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1.
Eur J Haematol ; 106(3): 398-407, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33301622

RESUMO

OBJECTIVE AND METHOD: Adult T-cell leukemia/lymphoma (ATL) is an aggressive peripheral T-cell lymphoma with poor prognosis. We retrospectively reviewed the medical records of 312 patients with aggressive ATL and analyzed the effect of chemotherapy dose intensity on prognosis in clinical practice. RESULT: As first-line therapy, 62 patients underwent best supportive care (BSC) or single-agent chemotherapy, and 235 underwent intensive chemotherapy. The median survival time (MST) was 0.58 years in the 312 total patients, and 0.13 years and 0.75 years in the BSC/single-agent chemotherapy group and intensive chemotherapy group, respectively. The median average relative dose intensity (ARDI) of patients who received intensive chemotherapy was 60%. We divided patients into 3 groups according to ARDI. Those in the top tertile of ARDI (ARDI ≥ 75%, n = 82) had better overall survival compared with those in the intermediate tertile (45% ≤ ARDI < 75%, n = 79) (P < .0001), with MSTs of 4.69 and 0.75 years, respectively. The occurrence of organ dysfunction and infectious complications was comparable between the two ARDI groups. CONCLUSION: Higher ARDI improves prognosis in patients with aggressive ATL in clinical practice.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Tomada de Decisão Clínica , Gerenciamento Clínico , Progressão da Doença , Humanos , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
2.
Clin Lymphoma Myeloma Leuk ; 18(5): 353-360.e1, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29610029

RESUMO

INTRODUCTION: We previously reported an interim analysis of the DADI (dasatinib discontinuation) trial. The results showed that 48% of patients with chronic myeloid leukemia in the chronic phase who maintained a deep molecular response (DMR) for ≥ 1 year could discontinue second- or subsequent-line dasatinib treatment safely at a median follow-up of 20 months. However, the results from longer follow-up periods would be much more useful from a clinical perspective. PATIENTS AND METHODS: The DADI trial was a prospective, multicenter trial conducted in Japan. After confirming a stable DMR for ≥ 1 year, dasatinib treatment subsequent to imatinib or nilotinib was discontinued. After discontinuation, the loss of DMR (even of 1 point) was defined as stringent molecular relapse, thereby triggering therapy resumption. The predictive factors of treatment-free remission (TFR) were analyzed. RESULTS: The median follow-up period was 44.0 months (interquartile range, 40.5-48.0 months). The estimated overall TFR rate at 36 months was 44.4% (95% confidence interval, 32.0%-56.2%). Only 2 patients developed a molecular relapse after the 1-year cutoff point. The presence of imatinib resistance was a significant risk factor for molecular relapse. Moreover, high natural killer cell and low γδ+ T-cell and CD4+ regulatory T-cell (CD25+CD127low) counts before discontinuation correlated significantly with successful therapy discontinuation. CONCLUSION: These findings suggest that discontinuation of second- or subsequent-line dasatinib after a sustained DMR of ≥ 1 year is feasible, especially for patients with no history of imatinib resistance. In addition, the natural killer cell count was associated with the TFR.


Assuntos
Antineoplásicos/uso terapêutico , Dasatinibe/uso terapêutico , Desprescrições , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Feminino , Seguimentos , Proteínas de Fusão bcr-abl/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Fatores de Risco , Resultado do Tratamento
3.
Leuk Lymphoma ; 49(2): 315-21, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18231919

RESUMO

We examined human T-lymphotropic virus type I (HTLV-I) infection among patients with myelodysplastic syndrome (MDS), refractory anemia with excess of blasts (RAEB)/RAEB in transformation (RAEBt) and acute myelogenous leukemia (AML). The study population consisted of 151 patients: 46 with MDS RAEB/RAEBt and 105 with AML (M1, n = 15; M2, n = 39; M3, n = 18; M4, n = 19; M5, n = 9; M6, n = 3; M7, n = 2). As a reference, we examined 92 patients with refractory anemia (RA) and 405 patients with cardiovascular diseases (CVD). Thirteen patients with RAEB/RAEBt (28.3%), 11 with AML (11.6%), 27 with RA (29.3%), and 45 with CVD (11.0%) were positive for HTLV-I. Seven AML patients with HTLV-I infection had M3 acute promyelocytic leukemia (APL). The prevalences of HTLV-I infection among patients with RAEB/RAEBt (P < 0.001), APL (P = 0.001), and RA (P < 0.001) were significantly higher than that in patients with CVD. The prevalences of HTLV-I infection were still significantly higher in patients with RAEB/RAEBt (P = 0.007), APL (P = 0.017) and RA (P < 0.001) than in those with CVD matched by sex and age. Platelet counts and survival times of RAEB/RAEBt patients with infection were significantly lower than those of patients without infection.


Assuntos
Anemia Refratária com Excesso de Blastos/virologia , Infecções por HTLV-I/epidemiologia , Leucemia Promielocítica Aguda/virologia , Síndromes Mielodisplásicas/virologia , Adulto , Idoso , Transformação Celular Neoplásica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prevalência , Taxa de Sobrevida
4.
Clin Nucl Med ; 32(10): 775-8, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17885356

RESUMO

We report 2 patients with chronic myeloid leukemia in the chronic phase showing diffusely increased F-18 fluorodeoxyglucose (FDG) uptake in the bone marrow before treatment. Follow-up FDG positron emission tomography (PET) scans were performed in a patient after cessation of treatment and in the other under treatment. Both FDG PET findings showed reduced FDG uptake in the bone marrow. A series of these FDG PET findings suggest the usefulness of FDG PET for the diagnosis and monitoring of chronic myeloid leukemia after treatment.


Assuntos
Fluordesoxiglucose F18 , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico por imagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Pirimidinas/uso terapêutico , Idoso , Antineoplásicos/uso terapêutico , Benzamidas , Feminino , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Prognóstico , Compostos Radiofarmacêuticos , Resultado do Tratamento
6.
Acta Haematol ; 116(1): 62-6, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16809892

RESUMO

A 24-year-old Japanese man was admitted due to bloody phlegm in May 2002. A diagnosis of mediastinal germ cell tumor, mixed type involving seminoma, immature teratoma and embryonal carcinoma, was made by transthoracic needle biopsy. Three months later, his complete blood counts revealed pancytopenia with high fever. Examination of bone marrow revealed increased atypical large histiocytes (5.6%) with hemophagocytosis, and thus, hemophagocytic syndrome related to germ cell tumor was diagnosed. In addition, chromosomal analysis of the bone marrow cells revealed a 47, XY, +9 genotype. Chemotherapies for germ cell tumor and hemophagocytic syndrome were performed without any improvement, and he died of diffuse alveolar damage. Autopsy revealed diffuse infiltration of immature histiocytes with hemophagocytosis in the liver, spleen and bone marrow. The atypical histiocytes were positive for CD68 and lysozyme and negative for lymphoid markers, and the diagnosis of true malignant histiocytosis associated with mediastinal germ cell tumor was made. The rare chromosomal abnormality of trisomy 9, a marker for benzene-related leukemia, was seen in the present case without apparent benzene exposure.


Assuntos
Cromossomos Humanos Par 9 , Sarcoma Histiocítico/patologia , Linfo-Histiocitose Hemofagocítica/patologia , Neoplasias do Mediastino/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , Segunda Neoplasia Primária/patologia , Trissomia , Adulto , Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Biópsia por Agulha , Medula Óssea/patologia , Cromossomos Humanos Par 9/genética , Histiócitos/patologia , Sarcoma Histiocítico/tratamento farmacológico , Sarcoma Histiocítico/genética , Humanos , Japão , Fígado/patologia , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/genética , Masculino , Neoplasias do Mediastino/tratamento farmacológico , Neoplasias do Mediastino/genética , Muramidase , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/genética , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/genética , Alvéolos Pulmonares/patologia , Fatores de Tempo , Falha de Tratamento , Trissomia/genética
7.
Intern Med ; 45(5): 297-301, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16595998

