Influence of late treatment on how chronic myeloid leukemia responds to imatinib

ABSTRACT: INTRODUCTION: In Brazil, patients with chronic myeloid leukemia (CML) in the chronic phase were not given first-line imatinib treatment until 2008. Therefore, there was a long period of time between diagnosis and the initiation of imatinib therapy for many patients. This study aims to compare the major molecular remission (MMR) rates of early versus late imatinib therapy in chronic phase CML patients. METHODS: Between May 2002 and November 2007, 44 patients with chronic phase CML were treated with second-line imatinib therapy at the Hematology Unit of the Ophir Loyola Hospital (Belém, Pará, Brazil). BCR-ABL transcript levels were measured at approximately six-month intervals using quantitative polymerase chain reaction. RESULTS: The early treatment group presented a 60% probability of achieving MMR, while the probability for those patients who received late treatment was 40%. The probability of either not achieving MMR within one year of the initiation of imatinib therapy or losing MMR was higher in patients who received late treatment (79%), compared with patients who received early treatment (21%, odds ratio=5.75, P=0.012). The probability of maintaining MMR at 30 months of treatment was 80% in the early treatment group and 44% in the late treatment group (P=0.0005). CONCLUSIONS: For CML patients in the chronic phase who were treated with second-line imatinib therapy, the probability of achieving and maintaining MMR was higher in patients who received early treatment compared with those patients for whom the time interval between diagnosis and initiation of imatinib therapy was longer than one year.

Lack of evidence for human infection with Xenotropic murine leukemia virus-related virus in the Brazilian Amazon basin

Introduction: This study confirmed the absence of natural infection with Xenotropic murine leukemia virus-related virus (XMRV) or XMRV-related disease in human populations of the Brazilian Amazon basin. We demonstrated that 803 individuals of both sexes, who were residents of Belem in the Brazilian State of Pará, were not infected with XMRV. Methods: Individuals were divided into 4 subgroups: healthy individuals, individuals infected with human immunodeficiency virus, type 1 (HIV-1), individuals infected with human T-lymphotrophic virus, types 1 or 2 (HTLV-1/2), and individuals with prostate cancer. XMRV infection was investigated by nested PCR to detect the viral gag gene and by quantitative PCR to detect pol. Results: There was no amplification of either gag or pol segments from XRMV in any of the samples examined. Conclusions: This study supports the conclusions of the studies that eventually led to the retraction of the original study reporting the association between XMRV and human diseases.

Prevalence of human T cell leukemia virus-I (HTLV-I) antibody among populations living in the Amazon region of Brazil (preliminary report)

Prevalence of human T cell leukemia virus-I (HTLV-I) antibody among populations living in the Amazon region of Brazil (preliminary report)NakauchiC. M.LinharesA. C.MaruyamaK.KanzakiL. I.MacedoJ. E.AzevedoV. N.CassebJ. S. R. Fundação Serviços de Saúde Pública, Seção de Vírus, Instituto Evandro Chagas Belém Brasil Chiba Cancer Research Institute, Department of Pathology Chiba Japan Universidade Federal do Pará Belém Brasil Instituto Offir Loyola Belém Brasil Faculdade Estadual de Medicina Belém Brasil 0319908512933Forty-tree (31.4%) out of 137 serum samples obtained from two Indian communities living in the Amazon region were found to be positive for HTLV-I antibody, as tested by enzyme-linked immunosorbent assay (Elisa). Eighty-two sera were collected from Mekranoiti Indians, yielding 39% of positivity, whereas 11 (20.0%) or the 55 Tiriyo serum samples had antibody to HTLV-I. In addition, positive results occurred in 10 (23.2%) out of 43 sera obtained from patients living in the Belem area, who were suffering from cancer affecting different organs. Five (16.7%) out of 30 Elisa positive specimens were also shown to be positive by either Western blot analysis (WB) or indirect immunogold electron microscopy (IIG-EM).

