Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 223
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Cancer Sci ; 114(3): 995-1006, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36336963

RESUMEN

Age and comorbidities are important factors to be considered in the selection of tyrosine kinase inhibitors (TKIs) for first-line treatment in patients with chronic myeloid leukemia in chronic phase (CML-CP). However, it is yet unclear whether TKI selection, particularly, imatinib versus second-generation TKIs (2GTKIs), impacts treatment outcomes in the clinical practice. To address this, we compared the clinical outcomes of prospectively registered 452 patients with CML-CP treated with imatinib and 2GTKIs, taking into consideration their age and/or comorbidities. A total of 136 patients (30.1%) were classified into an older cohort (≥65 years) and 316 (69.9%) into a younger cohort (18-64 years). The TKI selection did not vary based on age (70.6% received 2GTKIs in the younger cohort and 66.2% in the older cohort). The median follow-up period was 5.4 years. Treatment responses including the cumulative incidence of deep molecular response (BCR-ABL1 international scale ≤0.0032%) at any time were similar between the two age cohorts regardless of the type of TKI. The 5-year overall survival (OS) in the older cohort was lower than that in the younger cohort (95.9% vs 83.8%; p < 0.0001), whereas the 5-year OS in patients treated with 2GTKIs was not influenced by age factors and comorbidities. Therefore, our results suggest that the selection of 2GTKIs as first-line treatment is an effective option for both younger and older CML-CP patients with or without comorbidities. This trial was registered at UMIN-CTR as 00003581.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva , Anciano , Humanos , Proteínas de Fusión bcr-abl , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico
2.
Br J Haematol ; 203(3): 446-459, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37614023

RESUMEN

The graft-versus-lymphoma (GVL) effect and its association with acute and chronic GVHD (aGVHD, cGVHD) has not been comprehensively elucidated. We retrospectively analysed 2204 Japanese patients with non-Hodgkin lymphomas (NHLs; indolent B-NHLs, n = 689; aggressive B-NHLs, n = 720; mature T/NK-NHLs, n = 795) receiving a first allo-HSCT in 2003-2017. Pre-transplant lymphoma control showed complete response (CR) in 759 and non-CR in 1445. We assessed the impact of aGVHD/cGVHD on lymphoma progression and other outcomes. Although aGVHD/cGVHD showed no statistical impact on lymphoma progression in the overall cohort, their impact was clear in certain groups: Grade I-II aGVHD in CR patients (HR, 0.63; 95% CI, 0.43-0.91), especially in mature T/NK-NHL (HR, 0.46; 95% CI, 0.26-0.83) and extensive cGVHD in patients with mature aggressive B-NHLs (HR, 0.55; 95% CI, 0.31-0.97). In total, limited cGVHD was associated with superior survivals (progression-free survival: HR, 0.71; 95% CI, 0.56-0.90), whereas severe GVHDs showed negative impacts on them. Our results support the presence of GVL effects differentially associated with GVHD in different lymphoma subtypes/controls. Meanwhile, it was also suggested that we should manage GVHDs within a limited activity, considering the negative impact of severe GVHDs. As pre-transplant lymphoma control remains a strong factor influencing transplant outcomes, improving its management is an important issue to be addressed.

3.
J Infect Chemother ; 29(7): 726-730, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37088144

RESUMEN

Pneumococcal diseases are one of the most important infectious complications in the late period following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The importance of long-term follow-up care is increasing, as the number of long-term survivors following allo-HSCT increases, but there has been a dearth of research specifically focusing on pneumococcal diseases during the late post-transplant period (day >100). Using a transplant registry database between January 1, 2001 and December 31, 2011, we aimed to assess the clinical spectrum and risk factors for pneumococcal diseases in the late post-transplant period. Among the 22,514 recipients who received allo-HSCT over an 11-year period and could be followed for ≥100 days, 43 patients developed 49 episodes of pneumococcal diseases. Six of the 43 patients died from pneumococcal diseases, and four of these six patients died within a week, despite having undergone allo-HSCT two or more years ago. A history of chronic graft-versus-host disease (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.15-4.66; P = 0.02), viral infection (OR, 3.38; 95% CI, 1.70-6.72; P < 0.01), and complete remission of the underlying disease at the time of transplantation (OR, 2.38; 95%CI, 1.10-5.14; P = 0.03) were identified as risk factors. Given the risk of sudden death and the high mortality rate, attention should be paid to pneumococcal diseases in providing long-term follow-up care, even several years after allo-HSCT.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Infecciones Neumocócicas , Humanos , Trasplante Homólogo/efectos adversos , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/complicaciones , Factores de Riesgo , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología
4.
Allergol Int ; 72(3): 444-450, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36641300

RESUMEN

BACKGROUND: In patients with wheat-dependent exercise-induced anaphylaxis (WDEIA), anaphylactic shock occurs frequently, therefore avoidance of wheat products is recommended. We aimed to evaluate efficacy and safety of long-term omalizumab treatment for adult patients with WDEIA. METHODS: In this phase 2, multicentre single-arm trial, 20 adult patients with WDEIA were enrolled (UMIN 000019250). All patients were administered 150-600 mg of omalizumab subcutaneously and evaluations (basophil activation and blood examination) were performed at regular intervals during administration period (0-48 weeks) and observation period (48-68 weeks). Primary endpoint was proportion of the patients who achieved a basophil activation rate below 10% with fractionated wheat preparations, and secondary endpoint was proportion of the patients with no allergic reactions after wheat products ingestion. RESULTS: During the omalizumab treatment, more than 80% of the patients achieved the basophil activation rate less than 10% against all fractionated wheat preparations, and 68.8% of the patients who achieved the primary endpoint experienced no allergic reaction. During the observation period, the proportion of the patients who achieved a basophil activation rate below 10% decreased gradually, and the proportion of patients with positive allergic reactions increased gradually thereafter and reached maximum of 46.7%. Severe adverse events were not observed during the study. CONCLUSIONS: Long-term omalizumab treatment is safe and effective for adult patients with WDEIA when assessed by basophil activation rate with wheat allergens as well as allergic reactions after lifting of restrictions on wheat intake. However, this is not enough to achieve desensitization.


Asunto(s)
Anafilaxia , Alergias Inducidas por el Ejercicio , Hipersensibilidad al Trigo , Adulto , Humanos , Alérgenos , Anafilaxia/tratamiento farmacológico , Anafilaxia/etiología , Anafilaxia/diagnóstico , Basófilos , Ejercicio Físico , Gliadina , Omalizumab/efectos adversos , Hipersensibilidad al Trigo/tratamiento farmacológico , Hipersensibilidad al Trigo/diagnóstico
5.
Rinsho Ketsueki ; 64(9): 1041-1046, 2023.
Artículo en Japonés | MEDLINE | ID: mdl-37899181

RESUMEN

Correct interpretation of clinical trial results is important. Overall survival was once considered the primary endpoint for neoplastic disease, but surrogate endpoints are increasingly being used for diseases whose prognosis has improved. This is due to the longer trial duration required to obtain conclusions and to poor statistical power. Clinical decision-making in practice is also shifting to using these surrogate endpoints. In clinical trials, eligibility criteria are set to obtain differences between arms. However, this does not mean that results should only be applied to eligible populations, as it is not realistic to conduct a clinical trial in patients with all possible characteristics. Rather, results should be applied to patients who do not meet the eligibility criteria, with careful consideration. A single clinical trial often presents the results of many subgroup analyses, but the main conclusion should not be judged differently by subgroup. The purpose of subgroup analysis is to find potential confounders that interact with the conclusion, and results of subgroup analysis should not be overestimated. Non-inferiority trials have become increasingly common in recent years, and their importance is not limited to demonstrating the non-inferiority of the primary endpoint. Specifically, they are also important for understanding the benefits in the experimental arm outside those in primary analysis. Some secondary endpoints are very important for making conclusions about these benefits.


Asunto(s)
Biomarcadores , Ensayos Clínicos como Asunto , Humanos
6.
Blood ; 136(22): 2548-2556, 2020 11 26.
Artículo en Inglés | MEDLINE | ID: mdl-32584959

RESUMEN

Because non-anthracycline-based chemotherapy with l-asparaginase has improved survival outcomes in patients with extranodal natural killer/T-cell lymphoma (ENKTL), the incidence of central nerve system (CNS) relapse can be different when compared with that in previous reports. In this research, we sought to identify the incidence of and predictors for CNS relapse and to evaluate the necessity of CNS prophylaxis with intermediate-dose methotrexate (ID-MTX). The records of 399 patients in the training cohort and 253 patients in the validation cohort with ENKTL who received non-anthracycline-based chemotherapy were reviewed. Patients were divided into 2 groups according to whether the chemotherapy regimen included ID-MTX above 2 g/m2. A new central nervous system-prognostic index of natural killer (CNS-PINK) model was developed using 1-point powerful predictors of CNS relapse (PINK; hazard ratio [HR], 2.908; P = .030 and extranodal involvement [≥2]; HR, 4.161; P = .001) and was calculated as a sum of scores. The high-risk group of CNS-PINK was defined as 2 points. The cumulative incidence of CNS relapse was different between the CNS-PINK risk groups in the training (P < .001) and validation (P = .038) cohorts. Patients in the high-risk CNS-PINK group who were treated with SMILE or SMILE-like regimens with ID-MTX (S-ID-MTX) displayed a lower incidence rate of CNS relapse than did those who received other regimens without ID-MTX in the training cohort (P = .029). The CNS-PINK was demonstrated its strong predictability of CNS relapse in ENKTL patients. The effectiveness of S-ID-MTX in preventing CNS events in high-risk CNS-PINK patients should be verified in future studies.


Asunto(s)
Neoplasias del Sistema Nervioso Central/prevención & control , Linfoma Extranodal de Células NK-T/prevención & control , Metotrexato/administración & dosificación , Modelos Biológicos , Anciano , Neoplasias del Sistema Nervioso Central/metabolismo , Neoplasias del Sistema Nervioso Central/patología , Femenino , Humanos , Células Asesinas Naturales/metabolismo , Células Asesinas Naturales/patología , Linfoma Extranodal de Células NK-T/metabolismo , Linfoma Extranodal de Células NK-T/patología , Masculino , Persona de Mediana Edad , Factores de Riesgo
7.
Hematol Oncol ; 40(4): 667-677, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35142384

RESUMEN

To elucidate the long-term outcomes of non-anthracycline-containing therapies and central nervous system (CNS) events in patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL), the clinical data of 313 patients with ENKTL diagnosed between 2000 and 2013 in a nationwide retrospective study in Japan were updated and analyzed. At a median follow-up of 8.4 years, the 5-year overall survival (OS) and progression-free survival (PFS) were 71% and 64%, respectively, in 140 localized ENKTL patients who received radiotherapy-dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) in clinical practice. Nine (6.4%) patients experienced second malignancies. In 155 localized ENKTL patients treated with RT-DeVIC, 10 (6.5%) experienced CNS relapse (median, 12.8 months after diagnosis). In five of them, the events were confined to the CNS. Nine of the 10 patients who experienced CNS relapse died within 1 year after CNS relapse. Multivariate analysis identified gingival (hazard ratio [HR], 54.35; 95% confidence interval [CI], 8.60-343.35) and paranasal involvement (HR, 7.42; 95% CI, 1.78-30.89) as independent risk factors for CNS relapse. In 80 advanced ENKTL patients, 18 received steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy as first-line treatment. Patients who received SMILE as their first-line treatment tended to have better OS than those who did not (p = 0.071). Six (7.5%) advanced ENKTL patients experienced isolated CNS relapse (median, 2.6 months after diagnosis) and died within 4 months of relapse. No second malignancies were documented in advanced ENKTL patients. In the entire cohort, the median OS after first relapse or progression was 4.6 months. 12 patients who survived 5 years after PFS events were disease-free at the last follow-up. Of those, 11 (92%) underwent hematopoietic stem cell transplantation. Our 8-year follow-up revealed the long-term efficacy and safety of RT-DeVIC and SMILE. The risk of CNS relapse is an important consideration in advanced ENKTL.


Asunto(s)
Linfoma Extranodal de Células NK-T , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Asparaginasa , Carboplatino , Sistema Nervioso Central/patología , Dexametasona , Etopósido , Humanos , Ifosfamida , Células Asesinas Naturales/patología , Linfoma Extranodal de Células NK-T/diagnóstico , Linfoma Extranodal de Células NK-T/tratamiento farmacológico , Metotrexato , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios Retrospectivos
8.
Ann Hematol ; 101(1): 165-175, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34546409

RESUMEN

Thus far, there have been no large cohort studies on total body irradiation (TBI)-containing conditioning regimens without antithymocyte globulin (ATG) in adults with aplastic anemia (AA) undergoing umbilical cord blood (UCB) transplantation (UCBT). We retrospectively analyzed 115 adults with idiopathic AA undergoing UCBT using TBI-containing reduced-intensity conditioning (RIC) regimens without ATG between 2000 and 2018 on behalf of the Adult Aplastic Anemia Working Group of the Japanese Society for Hematopoietic Cell Transplantation. We then compared transplantation outcomes between a fludarabine (Flu)- and melphalan (Mel)-based regimen (FM) and a Flu- and cyclophosphamide (Cy)-based regimen (FC). The median patient age at UCBT was 41 years. The median total nucleated cell and total CD34+ cell doses in a UCB unit at cryopreservation were 2.5 × 107/kg and 0.7 × 105/kg, respectively. The median follow-up period for survivors was 47 months. The cumulative incidence rate of neutrophil engraftment was 76.5%, and the 4-year overall survival (OS) rate was 64.3%. In multivariate analysis, the covariates that were significantly associated with a higher neutrophil engraftment were total CD34+ cell dose in an UCB unit (≥ 0.7 × 105/kg; hazard ratio, 0.57, P = 0.01) and total dose of TBI (4 Gy of TBI; hazard ratio, 0.32, P = 0.01). There was no significant difference in the cumulative incidence of neutrophil engraftment and the 4-year OS between the FM and FC groups. In conclusion, TBI-containing RIC regimens without ATG are suitable for adults with AA undergoing UCBT. There were no significant differences in transplantation outcomes between the FM and FC groups.


Asunto(s)
Anemia Aplásica/terapia , Sangre Fetal/trasplante , Adolescente , Adulto , Anciano , Suero Antilinfocítico/uso terapéutico , Femenino , Enfermedad Injerto contra Huésped/etiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Resultado del Tratamiento , Irradiación Corporal Total , Adulto Joven
9.
Hematol Oncol ; 39(1): 66-74, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32979280

RESUMEN

The prognosis of diffuse large B-cell lymphoma (DLBCL) having MYC rearrangement (MYC-R), including double hit lymphoma (DHL), is poor by standard immunochemotherapy. To evaluate the significance of hematopoietic stem cell transplantation (SCT) for DLBCL with MYC-R, we retrospectively analyzed Japanese SCT registry data. In total, 54 patients with DLBCL with MYC-R were identified from 4336 registered adult DLBCL patients. Detailed clinical and cytogenetic information was obtained for 48 patients. The median age at diagnosis of the 48 patients was 54.5 (range 21-67) years. Twenty-six (54%) patients had MYC-R only (single hit), and 22 (46%) had MYC-R and BCL2, and/or BCL6 rearrangement (double/triple hit). In 12 patients who received auto-SCT during the first complete response (CR), both the 2-year overall survival (OS) and progression-free survival (PFS) rates were 75.0% (95% confidence interval [CI], 40.8%-91.2%). In 20 patients who received auto-SCT after relapsed or refractory state, the 2-year OS and PFS rates were 68.2% (95% CI, 41.9%-84.5%) and 59.6% (95% CI, 35.1%-77.4%), respectively. In 17 patients who received allo-SCT, only 4 patients underwent SCT in CR. The 2-year OS and PFS rates were 29.4% (95% CI, 10.7%-51.1%) and 17.6% (95% CI, 4.3%-38.3%), respectively. The rate of non-relapse mortality at 1 year was 41.2% (95% CI, 17.1%-64.0%) in this group. The outcomes of single hit and double or triple hit were not different. These findings suggest that auto-SCT may be effective for MYC-R DLBCL, including DHL patients of chemosensitive relapsed or refractory state. Since most patients received allo-SCT not in CR, the outcome of allo-SCT was unsatisfactory due to high non-relapse mortality and early relapse. To clarify the role of allo-SCT for MYC-R DLBCL, further accumulation of patients is necessary.


Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos Par 8/genética , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Proteínas Proto-Oncogénicas c-myc/genética , Adulto , Anciano , Autoinjertos , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia
10.
Hematol Oncol ; 39(1): 51-59, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32978820

RESUMEN

Bendamustine and rituximab (BR) are widely used in patients with follicular lymphoma (FL) previously treated with conventional immunochemotherapy, but the role of consolidation radioimmunotherapy in these patients is unknown. This study evaluated the efficacy and safety of consolidation with 90 Yttrium-ibritumomab tiuxetan (90 Y-IT) after re-induction therapy with BR in patients with previously treated FL. This study included adult patients with relapsed FL who had undergone one or two prior therapies. Re-induction therapy with BR was administered every 4 weeks up to 4-6 cycles. If patients achieved at least partial response, 90 Y-IT was administered as consolidation therapy. The primary endpoint was 2-year progression-free survival (PFS) after consolidation. A total of 24 FL patients (median age 60 years) who had undergone one (n = 17) or two (n = 7) prior treatments received BR. After BR therapy, 22 patients proceeded to consolidation with 90 Y-IT, resulting in an overall 88% response rate to the protocol treatment. Within a median observation period of 46.8 months, the estimated 2-year PFS rate after the consolidation among the 22 patients receiving 90 Y-IT was 59% (95% confidence interval [CI], 38%-77%). Patients whose remission after previous treatment had lasted ≥2 years had a significantly higher 2-year PFS rate than patients whose remission after previous treatment had been <2 years (68% vs. 33%, Wilcoxon p = 0.0211). Major adverse events during the protocol treatment and within 2 years after the consolidation were hematological toxicities, but they were generally acceptable. Consequently, the estimated 2-year overall survival after the consolidation was 95% (95% CI, 74%-99%). In conclusion, in a subset of patients with previously treated FL, 90 Y-IT consolidation after BR re-induction conferred a durable remission, indicating that consolidation therapy using 90 Y-IT may be a novel therapeutic option for patients with relapsed FL (UMIN000008793).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Quimioterapia de Consolidación , Linfoma Folicular/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Clorhidrato de Bendamustina/administración & dosificación , Clorhidrato de Bendamustina/efectos adversos , Femenino , Humanos , Linfoma Folicular/metabolismo , Linfoma Folicular/patología , Masculino , Persona de Mediana Edad , Recurrencia , Rituximab/administración & dosificación , Rituximab/efectos adversos
11.
Ann Hematol ; 100(3): 743-752, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33427909

RESUMEN

To overcome the delayed or failed engraftment after unrelated cord blood transplantation (CBT), we conducted a multicenter phase II study of intrabone single-unit CBT without antithymocyte globulin (ATG) for adult patients with hematological malignancies (UMIN-CTR, UMIN000020997). Sixty-four patients received an intrabone injection of unwashed (n = 61) or washed (n = 3) cord blood after local anesthesia. All injection-related adverse events were mild and resolved spontaneously. Sixty-two patients were evaluable for the efficacy of intrabone CBT of serological HLA-A, -B, and -DR ≥ 4/6 matched cord blood with a median number of 2.57 × 107/kg cryopreserved total nucleated cells. The probability of survival with neutrophil engraftment on day 28 was 77.4% (95% confidence interval, 67.0-85.8%), which exceeded the threshold value. The cumulative incidences of neutrophils ≥ 0.5 × 109/L on day 60 was 80.6% (68.2-88.6%), with a median time to recovery of 21 days after transplantation. The cumulative incidences of platelets ≥ 20 × 109/L and platelets ≥ 50 × 109/L on day 100 were 75.8% (62.6-84.9%) and 72.6% (59.4-82.1%), respectively, with median time to platelets ≥ 20 × 109/L and platelets ≥ 50 × 109/L of 38 and 45 days after transplantation, respectively. The cumulative incidences of grade II-IV and III-IV acute graft-versus-host disease were 29.0% and 6.5%, respectively. All responded to steroid therapy, and secondary treatments were not required. The present study suggests the efficacy of intrabone single-unit CBT without ATG in terms of early engraftment and controllable acute graft-versus-host disease.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Neoplasias Hematológicas/terapia , Infusiones Intraóseas/métodos , Adolescente , Adulto , Anciano , Suero Antilinfocítico , Huesos , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Femenino , Sangre Fetal/fisiología , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/patología , Neoplasias Hematológicas/epidemiología , Humanos , Incidencia , Infusiones Intraóseas/efectos adversos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Adulto Joven
12.
Rinsho Ketsueki ; 62(8): 1085-1093, 2021.
Artículo en Japonés | MEDLINE | ID: mdl-34497195

RESUMEN

Chronic lymphocytic leukemia (CLL) is a rare type of lymphoid malignancy among Japanese. Its clinical course is indolent, and the prognosis is good. The two types of CLL based on the mutation status of the IgH gene V segment have been documented in the literature. Then, the del (17p)/TP53 subtype is emphasized, and the treatment strategy for the three subtypes differs. Recent knowledge on molecular pathogenesis facilitated the usage of Bruton's tyrosine kinase (BTK) and BCL2 inhibitors for the treatment of CLL. A better response can be obtained with the use of these novel agents, resulting in a higher rate of negativity for measurable residual disease (MRD). The treatment strategy based on MRD negativity and the treatment outcomes of CLL will improve in future.


Asunto(s)
Antineoplásicos , Leucemia Linfocítica Crónica de Células B , Agammaglobulinemia Tirosina Quinasa , Antineoplásicos/uso terapéutico , Humanos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico
13.
Lancet Oncol ; 21(4): 593-602, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32171071

RESUMEN

BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease for which there is no available standard treatment. We aimed to ascertain the safety and activity of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) with high-dose methotrexate and intrathecal chemotherapy as CNS-oriented therapy for patients with previously untreated IVLBCL. METHODS: PRIMEUR-IVL is a multicentre, single-arm, phase 2 trial at 22 hospitals in Japan. Eligible patients had untreated histologically confirmed IVLBCL, were aged 20-79 years, had an Eastern Cooperative Group performance status of 0-3, and had no apparent CNS involvement at diagnosis. Patients received three cycles of R-CHOP (rituximab 375 mg/m2 intravenously on day 1 [except cycle one, which was on day 8]; cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 [maximum 2·0 mg] intravenously on day 1 of cycle one and day 2 of cycles two and three; and prednisolone 100 mg/day orally on days 1-5 of cycle one and days 2-6 of cycles two and three) followed by two cycles of rituximab with high-dose methotrexate (3·5 g/m2 intravenously on day 2 of cycles four and five) every 2 weeks and three additional cycles of R-CHOP. Intrathecal chemotherapy (methotrexate 15 mg, cytarabine 40 mg, and prednisolone 10 mg) was administered four times during the R-CHOP phase. The primary endpoint was 2-year progression-free survival. Efficacy analyses were done in all enrolled patients; safety analyses were done in all enrolled and treated patients. The trial is registered in the UMIN Clinical Trials Registry (UMIN000005707) and the Japan Registry of Clinical Trials (jRCTs041180165); the trial is ongoing for long-term follow-up. FINDINGS: Between June 16, 2011, and July 21, 2016, 38 patients were enrolled, of whom 37 were eligible; one patient was excluded because of a history of testicular lymphoma. Median follow-up was 3·9 years (IQR 2·5-5·5). 2-year progression-free survival was 76% (95% CI 58-87). The most frequent adverse events of grade 3-4 were neutropenia and leucocytopenia, which were reported in all 38 (100%) patients. Serious adverse events were hypokalaemia, febrile neutropenia with hypotension, hypertension, and intracerebral haemorrhage (reported in one [3%] patient each). No treatment-related deaths occurred during protocol treatment. INTERPRETATION: R-CHOP combined with rituximab and high-dose methotrexate plus intrathecal chemotherapy is a safe and active treatment for patients with IVLBCL without apparent CNS involvement at diagnosis, and this regimen warrants future investigation. FUNDING: The Japan Agency for Medical Research and Development, the Center for Supporting Hematology-Oncology Trials, and the National Cancer Center.


Asunto(s)
Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Metotrexato/administración & dosificación , Neoplasias Vasculares/tratamiento farmacológico , Adulto , Anciano , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Estudios Prospectivos , Rituximab/administración & dosificación , Vincristina/administración & dosificación , Adulto Joven
14.
Cancer Sci ; 111(10): 3714-3725, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33404088

RESUMEN

Comorbidities at diagnosis among patients with chronic myeloid leukemia in chronic phase (CML-CP) may affect their overall survival (OS) rate even in the tyrosine kinase inhibitor (TKI) era. However, the prognostic impact of comorbidities in patients with CML-CP treated with a second-generation TKI (2GTKI) has not been elucidated. We evaluated the effect of comorbidities on survival using the Charlson Comorbidity Index (CCI) in patients with CML-CP treated with imatinib or a 2GTKI (nilotinib and dasatinib). From April 2010 to March 2013, 506 patients with CML-CP were registered for the population-based cohort study, and 452 with a median age of 56 y were assessable. Treatment groups included 139 patients receiving imatinib, 169 receiving nilotinib, and 144 receiving dasatinib. Comorbidities were diagnosed in 99 patients. CCI scores were stratified as follows: 2, 353 patients; 3, 72 patients; and ≥4, 27 patients. Treatment response did not vary relative to CCI scores. However, across the entire cohort, the OS rate was significantly lower among patients with higher CCI scores than in those with a CCI score of 2 (94.4% in score 2, 89.0% in score 3, and 72.8% in score ≥4; P < .001). Multivariate analysis identified a CCI score of ≥4 as a strong adverse prognostic factor for OS rather than the disease-specific risk factor, older age, performance status, or selection of TKI (Wald test, P < .01). Our results demonstrated that comorbidities at diagnosis were the most important predictive factor for successful treatment, regardless of the TKI type used in CML-CP. This trial was registered at UMIN-CTR as 00003581.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/epidemiología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Comorbilidad , Dasatinib/uso terapéutico , Femenino , Humanos , Mesilato de Imatinib/uso terapéutico , Masculino , Persona de Mediana Edad , Pronóstico , Pirimidinas/uso terapéutico , Tasa de Supervivencia , Resultado del Tratamiento , Adulto Joven
15.
Biol Blood Marrow Transplant ; 26(1): 139-144, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31546004

RESUMEN

Almost comparable transplantation outcomes have been reported with HLA-matched unrelated donor transplantation (UDT) and cord blood transplantation (CBT). We conducted a prospective phase 2 study to assess the efficacy and safety of single-unit myeloablative CBT in adult leukemia and myelodysplastic syndrome. Because the day 180 survival of UDT was approximately 80%, we determined the alternative hypothesis of expected day 180 survival with a successful engraftment rate of 80% and set the null hypothesis of threshold rate at 65%. Sixty-two patients (median age, 37 years) were registered, including 28 with acute myelogenous leukemia, 25 with acute lymphoblastic leukemia, and 9 with myelodysplastic syndrome. Of 61 eligible patients, 52 were successfully engrafted and survived at day 180 (85%; 95% confidence interval, 74% to 93%). Single-unit CBT was judged to be effective because the null hypothesis was rejected (P < .001). Furthermore, neutrophil engraftment was observed in 57 patients (92%); the incidences of grade II-IV acute and chronic graft-versus-host disease were 30% and 32%, respectively; and the cumulative incidences of nonrelapse mortality and relapse at 2 years were 18% and 13%, respectively. The present study showed favorable survival outcomes with single-unit CBT. Therefore, this method may be considered if a well-HLA-matched UDT cannot be obtained.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Leucemia , Síndromes Mielodisplásicos , Enfermedad Aguda , Adolescente , Adulto , Aloinjertos , Enfermedad Crónica , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Leucemia/mortalidad , Leucemia/terapia , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Estudios Prospectivos , Tasa de Supervivencia , Factores de Tiempo
16.
J Hepatol ; 73(2): 285-293, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32194183

RESUMEN

BACKGROUND & AIMS: HBV reactivation is a risk in patients receiving anti-CD20 antibodies for the treatment of lymphoma. The purpose of this post hoc analysis was to evaluate the efficacy of an ultra-high sensitivity HBsAg assay to guide preemptive antiviral treatment in patients with lymphoma and resolved HBV infections using prospectively stored samples from an HBV DNA monitoring study. METHODS: HBV reactivation (defined as HBV DNA levels of ≥11 IU/ml) was confirmed in 22 of 252 patients. A conventional HBsAg assay (ARCHITECT, cut-off value: 0.05 IU/ml) and an ultra-high sensitivity HBsAg assay employing a semi-automated immune complex transfer chemiluminescence enzyme technique (ICT-CLEIA, cut-off value: 0.0005 IU/ml) were performed at baseline, at confirmed HBV reactivation and monitored after HBV reactivation. RESULTS: Baseline HBsAg was detected using ICT-CLEIA in 4 patients; in all of whom precore mutants with high replication capacity were reactivated. Of the 6 patients with HBV DNA detected below the level of quantification at baseline, 5 showed HBV reactivation and 3 of the 5 had precore mutations. Sensitivity for detection by ARCHITECT and ICT-CLEIA HBsAg assays at HBV reactivation or the next sampling after HBV reactivation was 18.2% (4 of 22) and 77.3% (17 of 22), respectively. Of the 5 patients undetectable by ICT-CLEIA, HBV reactivation resolved spontaneously in 2 patients. All 6 patients reactivated with precore mutations including preS deletion could be diagnosed by ICT-CLEIA HBsAg assay at an early stage of HBV reactivation. Multivariate analysis showed that an anti-HBs titer of less than 10 mIU/ml, HBV DNA detected but below the level of quantification, and HBsAg detected by ICT-CLEIA at baseline were independent risk factors for HBV reactivation (adjusted hazard ratios, 15.4, 31.2 and 8.7, respectively; p <0.05). CONCLUSIONS: A novel ICT-CLEIA HBsAg assay is an alternative method to diagnose HBV reactivation. CLINICAL TRIAL NUMBER: UMIN000001299. LAY SUMMARY: Hepatitis B virus can be reactivated in lymphoma patients receiving anti-CD20 antibodies such as rituximab. Currently, reactivation requires the monitoring of HBV DNA, but monitoring of the surface antigen (HBsAg) could provide a relatively inexpensive, quick and easy alternative. We assessed the performance of an ultra-high sensitivity HBsAg assay and showed that it could be effective for the diagnosis and monitoring of HBV reactivation.


Asunto(s)
Monitoreo de Drogas/métodos , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B Crónica , Linfoma , Reinfección , Rituximab , Anciano , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Comorbilidad , ADN Viral/aislamiento & purificación , Femenino , Antígenos de Superficie de la Hepatitis B/análisis , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/aislamiento & purificación , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/sangre , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/epidemiología , Humanos , Japón/epidemiología , Linfoma/tratamiento farmacológico , Linfoma/epidemiología , Linfoma/virología , Masculino , Reinfección/etiología , Reinfección/prevención & control , Reinfección/virología , Reproducibilidad de los Resultados , Rituximab/administración & dosificación , Rituximab/efectos adversos , Pruebas Serológicas/métodos
17.
Blood ; 131(23): 2528-2540, 2018 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-29602763

RESUMEN

Extranodal natural killer/T-cell lymphoma, nasal type (ENKL) is a subtype of mature T- and natural killer cell lymphomas characterized by its association with Epstein-Barr virus and extranodal involvement. Although there is geographic variance in the frequency of ENKL, its clinical features are similar between Western countries and endemic areas, such as East Asia. Anthracycline-containing chemotherapy is not recommended to treat ENKL. No standard treatment has been established based on the results of randomized controlled trials. In patients with localized disease, radiotherapy is a core component of the recommended first-line therapy. Radiotherapy administered at 50 to 54 Gy, extended involved-site radiotherapy considering tumor invasiveness, and the use of intensity modulated radiation therapy or volumetric modulated arc therapy are associated with efficacy of radiotherapy. Although the use of concurrent chemoradiotherapy has been supported by the results of clinical trials, accumulating evidence supports the use of sequential chemoradiotherapy with non-anthracycline-containing regimens that include l-asparaginase and/or platinum anticancer agents. l-asparaginase-containing chemotherapy is a key component of first-line treatments for systemic ENKL. Hematopoietic stem cell transplantation is recommended as a front-line consolidation therapy for newly diagnosed advanced-stage ENKL. Newer agents including immune checkpoint inhibitors are being investigated for treating ENKL. In this modern ENKL treatment era, multidisciplinary efforts are needed to identify the best timing and sequencing of radiotherapy, l-asparaginase, platinum, newer agents, and hematopoietic stem cell transplantation.


Asunto(s)
Linfoma Extranodal de Células NK-T/terapia , Neoplasias Nasales/terapia , Animales , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Asparaginasa/uso terapéutico , Quimioradioterapia/métodos , Infecciones por Virus de Epstein-Barr/complicaciones , Trasplante de Células Madre Hematopoyéticas/métodos , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Inmunoterapia/métodos , Linfoma Extranodal de Células NK-T/diagnóstico , Linfoma Extranodal de Células NK-T/patología , Linfoma Extranodal de Células NK-T/virología , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Recurrencia Local de Neoplasia/virología , Neoplasias Nasales/diagnóstico , Neoplasias Nasales/patología , Neoplasias Nasales/virología , Radioterapia/métodos
18.
Hematol Oncol ; 38(3): 266-271, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32011008

RESUMEN

Although allogeneic hematopoietic stem cell transplantation (HSCT) has been reported to provide prolonged remission of relapsed/refractory mycosis fungoides (MF) and Sézary syndrome (SS), its role has not been fully evaluated. Here, the outcomes of allogeneic HSCT for patients with MF/SS were retrospectively evaluated by using the registry database of the Japan Society for Hematopoietic Cell Transplantation. Forty-eight patients were evaluable and enrolled in the analysis. Median age was 45.5 years. Eighteen patients (38%) received myeloablative conditioning, and 33 (69%) received HSCT from an alternative donor. Disease status was complete or partial response in 25% of the patients and relapsed or refractory in the others. At the time of analysis, 18 patients were alive, with a median follow-up of 31.0 months (range, 3.8-31.1). Three-year overall survival (OS) and progression-free survival (PFS) were 30% (95%CI, 16-45%) and 19% (95%CI, 9-31%), respectively. Disease progression was not observed later than 17 months after transplantation. Both disease status and performance status at transplant significantly affected OS and PFS. Although our findings suggest that allogeneic HSCT provides long-term PFS in patients with MF/SS, the timing of transplantation should be decided carefully based on the disease status and the patient's condition in order to improve the outcome.


Asunto(s)
Enfermedad Injerto contra Huésped/mortalidad , Trasplante de Células Madre Hematopoyéticas/mortalidad , Micosis Fungoide/mortalidad , Síndrome de Sézary/mortalidad , Adulto , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/patología , Enfermedad Injerto contra Huésped/terapia , Humanos , Masculino , Persona de Mediana Edad , Micosis Fungoide/patología , Micosis Fungoide/terapia , Pronóstico , Estudios Retrospectivos , Síndrome de Sézary/patología , Síndrome de Sézary/terapia , Tasa de Supervivencia , Acondicionamiento Pretrasplante , Trasplante Homólogo , Adulto Joven
19.
Hematol Oncol ; 38(2): 146-152, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31953867

RESUMEN

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication after hematopoietic stem cell transplantation (HSCT). Several studies of risk factors for PTLD have been reported; however, the probability of, and risk factors for, PTLD in patients with lymphoma is unknown. Japanese nationwide transplant registry data from 5270 patients with lymphoma after allogeneic HSCT were analyzed. Mature B-cell, T/NK-cell, and T-cell lymphoblastic subtypes accounted for 49%, 26%, and 9.6% of lymphoma cases, respectively. Rituximab was used in 1678 lymphoma patients, most of whom (89%) received HSCT for mature B-cell lymphoma. Thirty-one patients with lymphoma developed PTLD, representing a probability of 0.77% at 2 years post-HSCT, which did not differ significantly from that in patients with other diseases (P = .98). Year of HSCT after 2010 (hazard ratio [HR] = 5.6, 95% confidence interval [CI], 1.48-21.3), antithymocyte globulin (ATG) use in the conditioning regimen (HR = 4.5, 95% CI, 1.61-12.5), and no rituximab use before HSCT (HR = 3.2, 95% CI, 1.26-7.90) were identified as risk factors for PTLD. Probabilities of PTLD at 1 year post-HSCT according to rituximab and ATG use were 0.23% (rituximab+, ATG-), 0.75% (rituximab-, ATG-), 1.25% (rituximab+, ATG+), and 3.53% (rituximab-, ATG+). Regarding lymphoma subtypes, patients with mature B-cell lymphoma had the lowest incidence of PTLD (0.35% at 2 years). Among high-risk patients receiving ATG, the mortality rate due to infection was elevated in those previously treated with rituximab (22%) relative to those without (14%); however, the difference was not significant (P = .10). Rituximab use before HSCT significantly reduces the risk of PTLD. Adding rituximab to the conditioning regimen is potentially a good strategy to prevent the development of PTLD in high-risk patients.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma de Células B/terapia , Trastornos Linfoproliferativos/epidemiología , Rituximab/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Japón/epidemiología , Linfoma de Células B/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante Homólogo , Adulto Joven
20.
Ann Hematol ; 99(7): 1635-1642, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32424672

RESUMEN

The role of stem cell transplantation (SCT) for patients with Waldenström's macroglobulinemia (WM) remains undetermined. Therefore, we retrospectively evaluated the outcome of autologous and allogeneic SCT for patients with WM using the registry database of the Japan Society for Hematopoietic Cell Transplantation. Forty-six patients receiving autologous and 31 receiving allogeneic SCT were analyzed. The allogeneic SCT group included more patients with advanced disease status at transplant and received more lines of chemotherapy. The cumulative incidences of non-relapse mortality (NRM) at 1 year were 30.0% (95% CI, 14.7-46.9%) in the allogeneic SCT and 0% in the autologous SCT group. The estimated 3-year overall (OS) and progression-free (PFS) survival rates were 84.5% (95% CI, 66.0-93.4%) and 70.8% (95% CI, 53.0-82.9%) in the autologous SCT group, and 52.2% (95% CI, 32.5-68.6%) and 45.0% (95% CI, 26.3-62.0%) in the allogeneic SCT group. No patients died after the first 2 years following allogeneic SCT. In univariate analyses, disease status at SCT was significantly associated with PFS in autologous SCT, and with OS and PFS in allogeneic SCT. These results suggest that both autologous and allogeneic SCT have each potential role in WM. Allogeneic SCT is more curative for WM, but is associated with high NRM.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Macroglobulinemia de Waldenström/mortalidad , Macroglobulinemia de Waldenström/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/mortalidad , Quimioterapia Adyuvante/estadística & datos numéricos , Terapia Combinada/mortalidad , Terapia Combinada/estadística & datos numéricos , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Japón/epidemiología , Linfoma/mortalidad , Linfoma/terapia , Masculino , Persona de Mediana Edad , Recurrencia , Sistema de Registros , Estudios Retrospectivos , Rituximab/uso terapéutico , Sociedades Médicas , Trasplante Homólogo , Resultado del Tratamiento , Macroglobulinemia de Waldenström/patología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA