Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27
Filtrar
1.
J Clin Exp Hematop ; 64(3): 191-202, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39085129

RESUMO

Immune checkpoint inhibitors (ICI) are promising therapeutic agents for relapsed or refractory classical Hodgkin's lymphoma (RRcHL). This retrospective study evaluated patients with RRcHL registered in the clinical research program Tohoku-Hematology-Forum-26, between 2016 and 2020, and treated with ICI in 14 centers in Northeast Japan. We analyzed the usage, efficacy, and safety of ICI therapy (ICIT). Among a total of 27 patients with RRcHL, 21 and nine were treated with nivolumab and/or pembrolizumab, respectively. The best response was complete response (CR), partial response (PR), stable disease (SD), and progressive disease in 11 (40.8%), seven (25.9%), eight (29.6%), and one (3.7%) patient, respectively. In all patients undergoing ICIT, the 2-year progression-free survival and 2-year overall survival (OS) were 48.6% and 87.4%, respectively. The 2-year OS for patients with CR, PR, and SD were 100%, 68.6%, and 87.5%, respectively. A total of 36 events of immune-related adverse events (irAEs) or immune-related like adverse events (irlAEs) were observed in 19 of the 27 patients (70.4%). Two thirds of these irAEs or irlAEs were grade 1-2 and controllable. During the observation period, ICIT was discontinued in 22 of 27 (81.4%) patients due to CR, inadequate response, irAE and patient circumstances in five (22.7%), seven (31.8%), eight (36.4%) and two patients (9.1%), respectively. Therapy-related mortality-associated irAE were observed in only one patient during ICIT. These results suggest that ICIT for RRcHL is effective and safe in real-world settings. The optimal timing of induction and duration of ICIT remains to be established.


Assuntos
Doença de Hodgkin , Inibidores de Checkpoint Imunológico , Humanos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Nivolumabe/uso terapêutico , Nivolumabe/efeitos adversos , Nivolumabe/administração & dosagem , Adulto Jovem , Recidiva , Adolescente
2.
Hematology ; 29(1): 2340149, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38626148

RESUMO

OBJECTIVES: Patients with myeloproliferative neoplasms (MPNs) are at higher risk of developing secondary malignancies. In this study, we focused on patients with MPNs that complicated lymphoid neoplasms. To analyze the real-world status of lymphoid neoplasm treatment in patients with pre-existing MPNs in Japan, we conducted a multicenter retrospective study. METHODS: Questionnaires were sent to collect the data on patients who were first diagnosed with either polycythemia vera, essential thrombocythemia or myelofibrosis and who later were complicated with lymphoid neoplasms defined as malignant lymphoma, multiple myeloma, or chronic lymphocytic leukemia/small cell lymphoma. RESULTS: Twenty-four patients with MPNs complicated by lymphoid neoplasms were enrolled (polycythemia vera, n = 8; essential thrombocythemia, n = 14; and primary myelofibrosis, n = 2). Among these, diffuse large B-cell lymphoma (DLBCL) was the most frequently observed (n = 13, 54.1%). Twelve (92.3%) of the patients with DLBCL received conventional chemotherapy. Among these 12 patients, regarding cytoreductive therapy for MPNs, 8 patients stopped treatment, one continued treatment, and two received a reduced dose. Consequently, most patients were able to receive conventional chemotherapy for DLBCL with a slightly higher dose of granulocyte colony-stimulating factor support than usual without worse outcomes. All 3 patients with multiple myeloma received a standard dose of chemotherapy. CONCLUSION: Our data indicate that if aggressive lymphoid neoplasms develop during the course of treatment in patients with MPNs, it is acceptable to prioritize chemotherapy for lymphoma.


