Use of Zidovudine and Interferon Alfa With Chemotherapy Improves Survival in Both Acute and Lymphoma Subtypes of Adult T-Cell Leukemia/Lymphoma

Purpose Adult T-cell leukemia/lymphoma (ATLL) is a mature (post-thymic) T-cell lymphoma associated with human T-lymphotropic virus type 1 infection. Survival in aggressive subtypes remains poor, and treatment resistance is frequent. Use of zidovudine (ZDV) and interferon alfa (IFN-alpha) has been associated with improved response rates in small studies and prolonged overall survival in leukemic ATLL subtypes in a recent meta-analysis. Patients and Methods We report the clinicopathologic characteristics, treatment, and outcome of 73 patients with aggressive ATLL (acute ATLL, 29; lymphoma ATLL, 44) diagnosed and treated in England between 1999 and 2009. The impact of ZDV/IFN-alpha on treatment response and survival was assessed. Results The overall response rate ranged from 49% with chemotherapy alone to 81% with combined first-line therapy (chemotherapy with concurrent/sequential ZDV/IFN-alpha). Median overall survival (OS) was 9 months: 7.5 months for acute ATLL and 10 months for lymphoma ATLL. Use of ZDV/IFN-alpha at any time prolonged survival in acute (P < .001) and lymphoma ATLL (P < .001) and was the sole factor associated with reduction in risk of death in aggressive ATLL (hazard ratio, 0.23; 95% CI, 0.09 to 0.60; P = .002). Combined first-line therapy prolonged median OS in acute (P = .0081) and lymphoma ATLL (P = .001) compared with chemotherapy alone. Conclusion These data support the use of low-dose ZDV/IFN-alpha with chemotherapy in first-line treatment of acute and lymphoma ATLL

Splenic diffuse red pulp small B-cell lymphoma: revision of a series of cases reveals characteristic clinico-pathological features

Background Splenic diffuse red pulp small B-cell lymphoma is an uncommon B-cell lymphoma, now recognized as a provisional entity in the 2008 update of the WHO Classification. Additional work is required to review this entity and establish its diagnostic features. Design and Methods We have retrospectively analyzed the disease features in a highly selected series of 17 patients diagnosed as splenic diffuse red pulp small B-cell lymphoma. Results The median age was 65.5 years (range 40-79 years) and there was a predominance of males (male/female ratio: 2.4). Clinical manifestations were mainly derived from splenomegaly. Splenectomy was the front-line treatment in 11 symptomatic patients; the remaining 6 received chemotherapy initially followed by splenectomy. After a mean follow-up of 72 months, the five-year overall survival was 93%. All cases showed a purely diffuse pattern of splenic infiltration by monomorphous small cells with small round nuclei and pale cytoplasm. All bone marrow biopsies showed tumoral infiltration, with intrasinusoidal infiltration. Peripheral blood cells were small to medium-sized, with clumped chromatin and round nuclear outline and villous cytoplasm. Neoplastic cells had a CD20(+), CD23(-), bcl6(-), Arinexin A1- phenotype, with frequent expression of DBA44+ (15/17) and IgG (10/15). FCM data had a B-cell phenotype (CD19(+), CD20(+), CD22(+)) with FMC7 (10/11) and CD11c (5/8) expression. Clonal IgH rearrangement studies in 4 cases showed IgVH mutations in all cases, without VH1.2 usage. Conclusions Our data suggest that splenic diffuse red pulp small B-cell lymphoma is a distinct entity with morphological and immunophenotypical features that differ from those of other splenic lymphomas

ATM germline heterozygosity does not play a role in chronic lymphocytic leukemia initiation but influences rapid disease progression through loss of the remaining ATM allele

Ataxia telangiectasia patients, with constitutional bi-allelic ATM mutations, have a marked risk of lymphoid tumors and ATM mutation carriers have a smaller risk of cancer. Sporadic ATM mutations occur in 10-20% of chronic lymphocytic leukemia and are often associated with chromosome 11q deletions which cause loss of an ATM allele. The role of constitutional ATM mutations in the pathogenesis of chronic lymphocytic leukemia is unknown. Here we investigated the frequency of constitutional ATM mutations in either of two chronic lymphocytic leukemia cohorts, those with and without a chromosome 11q deletion. We found that in comparison to controls, constitutional pathogenic ATM mutations were increased in patients with chromosome 11q deletions (6 of 140 vs. 0 of 281, P = 0.001) but not in those without 11q deletions (2 of 178 vs. 0 of 281, P = 0.15). These results suggest that ATM germline heterozygosity does not play a role in chronic lymphocytic leukemia initiation but rather influences rapid disease progression through ATM loss

Estudio comparativo de las propiedades magnéticas de ferritas hexagonales de Bario obtenidas por los métodos de coprecipitación y microemulsión

Por el m todo de coprecipitaci n qu mica se obtuvo un precursor formado por hidr xidos y carbonatos de hierro y bario que al calcinarlo a temperaturas superiores a 730oC se transforma en ferrita de bario. Al calcinar el precursor durante 2 horas se obtuvo la magnetizaci n m xima de 59.1 emu/g para la temperatura de 925oC. Por el m todo de microemulsi n se obtuvo un precursor fino de hidr xidos y carbonatos de hierro y bario que al calcinarlo a temperaturas superiores a 760oC se transforma en ferrita de bario. Al calcinar el precursor durante 12 horas se obtuvo la magnetizaci n m xima de 60.5 emu/g para la temperatura de 925oC. La coercitividad intr nseca del polvo de ferrita de bario obtenido por microemulsi n result ser un 20% menor que la coercitividad intr nseca del polvo de ferrita de bario obtenido por coprecipitaci n. Esta menor coercitividad debe favorecer al m todo de microemulsi n para la producci n de part culas de ferrita de bario que sirvan como medio de grabaci n magn tica perpendicular.Peer reviewe

CD8 (+)/V beta 5.1(+) large granular lymphocyte leukemia associated with autoimmune cytopenias, rheumatoid arthritis and vascular mammary skin lesions: successful response to 2‐deoxycoformycin.