Frequency of acute myeloid leukemia in children attended in Belém, Pará from August 2005 to May 2009

Introdução: A leucemia mieloide aguda (LMA) tem incidência variável nas diferentes regiões do Brasil. Objetivos: Determinar a frequência dos subtipos de LMA em crianças entre 0-17 anos, atendidas em Belém, Pará, no período de agosto de 2005 a maio de 2009. Casuística e métodos: Estudo retrospectivo com 278 pacientes com diagnóstico de leucemias agudas ou crônicas com base nos critérios clínicos, morfológicos (classificação franco-americana-britânica [FAB]/Organização Mundial da Saúde [OMS]) e de perfil imunofenotípico por citometria de fluxo para determinação da frequência de subtipos de LMA. Resultados: Foram encontrados 70 (25,18%) casos de LMA; destes, 37 (52,9%) eram crianças entre 0-17 anos (idade mediana de 7 anos e 8 meses). Não houve diferença estatística em relação ao gênero. Observou-se maior frequência de LMA dos subtipos M2 (18/37 - 48,6%) e M0/M1 (10/37 - 27%), principalmente na primeira década de vida (16/28 [57,1%] LMA M2 e 9/28 [32,1%] LMA M0/M1). Conclusão: Na população pediátrica, os tipos de LMA M2, M0/M1 e M3 foram, respectivamente, as mais frequentes.

Compartmentalized gene expression of toll-like receptors 2, 4 and 9 in the brain and peripheral lymphoid organs during canine visceral leishmaniasis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Expression of inducible nitric oxide synthase in macrophages inversely correlates with parasitism of lymphoid tissues in dogs with visceral leishmaniasis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

HPV16-associated tumors control myeloid cell homeostasis in lymphoid organs, generating a suppressor environment for T cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluating the equilibrium association constant between artinM lectin and myeloid leukemia cells by impedimetric and piezoelectric label free approaches

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Chemopreventive actions of blond and red-fleshed sweet orange juice on the loucy leukemia cell line

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

IGFBP7 participates in the reciprocal interaction between acute lymphoblastic leukemia and BM stromal cells and in leukemia resistance to asparaginase

The interaction of acute lymphoblastic leukemia (ALL) blasts with bone marrow (BM) stromal cells (BMSCs) has a positive impact on ALL resistance to chemotherapy. We investigated the modulation of a series of putative asparaginase-resistance/sensitivity genes in B-precursor ALL cells upon coculture with BMSCs. Coculture with stromal cells resulted in increased insulin-like growth factor (IGF)-binding protein 7 (IGFBP7) expression by ALL cells. Assays with IGFBP7 knockdown ALL and stromal cell lines, or with addition of recombinant rIGFBP7 (rIGFBP7) to the culture medium, showed that IGFBP7 acts as a positive regulator of ALL and stromal cells growth, and significantly enhances in-vitro resistance of ALL to asparaginase. In these assays, IGFBP7 function occurred mainly in an insulin-and stromal-dependent manner. ALL cells were found to contribute substantially to extracellular IGFBP7 levels in the conditioned coculture medium. Diagnostic BM plasma from children with ALL had higher levels of IGFBP7 than controls. IGFBP7, in an insulin/IGF-dependent manner, enhanced asparagine synthetase expression and asparagine secretion by BMSCs, thus providing a stromal-dependent mechanism by which IGFBP7 protects ALL cells against asparaginase in this coculture system. Importantly, higher IGFBP7 mRNA levels were associated with lower leukemia-free survival (Cox regression model, P = 0.003) in precursor B-cell Ph(-) ALL patients (n = 147) treated with a contemporary polychemotherapy protocol.

Evaluation of Long-Term Outcomes, Cytogenetic and Molecular Responses with Imatinib Mesylate in Early and Late Chronic-Phase Chronic Myeloid Leukemia: A Report from a Single Institute

Here we compare the management and survival outcomes of chronic myeloid leukemia (CML) patients who had early or late imatinib mesylate (IM) therapy. The cytogenetic and molecular responses of 189 CML patients were analyzed. Of this group, 121 patients were classified as the early chronic phase (ECP) group and started IM within 12 months of diagnosis. The other 68 patients were classified as the late chronic phase (LCP) group who had been treated with interferon (IFN)-alpha-2 and crossed over to IM more than 12 months after diagnosis. The overall rates of complete cytogenetic response (CCyR) and major molecular response (MMR) at last follow-up were 83.6 and 78.1% in the ECP and LCP groups, respectively. The CCyR rates were 89.3 (for ECP patients) versus 73.5% (for LCP patients; p < 0.0001). At last follow-up, 82.4% ECP and 64.2% LCP patients had achieved an MMR (p < 0.0001). No significant differences were noted between the two groups with regard to survival outcomes. Our experience reveals that IM is an effective rescue therapy in most CML LCP patients who are intolerant or in whom IFN-alpha therapy fails. Such therapeutic options should be considered in LCP patients, particularly in countries where IM may not be available. Copyright (C) 2012 S. Karger AG, Basel