Luís Arthur Flores Pelloso

Acute myeloid leukemia in elderly patients: experience of a single center

Acute myeloid leukemia (AML) is a disease predominantly of older adults. Treatment of AML in the elderly is complicated not only by comorbidities but also by the high prevalence of poor prognosis markers. Thirty-one consecutive unselected patients with AML older than 60 years (representing 33% of all AML cases diagnosed at our institution during the same period) were followed over a period of 5 years (1997-2002). A high incidence of AML with multilineage dysplasia (45%) and no favorable cytogenetic abnormalities but 62% intermediate and 38% unfavorable karyotypes were found. Sixteen patients (52%) were selected for induction of intensive cytotoxic treatment and complete remission was achieved only by some of these intensively treated patients (7 of 16). Of these, 3 remained alive without disease (median: 11 months), 1 patient died shortly after complete remission, and 3 patients relapsed and died from refractory disease. Only 1 patient that was refractory to intensive cytotoxic treatment remained alive with disease under supportive care. Fifteen patients (48%) were managed with palliative/supportive care: 7 received palliative treatment and supportive care, 8 received supportive care only, and 4 patients remained alive with disease under supportive care (median: 9 months). Mortality rate was 74% and overall survival at two years was 12%. To the best of our knowledge, there is no previous report regarding elderly patients with AML in Brazilian subsets. The present data are similar to previously reported studies showing that elderly AML patients are not only older but also biologically distinct from younger AML patients, particularly in terms of the high incidence of poor prognostic karyotypes and resistance to therapy.

Megakaryocytic blast crisis as a first presentation of chronic myeloid leukemia

Abstract: 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 × 106 L with 38% small blasts, eosinophilia of 5%, basophilia of 8%, and a platelet count of 580 × 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).

Cariótipo em leucemia mielóide aguda: importância e tipo de alteraçäo 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.

t(4;12)(q11;p13): a rare chromosomal translocation in acute myeloid leukemia

We present a case of acute myeloid leukemia with t(4;12). This translocation is rare and has been observed in acute leukemias with different but immature phenotypes. To the best of our knowledge, there are around 15 descriptions of t(4;12) in AML, and most interesting, presenting morphological aspects of a pseudo-lymphoid cell with dysplasia of other series.

CYP1A1 polymorphisms modify overall survival in acute myeloid leukemia patients

As recently published, CYP1A1 genetic polymorphism was recognized as a prognostic factor for acute myeloid leukemia (AML) [1]. Genetic and clinical interactions related to xenobiotic metabolism enzymes polymorphisms, both in phase 1 metabolism genes as phase 2 (Cytochrome P450 family known as CYP and glutathione S-transferase family known as GST), might play a critical role in AML course and overall survival (OS) [1 – 4]. Both gene families, from phase 1 and 2, carry genetic polymorphisms. These polymorphisms modify enzymatic activity and create faster or slower genotypes of compounds known as xenobiotics [2]. Genetic polymorphisms result in interindividual variation differences capacity, and as a consequence to alteration in metabolization rate of chemical compounds; genetic polymorphisms might influence OS of AML [1 – 4]. A relative paucity of work has been done to identify genetic variants that might predict the prognosis and response to treatment once AML is diagnosed. Four polymorphisms of the CYP1A1 gene have been identified: CYP1A1*2A, CYP1A1*2C, CYP1A1*3, and CYP1A1*4 [1 – 4]. Glutathione Stransferase systems (GST) harbor two genetic polymorphisms in both GSTM1 and GSTT1 genes, which cause the absence of the specific enzyme activity. Patients with AML present well-defined prognostic factors [5,6]. These factors are related to disease response, relapse risk, and overall survival (OS). Cytogenetic status is the most important prognostic factor for OS [5 – 11], but the recognition of new features or prognostic factors, other than those previously widely known (e.g., karyotype, age, de novo6secondary AML), is crucial to the understanding of biological pathways of AML [11]. To our knowledge, few data have been reported about the influence of these genetic polymorphisms on overall survival in patients with AML. The aim of this report was to evaluate the influence of CYP1A1, GSTM1, and GSTT1 genetic polymorphisms in the overall survival of AML patients.

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.

Trisomy 22: a subclone marker?

Universidade Federal de Sao Paulo, Disciplina Hematol & Hemoterapia, Escola Paulista Med, EPM, BR-04023900 Sao Paulo, Brazil