Assuntos
Leucemia Linfocítica Crônica de Células B , Linfoma , Mieloma Múltiplo , Transtornos Mieloproliferativos , Policitemia Vera , Trombocitemia Essencial , Humanos , Trombocitemia Essencial/tratamento farmacológico , Trombocitemia Essencial/epidemiologia , Estudos Retrospectivos , Japão/epidemiologia , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/epidemiologia , Transtornos Mieloproliferativos/diagnóstico , Linfoma/epidemiologia , Linfoma/etiologia , Linfoma/terapia
5.
Int J Hematol ; 118(6): 751-757, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37488284

RESUMO

A 37-year-old man with refractory classical Hodgkin lymphoma (cHL) underwent PD-1 blockade therapy with nivolumab, which resulted in a partial response. However, treatment was discontinued due to immune-related adverse events (irAEs), including myasthenia gravis and myositis. Retreatment with nivolumab resulted in a complete metabolic response and hepatic irAE. Subsequently, nivolumab was administered at extended dosing intervals. Intermittent infusion of ten doses of nivolumab for a total dose of 2400 mg/body helped control the relapsed/refractory cHL over three years. During nivolumab treatment, disease progression and emergence of irAEs were associated with the proportion of CD8 + T cells expressing nivolumab-free PD-1 relative to the total number of CD8 + T cells. The findings in this nivolumab-sensitive patient highlight the clinical utility of monitoring immune cells expressing nivolumab-free PD-1 in patients with cHL who have been treated with nivolumab and have experienced irAEs.


Assuntos
Doença de Hodgkin , Nivolumabe , Masculino , Humanos , Adulto , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Receptor de Morte Celular Programada 1 , Recidiva Local de Neoplasia/tratamento farmacológico , Linfócitos T CD8-Positivos/patologia , Linfócitos T/patologia
6.
Int J Hematol ; 117(5): 738-747, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36757523

RESUMO

Early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL) is generally considered to be a high-risk subtype. We retrospectively analyzed the clinical outcomes of adult patients diagnosed with ETP-ALL or other T-cell ALL (non-ETP T-ALL). The subjects were 82 patients (ETP-ALL: n = 18, non-ETP T-ALL: n = 64) for whom relevant immunophenotype data needed for classification were available. ETP-ALL patients were older (median age, 50.5 vs. 33.5 years, P = 0.042) and had less mediastinal involvement (27.8 vs. 73.4%, P < 0.001). The rate of complete remission (CR) with the first induction therapy was significantly lower in the ETP group (33.3 vs. 64.0%, P = 0.03), but the CR rate within 2 cycles of chemotherapy did not differ significantly (61.1 vs. 76.6%, P = 0.232). The 3-year overall survival (OS) rate was also similar in both groups (43.2 vs. 45.8%, P = 0.992). The ETP phenotype had no impact on survival in the transplant group or the non-transplant group. A multivariate analysis identified the male sex as a poor prognostic factor (HR: 4.43, P < 0.01), but not the immunophenotype of ETP. The prognosis for adult patients with ETP-ALL was comparable to that of non-ETP T-ALL patients. However, further studies aimed at improving the remission rate for ETP-ALL are needed.


Assuntos
Linfoma , Leucemia-Linfoma Linfoblástico de Células Precursoras , Células Precursoras de Linfócitos T , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Masculino , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Estudos Retrospectivos , Prognóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
7.
Int J Hematol ; 115(3): 382-390, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34981434

RESUMO

OBJECTIVE: This study was conducted to characterize lymphoma occurring during pregnancy and to investigate the outcomes of the patients and the fetuses. METHODS: Clinical data were gathered retrospectively from 29 patients at 13 participating institutions, and data from 28 eligible patients were analyzed. RESULTS: Six (21%) patients had Hodgkin lymphoma (HL) and 22 (79%) patients had non-Hodgkin lymphoma (NHL). All patients with HL presented with lymphadenopathy, but 15 (68%) of the 22 patients with NHL presented with extranodal sites only. At the median follow-up period of 1325 (range 6-4461) days, the 5-year overall survival rate was 63% for patients with NHL and 100% for patients with HL. Three of the 13 patients who received chemotherapy during pregnancy (23%) developed Pneumocystis jiroveci pneumonia (PCP). There was 1 intrauterine fetal death, 1 spontaneous abortion in the first trimester, and 15 (54%) preterm births. CONCLUSION: This study showed a higher proportion of NHL than HL during pregnancy in Japan, which was inconsistent with the proportions observed in Western countries. The high incidence of maternal PCP and preterm birth suggested the need for improvements in our management of lymphoma during pregnancy.


