Assuntos
Aminoglicosídeos/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas , Leucemia Promielocítica Aguda/terapia , Transplante de Células-Tronco de Sangue Periférico , Condicionamento Pré-Transplante , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Feminino , Gemtuzumab , Humanos , Pessoa de Meia-Idade , Indução de Remissão , Transplante AutólogoRESUMO
To investigate effects of the preautografting administration of rituximab on the mobilization and engraftment of peripheral blood stem cells (PBSC), we retrospectively analyzed the outcomes of 43 newly diagnosed diffuse-large B-cell lymphoma patients who received CHOP chemotherapy with or without rituximab as a first-line treatment before autologous PBSC transplantation (PBSCT). There was no difference in the number of CD34(+) cells among PBSC between the non-rituximab and the rituximab groups. Although B-cells were completely depleted from PBSC in the rituximab group, we found no difference in the expression of CXCR-4, VLA-4 and c-Kit on PBSC, indicating that rituximab did not affect the expression of these adhesion molecules, which might be involved in the mechanism of mobilization. There was no significant difference in the recovery of neutrophils and platelets, transplant-related toxicity and post-transplant complications between the two groups. Despite the short follow-up, there was no significant difference in progression-free survival between the two groups. These results indicated no adverse effect of rituximab on the mobilization and engraftment of PBSC. Larger studies are required to determine the impact of rituximab on the mobilization and function of PBSC as well as whether a survival advantage exists in patients who undergo auto-PBSCT with rituximab.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas , Linfoma de Células B/terapia , Linfoma Difuso de Grandes Células B/terapia , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Murinos , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma de Células B/sangue , Linfoma Difuso de Grandes Células B/sangue , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Rituximab , Transplante Autólogo , Vincristina/administração & dosagemRESUMO
The primary object of the conditioning regimen for allogeneic reduced-intensity stem cell transplantation (RIST) is immunosuppression to achieve stable engraftment of donor cells, rather than bone marrow ablation. Therefore, immune reconstitution after RIST might be different from that after conventional stem cell transplantation (CST). In this study, 22 patients underwent RIST and 28 underwent CST. The RIST regimen consisted of cladribine (2-CdA; 0.11 mg/kg/day for 6 days), BU (4 mg/kg/day for 2 days), and rabbit anti-thymocyte globulin (ATG; 2.5 mg/kg/day for 2-4 days). The CST group received either the BU (4 mg/kg/day x 4 days)/CY (60 mg/kg/day x 2 days) (n=13) or CY (60 mg/kg/day x 2 days)/TBI (4 Gy/day x 3 days) regimen (n=15). All patients underwent transplantation with G-CSF-mobilized blood stem cells. Engraftment speed after RIST was fast and seven of 22 patients did not require platelet transfusion. We noted that the numbers of CD4+, CD4+CD45RA+, and CD4+CD45RO+ T cells after transplant in the RIST group were significantly lower than those in the CST group (P=0.0001 for both the comparisons). However, the reconstitution of CD20+ B cells was faster in the RIST group (P=0.0001). The response of T cells to PHA stimulation was lower in the RIST group (P=0.0001 on day 30 and P=0.02 on day 90). Nevertheless, there were no significant differences in the incidence of bacterial, fungal, or viral infections between the two groups. We concluded that our RIST regimen might delay laboratory-evaluated T-cell immune reconstitution compared to CST; however, the observed setbacks did not directly translate into clinically significant increases in infectious episodes.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Sistema Imunitário/fisiologia , Regeneração , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Soro Antilinfocitário/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bussulfano/administração & dosagem , Cladribina/administração & dosagem , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Humanos , Sistema Imunitário/citologia , Terapia de Imunossupressão/métodos , Infecções/etiologia , Cinética , Contagem de Linfócitos , Subpopulações de Linfócitos , Masculino , Pessoa de Meia-Idade , Transplante HomólogoRESUMO
A 60-year-old Japanese woman who presented with right nasal congestion and high fever was admitted to our hospital in March 1999. She was diagnosed with nasal NK/T-cell lymphoma clinical stage IVB. Because her NK/T-cell lymphoma was highly aggressive and chemo-resistant, she underwent autologous peripheral blood stem cell transplantation (PBSCT). The patient received a pretransplantation conditioning regimen of ranimustine, etoposide, carboplatin, and cyclophosphamide. On July 29, 1999, 1.0 x 10(6)/kg CD34+ cells were infused. The patient achieved first complete remission. In January 2000, NK/T-cell lymphoma relapsed in the skin and fever developed. CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisolone) was administered, resulting in partial regression of the skin lesions, but fever persisted. L-asparaginase (L-Asp) at a dose of 6,000 U/m2 per day was administered for 7 days, resulting in the complete disappearance of the skin lesions and resolution of the fever. The patient has been in second complete remission for more than 18 months since the completion of L-Asp treatment (as of July 2001). The effect of L-Asp in this patient was dramatic. Several cases have been reported describing the effectiveness of L-Asp in patients with nasal lymphoma and cutaneous T-cell lymphoma. A front-line chemotherapy regimen containing L-Asp for NK/T-cell lymphoma may warrant further evaluation.
