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1.
J Clin Exp Hematop ; 60(2): 55-59, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32404572

RESUMO

We report a case of hepatosplenic T-cell lymphoma (HSTL) transplanted from an HLA-haploidentical daughter. A 51-year-old man was referred due to liver function test abnormalities and fever. He was confirmed to have γδ-type HSTL by bone marrow and liver biopsies. He was treated with five cycles of a CHOP regimen. Although metabolic complete response (CR), as defined by positron emission tomography, was achieved, his bone marrow still contained tumor cells on polymerase chain reaction (PCR). He underwent transplantation using unmanipulated peripheral blood stem cells from his HLA-haploidentical daughter. The preconditioning regimen consisted of fludarabine, melphalan, busulfan and antithymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and short-term methotrexate. Neutrophil engraftment was achieved on day 14. His bone marrow exhibited a completely female phenotype by fluorescence in situ hybridization, and no lymphoma cells were detected by PCR on day 30. Although he developed grade II acute GVHD on day 47, it was successfully treated by prednisolone. He has a limited type of skin chronic GVHD and still receives oral immunosuppressive therapy. He remains in CR four years after transplantation.

2.
Eur J Haematol ; 103(3): 164-171, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31132205

RESUMO

OBJECTIVE: We investigated whether minimal residual disease (MRD) status in adult patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) is useful for decision on clinical indications for allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: We prospectively monitored MRD after induction and consolidation therapy in adult patients with Ph-negative ALL. RESULTS: Among 103 adult ALL patients enrolled, 59 were Ph-negative, and MRD status was assessed in 51 patients. The probability of 3-year overall survival (OS) and disease-free survival (DFS) was 69% (95%CI 54-80) and 50% (95%CI 36-63), respectively. Patients who were MRD-negative after induction therapy (n = 15) had a significantly better 3-year DFS compared with those who were MRD-positive (n = 30; 73% vs 41%, P = 0.018). Patients who were MRD-positive after induction but became MRD-negative after consolidation chemotherapy C in the first course (n = 11) showed a significantly worse 3-year DFS compared with patients who were MRD-negative after induction chemotherapy A in the first course (45% vs 73%, P = 0.025). CONCLUSIONS: These results indicate that DFS of about 70% can be expected in MRD-negative patients after induction therapy, and the patients did not benefit from HSCT in 1CR. This study was registered with the UMIN Clinical Trials Registry (UMIN-CTR), number UMIN000001519.


Assuntos
Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Adolescente , Adulto , Idoso , Quimioterapia de Consolidação , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/genética , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Estudos Prospectivos , Gestão da Segurança , Translocação Genética , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
4.
Biol Blood Marrow Transplant ; 21(8): 1495-505, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25921715

RESUMO

This prospective, multicenter phase I/II study of unmanipulated HLA-haploidentical reduced-intensity stem cell transplantation using a low dose of anti-T lymphocyte globulin (ATG) and steroid was conducted in 5 institutions in Japan. Thirty-four patients with hematologic malignancies who were in an advanced stage or at a high risk of relapse at the time of transplantation were enrolled. Among them, 7 patients underwent transplantation as a second transplantation because of relapse after the previous allogeneic stem cell transplantation. The conditioning regimen consisted of fludarabine, busulfan, and ATG (Fresenius, 8 mg/kg), and graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methylprednisolone (1 mg/kg). All patients except 1 (97.1%) achieved donor-type engraftment. Rapid hematopoietic engraftment was achieved, with neutrophils > .5 × 10(9)/L on day 11 and platelets > 20 × 10(9)/L on day 17.5. Treatment was started for ≥grade I GVHD, and the cumulative incidences of acute grade I and grade II to IV GVHD were 27.5% and 30.7%, respectively. The incidence of chronic GVHD (extensive type) was 20%. Fourteen patients (41.2%) had a relapse. The cumulative incidence of transplantation-related mortality at 1 year after transplantation was 26.5%. The survival rate at day 100 was 88.2%. The survival rates at 1 year for patients with complete remission (CR)/chronic phase (n = 8) and non-CR (n = 26) status before transplantation were 62.5% and 42.3%, respectively. In the multivariate analysis, non-CR status before transplantation was the only factor significant prognostic factor of increased relapse (P = .0424), which tended to be associated with a lower survival rate (P = .0524). This transplantation protocol is safe and feasible, if a suitable donor is not available in a timely manner. As the main cause of death was relapse and not GVHD, more intensified conditioning or attenuation of GVHD prophylaxis and/or donor lymphocyte infusion may be desirable for patients with non-CR status.