Assuntos
Doença de Hodgkin/epidemiologia , Linfoma não Hodgkin/epidemiologia , Complicações Neoplásicas na Gravidez/epidemiologia , Adulto , Feminino , Seguimentos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Humanos , Incidência , Japão/epidemiologia , Linfadenopatia/epidemiologia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/mortalidade , Pneumonia por Pneumocystis/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Complicações Neoplásicas na Gravidez/mortalidade , Resultado da Gravidez , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
8.
Rinsho Ketsueki ; 62(10): 1499-1504, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34732623

RESUMO

A 67-year-old woman diagnosed with adult T-cell leukemia/lymphoma received an induction chemotherapy and showed a partial response. She then underwent allogeneic peripheral blood stem cell transplantation from an HLA-identical sibling donor. Although cyclosporine (CS) was stopped at 120 days after transplantation, chronic graft-versus-host disease (cGVHD) of the skin developed. She was treated with a topical steroid, without exacerbation of the GVHD. She was admitted to our hospital due to the sudden development of pancytopenia at 212 days after the transplantation. She had an EB virus-associated post-transplant lymphoproliferative disorder (PTLD) in the hilum of the lung. The cGVHD of the skin resolved after the administration of prednisolone and CS. However, pancytopenia and PTLD persisted. Treatment with four cycles of rituximab (4×375 mg/m2/week) led to the complete resolution of PTLD, but transfusion-dependent cytopenia did not improve. Secondary engraftment failure was diagnosed, and granulocyte colony-stimulating factor (G-CSF) and eltrombopag (100 mg/day) were administered, leading to gradual improvement of pancytopenia. It was observed that persistent pancytopenia was caused by secondary engraftment failure due to cGVHD in this case. This case suggested that the treatment with G-CSF and eltrombopag is effective for cGVHD-associated secondary engraftment failure.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma de Células T do Adulto , Linfoma , Transplante de Células-Tronco de Sangue Periférico , Idoso , Benzoatos , Transplante de Medula Óssea , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Hidrazinas , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Pirazóis , Transplante Homólogo
9.
Cancer Sci ; 112(12): 5034-5045, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34644446

RESUMO

New drugs for multiple myeloma (MM) have dramatically improved patients' overall survival (OS). Autologous stem cell transplantation (ASCT) remains the mainstay for transplant-eligible MM patients. To investigate whether the post-ASCT prognosis of MM patients has been improved by new drugs, we undertook a retrospective observational analysis using the Transplant Registry Unified Management Program database in Japan. We analyzed 7323 patients (4135 men and 3188 women; median age, 59 years; range 16-77 years) who underwent upfront ASCT between January 2007 and December 2018. We categorized them by when they underwent ASCT according to the drugs' introduction in Japan: group 1 (2007-2010), group 2 (2011-2016), and group 3 (2017-2018). We compared the groups' post-ASCT OS. The 2-year OS rates (95% confidence interval [CI]) of groups 1, 2, and 3 were 85.8% (84.1%-87.4%), 89.1% (88.0%-90.1%), and 92.3% (90.0%-94.2%) (P < .0001) and the 5-year OS (95% CI) rates were 64.9% (62.4%-67.3%), 71.6% (69.7%-73.3%), and not applicable, respectively (P < .0001). A multivariate analysis showed that the post-ASCT OS was superior with these factors: age less than 65 years, performance status 0/1, low International Staging System (ISS) stage, receiving SCT for 180 days or less post-diagnosis, better treatment response pre-ASCT, later year of ASCT, and receiving SCT twice. A subgroup analysis showed poor prognoses for the patients with unfavorable karyotype and poor treatment response post-ASCT. The post-ASCT OS has thus improved over time (group 1 < 2 < 3) with the introduction of new drugs for MM. As the prognosis of high-risk-karyotype patients with ISS stage III remains poor, their treatment requires improvement.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Adolescente , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Transplante Autólogo , Adulto Jovem
10.
Int J Hematol ; 114(4): 472-482, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34170481

RESUMO

OBJECTIVES: Bloodstream infection (BSI) is a frequent complication observed in patients with febrile neutropenia (FN). BSI risk factors and incidence vary depending on chemotherapy types and prophylactic antimicrobial agents. We clarified these issues by post-hoc analysis of a prospective clinical trial cohort for severe FN in hematological malignancy. METHODS: We performed an intention-to-treat analysis of 413 high-risk patients and 1272 blood culture sets. RESULTS: Overall, 356 patients (86.2%) developed FN, and 20.8% had BSI complications. Prophylactic antimicrobials did not prevent complications of FN and BSI, but the incidence of BSIs of Gram-negative (GN) bacteria was lower than in the non-prophylaxis group (23.8% vs. 56.7%). Multinational Association of Supportive Care in Cancer (MASCC) scores < 20 were significantly correlated with the incidence of BSI, whereas MASCC scores > 21 were not (41.7% vs. 17.2%). The only significant risk factors were hypotension and dehydration. axillary temperatures were higher in GN-caused BSIs than in Gram-positive-caused BSIs and in patients with negative blood culture results (38.7 °C vs. 38.2 °C vs. 38.0 °C). The higher the fever, the higher the incidence of BSI and GN bacteremia. CONCLUSIONS: MASCC score and axillary temperature are strong predictors of BSI. Non-administration of prophylactic antimicrobials and GN-caused BSI are correlated. THE CLINICAL TRIAL REGISTRATION NUMBER: UMIN00010411.


Assuntos
Neutropenia Febril/epidemiologia , Neutropenia Febril/etiologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/epidemiologia , Sepse/epidemiologia , Sepse/etiologia , Adulto , Idoso , Antibioticoprofilaxia , Neutropenia Febril/diagnóstico , Neutropenia Febril/prevenção & controle , Feminino , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Medição de Risco , Fatores de Risco , Sepse/diagnóstico , Sepse/prevenção & controle
11.
Anticancer Res ; 41(5): 2591-2596, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952488

RESUMO

BACKGROUND/AIM: Tacrolimus is an essential immunosuppressant for successful allogeneic haematopoietic stem cell transplantation (Allo-HSCT). This study aimed to examine the change in the blood concentration of tacrolimus during switching from intravenous to oral administration in allo-HSCT for paediatric cancer to predict the optimal dosage. PATIENTS AND METHODS: We retrospectively examined the medical records of 63 patients who received allo-HSCT and were administered tacrolimus. To compare bioavailability among different dose ranges, the blood concentration was divided by the dose (C/D). RESULTS: Thirty-nine patients (age range=children 1-15 years, adults 17-67 years) were switched to oral administration of tacrolimus. The C/D after switching was significantly lower in children than in adults (p=0.039). There was a strong positive correlation between age and C/D in children, whereas no correlation was observed in adults. CONCLUSION: In paediatric cancer patients, switching tacrolimus administration route may result in reduced blood concentrations. This tendency is more prominent in younger children.


Assuntos
Administração Intravenosa/métodos , Administração Oral , Neoplasias/tratamento farmacológico , Tacrolimo/administração & dosagem , Adolescente , Adulto , Idoso , Fenômenos Fisiológicos Sanguíneos/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/patologia , Pediatria , Tacrolimo/efeitos adversos , Adulto Jovem
12.
Transplant Cell Ther ; 27(8): 660.e1-660.e8, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33989832

RESUMO

Early prediction of nonrelapse mortality (NRM) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) based on the results of laboratory tests is challenging. Thus, there is a need to evaluate biomarkers for prediction of NRM, a major problem that offsets the advantages of allo-HSCT. We tested the validity and efficacy of 2 plasma biomarkers, ST2 and Reg3α, based on the Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm, for early prediction of NRM in Japanese patients who underwent allo-HSCT. We conducted a multicenter retrospective study to analyze the clinical data of 112 patients with hematopoietic malignancies who underwent allo-HSCT. Patient blood samples on day 7 after allo-HSCT were obtained from 6 hospitals. The plasma concentrations of ST2 and Reg3α were used to calculate a 6-month NRM risk score. Based on the scores determined in this study, we identified 64 low-risk patients and 48 high-risk patients for the 6-month NRM. The cumulative incidence of 6-month NRM was 29.2% in the high-risk group and 10.9% in the low-risk group (P < .05). The cumulative incidence of relapse mortality was similar in the high-risk and low-risk patients. The biomarker score was predictive in patients with an unrelated donor, an HLA-mismatched donor, high/very high Disease Risk Index, and Hematopoietic Cell Transplantation Comorbidity Index ≥1. Multivariate analysis identified high biomarker probability as a significant predictor of NRM. The MAGIC algorithm based on blood samples obtained at 7 days after allo-HSCT can identify individuals at high risk for NRM among patients with clinical risk factors for NRM in a Japanese cohort.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Biomarcadores , Doença Enxerto-Hospedeiro/diagnóstico , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos , Fatores de Risco , Doadores não Relacionados
13.
Int J Infect Dis ; 100: 292-297, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32891738

RESUMO

OBJECTIVES: The D-index is defined as the area over the neutrophil curve during neutropenia. The CEDMIC trial confirmed the noninferiority of D-index-guided early antifungal therapy (DET) using micafungin to empirical antifungal therapy (EAT). In this study, we evaluated the efficacy and safety of micafungin in these settings. METHODS: From the CEDMIC trial, we extracted 67 and 113 patients who received micafungin in the DET and EAT groups, respectively. Treatment success was defined as the fulfilment of all components of a five-part composite end point. Fever resolution was evaluated at seven days after the completion of therapy. RESULTS: The proportion of high-risk treatments including induction chemotherapy for acute leukemia and allogeneic hematopoietic stem cell transplantation was significantly higher in the DET group than in the EAT group (82.1% vs. 52.2%). The efficacy of micafungin was 68.7% (95%CI: 56.2-79.4) and 79.6% (71.0-86.6) in the DET and EAT groups, respectively. When we focused on high-risk treatments, the efficacy was 69.1% (55.2-80.9%) and 78.0% (65.3-87.7%), respectively (P = 0.30). There was no significant difference in any of the 5 components between the two groups. CONCLUSIONS: The efficacy of micafungin in patients undergoing high-risk treatment was not strongly impaired in DET compared to that in EAT.


Assuntos
Antifúngicos/uso terapêutico , Neutropenia Febril/tratamento farmacológico , Micafungina/uso terapêutico , Neutrófilos/efeitos dos fármacos , Adulto , Idoso , Antifúngicos/efeitos adversos , Neutropenia Febril/imunologia , Feminino , Humanos , Masculino , Micafungina/efeitos adversos , Pessoa de Meia-Idade , Neutrófilos/química , Resultado do Tratamento , Adulto Jovem
14.
J Clin Oncol ; 38(8): 815-822, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-31977270

RESUMO

PURPOSE: Empiric antifungal therapy (EAT) is recommended for persistent febrile neutropenia (FN), but in most patients, it is associated with overtreatment. The D-index, calculated as the area surrounded by the neutrophil curve and the horizontal line at a neutrophil count of 500/µL, reflects both the duration and depth of neutropenia and enables real-time monitoring of the risk of invasive fungal infection in individual patients at no cost. We investigated a novel approach for patients with persistent FN called D-index-guided early antifungal therapy (DET), in which antifungal treatment is postponed until a D-index reaches 5,500 or the detection of positive serum or imaging tests, and compared it with EAT in this multicenter open-label noninferiority randomized controlled trial. PATIENTS AND METHODS: We randomly assigned 423 patients who underwent chemotherapy or hematopoietic stem-cell transplantation for hematologic malignancies to the EAT or DET group. The prophylactic use of antifungal agents other than polyenes, echinocandins, or voriconazole was allowed. Micafungin at 150 mg per day was administered as EAT or DET. RESULTS: In an intent-to-treat analysis of 413 patients, the incidence of probable/proven invasive fungal infection was 2.5% in the EAT group and 0.5% in the DET group, which fulfilled the predetermined criterion of noninferiority of the DET group (-2.0%; 90% CI, -4.0% to 0.1%). The survival rate was 98.0% versus 98.6% at day 42 and 96.4% versus 96.2% at day 84. The use of micafungin was significantly reduced in the DET group (60.2% v 32.5%; P < .001). CONCLUSION: A novel strategy, DET, decreased the use and cost of antifungal agents without increasing invasive fungal infections and can be a reasonable alternative to empiric or preemptive antifungal therapy.


