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1.
Blood Cancer J ; 14(1): 141, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39168989

RESUMEN

We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40-65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Busulfano , Ciclofosfamida , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Acondicionamiento Pretrasplante , Trasplante Homólogo , Vidarabina , Humanos , Busulfano/administración & dosificación , Busulfano/uso terapéutico , Persona de Mediana Edad , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/tratamiento farmacológico , Adulto , Vidarabina/análogos & derivados , Vidarabina/administración & dosificación , Vidarabina/uso terapéutico , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Femenino , Masculino , Trasplante de Células Madre Hematopoyéticas/métodos , Anciano , Acondicionamiento Pretrasplante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios de Seguimiento
2.
Blood Adv ; 6(7): 2309-2318, 2022 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-34920451

RESUMEN

The aim of this study was to develop a predictive score for moderate-severe chronic graft-versus-host disease (cGVHD) on day +100 after allogeneic stem cell transplantation (HSCT). We studied 1292 patients allografted between 1990 and 2016, alive on day +100 after transplant, without cGVHD, and with full biochemistry laboratory values available. Patients were randomly assigned to a training and a validation cohort (ratio 1:1). In the training cohort, a multivariate analysis identified 4 independent predictors of moderate-severe cGVHD: gamma-glutamyl transferase ≥75 UI/l, creatinine ≥1 mg/dl, cholinesterase ≤4576 UI/l, and albumin ≤4 g/dl. A score of 1 was assigned to each variable, producing a low (0 to 1), intermediate (2 to 3), and high (4) score. The cumulative incidence of moderate-severe cGVHD was 12%, 20%, and 52% (P < .0001) in the training cohort, and 13%, 24%, and 33% (P = .002) in the validation cohort, respectively. The 5-year cumulative incidence of transplant-related mortality (TRM) was 5%, 14%, 27% (P < .0001) and 5%, 16%, 31% (P < .0001), respectively. The 5-year survival was 64%, 57%, 54% (P = .009) and 70%, 59%, 42% (P = .0008) in the 2 cohorts, respectively. In conclusion, Day100 score predicts cGVHD, TRM, and survival and, if validated in a separate group of patients, could be considered for trials of preemptive therapy.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Incidencia , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Homólogo/efectos adversos
3.
Biol Blood Marrow Transplant ; 22(11): 1983-1987, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27492792

RESUMEN

Allogeneic stem cell transplantation (alloHSCT) in first complete remission (CR1) remains the consolidation therapy of choice in Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). The prognostic value of measurable levels of minimal residual disease (MRD) at time of conditioning is a matter of debate. We analyzed the predictive relevance of MRD levels before transplantation on the clinical outcome of Ph+ ALL patients treated with chemotherapy and imatinib in 2 consecutive prospective clinical trials. MRD evaluation before transplantation was available for 65 of the 73 patients who underwent an alloHSCT in CR1. A complete or major molecular response at time of conditioning was achieved in 24 patients (37%), whereas 41 (63%) remained carriers of any other positive MRD level in the bone marrow. MRD negativity at time of conditioning was associated with a significant benefit in terms of risk of relapse at 5 years, with a relapse incidence of 8% compared with 39% for patients with MRD positivity (P = .007). However, thanks to the post-transplantation use of tyrosine kinase inhibitors (TKIs), disease-free survival was 58% versus 41% (P = .17) and overall survival was 58% versus 49% (P = .55) in MRD-negative compared with MRD-positive patients, respectively. The cumulative incidence of nonrelapse mortality was similar in the 2 groups. Achieving a complete molecular remission before transplantation reduces the risk of leukemia relapse even though TKIs may still rescue some patients relapsing after transplantation.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Adolescente , Adulto , Anciano , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Mesilato de Imatinib/uso terapéutico , Persona de Mediana Edad , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidad , Valor Predictivo de las Pruebas , Pronóstico , Recurrencia , Inducción de Remisión , Prevención Secundaria , Análisis de Supervivencia , Trasplante Homólogo , Resultado del Tratamiento , Adulto Joven
4.
Ann Hematol ; 92(1): 121-3, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22820997

Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Enfermedad de Hodgkin/tratamiento farmacológico , Compuestos de Mostaza Nitrogenada/uso terapéutico , Terapia Recuperativa , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Antineoplásicos Alquilantes/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Clorhidrato de Bendamustina , Bleomicina/administración & dosificación , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Terapia Combinada , Ciclofosfamida/administración & dosificación , Dacarbazina/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Resultado Fatal , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad de Hodgkin/radioterapia , Enfermedad de Hodgkin/cirugía , Humanos , Ifosfamida/administración & dosificación , Masculino , Compuestos de Mostaza Nitrogenada/administración & dosificación , Compuestos de Mostaza Nitrogenada/efectos adversos , Prednisolona/administración & dosificación , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Recurrencia , Reoperación , Rituximab , Trasplante Autólogo , Trasplante Homólogo , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , Vincristina/administración & dosificación , Vinorelbina , Adulto Joven , Gemcitabina
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