Assuntos
Antineoplásicos/administração & dosagem , Asparaginase/administração & dosagem , Linfoma de Células T/tratamento farmacológico , Neoplasias Nasais/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Células Matadoras Naturais/patologia , Linfoma de Células T/terapia , Pessoa de Meia-Idade , Neoplasias Nasais/terapia , Recidiva , Indução de Remissão , Transplante AutólogoRESUMO
The maintenance of telomere length is crucial for cell survival. Recently, it has been indicated that the human telomeric protein TRF1 is involved in the negative feedback mechanism that stabilizes telomere length. We studied TRF1 mRNA expression in hematopoietic cells to clarify the relation between TRF1 and telomerase by semiquantitative reverse transcriptase-polymerase chain reaction. In polymorphonuclear cells and monocytes isolated from peripheral blood, relatively low levels of TRF1 mRNA expression were seen, compared with those of lymphocytes and CD34+. We then assessed TRF1 mRNA expression in CD34+ cells cultured in vitro with growth factors. After 4 weeks of culture, all the cells showed myeloid differentiation, and telomerase activity was down-regulated. TRF1 mRNA was expressed in CD34+ cells but was down-regulated in cells cultured for 4 weeks. We conclude that TRF1 mRNA expression is down-regulated in accordance with telomerase down-regulation during the course of myeloid differentiation.
Assuntos
Proteínas de Ligação a DNA/genética , Regulação para Baixo , Células-Tronco Hematopoéticas/citologia , Antígenos CD34/metabolismo , Técnicas de Cultura de Células , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Células HL-60/imunologia , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/fisiologia , Humanos , RNA Mensageiro/biossíntese , Sequências Repetitivas de Aminoácidos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Telômero , Proteína 1 de Ligação a Repetições Teloméricas , Tretinoína/farmacologiaRESUMO
Homeobox genes have important roles in haematopoiesis and are regulated in an activated state by the trithorax group (trxG) of genes. In a repressed state, they are regulated by the Polycomb group (PcG) of genes. ENX-1, a putative human PcG gene product, interacts with the proto-oncogene product Vav. We report an investigation of the role of ENX-1 in human haematopoiesis. CD34+ cells mobilized to peripheral blood strongly expressed ENX-1. When stimulated to proliferate, both T and B lymphocytes rapidly up-regulated ENX-1. ENX-1 was expressed in all cell lines of the various lineages examined. When HL-60 cells were differentiated to mature granulocytes with all-trans retinoic acid, ENX-1 was down-regulated. Moreover, ENX-1 antisense oligodeoxynucleotide suppressed DNA synthesis in HL-60 cells. Our data indicate that ENX-1 is involved in the proliferation of both normal and malignant haematopoietic cells.