Assuntos
Antifúngicos/administração & dosagem , Neutropenia Febril/tratamento farmacológico , Neutropenia Febril/microbiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Micoses/prevenção & controle , Adulto , Idoso , Neutropenia Febril/sangue , Feminino , Fluconazol/administração & dosagem , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/microbiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Itraconazol/administração & dosagem , Contagem de Leucócitos , Masculino , Micafungina/administração & dosagem , Pessoa de Meia-Idade , Micoses/sangue , Micoses/etiologia , Neutrófilos/patologia , Adulto Jovem
15.
Ann Hematol ; 98(5): 1209-1216, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30824955

RESUMO

Febrile neutropenia is often observed in patients with hematologic malignancies, especially in those with acute leukemia. Meropenem has potent and broad antibacterial activity against gram-positive and gram-negative bacteria, and is recommended as first-line empiric therapy for febrile neutropenia. In contrast, the safety and efficacy of doripenem in patients with febrile neutropenia and hematologic malignancies is limited. In this randomized, prospective, cooperative, open-label trial, we compared doripenem (1.0 g every 8 h) to meropenem (1.0 g every 8 h) as first-line empiric antibacterial treatment of febrile neutropenia. To evaluate efficacy and safety, 133 hospitalized patients with acute leukemia or high-risk myelodysplastic syndrome, who developed febrile neutropenia during or after chemotherapy, were randomized to each drug. Resolution of fever within 3 to 5 days without treatment modification (i.e., the primary endpoint) did not significantly differ between the doripenem and meropenem groups (60.0% vs. 45.6%, respectively; P = 0.136). However, resolution of fever within 7 days of treatment was significantly higher in the doripenem group than in the meropenem group (78.4% vs. 60.2%, respectively; P = 0.037). Similar rates of adverse events (grades 1-2) were observed in both groups. Thus, we conclude that both drugs are safe and well-tolerated for the treatment of febrile neutropenia in patients with acute leukemia or high-risk myelodysplastic syndrome, and that the clinical efficacy of doripenem is noninferior to that of meropenem. UMIN Clinical Trial Registry number: 000006124.


Assuntos
Neutropenia Febril Induzida por Quimioterapia/tratamento farmacológico , Doripenem/administração & dosagem , Leucemia/tratamento farmacológico , Meropeném/administração & dosagem , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doripenem/efeitos adversos , Feminino , Febre/tratamento farmacológico , Humanos , Masculino , Meropeném/efeitos adversos , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/tratamento farmacológico , Estudos Prospectivos
17.
Bone Marrow Transplant ; 54(5): 674-680, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30127466

RESUMO

Sinusoidal obstruction syndrome (SOS) is a lethal complication after hematopoietic stem cell transplantation (HSCT). Defibrotide (DF) is the only drug internationally recommended for SOS treatment in Western countries. Recombinant human soluble thrombomodulin (rhTM), which is promising for the treatment of patients with disseminated intravascular coagulation, is also reported to be potentially effective for SOS. To clarify the safety and efficacy of DF and rhTM, we conducted a retrospective survey of these agents in Japan. Data from 65 patients who underwent allogeneic HSCT and received DF (n = 24) or rhTM (n = 41) for SOS treatment were collected. The complete response rates for SOS on day 100 were 50% and 54% in the DF and rhTM groups, respectively. The 100-day overall survival rates were 50% in the DF group, and 48% in the rhTM group. Several severe hemorrhagic adverse events were observed in one patient in the DF group and five patients in the rhTM group. The main causes of death were SOS-related death, and no patient died of direct adverse events of DF or rhTM. Our results suggest that rhTM, as well as DF, can be effective as a novel treatment option for SOS.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Polidesoxirribonucleotídeos/administração & dosagem , Trombomodulina/administração & dosagem , Adolescente , Adulto , Idoso , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Hepatopatia Veno-Oclusiva/tratamento farmacológico , Hepatopatia Veno-Oclusiva/etiologia , Hepatopatia Veno-Oclusiva/mortalidade , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Taxa de Sobrevida
18.
Int J Hematol ; 109(2): 175-186, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30430419

RESUMO

High-dose chemotherapy with autologous stem cell transplantation (HDC-ASCT) is an option for patients with peripheral T-cell lymphoma (PTCL); however, neither prospective nor retrospective studies support proceeding with ASCT upfront, and the timing of HDC-ASCT remains controversial. We retrospectively analyzed the risk factors for outcomes of 570 patients with PTCL, including PTCL not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL), who received ASCT for frontline consolidation (n = 98 and 75, respectively) or alternative therapies after either relapse (n = 112 and 75) or primary induction failure (PIF; n = 127 and 83) between 2000 and 2015. Significant risk factors for overall survival (OS) after upfront ASCT were a ≥ 2 prognostic index for T-cell lymphoma (P < 0.001) and partial response (PR) at ASCT (P = 0.041) in PTCL-NOS patients, and > 60 years of age (P = 0.0028) and PR at ASCT (P = 0.0013) in AITL patients. Performance status of ≥ 2 at ASCT (P < 0.001), receiving ≥ 3 regimens before ASCT (P = 0.018), and PR at ASCT (P = 0.018) in PTCL-NOS patients and > 60 years of age at ASCT (P = 0.0077) in AITL patients were risk factors for OS after ASCT with a chemosensitive PIF status. Strategies that carefully select PTCL patients may allow identification of individuals suitable for ASCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma de Células T Periférico/terapia , Adolescente , Adulto , Idoso , Feminino , Humanos , Linfadenopatia Imunoblástica/mortalidade , Linfadenopatia Imunoblástica/terapia , Linfoma de Células T Periférico/mortalidade , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Transplante Autólogo
19.
Eur J Haematol ; 100(1): 27-35, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28895203

RESUMO

OBJECTIVES: We conducted a phase-II study to evaluate the efficacy and safety of dasatinib in patients newly diagnosed with chronic-phase chronic myeloid leukaemia (CML-CP) in Japan (IMIDAS PART 2 study). METHODS: Seventy-nine patients were administered 100 mg dasatinib once daily. We examined pretreatment and post-treatment influences of various factors. The BCR-ABL1 international scale (IS), halving time (HT) and reduction rate of BCR-ABL1 transcript within the initial 1 or 3 months of therapy (RR-BCR-ABL11m,3m ) were the post-treatment factors investigated to predict the molecular response. RESULTS: The estimated major molecular response (MMR), molecular response 4.0 (MR4.0) and molecular response 4.5 (MR4.5) rates were 77.2%, 49.4% and 35.4%, respectively, at 12 months. Grade 3/4 non-haematologic adverse events were infrequent. Multivariate analysis showed that age >65 years was significantly correlated with MR4.0 and MR4.5 (deep molecular response: DMR) at 12 months. All post-treatment factors at 3 months predicted DMR by univariate analysis. However, RR-BCR-ABL13m was the only significant landmark for predicting DMR by multivariate analysis. CONCLUSIONS: Primary treatment of CML-CP with dasatinib enabled early achievement of MMR and DMR, particularly in elderly patients, with high safety. Furthermore, RR-BCR-ABL13m was found to be a more useful predictor of DMR than HT-BCR-ABL1 and BCR-ABL1 IS.


Assuntos
Antineoplásicos/uso terapêutico , Dasatinibe/uso terapêutico , Proteínas de Fusão bcr-abl/genética , Expressão Gênica , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/genética , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Dasatinibe/administração & dosagem , Dasatinibe/efeitos adversos , Feminino , Humanos , Leucemia Mieloide de Fase Crônica/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
20.
Rinsho Ketsueki ; 57(8): 1011-7, 2016 08.
Artigo em Japonês | MEDLINE | ID: mdl-27599417

RESUMO

Recent advances in surgical corrections and supportive care for congenital heart disease have resulted in increasing numbers of adult survivors who may develop hematological malignancies. Treatments including chemotherapy for such patients may cause serious hemodynamic or cardiac complications, especially in those receiving stem cell transplantation. We present a 29-year-old woman with acute lymphoblastic leukemia and congenital heart disease. She had been diagnosed with pulmonary atresia with an intact ventricular septum at birth, and the anomaly was surgically corrected according to the Fontan technique at age 9 years. Her induction chemotherapy required modifications due to poor cardiac status with Fontan circulation. However, after surgical procedures including total cavopulmonary connection and aortic valve replacement at first complete remission, her cardiac status was significantly improved. Subsequently, she underwent cord blood stem cell transplantation at the third complete remission. She required intensive supportive care for circulatory failure as a pre-engraftment immune reaction and stage III acute graft versus host disease of the gut, but recovered from these complications. She was discharged on day 239, and remained in complete remission at 1-year post-transplantation.


Assuntos
Cardiopatias Congênitas/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Feminino , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA