RESUMEN
There is currently no consensus on the role of upfront autologous transplantation (ASCT) for patients with peripheral T-cell lymphomas (PTCL), especially in patients achieving first complete remission (CR1) following chemotherapy, and data in the literature is conflicting. A systematic review and meta-analysis was performed to address this question. We searched key databases from January 2000 to February 2022. Six prospective and eleven retrospective studies were included among 2959 unique records. Median follow up in these studies ranged from 22 to 94 months. There was a trend towards benefit in PFS (HR = 0.80, 95% CI 0.62-1.05, p = 0.11) and OS (HR = 0.79, 95% CI 0.57-1.09, p = 0.15) in the ASCT compared to chemotherapy only group. Importantly, in transplant eligible patients in CR1, a significant benefit was demonstrated in both OS (HR = 0.59, 95% CI 0.36-0.95, p = 0.03) and PFS (HR = 0.61, 95% CI 0.47-0.81, p = 0.0004) in the ASCT group. Amongst the nodal PTCL subgroups, ASCT showed a significant PFS benefit for the AITL subgroup (HR = 0.43, 95% CI 0.20-0.94, p < 0.03) but not PTCL-NOS or ALK-ve ALCL subgroups. Our findings support upfront ASCT for transplant eligible PTCL patients achieving CR1 post chemotherapy. In particular, patients with AITL exhibited a significantly better PFS after upfront ASCT.
Asunto(s)
Linfoma de Células T Periférico , Inducción de Remisión , Trasplante Autólogo , Linfoma de Células T Periférico/terapia , Linfoma de Células T Periférico/mortalidad , Humanos , Trasplante Autólogo/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , AutoinjertosAsunto(s)
Neoplasias Hematológicas/complicaciones , Infecciones Fúngicas Invasoras/diagnóstico , Volvariella/aislamiento & purificación , Antifúngicos/uso terapéutico , Humanos , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/patología , Infecciones Fúngicas Invasoras/fisiopatología , Masculino , Técnicas Microbiológicas , Persona de Mediana Edad , Estudios Retrospectivos , Singapur , Resultado del TratamientoRESUMEN
BACKGROUND: Genotype-guided warfarin dosing has been shown in some randomized trials to improve anticoagulation outcomes in individuals of European ancestry, yet its utility in Asian patients remains unresolved. METHODS: An open-label, non-inferiority, 1:1 randomized trial was conducted at three academic hospitals in South East Asia, involving 322 ethnically diverse patients newly indicated for warfarin (NCT00700895). Clinical follow-up was 90 days. The primary efficacy measure was the number of dose titrations within the first 2 weeks of therapy, with a mean non-inferiority margin of 0.5 over the first 14 days of therapy. RESULTS: Among 322 randomized patients, 269 were evaluable for the primary endpoint. Compared with traditional dosing, the genotype-guided group required fewer dose titrations during the first 2 weeks (1.77 vs. 2.93, difference -1.16, 90% CI -1.48 to -0.84, P < 0.001 for both non-inferiority and superiority). The percentage of time within the therapeutic range over 3 months and median time to stable international normalized ratio (INR) did not differ between the genotype-guided and traditional dosing groups. The frequency of dose titrations (incidence rate ratio 0.76, 95% CI 0.67 to 0.86, P = 0.001), but not frequency of INR measurements, was lower at 1, 2, and 3 months in the genotype-guided group. The proportions of patients who experienced minor or major bleeding, recurrent venous thromboembolism, or out-of-range INR did not differ between both arms. For predicting maintenance doses, the pharmacogenetic algorithm achieved an R2 = 42.4% (P < 0.001) and mean percentage error of -7.4%. CONCLUSIONS: Among Asian adults commencing warfarin therapy, a pharmacogenetic algorithm meets criteria for both non-inferiority and superiority in reducing dose titrations compared with a traditional dosing approach, and performs well in prediction of actual maintenance doses. These findings imply that clinicians may consider applying a pharmacogenetic algorithm to personalize initial warfarin dosages in Asian patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00700895 . Registered on June 19, 2008.
Asunto(s)
Anticoagulantes/uso terapéutico , Dosis Máxima Tolerada , Warfarina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Anticoagulantes/farmacología , Pueblo Asiatico , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Warfarina/administración & dosificación , Warfarina/farmacología , Adulto JovenAsunto(s)
Encéfalo/patología , Inmunoconjugados/uso terapéutico , Linfoma Anaplásico de Células Grandes/tratamiento farmacológico , Terapia Recuperativa , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Barrera Hematoencefálica , Encéfalo/diagnóstico por imagen , Brentuximab Vedotina , Femenino , Humanos , Inmunoconjugados/farmacocinética , Linfoma Anaplásico de Células Grandes/diagnóstico por imagen , Linfoma Anaplásico de Células Grandes/patología , Imagen por Resonancia Magnética , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Recurrencia , Inducción de RemisiónRESUMEN
Loss of heterozygosity (LOH) has been shown to be associated with leukemia relapse after haploidentical transplantation. Whether such changes are an important cause of relapse after HLA-matched transplantation remains unclear. We retrospectively HLA-typed leukemic blasts for 71 patients with AML/myelodysplastic syndrome obtained from stored samples, and the results were compared with those obtained at diagnosis and/or before the transplant. No LOH or any other changes in HLA Ag were found in any of the samples tested post transplant as compared with pretransplant specimens. One patient had LOH in HLA class I Ag (HLA-A,-B and -C); however, these changes were present in the pretransplant sample indicating that they occurred before the transplant. We concluded that, in contrast with haploidentical transplantation, HLA loss does not have a major role as a mechanism of relapse after allogeneic transplantation with a closely HLA-matched donor.
Asunto(s)
Antígenos HLA/inmunología , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia/inmunología , Leucemia/terapia , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Trasplante Homólogo , Adulto JovenRESUMEN
Allogeneic stem cell transplantation for patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) has been performed primarily with an HLA-matched donor. Outcomes of haploidentical transplantation have recently improved, and a comparison between donor sources in a uniform cohort of patients has not been performed. We evaluated outcomes of 227 patients with AML/MDS treated with melphalan-based conditioning. Donors were matched related (MRD) (n = 87, 38%), matched unrelated (MUD) (n = 108, 48%), or haploidentical (n = 32, 14%). No significant differences were found between haploidentical and MUD transplantation outcomes; however, there was a trend for improved outcomes in the MRD group, with 3-year progression-free survival for patients in remission of 57%, 45%, and 41% for MRD, MUD, and haploidentical recipients, respectively (P = .417). Recovery of T cell subsets was similar for all groups. These results suggest that haploidentical donors can safely extend transplantation for AML/MDS patients without an HLA-matched donor. Prospective studies comparing haploidentical and MUD transplantation are warranted.
Asunto(s)
Antígenos HLA , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Trasplante de Células Madre , Donante no Emparentado , Adulto , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Prueba de Histocompatibilidad , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
For patients with ALL who relapse following allo-SCT, only a second SCT provides a realistic chance for long-term disease remission. We retrospectively analyzed the outcomes of 31 patients with relapsed ALL after a prior allo-SCT, who received a second SCT (SCT2) at our center. With a median follow-up of 3 years, 1- and 3-year PFS was 23 and 11% and 1- and 3 year OS rates were 23 and 11%. Twelve patients (39%) were transplanted with active disease, of whom 75% attained a CR. We found a significant relationship between the time to treatment failure following first allograft (SCT1) and PFS following SCT2 (P=0.02, hazard ratio=0.93/month). In summary, a second transplant remains a potential treatment option for achieving response in a highly refractory patient population. While long-term survival is limited, a significant proportion of patients remains disease-free for up to 1 year following SCT2, providing a window of time to administer preventive interventions. Notably, our four long-term survivors received novel therapies with their second transplant underscoring the need for a fundamental change in the methods for SCT2 to improve outcome.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is an effective post-remission therapy in patients with acute lymphoblastic leukemia (ALL), but is associated with significant toxicity, so the optimal timing and use of this modality remains an issue of debate. Increased advances in reduced-intensity transplant preparative regimens and alternative donors has increased the accessibility of allogeneic transplantation. A risk adapted paradigm, using minimal residual disease analysis, may help in the selection of patients at highest risk for relapse, who may benefit most from alloHSCT. In this review, we summarize the indications for allogeneic transplantation within the risk-oriented paradigm, and also explore the latest literature on reduced intensity transplant regimens, as well as alternative donor transplantation for patients with ALL.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Humanos , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Ensayos Clínicos Controlados Aleatorios como Asunto , Inducción de Remisión , Acondicionamiento Pretrasplante/métodos , Trasplante HomólogoAsunto(s)
Sistema del Grupo Sanguíneo ABO , Antineoplásicos/administración & dosificación , Ácidos Borónicos/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Pirazinas/administración & dosificación , Aplasia Pura de Células Rojas/tratamiento farmacológico , Aplasia Pura de Células Rojas/etiología , Adulto , Bortezomib , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Trasplante HomólogoRESUMEN
NDM-1 is a new metallo-beta-lactamase that readily hydrolyses carbapenems, penicillins and cephalosporins. Its rising incidence has been reported in many countries around the world, with many cases linked to a possible origin from the Indian subcontinent. Due to the lack of effective antibiotic regimes to treat these infections, the increased prevalence of NDM-1 is alarming. We describe a case of NDM-1 infection in an immunocompromised foreign patient, and discuss its implications.
Asunto(s)
Antibacterianos/uso terapéutico , Escherichia coli/metabolismo , Fiebre/diagnóstico , Neutropenia/diagnóstico , beta-Lactamasas/biosíntesis , Farmacorresistencia Bacteriana , Resistencia a Múltiples Medicamentos , Femenino , Fiebre/etiología , Humanos , Huésped Inmunocomprometido , Incidencia , Turismo Médico , Persona de Mediana Edad , Neutropenia/etiología , Resultado del Tratamiento , beta-Lactamasas/metabolismoAsunto(s)
Infecciones por Coronavirus/mortalidad , Gripe Humana/mortalidad , Vigilancia de la Población , Infecciones por Virus Sincitial Respiratorio/mortalidad , Adolescente , Adulto , Anciano , Autopsia , Niño , Enfermedades Transmisibles Emergentes/diagnóstico , Enfermedades Transmisibles Emergentes/mortalidad , Coronavirus/aislamiento & purificación , Infecciones por Coronavirus/diagnóstico , Femenino , Hong Kong/epidemiología , Humanos , Incidencia , Lactante , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/diagnóstico , Masculino , Persona de Mediana Edad , Proyectos Piloto , Reacción en Cadena de la Polimerasa/métodos , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Adulto JovenAsunto(s)
Subtipo H5N1 del Virus de la Influenza A/genética , Subtipo H5N1 del Virus de la Influenza A/patogenicidad , Macrófagos/virología , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas no Estructurales Virales/genética , Animales , Células Cultivadas , Pollos , Humanos , Gripe Aviar , Gripe Humana , VirulenciaRESUMEN
Hepatosplenic candidiasis (HSC) in patients with acute leukemia poses management challenges because the therapeutic limitations of the present antifungal armamentarium may adversely impact on treatment outcomes of the underlying leukemia. We report a patient with acute myeloid leukemia who developed HSC during post-remission consolidation chemotherapy and was treated with a prolonged course of caspofungin followed by fluconazole. The stabilization of infection permitted further chemotherapy and autologous hematopoietic cell transplant (HCT) without breakthrough fungemia and further dissemination of candidiasis. The favorable outcome provides further evidence that with optimal treatment, the presence of stable or non-progressive HSC is not an absolute contraindication for HCT. The use of caspofungin in the primary treatment of HSC appears to be a promising approach. The favorable outcome seen in this case is encouraging, although further study on its efficacy is warranted.