Hematol Oncol. 2002 Jun;20(2):87-93. Cd8(+)/V beta 5.1(+) large granular lymphocyte leukemia associated with autoimmune cytopenias, rheumatoid arthritis and vascular mammary skin lesions: successful response to 2-deoxycoformycin. Granjo E, Lima M, Correia T, Lisboa C, Magalhães C, Cunha N, Teixeira MA, Queirós ML, Candeias J, Matutes E. Department of Clinical Haematology, Hospital Geral de São João, Porto, Portugal. [email protected] Abstract We report a case of CD8(+)/V beta 5.1(+) T-cell large granular lymphocyte leukemia (T-LGL leukemia) presenting with mild lymphocytosis, severe autoimmune neutropenia, thrombocytopenia, polyarthritis and recurrent infections with a chronic disease course. Immunophenotyping showed an expansion of CD3(+)/TCR alpha beta(+)/CD8(+bright)/CD11c(+)/CD57(-)/CD56(-) large granular lymphocytes with expression of the TCR-V beta 5.1 family. Southern blot analysis revealed a clonal rearrangement of the TCR beta-chain gene. Hematopoietic growth factors, high dose intravenous immunoglobulin and corticosteroids were of limited therapeutic benefit to correct the cytopenias. During the disease course, the patient developed a severe cutaneous leg ulcer and bilateral vascular mammary skin lesions. Treatment with 2-deoxycoformycin resulted in both clinical and hematological complete responses, including the resolution of vascular skin lesions. Combined immuno-staining with relevant T-cell associated and anti-TCR-V beta monoclonal antibodies proved to be a sensitive method to assess the therapeutic effect of 2-deoxycoformicin and to evaluate the residual disease. Copyright 2002 John Wiley & Sons, Ltd. PMID: 12111871 [PubMed - indexed for MEDLIN

Intraclonal diversity in a Sezary syndrome with a differential response to 2‐deoxycoformycin of the two lymphoma cell populations

Br J Haematol. 2002 Dec;119(3):629-33. Intraclonal diversity in a Sezary syndrome with a differential response to 2-deoxycoformycin of the two lymphoma cell populations. Granjo E, Lima M, Lopes JM, Cunha N, Teixeira Mdos A, Santos F, Candeias J, Resende C, Santos AH, Balanzategui A, Orfão A, Matutes E. Department of Clinical Haematology, Hospital Geral de São João, Porto, Portugal. [email protected] Abstract We report a case of Sezary syndrome with two abnormal CD4+ T-cell populations detected in the peripheral blood by flow cytometry immunophenotyping and DNA cell content, suggesting a biclonal T-cell lymphoproliferative disorder. Despite these findings, molecular analysis of the T-cell receptor genes was consistent with a monoclonal T-cell proliferation, supporting the existence of intraclonal diversity rather than a true biclonal disease. The patient achieved a transient response with 2-deoxycoformycin, with a selective decrease of the larger/hyperploid T-cell population; later on, an increased representation of this T-cell population was observed concomitantly with clinical relapse. PMID: 12437636 [PubMed - indexed for MEDLINE

Automated pattern-guided principal component analysis vs expert-based immunophenotypic classification of B-cell chronic lymphoproliferative disorders: a step forward in the standardization of clinical immunophenotyping

Immunophenotypic characterization of B-cell chronic lymphoproliferative disorders (B-CLPD) is becoming increasingly complex due to usage of progressively larger panels of reagents and a high number of World Health Organization (WHO) entities. Typically, data analysis is performed separately for each stained aliquot of a sample; subsequently, an expert interprets the overall immunophenotypic profile (IP) of neoplastic B-cells and assigns it to specific diagnostic categories. We constructed a principal component analysis (PCA)-based tool to guide immunophenotypic classification of B-CLPD. Three reference groups of immunophenotypic data files—B-cell chronic lymphocytic leukemias (B-CLL; n=10), mantle cell (MCL; n=10) and follicular lymphomas (FL; n=10)—were built. Subsequently, each of the 175 cases studied was evaluated and assigned to either one of the three reference groups or to none of them (other B-CLPD). Most cases (89%) were correctly assigned to their corresponding WHO diagnostic group with overall positive and negative predictive values of 89 and 96%, respectively. The efficiency of the PCA-based approach was particularly high among typical B-CLL, MCL and FL vs other B-CLPD cases. In summary, PCA-guided immunophenotypic classification of B-CLPD is a promising tool for standardized interpretation of tumor IP, their classification into well-defined entities and comprehensive evaluation of antibody panels

T-cell prolymphocytic leukaemia: spontaneous immunophenotypical switch from CD4 to CD8 expression

published_or_final_versionSpringer Open Choice, 21 Feb 201