RESUMEN
Data comparing HLA-haploidentical donors and HLA-matched sibling donors (MSDs) in peripheral blood stem cell transplantation (PBSCT) for lymphoma are scarce. We retrospectively analyzed 465 patients with lymphoma aged 16 years or older who underwent PBSCT using haploidentical donors with post-transplant cyclophosphamide (PTCy-haplo) (n = 166) or MSDs with calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis (n = 299). Two-year overall survival (OS), progression-free survival (PFS), and GVHD-free, relapse-free survival (GRFS) in the PTCy-haplo and MSD groups were 49.2% versus 51.9% (P = 0.64), 38.0% versus 39.9% (P = 0.97), and 27.7% versus 18.5% (P = 0.006), respectively. In multivariable analyses, PTCy-haplo recipients had slower neutrophil recovery (hazard ratio [HR], 0.62; P < 0.001) and platelet recovery (HR, 0.54; P < 0.001), lower risk of chronic GVHD (HR, 0.64; P = 0.038) and extensive chronic GVHD (HR, 0.45; P = 0.008), and better GRFS (HR, 0.66; P = 0.003) than MSD transplant recipients. OS, PFS, relapse or progression, and non-relapse mortality were similar between the groups. The difference might be mainly due to PTCy use rather than donor type; however, the results suggested that PTCy-haplo could be a possible option as an alternative to conventional MSD transplantation for lymphoma in PBSCT.
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Ciclofosfamida , Linfoma , Trasplante de Células Madre de Sangre Periférica , Hermanos , Humanos , Ciclofosfamida/uso terapéutico , Trasplante de Células Madre de Sangre Periférica/métodos , Persona de Mediana Edad , Femenino , Masculino , Adulto , Linfoma/terapia , Linfoma/mortalidad , Estudios Retrospectivos , Anciano , Adolescente , Donantes de Tejidos , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/mortalidad , Antígenos HLA , Adulto Joven , Trasplante Haploidéntico/métodos , Supervivencia sin EnfermedadRESUMEN
The Japanese Society of Hematology performed an observational cross-sectional study to clarify the morbidity, prognosis, and prognostic factors in patients with COVID-19 with hematological diseases (HDs) in Japan. The study included patients with HDs who enrolled in our epidemiological survey and had a COVID-19 diagnosis and a verified outcome of up to 2 months. The primary endpoints were characteristics and short-term prognosis of COVID-19 in patients with HDs. A total of 367 patients from 68 institutes were enrolled over 1 year, and the collected data were analyzed. The median follow-up among survivors was 73 days (range, 1-639 days). The 60-day overall survival (OS) rate was 86.6%. In the multivariate analysis, albumin ≤ 3.3 g/dL and a need for oxygen were independently associated with inferior 60-day OS rates (hazard ratio [HR] 4.026, 95% confidence interval (CI) 1.954-8.294 and HR 14.55, 95% CI 3.378-62.64, respectively), whereas 60-day survival was significantly greater in patients with benign rather than malignant disease (HR 0.095, 95% CI 0.012-0.750). Together, these data suggest that intensive treatment may be necessary for patients with COVID-19 with malignant HDs who have low albumin levels and require oxygen at the time of diagnosis.
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COVID-19 , Enfermedades Hematológicas , Humanos , Japón/epidemiología , Estudios Transversales , COVID-19/epidemiología , Prueba de COVID-19 , Pronóstico , Enfermedades Hematológicas/epidemiología , Albúminas , Oxígeno , Estudios RetrospectivosRESUMEN
Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the sole curative therapy for myelodysplastic syndrome (MDS). However, whether bridging therapy (BRT) including azacitidine (AZA) and combination chemotherapy (CCT) prior to allo-SCT should be performed is unclear. We analyzed BRT and the outcomes of patients with myelodysplastic syndrome with excess blasts (MDS-EB) who were ≤ 70 years old at the time of registration for a prospective observational study to clarify the optimal allo-SCT strategy for high-risk MDS. A total of 371 patients were included in this study. Among 188 patients (50.7%) who were considered for allo-SCT, 141 underwent allo-SCT. Among the patients who underwent allo-SCT, 64 received AZA, 29 received CCT, and 26 underwent allo-SCT without BRT as the initial treatment. Multivariate analysis identified BRT as an independent factor influencing overall survival (AZA vs. without BRT, hazard ratio [HR] 3.33, P = 0.005; CCT vs. without BRT, HR 3.82, P = 0.003). In multivariate analysis, BRT was independently associated with progression-free survival (AZA vs. without BRT: HR, 2.23; P = 0.041; CCT vs. without BRT: HR, 2.94; P = 0.010). Transplant-eligible patients with MDS-EB should undergo allo-SCT when clinically acceptable, and upfront allo-SCT without BRT may be superior to AZA or CCT.
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Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos , Humanos , Anciano , Azacitidina/uso terapéutico , Trasplante Homólogo , Aloinjertos , Estudios RetrospectivosRESUMEN
This report covers acute myeloid leukemia (AML) results from a multicenter, prospective observational study of AML, myelodysplastic syndromes, and chronic myelomonocytic leukemia in Japan. From August 2011 to January 2016, 3728 AML patients were registered. Among them, 42% were younger than 65, and the male-to-female ratio was 1.57:1. With a median follow-up time of 1807 days (95% confidence interval [CI]: 1732-1844 days), the estimated 5-year overall survival (OS) rate in AML patients (n = 3707) was 31.1% (95% CI: 29.5-32.8%). Trial-enrolled patients had a 1.7-fold higher OS rate than non-enrolled patients (5-year OS, 58.9% [95% CI: 54.5-63.1%] vs 35.5% [33.3-37.8%], p < 0.0001). Women had a higher OS rate than men (5-year OS, 34% [95% CI; 31.4-36.7%] vs 27.7% [25.7-29.7%], p < 0.0001). The OS rate was lower in patients aged 40 and older than those under 40, and even lower in those over 65 (5-year OS for ages < 40, 40-64, 65-74, ≥ 75: 74.5% [95% CI; 69.3-79.0%] vs 47.5% [44.4-50.6%] vs 19.3% [16.8-22.0%] vs 7.3% [5.5-9.4%], respectively). This is the first paper to present large-scale data on survival and clinical characteristics in Japanese AML patients.
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Leucemia Mieloide Aguda , Leucemia Mielomonocítica Crónica , Síndromes Mielodisplásicos , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Japón/epidemiología , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/terapia , Estudios ProspectivosRESUMEN
We conducted a multicenter, prospective observational study of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia (CMML) in Japan. From August 2011 to January 2016, we enrolled 6568 patients. Herein, we report the results for MDS (n = 2747) and CMML (n = 182). The percentage of patients aged 65 years or older was 79.5% for MDS and 79.7% for CMML. The estimated overall survival (OS) rate and cumulative incidence of AML evolution at 5 years were 32.3% (95% confidence interval: 30.2-34.5%) and 25.7% (23.9-27.6%) for MDS, and 15.0% (8.9-22.7%) and 39.4% (31.1-47.6%) for CMML. Both diseases were more common in men. The most common treatment for MDS was azacitidine, which was used in 45.4% of higher-risk and 12.7% of lower-risk MDS patients. The 5-year OS rate after treatment with azacitidine was 12.1% (9.5-15.1%) for of higher-risk MDS patients and 33.9% (25.6-42.4%) for lower-risk patients. The second most common treatment was erythropoiesis-stimulating agents, given to just 20% of lower-risk patients. This is the first paper presenting large-scale, Japanese data on survival and clinical characteristics in patients with MDS and CMML.
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Leucemia Mieloide Aguda , Leucemia Mielomonocítica Crónica , Síndromes Mielodisplásicos , Masculino , Humanos , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Leucemia Mielomonocítica Crónica/epidemiología , Japón/epidemiología , Antimetabolitos Antineoplásicos/uso terapéutico , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/epidemiología , Azacitidina/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológicoRESUMEN
OBJECTIVE: We sought to assess the safety and feasibility of outpatient management in Japanese patients with relapsed/refractory lymphoma who had received pegfilgrastim after salvage therapy. METHOD: This was a single-center, open-label, non-randomized, prospective interventional analysis. Patients were completely hospitalized for cycle 1 of chemotherapy. Those who met the outpatient management criteria (outpatient group) were subsequently admitted to the hospital for chemotherapy cycles but were discharged after each cycle was completed. The inpatient group was discharged when white blood cell and platelet counts improved. Pegfilgrastim was given as a single 3.6 mg dose by subcutaneous injection 2 days after the completion of each chemotherapy cycle. RESULTS: The percentage of outpatient management days (primary endpoint) ranged from 68.2%-75.0% in the outpatient group and 28.6%-50.0% in the inpatient group. According to the secondary endpoints, there were no hospitalizations due to febrile neutropenia during the outpatient period. There were no major safety concerns raised. CONCLUSIONS: For patients with relapsed/refractory lymphoma, pegfilgrastim administration after salvage therapy in an outpatient setting was feasible and safe for those who satisfied the outpatient management criteria.
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Factor Estimulante de Colonias de Granulocitos , Linfoma , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios de Factibilidad , Linfoma/tratamiento farmacológico , Pacientes Ambulatorios , Estudios Prospectivos , Terapia RecuperativaRESUMEN
Unrelated donor bone marrow transplantation (UR-BMT), unrelated donor cord blood stem cell transplantation (UR-CBT), and haploidentical peripheral blood stem cell transplantation (Haplo-PBSCT) are the main alternative stem cell sources for allogeneic hematopoietic cell transplantation (HCT) in Japan. The present study aimed to identify factors associated with the outcomes of UR-BMT, UR-CBT, and Haplo-PBSCT in older patients with acute myeloid leukemia (AML) and intermediate- or poor-risk cytogenetics to improve the clinical efficacy and safety of allogeneic HCT. We retrospectively analyzed data for 448 AML patients aged > 65 years who received UR-BMT (n = 102), UR-CBT (n = 250), or Haplo-PBSCT (n = 96) between 2014 and 2020. Overall survival (OS) in the UR-BMT group was superior (P = 0.033) to that in the other groups. However, all patients without complete remission (non-CR) who had Karnofsky performance status (KPS) < 80 at HCT and poor-risk cytogenetics died within 1 year after HCT. Multivariate Cox regression analysis identified KPS <80 at HCT and poor-risk cytogenetics as independent predictors of worse OS in non-CR patients. KPS < 80 may be an alternative indicator for non-CR AML patients with poor-risk cytogenetics during the selection of HCT, alternative treatments, or best supportive therapy, and the optimal KPS is important for the success of HCT.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Anciano , Estudios Retrospectivos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Trasplante de Médula Ósea , Análisis Citogenético , Acondicionamiento PretrasplanteRESUMEN
OBJECTIVE: The prognostic significance of IKZF1plus in adult Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) patients had remained to be clarified. METHODS: We conducted a prospective, multicenter study, the ALL/MRD2008 trial, and investigated the clinical significance of IKZF1plus . RESULTS: From December 2008 to November 2013, 38 untreated Ph+ ALL patients were enrolled. At the end of the induction, 97.4% of patients (37/38) achieved complete hematological remission, with MRD-negativity of 48.6% (18/37). There were 19 patients with IKZF1plus , 13 with IKZF1 deletion alone (ΔIKZF1) and 4 with no IKZF1 deletions (no ΔIKZF1). The probability of 3-year DFS and OS in these Ph+ ALL patients were 50% (95% confidence interval [CI], 33-65) and 55% (95% CI, 38-69), respectively. There was no significant difference between IKZF1plus , ΔIKZF1, and no ΔIKZF1 in DFS (47%, 54%, 75% [p = .63]) or OS (47%, 62%, NA [p = .39]). CONCLUSIONS: We revealed no relationship between IKZF1plus status and survival outcomes in Ph+ ALL patients treated with imatinib/dasatinib combination chemotherapy. Further investigations are warranted to clarify the prognostic significance of IKZF1plus in adult Ph+ ALL patients.
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Factor de Transcripción Ikaros , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Estudios Prospectivos , Factor de Transcripción Ikaros/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Mesilato de Imatinib/uso terapéutico , Dasatinib/uso terapéutico , PronósticoRESUMEN
Castleman disease is a rare disease borne of a B cell lymphoproliferative disorder of uncertain cause. Standard therapy for the unicentric type of Castleman disease localized as a single mass or single lymph-node station is surgical extirpation. Nevertheless, in the thoracic cavity, unresectable cases or cases of incomplete extirpation of the tumor without lung scarring owing to tumor size/location have been noted. In such cases, lung resection (e.g., lobectomy, pneumonectomy) or additional therapy (immunotherapy, chemotherapy, radiotherapy) after resection is required. However, few instances of patients receiving induction immunotherapy or chemotherapy followed by surgery have been reported. Here, we describe a 21-year-old woman with unicentric Castleman disease originating from the left hilum. The tumor seemed to involve/be in contact with the pulmonary vein and bronchus. Tumor location indicated that initial resection was necessary to sacrifice upper and lower pulmonary lobes. To avoid these pulmonary resections, induction therapy followed by surgery was selected. Induction therapy using rituximab was very efficacious. Resection after induction therapy was completed only by tumor extirpation, and resulted in preservation of pulmonary function. Thoracic surgeons might consider induction therapy followed by resection if the tumor is resectable UCAD, but initial resection is needed and sacrifices a large amount of pulmonary function.
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Enfermedad de Castleman , Adulto , Enfermedad de Castleman/patología , Enfermedad de Castleman/cirugía , Femenino , Humanos , Inmunoterapia , Pulmón/patología , Neumonectomía , Rituximab , Adulto JovenRESUMEN
PURPOSE: Comprehensive geriatric assessment (CGA) has been used to help identify elderly patients with diffuse large B-cell lymphoma (DLBCL) who were suitable for rituximab combined with CHOP therapy (cyclophosphamide, Adriamycin, vincristine, and prednisolone), but there are few reports of CGA for elderly patients with DLBCL who received R-mini-CHOP. METHODS: We retrospectively analyzed the risk factors for outcomes among 142 patients aged 80 years and older (≤ 85 years, n = 102; > 85 years, n = 40) with DLBCL who received R-mini-CHOP at 4-week intervals at our institute between 2008 and 2019. We performed a comparison between CGA and treatment outcomes. RESULTS: There were significant differences in progression-free survival between patients with international prognostic index (IPI) scores of > 3 and ≤ 3 at diagnosis and in overall survival between patients with instrumental activities of daily living (IADL) scores of ≥ 5 and IADL < 5 before the initial treatment and patients aged ≤ 85 years and > 85 years. CONCLUSION: Strategies that carefully select elderly patients aged 80 years and older with DLBCL using CGA may help to identify individuals suitable for novel therapies.
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Evaluación Geriátrica , Linfoma de Células B Grandes Difuso , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Estudios Retrospectivos , Rituximab/uso terapéuticoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Clorhidrato de Bendamustina/efectos adversos , Linfoma Folicular/tratamiento farmacológico , Linfopenia/inducido químicamente , Rituximab/efectos adversos , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Clorhidrato de Bendamustina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Rituximab/uso terapéuticoRESUMEN
Aggressive adult T-cell leukemia/lymphoma (ATL) is a hematological malignancy that is difficult to treat with chemotherapy alone, and allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy. We conducted a multicenter, prospective, observational study to clarify the treatment outcomes of aggressive ATL in the current era. Between 2015 and 2018, 113 patients aged 70 years or younger with newly diagnosed aggressive ATL were enrolled. The median age at diagnosis was 61 years. Treatment outcomes were compared with those of 1792 ATL patients diagnosed between 2000 and 2013 in our previous retrospective study. The inclusion criteria were the same in both studies. The prospective cohort demonstrated better overall survival (OS) than the retrospective cohort (2-year OS, 45% vs 29%, respectively; P < .001), with a much higher proportion of patients receiving allo-HCT (80% vs 34%, respectively; P < .001) and a shorter interval from diagnosis to allo-HCT (median, 128 vs 170 days, respectively; P < .001). Among the 90 patients who received allo-HCT (cord blood, n = 30; HLA-haploidentical related donors, n = 20; other related donors, n = 14; other unrelated donors, n = 26), the 2-year probabilities of OS, non-relapse mortality (NRM), and disease progression were 44%, 23%, and 46%, respectively. OS and NRM did not differ statistically according to donor type. Our results suggest that increased application of allo-HCT improved the survival of patients with aggressive ATL. The use of cord blood or HLA-haploidentical donors may be feasible for aggressive ATL when HLA-matched related donors are unavailable. This study was registered at the UMIN Clinical Trials Registry as #000017672.
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Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma de Células T del Adulto , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Donante no EmparentadoRESUMEN
Adult T cell leukemia/lymphoma (ATL) is a highly aggressive hematologic malignancy with a very poor prognosis, and most patients with ATL are elderly. Although post-transplantation cyclophosphamide (PTCy) has yielded promising results in various diseases, available data are limited regarding its outcomes in ATL. The aim of this study was to determine the safety and efficacy of reduced-intensity peripheral blood stem cell transplantation (PBSCT) from a human leukocyte antigen (HLA)-haploidentical donor using PTCy as graft-versus-host disease (GVHD) prophylaxis. This was a prospective, multicenter phase I/II study (UMIN000021783) conducted at 16 hospitals in Japan. The primary endpoint was the probability of survival with engraftment and without grade III/IV acute GVHD at day 60 after PBSCT. The expected probability of the primary endpoint was estimated to be 60%, and the threshold probability was set at 30% on the basis of previous studies. The conditioning regimen consisted of fludarabine (30 mg/m2/d from day -7 to -2), melphalan (40 mg/m2/d on days -3 and -2), and total body irradiation (2 Gy on day -1). GVHD prophylaxis consisted of tacrolimus starting at 0.02 mg/kg/d on day -1, PTCy (50 mg/kg/d on days +3 and +5), and mycophenolate mofetil 2000 mg/d starting on day +6. Eighteen ATL patients underwent PBSCT. The probability of patients who met the primary endpoint was 89% (95% confidence interval, 65% to 99%). The cumulative incidences of grade II to IV acute GVHD, III/IV acute GVHD, and moderate-to-severe chronic GVHD were 39%, 11%, and 17%, respectively. The probabilities of overall survival were 83% at 1 year and 73% at 2 years. The cumulative incidences of non-relapse mortality and disease progression at 1 year were 11% and 28%, respectively. HLA-haploidentical PBSCT with PTCy as GVHD prophylaxis is a valid option for patients with aggressive ATL.
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Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma de Células T del Adulto , Linfoma , Trasplante de Células Madre de Sangre Periférica , Anciano , Ciclofosfamida/uso terapéutico , Antígenos HLA , Humanos , Leucemia-Linfoma de Células T del Adulto/terapia , Estudios ProspectivosRESUMEN
BACKGROUND: Systemic Epstein-Barr virus+ T-cell lymphoma (sEBV+ TCL) occurs in childhood and young adults, and is exceptionally rare in older adults. METHODS: We investigated clinicopathological features in 16 patients of various ages with systemic EBV+ CD8+ T-lymphoproliferative diseases. RESULTS: Eight younger patients and four of eight older adults had sEBV+ CD8+ TCL, with invasion by medium-sized to/or large atypical lymphocytes primarily in bone marrow and lymph nodes, hemophagocytic lymphohistiocytosis (HLH), and progressive clinicopathological course. A further two patients demonstrated EBV+ node-based CD8+ large TCL without HLH, while the remaining two had the systemic form of chronic active EBV infection (sCAEBV) with CD8+ small lymphocytes. Past history of sCAEBV-like lesions was observed in one sEBV+ TCL patient (8.3%). Immunohistologically, in 12 sEBV+ TCL patients, atypical lymphocytes were positive for phosphate signal transducer and activator of transcription 3 (66.7%), CMYC (83.3%), and p53 (75%). Strong reactions of programmed cell death-ligand (PD-L)1+ tumor or non-neoplastic cells were detected in nine sEBV+ TCL patients (75%). Clonal peaks of the T-cell receptor (TCR) γ gene were detected in eight sEBV+ TCL patients by polymerase chain reaction. Four younger patients in sEBV+ TCL (33.3%) are in remission with chemotherapies including etoposide, and three of the four underwent allogeneic stem cell transplantation (SCT). CONCLUSION: sEBV+ CD8+ TCL was observed in younger and older adults with less history of sCAEBV. HLH, tumor cell atypia, immunohistological findings, and progressive clinical course were characteristic of sEBV+ CD8+ TCL. Prompt chemotherapy and SCT induced tumor regression in sEBV+ CD8+ TCL patients.
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Linfocitos T CD8-positivos/patología , Proliferación Celular , Infecciones por Virus de Epstein-Barr/patología , Herpesvirus Humano 4/patogenicidad , Linfohistiocitosis Hemofagocítica/patología , Linfoma de Células T/patología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/análisis , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/virología , Transformación Celular Viral , Preescolar , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/terapia , Infecciones por Virus de Epstein-Barr/virología , Femenino , Interacciones Huésped-Patógeno , Humanos , Linfohistiocitosis Hemofagocítica/inmunología , Linfohistiocitosis Hemofagocítica/terapia , Linfohistiocitosis Hemofagocítica/virología , Linfoma de Células T/inmunología , Linfoma de Células T/terapia , Linfoma de Células T/virología , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Trasplante de Células Madre , Resultado del Tratamiento , Adulto JovenRESUMEN
Recently, the use of targeted synthetic or biological disease-modifying anti-rheumatic drugs (ts/bDMARDs) in addition to conventional synthetic (cs)DMARDs including methotrexate (MTX) for rheumatoid arthritis (RA) has increased. However, whether ts/bDMARDs are associated with the development and clinicopathological features of MTX-associated lymphoproliferative disorder (MTX-LPD) in patients with RA remains unknown. Therefore, we evaluated the clinical outcomes of 121 patients with MTX-LPD. Results showed that prior use of ts/bDMARDs was not associated with the different histopathological subtypes of MTX-LPD. Patients with polymorphic-type LPD had a better event-free survival than those with diffuse large B-cell lymphoma (DLBCL), classical Hodgkin lymphoma and peripheral T-cell lymphoma. The pathological subtype of lymphoma could predict the clinical outcome of MTX-LPD. In patients with DLBCL, the use of tumour necrosis factor-alpha (TNF-α) inhibitors prior to MTX-LPD onset was associated with a higher non-relapse mortality. Further, patients with RA previously treated with Janus kinase (JAK) inhibitors more commonly required chemotherapy than those treated with csDMARDs alone, indicating disease aggressiveness. Hence, special caution should be observed when managing patients with MTX-LPD previously treated with JAK or TNF-α inhibitors for RA.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Trastornos Linfoproliferativos/tratamiento farmacológico , Metotrexato/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Dacarbazina/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Quinasas Janus/antagonistas & inhibidores , Estimación de Kaplan-Meier , Linfoma no Hodgkin/mortalidad , Trastornos Linfoproliferativos/inducido químicamente , Trastornos Linfoproliferativos/mortalidad , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Prednisona/administración & dosificación , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Rituximab/administración & dosificación , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Vinblastina/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
A novel anti-cytomegalovirus (CMV) agent, letermovir (LMV), could reportedly improve the outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) recipients because of its high potential to prevent CMV reactivation. Therefore, 685 Japanese allo-HCT recipients, of whom ~80% had a high risk of CMV reactivation, were retrospectively analyzed to assess the impacts of prophylactic LMV on the incidence of clinically significant CMV (csCMV) infection as well as their transplant outcome. By comparing 114 patients who received LMV prophylaxis for a median 92 days to 571 patients without prophylaxis, we observed that prophylactic LMV could significantly (1) reduce the 180-day cumulative incidence of csCMV infection (44.7 vs. 72.4%, p < 0.001), (2) delay the median time until initiation of CMV antigenemia-guided preemptive therapy (90 vs. 36 days, p < 0.001), (3) shorten the duration of anti-CMV preemptive treatment (21 vs. 25 days, p = 0.006), and (4) improve the overall survival rate at 180 days after transplant (80.4 vs. 73.0%, p = 0.033) with a trend of lower non-relapse mortality (8.9 vs. 14.9%, p = 0.052). Our findings demonstrate that prophylactic LMV treatment is highly effective in preventing the development of csCMV infection and ultimately reduces transplant-related mortality.
Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Acetatos , Antivirales/uso terapéutico , Citomegalovirus , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/prevención & control , Humanos , Quinazolinas , Estudios RetrospectivosRESUMEN
In the original publication of the article, the "CNS involvement" in the last row under the column "Total N=50" has been published incorrectly. The correct Table 1 is given in this correction.
RESUMEN
Guillain-Barré (GBS) and Fisher (FS) syndromes rarely recur and the characteristics of recurrence have not been fully elucidated. We describe the cases of 2 patients with GBS or FS that recurred more than twice and who were subsequently diagnosed with aplastic anemia. Case 1 was a 66-year-old man who was diagnosed with aplastic anemia 10 months before admission with limb ataxia and a sensory disturbance of the distal limbs that developed 3 days after an upper respiratory tract infection. He had a history of double vision with ataxia at the ages of 38 and 56 years. Case 2 was a 66-year-old woman who had been treated for aplastic anemia 1 year previously. She had a history of upper limb weakness after upper respiratory tract infections at the ages of 39 and 60 years. Tendon reflexes were absent in both patients at the time of onset and they were respectively diagnosed with FS and GBS and treated with intravenous immunoglobulin. No neurological deficits persisted. Blood findings showed that both were positive for IgG type ganglioside antibodies and HLA-DR15. The positive HLA-DR15 might have been associated with the recurrent GBS or FS and the development of aplastic anemia.
RESUMEN
We stratified patients with newly diagnosed acute promyelocytic leukemia (APL) according to a white blood cell (WBC) count of ≥ 3 × 109/L (high risk) or < 3 × 109/L (low risk) before administering risk-adapted chemotherapy in combination with all-trans retinoic acid (ATRA). In total, 27 low-risk and 23 high-risk patients were assigned to receive induction and three courses of consolidation with ATRA and anthracycline, followed by 2-year maintenance regimen. High-risk group additionally received cytarabine during 1st consolidation and another one-shot idarubicin treatment during 3rd consolidation. We prospectively monitored measurable residual disease (MRD) after induction and each consolidation. In the low-risk and high-risk groups, 5-year disease-free survival (DFS) rates were 86.5% and 81.2% (p = 0.862), and 5-year overall survival rates were 100% and 84.8% (p = 0.062), respectively. In the MRD-negative and MRD-positive groups, 5-year DFS rates were 91.7% and 78.4% (p = 0.402) and 84.7% and 60.0% (p = 0.102) after induction and 1st consolidation, respectively. Relapse rates were 8.3% and 13.3% (p = 0.570) and 9.0% and 40.0% (p = 0.076) after induction and 1st consolidation, respectively. Achieving MRD-negativity after 1st consolidation, rather than after induction, was a potential predictor of relapse and DFS in patients with APL treated with ATRA + chemotherapy.
Asunto(s)
Quimioterapia de Consolidación , Leucemia Promielocítica Aguda/tratamiento farmacológico , Neoplasia Residual/mortalidad , Tretinoina/uso terapéutico , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina/administración & dosificación , Femenino , Predicción , Humanos , Idarrubicina/administración & dosificación , Leucemia Promielocítica Aguda/mortalidad , Masculino , Persona de Mediana Edad , Neoplasia Residual/diagnóstico , Pronóstico , Estudios Prospectivos , Recurrencia , Tasa de Supervivencia , Resultado del Tratamiento , Tretinoina/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: Fungal infections are a major complication of neutropaenia following chemotherapy. Their early diagnosis is difficult, and empirical antifungal treatment is widely used, and uses of less toxic drugs that reduce breakthrough infection are required. OBJECTIVE: We conducted a multicentre, open-label, randomised, non-inferiority trial to compare the safety and efficacy of intravenous itraconazole (ivITCZ) and liposomal amphotericin B (LAmB) as empirical antifungal therapy in patients with haematological malignancies with neutropaenia and persistent fever. METHODS: Patients with haematological malignancies who developed fever refractory to broad-spectrum antibacterial agents under neutropaenia conditions were enrolled. Patients were randomised for treatment with LAmB (3.0 mg/kg/d) or ivITCZ (induction: 400 mg/d, maintenance: 200 mg/d). RESULTS: Observed overall favourable response rates of 17/52 (32.7%) and 18/50 (36.0%) in the LAmB and ivITCZ groups, with a model-based estimate of a 4% difference (90% CI, -12% to 20%), did not fulfil the statistical non-inferiority criterion. In the LAmB group, there were two cases of breakthrough infection and five cases of probable invasive fungal disease, whereas in the itraconazole group, neither breakthrough infection nor probable invasive fungal disease occurred. Patients in the ivITCZ group had significantly fewer grade 3-4 hypokalaemia-related events than LAmB group patients (P < .01). The overall incidence of adverse events tended to be lower in the ivITCZ group (P = .07). CONCLUSION: ivITCZ showed similar efficacy and safety as LAmB as empirical antifungal therapy in haematological malignancy patients with febrile neutropaenia, although the small sample size and various limitations prevented demonstration of its non-inferiority.