RESUMO

A 66-year-old woman who was positive for human T-lymphotropic virus type I (HTLV-I) antibody developed mixed connective tissue disease (MCTD) with interstitial pneumonia, and was successfully treated with corticosteroid. One year later, under maintenance treatment of prednisolone (PSL), she contracted acute type adult Tcell leukemia/lymphoma (ATLL) without flaring of MCTD. MCTD is considered to be as one of the HTL-V-I-related inflammatory diseases, however the development of ATLL during the treatment of HTL-V-I-related MCTD has not been well studied. Here, we review the literature and raise the issue of the mutual interactions between MCTD-causative anti-HTLV-I immune response and anti-ATLL immune response.


Assuntos
Leucemia-Linfoma de Células T do Adulto/imunologia , Doença Mista do Tecido Conjuntivo/tratamento farmacológico , Idoso , Autoanticorpos/sangue , Southern Blotting , Evolução Fatal , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Leucemia-Linfoma de Células T do Adulto/sangue , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Doenças Pulmonares Intersticiais/complicações , Metilprednisolona/uso terapêutico , Doença Mista do Tecido Conjuntivo/complicações , Doença Mista do Tecido Conjuntivo/diagnóstico , Doença Mista do Tecido Conjuntivo/imunologia , Prednisolona/uso terapêutico , Receptores de Interleucina-2/sangue , Timidina Quinase/sangue
8.
Int J Hematol ; 82(4): 357-61, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16298831

RESUMO

A 61-year-old man with progressive adult T-cell leukemia/lymphoma (ATLL) successfully received reduced-intensity conditioning stem cell transplantation (RIST) without T-cell depletion (TCD) from his HLA-incompatible son, who had negative results for human T-lymphotropic virus type 1 (HTLV-1) (1-locus, 1-allele mismatch in the graft-versus-host [GVH] direction; 2-loci, 1-allele mismatch in the host-versus-graft direction). The preparatory regimen consisted of fludarabine, busulfan, and rabbit antithymocyte globulin. GVH disease (GVHD) prophylaxis consisted of short-term administration of methotrexate, tacrolimus, and methylprednisolone. The patient achieved complete donor chimerism on day 30 after transplantation. On approximately day 50 the patient started to experience steroid-refractory skin GVHD (grade IV), which was successfully managed with basiliximab (anti-CD25 monoclonal antibody) and mycophenolate mofetil (MMF). Serial analysis of HTLV-1 proviral load by quantitative polymerase chain reaction analysis using whole peripheral blood demonstrated undetectable levels from day 90. At the time of this writing the patient had been in complete remission for more than 16 months. The results in this case suggest the potential of non-TCD RIST from an HLA-incompatible relative donor as an alternative source of hematopoietic stem cells even for an elderly patient with advanced ATLL. In addition, basiliximab combined with MMF may be effective for the treatment of steroid-refractory skin GVHD without deteriorating the graft-versus-ATL effect.


Assuntos
Teste de Histocompatibilidade , Leucemia-Linfoma de Células T do Adulto/imunologia , Leucemia-Linfoma de Células T do Adulto/terapia , Transplante de Células-Tronco , Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Reação Enxerto-Hospedeiro , Antígenos HLA/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Quimeras de Transplante , Resultado do Tratamento
9.
Acta Haematol ; 113(4): 255-7, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15983432

RESUMO

The spleen is an immunological organ commonly involved in both hematological and nonhematological diseases. Pathological rupture of the spleen has been described in a variety of diseases affecting the spleen. Infections have been cited in most cases involving splenic rupture, but are rare in hematological malignancies despite frequent involvement of the spleen. The present report describes a fatal case of splenic rupture caused by infiltration of adult T cell leukemia cells and reports the mechanism of splenic rupture. The importance of rapid diagnosis and surgery is emphasized.


Assuntos
Leucemia de Células T/complicações , Ruptura Esplênica/etiologia , Evolução Fatal , Feminino , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Leucemia de Células T/tratamento farmacológico , Leucemia de Células T/virologia , Pessoa de Meia-Idade , Ruptura Esplênica/patologia
10.
Haematologica ; 90(3): ECR10, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15753051

RESUMO

Granulocyte-colony stimulating factor (G-CSF), a hematopoietic growth factor, is widely used to accelerate recovery from neutropenia after severe chemotherapy, both decreasing the risk of infection and mobilizing peripheral blood stem cells. Adverse effects occur with G-CSF use in approximately 30% of cases, comprised predominantly of bone pain, headache, and general fatigue. Pulmonary toxicity is very rare. Here, we describe a healthy donor for allogeneic hematopoietic stem cell transplantation who developed acute lung injury (ALI) after 4 days of G-CSF administration. Among the serum cytokines examined, only Interleukin (IL)-1beta level was elevated in this case. As a high level of IL-1beta was detected at the onset of ALI, on day 4 after G-CSF administration, and decreased to below the level of detection on day 11, it is possible in a certain part that IL-1beta was involved in the onset of G-CSF-related ALI in the present case. Granulocyte-colony stimulating factor (G-CSF) is commonly administered to healthy donors to mobilize peripheral blood stem cells (PBSC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adverse events from G-CSF use in healthy donors have been described in approximately 30% of cases, and are comprised predominantly of bone pain, headache, and general fatigue. Pulmonary complications caused by G-CSF include cough, dyspnea, and interstitial or alveolar pulmonary edema with mild-to-severe deterioration of blood oxygen level. Few cases of acute respiratory distress syndrome (ARDS) following G-CSF administration have been reported. The present report describes a healthy donor for allo-HSCT with acute lung injury (ALI) after 4 days of G-CSF administration. The cytokine-related mechanisms of G-CSF administration that contribute to ALI are discussed.


Assuntos
Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Síndrome do Desconforto Respiratório/induzido quimicamente , Doadores de Tecidos , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante Homólogo
11.
Acta Haematol ; 112(4): 217-8, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15564735

RESUMO

Interferon (IFN)-alpha is a leukocyte-derived cytokine and is used to treat several hematopoietic malignancies. The most common adverse effects of IFN-alpha are flu-like symptoms and usually insignificant. However, adverse effects due to autoimmune mechanisms are often hazardous and irreversible, although their frequency is low. In the present report, we describe a 55-year-old female with chronic myelogenous leukemia who developed severe autoimmune thrombocytopenia during IFN-alpha therapy. The lowest platelet count was 6 x 10(9)/l with severe hemorrhagic tendency. The present report strongly suggests the clinical importance of autoimmune thrombocytopenia as an adverse effect of IFN-alpha.


Assuntos
Interferon-alfa/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Antineoplásicos/efeitos adversos , Benzamidas , Feminino , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Prednisolona/uso terapêutico , Pirimidinas/uso terapêutico , Indução de Remissão
12.
Eur J Haematol ; 73(1): 17-24, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15182333

RESUMO

BACKGROUND AND OBJECTIVES: We examined the involvement of apoptosis with myelodysplastic syndrome (MDS) accompanied by peripheral cytopenias despite normo-hypercellular bone marrow. MATERIALS AND METHODS: Bone marrow smears from 31 patients with MDS-refractory anemia (RA) and five normal controls were stained using the in situ end labeling (ISEL) method. Next, the inhibitory effects of a caspase-3 inhibitor, matrix metalloproteinase inhibitor (MMPI), anti-tumor necrosis factor (TNF)-alpha or anti-Fas antibody upon the apoptosis induction in overnight cultures of bone marrow cells from the patients were examined. Further, TNF-alpha, transforming growth factor (TGF)-beta and soluble Fas ligand (sFasL) concentrations in culture supernatants of the cells were assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS: The incidence of ISEL-positive cells among MDS patients was significantly higher than in normal controls (50.8 +/- 14.0% vs. 11.3 +/- 2.4%; P < 0.0001). A caspase-3 inhibitor reduced significantly the ISEL-positive rates (32.6 +/- 15.2% vs. 50.2 +/- 16.5%; P < 0.0001). Anti-TNF-alpha or anti-Fas antibody reduced the ISEL-positive rates significantly (28.2 +/- 6.0%, 29.2 +/- 5.8%, vs. 44.2 +/- 3.4%, P < 0.001, P = 0.001, respectively). KB-R7785 also significantly decreased the ISEL-positive rates (18.0 +/- 9.3% vs. 43.6 +/- 14.0%; P < 0.0001). The concentration of TNF-alpha was significantly reduced by KB-R7785 (P < 0.05), whereas that of TGF-beta was not. Concentration of sFasL was under detectable level in the present assay system. The derivatives of KB-R7785 that can be administrated orally showed inhibitory effect on apoptosis induction as well. CONCLUSIONS: These findings suggest that MMPIs inhibits the apoptosis induction of MDS bone marrow cells via the inhibition of TNF-alpha and probably sFasL secretion, and that MMPIs can be used to control the abnormal induction of apoptosis in MDS.


Assuntos
Anemia Refratária/patologia , Apoptose/efeitos dos fármacos , Células da Medula Óssea/patologia , Inibidores de Metaloproteinases de Matriz , Inibidores de Proteases/farmacologia , Adulto , Idoso , Anticorpos/farmacologia , Células da Medula Óssea/química , Células da Medula Óssea/metabolismo , Caspase 3 , Inibidores de Caspase , Citocinas/metabolismo , Inibidores Enzimáticos/farmacologia , Proteína Ligante Fas , Humanos , Glicoproteínas de Membrana/análise , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta/análise , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/imunologia , Receptor fas/imunologia
13.
Exp Hematol ; 32(2): 195-201, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15102481

RESUMO

OBJECTIVE: We examined the anti-tumor effect of pyrrolidinedithiocarbamate (PDTC) on HTLV-1-infected T clones and the mechanism of HTLV-1 Tax protein inhibition of PDTC-induced apoptosis. MATERIALS AND METHODS: Tax-nonproducing clones S1T and Su9T01, Tax-producing clones K3T and F6T, and Tax cDNA stably transfected S1TcTax clones S1TcTax04 and S1TcTax05 were examined for PDTC inhibition of thymidine incorporation and apoptosis induction by ISEL method. In addition, S1TcTax clones were analyzed by DNA histography and DNA fragmentation and also examined for p53, p21, or Bax protein expression by Western blot. RESULTS: PDTC inhibited thymidine incorporation of all four HTLV-1-infected T cells in a similar dose-dependent manner, but K3T and F6T were more resistant than S1T and Su9T01 in apoptosis induction. S1TcTax clones also showed resistance to PDTC-induced apoptosis as compared to Tax-nonproducing S1T and S1Tneo. DNA histography demonstrated that PDTC induces G1 arrest and apoptosis in S1T and S1Tneo, and that S1TcTax clones are also sensitive to PDTC in G1 arrest but resistant in apoptosis induction. DNA fragmentation also demonstrated ladder formation only in S1Tneo but not in S1TcTax04. Western blots demonstrated higher expression of p53 and p21 proteins in S1Tneo than in S1TcTax04 during whole phase after PDTC stimulation with moderate enhancement in S1Tneo but small in S1TcTax04. Bax protein expression was detected only at early phase in S1Tneo but was not detected in S1TcTax04. CONCLUSION: These findings suggest that PDTC-induced apoptosis is related with Bax, and that G1 arrest is possibly related with p21. Tax might inhibit apoptosis induction mainly via inhibition of Bax expression preceded at least in part by p53 inhibition.


Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Fase G1/efeitos dos fármacos , Produtos do Gene tax/fisiologia , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2 , Pirrolidinas/farmacologia , Tiocarbamatos/farmacologia , Western Blotting , Linhagem Celular , Humanos , Leucemia-Linfoma de Células T do Adulto/patologia , Proteínas Proto-Oncogênicas/fisiologia , Timidina/metabolismo , Proteína X Associada a bcl-2
15.
Br J Haematol ; 119(2): 467-74, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12406087

RESUMO

We previously demonstrated that interleukin 2 (IL-2) autocrine/paracrine growth in adult T-cell leukaemia (ATL) cells was closely correlated with clinical aggressiveness. In the present study, we compared the significance of IL-15 and IL-2 in growth of ATL cells and clinical aggressiveness. Thirty-seven patients with ATL were examined: 19 acute and 18 chronic. Autonomous growth and IL-2- or IL-15-responsive growth activities of ATL cells were measured by [3H]-thymidine incorporation after 24 h cultures in vitro. All of the autonomous, IL-15- and IL-2-responsive growth activities of acute-type cells were higher than those of chronic type (P = 0.04, P = 0.03 and P = 0.02 respectively). IL-15- and IL-2-responsive growth activities were highly correlated (P = 0.0001, R2 = 0.837). Enzyme-linked immunosorbent assay (ELISA) showed detectable serum levels of IL-15 and IL-2 in 18 out of 19 and 14 out of 17 patients respectively. Reverse transcription polymerase chain reaction (RT-PCR) revealed IL-15 and IL-2 mRNA expression in 8 out of 11 patients' cells. Anti-IL-2 antibody partially inhibited autonomous growth of ATL cells; anti-IL-15 antibody was less effective. In situ immunochemistry detected IL-15 in cells of three patients and was consistent with the results of RT-PCR. These results suggest that ATL cells grow in an IL-15 autocrine/paracrine manner and that this growth is related to disease aggressiveness in a manner similar to IL-2.


Assuntos
Interleucina-15/farmacologia , Leucemia de Células T/patologia , Adulto , Idoso , Anticorpos Monoclonais/farmacologia , Comunicação Autócrina , Divisão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Imuno-Histoquímica , Interleucina-15/genética , Interleucina-15/imunologia , Interleucina-2/farmacologia , Leucemia Prolinfocítica de Células T/patologia , Leucemia-Linfoma de Células T do Adulto/patologia , Masculino , Pessoa de Meia-Idade , Comunicação Parácrina , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa
16.
Am J Hematol ; 71(1): 20-3, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12221669

RESUMO

We describe the unique clinical characteristics of patients with idiopathic thrombocytopenic purpura (ITP) who are infected by human T-lymphotropic virus type I (HTLV-I). Thirty-seven patients with ITP were examined in the present study: 10 patients had HTLV-I infection, and the remaining 27 did not. The mean age of the group with HTLV-I infection was significantly older than that of the group without infection (57.8 +/- 14.0 and 42.4 +/- 20.1, P = 0.022). The difference in mean platelet counts at diagnosis between the two groups was not significant, 29 x 10(9)/L and 21 x 10(9)/L, respectively. The levels of platelet associated IgG, red blood cell count, white blood cell count, bone marrow cell count, and megakaryocyte count did not show any significant difference. Nine patients in the group with HTLV-I infection were treated with prednisolone (1 mg/kg, daily oral). Only 3 of them responded to the therapy (one complete response [CR] and two partial responses [PR]). However, 17 of 22 patients not infected with HTLV-I were treated with prednisolone successfully: 14 patients achieved CR, and 3 patients achieved PR. There was a significant difference in response to prednisolone between the two groups (P = 0.034). Two patients with the infection and one patient without the infection achieved CR with splenectomy. These results suggest that HTLV-I infection may cause immune thrombocytopenia by a different mechanism than classical ITP; HTLV-I may modify the clinical features of ITP through an unknown immune pathway.


Assuntos
Infecções por HTLV-I/complicações , Imunossupressores/uso terapêutico , Prednisolona/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Feminino , Hemorragia/epidemiologia , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/complicações , Falha de Tratamento
17.
Am J Hematol ; 71(2): 80-4, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12353304

RESUMO

The present study examines the clinical significance of serum neuron-specific enolase (NSE) in patients with adult T cell-leukemia (ATL). Serum NSE values were measured using a radioimmunoassay in 35 patients (acute type, n = 15; lymphoma type, n = 10; chronic type, n = 10) and in 7 controls carrying T lymphotropic virus type-1 (HTLV-1). Serum NSE values >10 ng/mL were detected in 9 of 15 patients with acute type (60%), 5 of 10 with lymphoma type (50%), and in one of 10 patients with chronic type (10%) ATL, but in none of the HTLV-1 carriers. Contrary to previous findings demonstrating that 20% of patients with non-Hodgkin's lymphoma (NHL) had positive serum NSE, the frequency of a high NSE value in patients with acute and lymphoma type ATL was much higher (60% and 50%, respectively). The serum NSE value positively correlated with serum thymidine kinase activity (TK) and serum soluble interleukin-2 receptor (sIL-2R) levels (P < 0.04 and P < 0.01, respectively). Serum NSE values at the initial diagnosis were adversely related to overall survival time according to the log-rank test (P < 0.02). Pathological examinations demonstrated that both patients with anaplastic large cell lymphoma type ATL had cytoplasmic NSE and CD30 markers on cell membranes. These findings suggest that serum NSE is partially produced by ATL cells and that ATL tumor cells seem preferentially produce NSE compared with other NHL cells. Serum NSE may be a novel marker of disease aggressiveness as well as a prognostic factor for ATL.


Assuntos
Leucemia-Linfoma de Células T do Adulto/enzimologia , Fosfopiruvato Hidratase/sangue , Idoso , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Feminino , Humanos , Antígeno Ki-1/metabolismo , Leucemia-Linfoma de Células T do Adulto/mortalidade , Leucemia-Linfoma de Células T do Adulto/patologia , Masculino , Proteínas de Neoplasias/sangue , Prognóstico , Radioimunoensaio , Receptores de Interleucina-2/sangue , Solubilidade , Análise de Sobrevida , Timidina Quinase/sangue
18.
Acta Haematol ; 107(4): 213-9, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12053149

RESUMO

In the present report, we describe a case of adult T cell leukemia/lymphoma (ATLL), a 58-year-old woman, successfully treated with interferon (IFN)-alpha following autologous peripheral blood stem cell transplantation (auto-PBSCT). The patient remains in remission with full performance status for more than 12 months. Auto-PBSCT reduced the abdominal lymphoma mass and IFN-alpha eliminated residual tumor cells, possibly through the induction of specific T-cell subsets expressing CD3, CD8 on their surfaces and either IFN-gamma or tumor necrosis factor (TNF)-alpha in cytoplasm. We have treated a total of 4 ATLL patients with auto-PBSCT, including the case presented herein. All other patients treated with auto-PBSCT were not followed by adjuvant chemotherapy or cytokine therapy and relapsed within 3 months after auto-PBSCT. This evidence suggests that the therapeutic success of the present case was attributable to the administration of IFN-alpha immunotherapy following auto-PBSCT.


Assuntos
Antivirais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Interferon-alfa/uso terapêutico , Leucemia-Linfoma de Células T do Adulto/terapia , Neoplasias Abdominais/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Etoposídeo/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Vírus Linfotrópico T Tipo 1 Humano/efeitos dos fármacos , Humanos , Fatores Imunológicos/uso terapêutico , Células Matadoras Naturais/imunologia , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/imunologia , Pessoa de Meia-Idade , Compostos de Nitrosoureia/administração & dosagem , Indução de Remissão , Linfócitos T Citotóxicos/imunologia , Transplante Autólogo , Vincristina/administração & dosagem
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