM, NuMA, and STAT5b genes, respectively, have been described. These cases are characterized by distinct morphology, clinical presentation, and in respect to PLZF, a lack of differentiation response to retinoids leading to the need of different approaches concerning diagnostic methods and therapeutics. This paper describes two cases of APL associated with the PLZF-RARA fusion gene enrolled in the IC-APL trial that is a non-randomized, multicenter study conducted in Brazil, Mexico, Chile and Uruguay with the aim to improve the treatment outcome of APL patients in developing countries. These cases, although rare, offer a challenge to its early recognition and proper conduction.

Chronic myeloid leukemia following kidney transplantation.

Immunosuppressed renal recipients are at an increased risk of developing cancer. Leukemias are less frequent than other hematopoietic tumours and development of CML after immunosuppression is rare. We describe a 37-year-old male who presented with left-shifted leukocytosis, hypercellular bone marrow 32 months after the kidney transplant. G-banding karyotype revealed 46,XY,t(9;22)(q34;q11) and the diagnosis of chronic myeloid leukemia was made. This is the 13th case of CML after kidney transplant reported. Whether this CML appeared as a random phenomenon or chemically induced is a matter of debate. Some individuals might have an increased susceptibility to the effects of azathioprine.

Estudo dos polimorfismos gênicos do GSTM1, GSTT1, CYP1A1 em pacientes com leucemia mielóide aguda / Study of the genetic polymorphisms of GSTM1, GSTT1 and CYP1A1 among acute myeloide leukemia patients

Introdução: Leucemia Mielóide Aguda (LMA) é uma doença clonal maligina cujo prerrequisito para seu desenvolvimento é dano ao DNA. Os xenobióticos induzem dano no DNA e são metabolizados pelos sistemas enzimáticos em duas fases: Citocromo P450 e Glutationa-S-Transferase). Polimorfismos gênicos destes genes de metabolismo de drogas podem aumentar o risco de desenvolvimento de tumores, entre eles, a leucemia. O objetivo deste trabalho foi avaliar a freqüência dos polimorfismos gênicos do GSTM1, GSTT1 e CYP1A1 (polimorfismos M1, M2, M3 e M4) nos pacientes com LMA e compará-los com um grupo-controle. Material e Métodos: Foram estudados cinqüenta e oito pacientes com LMA, cujos polimorfismos gênicos de GSTM1, GSTT1 e CYP1A1 (M1, M2, M3 e M4) foram pesquisados pela técnica de PCR e PCR-RFLP. Um grupo-controle pareado por sexo e idade constando de 174 indivíduos teve seus genótipos dos referidos genes analisados. As variantes alélicas foram correlacionadas com as características clínicas e biológicas dos pacientes. Resultados: O polimorfismo heterozigoto M3 CYP1A1 foi encontrado em 65 por cento dos casos de LMA e 47,6 por cento dos controles (p < 0,001). O polimorfismo CYP1A1 M4 encontrado em 74,1 por cento dos pacientes com LMA e 66,7 por cento dos controles (P< 0,001). Os polimorfismos M1 e M2 do CYP1A1 foram mais freqüentes no grupo-controle (p < 0,001). O Odds Ratio (OR) para o risco de LMA 2,36 (IC1, 2-4,5) para o polimorfismo CYP1A1 M3 heterozigoto e para o polimorfismo M4 CYP1A1 foi de 2,38 (IC 0,8-6,8). Discussão: O risco de adquirir LMA foi correlacionado ao polimorfismo M4 CYP1A1 e polimorfismo heterozigoto M3 CYP1A1. O significado funcional do CYP1A1 M4 é desconhecido, mas pode ter influência sobre a ativação dos hidrocarbonetos policíclicos aromáticos, um agente carcinógeno. Conclusão: Os resultados sugerem polimorfismo CYP1A1 M3 heterozigoto esteve correlacionado aos pacientes com LMA; estudos posteriores poderão compreender melhor estes achados

[Karyotype in acute myeloid leukemia: importance and type of aberrations in 30 patients at diagnosis]. / Cariótipo em leucemia mielóide aguda: importância e tipo de alteração em 30 pacientes ao diagnóstico.

INTRODUCTION: Cytogenetics in AML at diagnosis is a well defined prognostic tool. OBJECTIVE: The authors analized karyotype (KT) and clinical data of newly diagnosed AML patients. METHODS: Thirty patients were studied, 16 male and 14 female. Age ranged from 19 to 84 years. Diagnostic criteria were based on WHO classification, immunophenotyping and G banding cytogenetics. They were treated according to standard protocol (daunorrubicin and cytarabine - 3+7) and those who had Acute Promyelocytic Leukemia additionally received ATRA. RESULTS: KT success rate was 84%. According to KT patients were divided into 4 groups: favourable prognosis (FP) (6) (t(8;21), t(15;17)); intermediary prognosis (IP) (7)(four normal karyotypes, + 8, t(1;2) and del 18(q)); unfavourable prognosis (UP); and 3 secondary AML; two evolving from prior Mylelodysplastic Syndrome and one presenting as an initial blast crisis of chronic myeloid leukemia. The median age of FP was 23 years while UP was 60 years (p<0.003). In the FP, 5/6 (83%) achieved complete remission (CR) while only 1/7 (20%)in the IP and 1/8 (12,5%) in the UP. There was a tendency of higher leukocyte count in the unfavourable group. CONCLUSIONS: The rate of karyotype aberrations in AML was 80% and in accordance to literature data (65-95%). There was a clear difference in CR rates between favourable and unfavourable prognosis group.

Cariótipo em leucemia mielóide aguda: importância e tipo de alteraçäo em 30 pacientes ao diagnóstico / Karyotype in acute myeloid leukemia: importance and type of aberrations in 30 patients at diagnosis

OBJETIVO: Análise sob o ponto de vista citogenético e clínico de pacientes com LMA. MÉTODOS: Foram estudados 30 pacientes, sendo 16 homens e 14 mulheres. A idade variou de 19 a 84 anos. O diagnóstico baseou-se na classificaçäo OMS, imunofenotipagem e citogenética clássica por banda G. Foram tratados com o protocolo daunorrubicina e citarabina (3+7), com adiçäo de ATRA na Leucemia Promielocítica Aguda. RESULTADOS: A taxa de sucesso de cariótipo foi 84 por cento. De acordo com o cariótipo, os pacientes foram divididos em quatro grupos: prognóstico favorável (PF) (6) (t(8;21), t(15;17)); intermediário (PI) (7) (quatro casos com cariótipo normal,+ 8, t(1;2) e del 18(q)); desfavorável (PD) (10) e três casos eram LMA secundária (dois evoluídos de síndrome mielodisplásica e uma apresentaçäo de LMC em crise blástica. No grupo de PF, a idade mediana foi 23 e no PD 60 anos(p<0,003). No grupo PF, 5/6 pacientes (83 por cento) entraram em remissäo completa (RC), no PI 1/7 (20 por cento) e no PD 1/8 (12,5 por cento). Houve tendência à leucometria mais elevada no grupo de PD. CONCLUSÕES: A porcentagem de cariótipo alterado em LMA (80 por cento) está dentro dos valores relatados pela literatura (65 por cento-95 por cento). Ficou nítida a diferença entre a taxa de RC do grupo PF versus PD, confirmando a importância do cariótipo na diferenciaçäo dos grupos de risco

Síndrome ATRA: experiência de 10 anos / ATRA Syndrome: 10 year experience

A leucemia promielocítica aguda (LPA) é um subtipo de leucemia mielóide aguda (LMA) responsável por 10 por cento de todas as LMAs. Geralmente, o tratamento da LPA consiste de quimioterapia e uso de ácido transretinóico (ATRA). O maior efeito colateral do ATRA é a "Síndrome ATRA", que ocorre com uma freqüência de quase 30 por cento. Estudamos a apresentação clínica e a incidência da Síndrome ATRA em pacientes com LPA admitidos no Hospital São Paulo (da Escola Paulista de Medicina-UNIFESP). Treze pacientes com LPA fizeram uso de ATRA. A síndrome foi diagnosticada em cinco pacientes (38 por cento) com idade média de 29 anos e que estavam,em média, no décimo dia do uso de ATRA. Os achados clínicos mais freqüentes foram insuficiência respiratória, infiltrado pulmonar à radiografia e febre. Este relato chama a atenção para a necessidade do diagnóstico precoce dessa síndrome, com a introdução de dexametasona ao primeiro sinal no intuito de êxito terapêutico.

Megakaryocytic blast crisis as a first presentation of chronic myeloid leukemia.

UNLABELLED: Acute megakaryocytic leukemia (AmegL) corresponds to 5.0-10.0% of all acute myeloid leukemias (AML). Blast crisis as the first presentation of chronic myeloid leukemia (CML) accounts for 10.0% of all cases. OBJECTIVE: We report a case of megakaryocytic blast crisis as the first presentation of CML. CASE REPORT: A 25-yr-old-female with a 2-month history of dry cough and a large, non-tender splenomegaly was found to have a hemoglobin concentration of 10.5 g/dL, a hematocritof 33.0%, a white blood cell count (WBC) of 11.4 x 106 L with 38% small blasts, eosinophilia of 5%, basophilia of 8%, and a platelet count of 580 x 109 L. Bone marrow aspiration revealed 24% of blast cells with cytoplasmatic blebs and hyperplastic megakaryocytic lineage with dysplasia. Cytochemical stains were all negative, immunophenotyping studies showed CD41 and CD61 positivity in blast cells. Bone marrow biopsy showed grade II fibrosis. Karyotype revealed 46, XX, t(9,22) (q34.1;q11.2)[20] and the reverse-transcriptase-PCR (RT-PCR) gave rise a product with a size corresponding to the 210 kDa protein (p210). No matched donor was found. After induction therapy 5.9% of blast cells persisted. The patient received Imatinib Mesylate and is doing well after a 12-month follow-up. DISCUSSION: AmegL as the first presentation of CML is a rare and often fatal event. Some characteristics point towards the diagnosis of a blast crisis instead of AmegL de novo with t(9,22).