Assuntos
Regulação da Expressão Gênica , Células-Tronco Hematopoéticas/citologia , Proteínas Repressoras/genética , Antineoplásicos/farmacologia , Linfócitos B/metabolismo , Diferenciação Celular/efeitos dos fármacos , Divisão Celular , Linhagem Celular , DNA/biossíntese , Eritrócitos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Granulócitos/metabolismo , Humanos , Megacariócitos/metabolismo , Oligonucleotídeos Antissenso/farmacologia , Proteínas do Grupo Polycomb , Proto-Oncogene Mas , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Linfócitos T/metabolismo , Tretinoína/farmacologiaRESUMO
An 84-year-old patient with adult T cell leukemia lymphoma (ATLL) developed diarrhea on day 5 of chemotherapy and was diagnosed with cytomegalovirus (CMV) colitis. Sigmoidoscopy revealed multiple superficial erosions surrounded by a flare. Computed tomography (CT) and ultrasonogram of the abdomen revealed marked thickening of the colonic mucosa. There were 186 CMV antigen-positive leukocytes per 31,000 white blood cells (WBC). A colonic biopsy specimen showed typical CMV nuclear inclusions. Immunohistological study of the specimen was positive for CMV antigen. Administration of ganciclovir (DHPG) 500 mg/day for 14 days improved the diarrhea and other symptoms. On day 30 of the chemotherapy, the patient developed diarrhea again but was diagnosed with pseudomembranous colitis instead of CMV colitis. At that time, CMV antigenemia and a histologic study for CMV were negative. The stool was positive for Clostridium difficile toxin antigen. ATLL patients are believed to be immunocompromised hosts and often develop opportunistic infections such as CMV infection. Most suffer from CMV pneumonia at the end of their course of therapy. Few gastrointestinal (GI) CMV infections are seen in ATLL patients and details of CMV colitis have never been reported. When an ATLL patient develops diarrhea that barely responds to conventional therapy, CMV colitis and pseudomembranous colitis should be listed in the differential diagnosis.
Assuntos
Colite/tratamento farmacológico , Infecções por Citomegalovirus/tratamento farmacológico , Ganciclovir/uso terapêutico , Leucemia-Linfoma de Células T do Adulto/virologia , Idoso , Colite/imunologia , Colite/virologia , Infecções por Citomegalovirus/imunologia , Humanos , Hospedeiro Imunocomprometido , Leucemia-Linfoma de Células T do Adulto/imunologia , Masculino , Resultado do TratamentoRESUMO
Telomerase is an enzyme that adds hexameric TTAGGG nucleotide repeats to the ends of vertebrate chromosomal DNAs (i.e. telomeres) to compensate for losses that occur with each round of DNA replication. Telomerase activity, demonstrable in most human tumors, enables them to maintain telomere stability. Peripheral blood mononuclear cells were sampled from 57 patients seropositive for human T-lymphotropic virus type I (HTLV-I), including 24 asymptomatic viral carriers, ten smoldering type, five chronic type, and 18 acute type adult T-cell leukemia (ATL). Telomerase activity was determined in samples using a modified telomeric repeat amplification protocol. We semiquantitatively determined telomerase activity by serial dilution of each sample. All of 23 samples from acute and chronic type ATL patients were positive, seven of ten (70%) smoldering type patients and seven of 24 (29.2%) asymptomatic viral carriers were positive. Disease progression from asymptomatic viral carrier to acute type correlated with telomerase activity. Two samples from chronic type ATL patients with relatively high telomerase activity progressed to the acute type within 1 month. Serum lactate dehydrogenase level also correlated with telomerase activity. These results indicate that reactivation of telomerase activity is a key event in development and progression of ATL, and telomerase could be a useful marker for predicting the course of disease. Accordingly, ATL could be a good candidate disease for trials of telomerase inhibitors, as novel anticancer drugs.
Assuntos
Leucemia de Células T/enzimologia , Telomerase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Ativação Enzimática , Humanos , Leucemia de Células T/etiologia , Pessoa de Meia-Idade , PrognósticoRESUMO
A rare hemoglobin variant, Hb JLome, was identified by chance in a male patient with diabetes mellitus (DM). The patient had no evidence of anemia or hemolysis. However, when his glycated hemoglobin (Hb A1c) was examined by high-performance liquid chromatography (HPLC) to assess the state of his DM, an abnormal Hb was unexpectedly detected on the chromatogram. The morphology of the red blood cells was normal. A fast-moving band as well as a normally moving Hb band, of roughly equal intensities, were observed by cellulose acetate membrane electrophoresis. The oxygen equilibrium curve was essentially normal (P50 = 3.59 kPa). In other words, the ability of the patient's Hb to carry oxygen was nearly the same as that of typical Hb A. The stability of his Hb in isopropanol was normal, and all the functions of his Hb that were tested were essentially normal. The identity of the abnormal Hb was finally determined, by sequencing the globin gene, to be Hb JLome, which is produced by a point mutation changing AAG to AAC at the 59th codon in exon 2 of the Hb beta chain. As previously reported, replacing the beta 59 lysine with asparagine does not affect the function of Hb or the red blood cells. There have been only five documented cases of Hb JLome in Japan. Interestingly, all these cases are from Kyushu Island. When an abnormal chromatogram for Hb A1c is unexpectedly obtained, it is worthwhile searching for an abnormal Hb, even if there are no signs that suggest its existence, such as anemia, hemolysis, erythrocytosis, or cyanosis.
Assuntos
Hemoglobinas Glicadas/análise , Hemoglobina J/análise , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida de Alta Pressão , Humanos , MasculinoRESUMO
The vav proto-oncogene product (Vav), which is specifically expressed in hematopoietic cells, contains multiple structural motifs commonly used by intracellular signaling molecules. Although a variety of stimuli including erythropoietin (Epo) have been shown to tyrosine phosphorylate Vav, little is known about the Vav signal transduction pathway. Here, we have investigated the role of Vav in the Epo signaling pathway by characterizing its interaction with other proteins, using the human Epo-responsive cell line, F-36P. Immunoprecipitation and immunoblot analyses have demonstrated that Vav was associated with the Epo receptor (EpoR) in an Epo-independent manner and was tyrosine-phosphorylated after Epo stimulation. Furthermore, two phosphotyrosine proteins (pp70 and pp100) co-immunoprecipitated with the regulatory subunit of phosphatidylinositol 3-kinase (PI3-kinase) (p85) were identified as EpoR and Vav, respectively. The interaction between Vav and p85 was shown to be mediated through the SH2 domains of p85 by an in vitro binding assay and confirmed by the presence of in vitro PI3-kinase activity associated with Vav. Treatment of the cells with antisense-vav and -p85 abrogated Epo-induced cell proliferation and PI3-kinase activity. Finally, we found that JAK2 was associated with Vav in vivo and that Vav could be tyrosine-phosphorylated by activated JAK2 in vitro. These results suggest the possible role of JAK2 for tyrosine phosphorylation of Vav and involvement of Vav and PI3-kinase in Epo-induced proliferative signals.
Assuntos
Proteínas de Ciclo Celular , Eritroblastos/metabolismo , Eritropoetina/farmacologia , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Eritroblastos/efeitos dos fármacos , Hematopoese , Humanos , Fosfatidilinositol 3-Quinases , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-vavRESUMO
We studied the generation of human natural killer (NK) cells from CD34+ cells that were isolated from peripheral blood stem cells (PBSC) mobilized by granulocyte colony-stimulating factor (g-CSF). The isolated CD34+ cells were cultured in the presence of a combination of interleukin-1 (IL-1alpha), IL-2, and stem cell factor for 5 weeks without marrow stroma. We found that the CD34+ cells isolated from G-CSF-mobilized PBSC (G-CSF/PBSC) could differentiate into a population of NK cells which were CD56+(bright)/CD3- and showed morphologic characteristics of large granular lymphocytes. Immunophenotypic analysis of the NK cells thus generated showed that a small proportion of them expressed CD2, CD8 and CD16 surface markers and approximately half of them coexpressed CD7. This NK population exhibited cytotoxic activity against a NK-sensitive cell line, K562. These observations suggest that CD34+ cells from G-CSF/PBSC contain precursors of NK cells that can differentiate into functional NK cells.
Assuntos
Antígenos CD34 , Fator Estimulador de Colônias de Granulócitos/farmacologia , Células-Tronco Hematopoéticas/imunologia , Células Matadoras Naturais/citologia , Adulto , Células da Medula Óssea , Divisão Celular , Células Cultivadas , Feminino , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-IdadeRESUMO
Granulocyte colony-stimulating factor (G-CSF) stimulates a rapid phosphorylation on tyrosines of several proteins of Mr. 130, 100, 90, 70, 44 kd in human myeloid leukemia cell line cells, Kasumi-1, which respond to G-CSF to proliferate in vitro. In HL60 cells, only a 100 kd protein was phosphorylated, and no detectable phosphorylated proteins were observed in neutrophils by the stimulation of G-CSF. Among these proteins, the 130 kd protein was immunoprecipitated by anti- JAK2 serum. While JAK2 is a non receptor tyrosine kinase and is reported to be involved in the signal transduction by various cytokines including growth hormone, erythropoietin, and granulocyte-macrophage colony-stimulating factor/interleukin-3, it is strongly suggested that a signaling pathway that relates to the cell proliferation triggered by G-CSF in immature hematopoietic cells also involves JAK2.
Assuntos
Fator Estimulador de Colônias de Granulócitos/farmacologia , Leucemia Mieloide Aguda/metabolismo , Neutrófilos/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas , Tirosina/análogos & derivados , Divisão Celular , Humanos , Técnicas de Imunoadsorção , Janus Quinase 2 , Cinética , Leucemia Mieloide Aguda/patologia , Fosforilação , Fosfotirosina , Células Tumorais Cultivadas , Tirosina/metabolismoRESUMO
A 51-year-old man had suffered from massive pleural effusion due to invasion of malignant cells. The analysis of bone marrow aspiration showed the proliferation of myeloperoxidase-positive blasts. The surface marker analysis of the blasts revealed the positivities for CD7 and CD19 as well as CD13, CD33 and CD34, while the karyotypes of 20 cells were normal. Therefore, CD7 positive AML was diagnosed. The patient was treated with araC and daunorubicin as a remission induction therapy. Peripheral blood stem cells were harvested by leukapheresis after first and second consolidation therapies. Then, 3 x 10(4) cells/kg of CFU-GM were infused. Complete remission has been maintained for 8 months after autologous blood stem cell transplantation. Pleural involvement as an initial manifestation is rare in AML. Extramedullary growth of AML cells may be related to their immaturity, indicated by the expression of the cell surface antigens.
Assuntos
Antígenos CD/análise , Antígenos de Diferenciação de Linfócitos T/análise , Biomarcadores Tumorais/análise , Leucemia Mieloide Aguda/complicações , Derrame Pleural/etiologia , Antígenos CD7 , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Transplante de Células-TroncoRESUMO
We presented five cases of Crow-Fukase syndrome. Plasma cell hyperplasia or dyscrasia in bone marrow were recognized in all cases and localized bone lesion was seen in three cases. Thyroid dysfunction was seen in three cases; hyperthyroidism in one case and hypothyroidism in two cases, which was considered to be one of the characteristics though it has seldom been described in this disease. Two of four cases treated with prednisolone had good responses but two cases treated with interferon had no effect.
Assuntos
Hipertireoidismo/fisiopatologia , Hipotireoidismo/fisiopatologia , Paraproteinemias/fisiopatologia , Adulto , Feminino , Humanos , Hipertireoidismo/diagnóstico , Hipotireoidismo/diagnóstico , Masculino , Pessoa de Meia-Idade , Paraproteinemias/diagnóstico , Transtornos da Pigmentação/diagnóstico , Transtornos da Pigmentação/fisiopatologia , Polineuropatias/diagnóstico , Polineuropatias/fisiopatologia , SíndromeRESUMO
Os autores apresentam os resultados do tratamento com osteossintese por compressao de 42 fraturas diafisarias dos ossos do antebraco de 29 adultos operados no periodo compreendido entre setembro de 1976 a setembro de 1979, no Hospital de Clinicas da Universidade do Estado do Rio de Janeiro. Houve consolidacao em 37 (88,9%) destas fraturas. Foram identificadas falhas tecnicas que explicaram a falta de consolidacao das 5 outras