Assuntos
Soro Antilinfocitário/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bussulfano/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Esteroides/uso terapêutico , Condicionamento Pré-Transplante/métodos , Vidarabina/análogos & derivados , Adulto , Soro Antilinfocitário/administração & dosagem , Soro Antilinfocitário/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bussulfano/efeitos adversos , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Esteroides/efeitos adversos , Vidarabina/efeitos adversos , Vidarabina/uso terapêutico
5.
Exp Hematol ; 41(10): 894-902, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23727584

RESUMO

Polymerase chain reaction (PCR)-negative molecular complete remission (mCR) can be induced by stem cell transplantation in some patients with multiple myeloma (MM) and is associated with long-term progression-free survival (PFS). The detection of molecular minimal residual disease (MRD), however, requires fresh or frozen materials for designing clone-specific primers, which are not always readily available. In this study, we used DNA extracted from archival bone marrow (BM) slides for PCR to detect MRD in 50 patients with MM who received various induction therapies and autologous peripheral blood stem cell transplantation (ASCT). Clonotype-specific immunoglobulin (Ig) H PCR primers were prepared for 32 of 50 cases (64%) using BM slides, and for 9 of 14 cases (64%) using fresh BM cells. DNA in peripheral blood stem cell autografts of the 22 patients who achieved at least a partial response after ASCT was subjected to PCR to amplify clonotype-specific rearranged IgH gene sequences. The median PFS of the eight patients with MRD-positive autografts was 18 months, whereas that of 14 patients with MRD-negative autografts was not reached at a median follow-up of 27 months (p = 0.012). Post-ASCT PFS of the four patients who achieved mCR was 100% at a median follow-up of 47 months. These results indicate that archival BM slides can serve as a source of DNA for preparing clonotype-specific primers for MRD monitoring in patients with MM whose cryopreserved myeloma cells are not available for DNA preparation. Our results also suggest that patients with MM who received MRD-negative autografts and achieved mCR have a long PFS.


Assuntos
Medula Óssea/patologia , Primers do DNA/genética , Mieloma Múltiplo/diagnóstico , Neoplasia Residual/diagnóstico , Reação em Cadeia da Polimerase , Adulto , Idoso , Feminino , Genes de Cadeia Pesada de Imunoglobulina/genética , Técnicas de Preparação Histocitológica , Humanos , Imunoglobulinas/genética , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Neoplasia Residual/genética , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos
6.
Med Mol Morphol ; 46(3): 172-6, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23512149

RESUMO

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma (BCLu-DLBCL/CHL), also known as gray-zone lymphoma, has overlapping clinical and biological characteristics of both diffuse large B-cell lymphoma and classical Hodgkin lymphoma (CHL). These lymphomas are typically associated with mediastinal disease, and extranodal involvement is rare. In the present report, we describe a case of a 78-year-old woman with BCLu-DLBCL/CHL found to have extranodal lesions and no evidence of mediastinal disease. Although biopsy specimens were histologically similar to nodular sclerosis CHL, the tumor cells were positive for CD30 and mature B-cell markers, such as CD20, CD79a, PAX5, BOB.1, and OCT-2, but negative for CD15. Furthermore, the patient had extranodal lesions and an increased level of soluble IL-2 receptor. These findings are unusual in CHL. Therefore, we diagnosed the patient with BCLu-DLBCL/CHL. She received adriamycin, bleomycin, vincristine, and dacarbazine therapy and exhibited partial response. Some cases without mediastinal disease, such as our case, have been reported; however, these cases are rare and further studies are required.


Assuntos
Neoplasias Abdominais/diagnóstico por imagem , Doença de Hodgkin/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Doenças do Mediastino/diagnóstico por imagem , Neoplasias Abdominais/patologia , Idoso , Diagnóstico Diferencial , Feminino , Doença de Hodgkin/patologia , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfoma Difuso de Grandes Células B/patologia , Cintilografia
7.
Int J Hematol ; 96(3): 357-63, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22893108

RESUMO

Imatinib was the first BCR-ABL tyrosine kinase inhibitor to become clinically available. In this study, we retrospectively evaluated the long-term efficacy of low-dose imatinib (final maintenance dose <300 mg per day) due to intolerance, in comparison to optimal-dose imatinib (≥300 mg per day) in patients with Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase. The Kaplan-Meier estimates of the median time to complete cytogenetic response, major molecular response, and complete molecular response were longer for 31 patients receiving low-dose imatinib (360, 1360, and 1420 days, respectively) than 74 patients receiving optimal-dose imatinib (170, 420, and 720 days, respectively). However, the differences in response shrank over time and progression-free survival were comparable between the two groups. These findings suggest that long-term treatment with low-dose imatinib is an acceptable alternative for patients with intolerance to the optimal dose.


Assuntos
Antineoplásicos/administração & dosagem , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Piperazinas/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzamidas , Criança , Feminino , Humanos , Mesilato de Imatinib , Leucemia Mieloide de Fase Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
8.
Ann Hematol ; 90(10): 1209-17, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21695388

RESUMO

This study was conducted as a prospective, multicenter trial to evaluate the efficacy and safety of micafungin as an empirical therapy for suspected invasive fungal infections (IFIs), including febrile neutropenia (FN), and to evaluate the usefulness of ß-D: -glucan (BG) and Aspergillus galactomannan (GM) antigen in patients with hematologic diseases. A total of 121 patients were enrolled and assessed for safety, and 119 were examined for clinical efficacy. The main underlying diseases were acute myeloid leukemia (38.0%), acute lymphoblastic leukemia (18.2%), and malignant lymphoma (18.2%). The median initial daily dose and duration of micafungin treatment were 150 mg/day and 13 days, respectively. The overall response rate for suspected IFIs (n = 119), based on four composite endpoints, including baseline IFI, breakthrough IFIs (proven and probable), survival, and premature discontinuation, was 79.0%. In addition, the response rate for FN (n = 81), based on these four endpoints as well as defervescence during neutropenia, was 39.5%. Breakthrough IFIs (proven, probable, and possible) occurred in five patients during micafungin treatment. All of these patients were positive for either BG or GM before the breakthrough IFIs. The incidence of adverse events (AEs) associated with micafungin was 10.7% and most were mild. The majority of AEs were liver dysfunction. These results indicate the effectiveness and safety of micafungin as an empirical therapy for suspected IFIs, including FN, and the usefulness of monitoring both BG and GM to detect breakthrough IFIs.


Assuntos
Antifúngicos/efeitos adversos , Equinocandinas/efeitos adversos , Neoplasias Hematológicas/complicações , Lipopeptídeos/efeitos adversos , Micoses/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Antígenos de Bactérias/sangue , Aspergilose/complicações , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergilose/prevenção & controle , Candidíase Invasiva/complicações , Candidíase Invasiva/diagnóstico , Candidíase Invasiva/tratamento farmacológico , Candidíase Invasiva/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Diagnóstico Precoce , Equinocandinas/uso terapêutico , Feminino , Humanos , Leucemia Mieloide Aguda/complicações , Lipopeptídeos/uso terapêutico , Linfoma/complicações , Masculino , Mananas/sangue , Micafungina , Pessoa de Meia-Idade , Micoses/complicações , Micoses/diagnóstico , Micoses/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Adulto Jovem , beta-Glucanas/sangue
9.
Hematol Oncol ; 29(1): 5-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20552573

RESUMO

Sixty-six B-cell lymphoma patients were treated with a CHOP-based chemotherapy containing rituximab (R-CHOP-like regimen). Immune reconstitution was assessed by measuring lymphocyte subsets and immunoglobulins. Fifty-five patients (83.3%) underwent six cycles of the R-CHOP-like regimen. CD19(+) and CD20(+) cells were completely eliminated from the peripheral blood after one cycle of the R-CHOP-like regimen; they were detected again 6 months after the therapy. One year after the therapy, B-cell numbers recovered to their level at diagnosis and almost doubled 2 years after the therapy. The lowest numbers of CD3(+) , CD8(+) and CD56(+) cells were seen after three cycles of the regimen, but continued to increase until 1 year after the therapy, remaining stable thereafter. CD4(+) T-cells were at their lowest after six cycles of the regimen and recovered slowly for 2 years after the therapy; however, their numbers were still lower than that at diagnosis. Immunoglobulins decreased over six cycles of the R-CHOP-like regimen and then recovered gradually for 2 years after the therapy. The percentage of IgG, IgA and IgM 2 years after the therapy compared with those at diagnosis was 93.9%, 90.1%, 76.3%, respectively. Twelve infectious complications occurred which consisted of three febrile neutropenia, three Herpes Zoster, two tympanitis, two Pneumocystis jiroveci pneumonia and two hepatitis B virus reactivation. B-cells required 1 year and CD4(+) T-cells and immunoglobulins needed 2 years to recover after the therapy.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/imunologia , Adulto , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Humanos , Imunoglobulinas/sangue , Subpopulações de Linfócitos/imunologia , Linfoma de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Recidiva , Rituximab , Vincristina/administração & dosagem , Vincristina/uso terapêutico
10.
Endocr J ; 58(1): 7-12, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21068513

RESUMO

Thyroid MALT lymphoma is an extremely rare malignancy believed to arise against a background of Hashimoto's thyroiditis. Rituximab is a monoclonal antibody directed against B cell specific antigen CD20. Recently, there have been reports that rituximab is effective for autoimmune thyroid diseases such as Graves' disease as well as for treatment of B cell malignant lymphoma. We present the changes in thyroid autoantibodies in Hashimoto's thyroiditis after rituximab administration for 3 cases of thyroid MALT lymphoma. Case 1 had been taking levothyroxine and was diagnosed with thyroid MALT lymphoma. She was treated with rituximab monotherapy, and her thyroid enlargement improved. Anti-thyroid peroxidase antibody (TPOAb) turned negative after rituximab monotherapy, and TSH levels decreased with the same levothyroxine dosage. Case 2 was diagnosed with recurrent thyroid MALT lymphoma after chemotherapy (CHOP). He suffered from leg sensory disturbance because of vincristine sulfate. The patient was treated with rituximab. TPOAb decreased, but did not turn negative. TSH levels were within normal range during the disease course, but TSH levels were low in comparison with before rituximab therapy. Case 3 was diagnosed with thyroid MALT lymphoma after radiation therapy on the neck for laryngeal cancer. Thyroid enlargement improved after rituximab monotherapy, and thyroid autoantibody levels decreased. TSH increased transiently after radiation therapy, but TSH decreased gradually without levothyroxine after rituximab monotherapy. We report 3 cases in which thyroid autoantibody levels in Hashimoto's thyroiditis decreased after rituximab monotherapy for thyroid MALT lymphoma, but it is controversial whether thyroid dysfunction due to Hashimoto's thyroiditis is restored.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Doença de Hashimoto/imunologia , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Glândula Tireoide/imunologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Doença de Hashimoto/radioterapia , Humanos , Iodeto Peroxidase/imunologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Prednisona/uso terapêutico , Rituximab , Glândula Tireoide/patologia , Tiroxina/uso terapêutico , Vincristina/uso terapêutico
11.
J Clin Exp Hematop ; 50(2): 159-62, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21123974

RESUMO

We report two cases of Pneumocystis jiroveci pneumonia (PCP) with CD20(+) B-cell lymphoma. They were treated by several courses of CHOP-based chemotherapy containing rituximab. We confirmed by flow cytometric analysis that both of them completely lost CD19(+) and CD20(+) B-cells from their peripheral blood after the first course of chemotherapy. They were successfully treated with Trimethoprim-sulfamethoxazole (TMP-SMX) after the diagnosis of PCP by polymerase chain reaction (PCR). We overviewed CD20(+) B-cell lymphoma patients treated with CHOP-based regimens from 1997 until 2005 in our hospital. We treated 114 patients with and 121 patients without rituximab. Five patients in the group with rituximab developed interstitial pneumonia (IP). Two of them were confirmed to have PCP and the other three were suspected cases ; however, no patients with IP were seen in the group without rituximab. We strongly suggest the necessity of PCP prophylaxis with oral TMP-SMX when treating B-cell lymphoma patients with chemotherapy containing rituximab.


Assuntos
Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linfoma não Hodgkin/tratamento farmacológico , Pneumocystis carinii , Pneumonia por Pneumocystis/induzido quimicamente , Idoso , Anti-Infecciosos/uso terapêutico , Anticorpos Monoclonais Murinos/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/tratamento farmacológico , Reação em Cadeia da Polimerase , Prednisona/efeitos adversos , Rituximab , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Vincristina/efeitos adversos
12.
J Infect Dis ; 201(12): 1923-32, 2010 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-20443735

RESUMO

Epstein-Barr virus (EBV) is the pathogen that most commonly triggers infection-associated hemophagocytic lymphohistiocytosis (HLH) and ectopically infects CD8(+) T cells in EBV-associated HLH (EBV-HLH). We recently described an EBV-HLH patient who had a clonally expanded population of EBV-infected CD8(+) T cells with CD5 down-regulation. To determine whether this finding could serve as a useful marker for EBV-HLH, we investigated 5 additional patients. We found a significant increase in the subpopulation of CD8(+) T cells with CD5 down-regulation and bright human leukocyte antigen (HLA)-DR expression in all patients with EBV-HLH but not in patients with infectious mononucleosis or in control subjects. Such T cells were frequently found to be larger cells that stained positive for a specific T cell receptor VB. We also demonstrated that those cells were the major cellular target of EBV, and their numbers progressively declined in parallel with the serum ferritin levels. All together, our findings reveal the immunophenotypic characteristics of EBV-infected CD8(+) T cells and may provide a valuable tool for the diagnosis of EBV-HLH.


Assuntos
Antígenos CD5/biossíntese , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/patogenicidade , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/virologia , Criança , Pré-Escolar , Regulação para Baixo , Infecções por Vírus Epstein-Barr/complicações , Feminino , Antígenos HLA-DR/biossíntese , Herpesvirus Humano 4/imunologia , Humanos , Lactente , Masculino , Receptores de Antígenos de Linfócitos T/biossíntese , Adulto Jovem
13.
Int J Hematol ; 91(4): 661-9, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20390388

RESUMO

Sixty-six adult patients with hematologic malignancies underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) without T cell depletion. The patients were preconditioned with a reduced intensity regimen, and tacrolimus was used for graft-versus-host disease (GVHD) prophylaxis. Successful engraftment occurred in 60 patients (90.1%) and graft rejection in only 4 patients (6.1%). Among the 60 engrafted patients, only 5 developed severe (grade III or IV) acute GVHD. Twenty patients, including 19 relapse-free patients were alive at a median follow-up of 48 months (range 6-77 months). The overall survival (OS) at 6 years was 29.3%. The OS of 45 patients < 60 years of age was 43.6%, which was superior to that of 21 patients who were 60 years of age and older (9.5%) (P < 0.01). The OS of 11 patients from human leukocyte antigen (HLA) 1 locus-mismatched donors (63.6%) was higher than that of 28 patients from HLA 3 loci-mismatched donors (12.5%) (P < 0.01). Organ injury and infection were the main causes of mortality. Notably, immunosuppressive therapy could be successfully stopped in 9 patients transplanted from HLA 2 or 3 loci-mismatched donors with a median duration of 45 months (range 5-71 months). These data suggest that haplo-HSCT is a promising treatment for patients who need urgent allogeneic transplantation but lack HLA-identical family donors.


Assuntos
Haplótipos , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas/mortalidade , Transplante de Células-Tronco Hematopoéticas/métodos , Adolescente , Adulto , Idoso , Infecções por Citomegalovirus/mortalidade , Feminino , Seguimentos , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/mortalidade , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Imunossupressores/uso terapêutico , Japão/epidemiologia , Contagem de Linfócitos , Subpopulações de Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Recidiva , Análise de Sobrevida , Tacrolimo/uso terapêutico , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Adulto Jovem
14.
Eur J Haematol ; 79(1): 72-5, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17532761

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a severe and often fatal condition characterized by uncontrolled activation of T cells and macrophages. In Epstein-Barr virus (EBV)-associated HLH (EBV-HLH), the pathogenic roles of ectopic EBV infection in the T-cell population and of clonal proliferation of EBV-infected T cells has been described. However, the immunophenotype of EBV-infected T cells has not been fully characterized. Here we describe a case of EBV-HLH presenting with a massive clonal proliferation of CD8(+) T cells with TCR VB14. Analysis of in situ hybridization for EBV-encoded small RNA1 showed that only CD8(+) T cells harbored EBV in this patient. The EBV-infected TCR VB14(+) CD8(+) T cells exhibited unique immunophenotypic features including lacked CD5 expression and a markedly bright expression of HLA-DR. After initiation of treatment with prednisolone, etoposide, and cyclosporin A, the percentage of infected cells declined progressively in parallel with other serum markers such as ferritin. These findings suggest that lacking expression of CD5 on CD8(+) T cells with specific TCR VB may serve as a useful marker of dysregulated T-cell activation and proliferation in EBV-HLH.


Assuntos
Linfócitos T CD8-Positivos/virologia , Herpesvirus Humano 4/isolamento & purificação , Imunofenotipagem , Linfo-Histiocitose Hemofagocítica/imunologia , Adulto , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/virologia
15.
Intern Med ; 45(22): 1291-5, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17170503

RESUMO

We report a case with immunoglobulin A (IgA) nephropathy, showing IgA deposition which disappeared after peripheral blood stem cell transplantation (PBSCT) for acute lymphocytic leukemia (ALL). In 1996, a 28-year-old man was diagnosed with IgA nephropathy by renal biopsy. Steroid therapy improved proteinuria from 3 g/day to 1 g/day. In 2003, he received PBSCT following the initial therapy for ALL. After complete remission, urinary protein and hematuria remained at between (-) and (+/-). In 2004, the second renal biopsy specimen revealed no deposit of IgA or C3. These findings suggested that immune reconstruction with PBSCT following immunosuppression therapy was of benefit to IgA nephropathy.


Assuntos
Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/patologia , Imunossupressão , Transplante de Células-Tronco de Sangue Periférico , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Adulto , Humanos , Rim/patologia , Masculino , Indução de Remissão
16.
Int J Cancer ; 101(1): 52-60, 2002 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-12209588

RESUMO

It has been shown that after allogeneic peripheral blood stem cell transplantation (PBSCT), donor T cells can induce potent graft-versus-tumor (GVT) effects in hematologic malignancies and possibly solid tumors such as renal cell carcinoma. Two patients (27 and 30 years old) with metastatic melanoma received allogeneic PBSCT from an HLA-identical sibling donor after reduced conditioning with fludarabine, carmustine and melphalan. One patient showed a delayed mixed response with complete regression of lymph node metastases but persistent liver metastasis at day +60 and +120, consistent with a GVT response. In order to generate donor-derived tumor-reactive cytotoxic T lymphocytes (CTLs), peripheral blood mononuclear cells were stimulated with donor dendritic cells (DCs) loaded with host tumor lysate. Using these culture conditions, a marked increase in CD8(+) CTLs was observed in both donors exhibiting a strong MHC class I-restricted cytotoxic activity against the host tumor without cross-reactivity against nonmalignant host cells. CDR3 spectratyping was used to analyze the complexity of T-cell subpopulations in both CTL lines. Results demonstrate that oligoclonal T cells are expanded in vitro, exhibiting a marked overexpression of TCRVbeta3 (donor 1) and TCRVbeta4/Vbeta11 (donor 2) subfamilies. Functional (ELISPOT assay) and phenotypic (CDR3 spectratyping, sequencing Vbeta transcripts) analysis of patients' T cells at different time points after transplantation demonstrated an expansion of alloreactive T cells with a limited TCR Vbeta pattern. The Vbeta3 cDNA clone, being predominant in the CTL line from donor 1, could not be identified in patient 1 peripheral blood lymphocytes after transplant. Altogether, our results provide the first evidence that GVT effects against melanoma can induce tumor regression and that oligoclonal donor-derived CTLs specific against host tumor cells can be generated in vitro that may be used for adoptive T-cell transfer after allogeneic transplantation.


Assuntos
Efeito Enxerto vs Tumor/imunologia , Transplante de Células-Tronco Hematopoéticas , Melanoma/imunologia , Transplante Homólogo/imunologia , Adulto , Células Dendríticas/imunologia , Feminino , Humanos , Interferon gama/metabolismo , Ativação Linfocitária , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T Citotóxicos/citologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Tomografia Computadorizada de Emissão , Células Tumorais Cultivadas
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