RESUMEN
Haploidentical hematopoietic-cell transplantation using post-transplant cyclophosphamide(Haplo-PTCy) is a feasible procedure in children with haematologic malignancies. However, data of a large series of children with acute leukaemia(AL) in this setting is missing. We analysed 144 AL Haplo-PTCy paediatric recipients; median age was 10 years. Patients had acute lymphoblastic(ALL; n = 86) or myeloblastic leukaemia(AML; n = 58) and were transplanted in remission(CR1: n = 40; CR2: n = 57; CR3+: n = 27) or relapse (n = 20). Bone marrow was the graft source in 57%; donors were father (54%), mother (35%), or sibling (11%). Myeloablative conditioning was used in 87%. Median follow-up was 31 months. At day +100, cumulative incidence (CI) of neutrophil recovery and acute GVHD (II-IV) were 94% and 40%, respectively. At 2-years, CI of chronic GVHD and relapse, were 31%, 40%, and estimated 2-year overall survival (OS), leukaemia-free survival (LFS) and graft-versus-host-relapse-free survival (GRFS) were 52%, 44% and 34% respectively. For patients transplanted in remission, positive measurable residual disease (MRD) prior to transplant was associated with decreased LFS (p = 0.05) and GRFS (p = 0.003) and increased risk of relapse (p = 0.02). Mother donor was associated with increased risk of chronic GVHD (p = 0.001), decreased OS (p = 0.03) and GRFS (p = 0.004). Use of PBSC was associated with increased risk of chronic GVHD (p = 0.04). In conclusion, achieving MRD negativity pre-transplant, avoiding use of mother donors and PBSC as graft source may improve outcomes of Haplo-PTCy in children with AL.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Células Madre de Sangre Periférica , Niño , Ciclofosfamida/uso terapéutico , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Leucemia Mieloide Aguda/complicaciones , Madres , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Trasplante Haploidéntico/efectos adversosRESUMEN
BACKGROUND: We analyzed the incidence of acute kidney injury and chronic renal failure in chronic myeloid leukemia (CML) patients using imatinib and investigated whether there is a relation between duration of imatinib therapy and decrease in estimated glomerular filtration rate (GFR). PATIENTS AND METHODS: One hundred five CML patients on imatinib therapy were enrolled. Creatinine, urea, uric acid, and potassium measurements from imatinib treatment onset until the end of follow-up (median 4.5 years) were included in the analysis. GFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: During follow-up, 7% of patients developed acute kidney injury; creatinine levels returned to baseline in only one of them. According to the regression equation, the mean baseline value of the estimated GFR was 88.9 ml/min/1.73 m(2). Estimated GFR decreased significantly with imatinib treatment duration; the mean decrease per year was 2.77 ml/min/1.73 m(2) (P < 0.001); 12% of patients developed chronic renal failure. Age, hypertension, and a history of chronic renal failure or interferon usage were not significantly related to the mean decrease in the estimated GFR over time. CONCLUSION: The introduction of imatinib therapy in nonclinical trial CML patients is associated with potentially irreversible acute renal injury, and the long-term treatment may cause a clinically relevant decrease in the estimated GFR.
Asunto(s)
Lesión Renal Aguda/inducido químicamente , Antineoplásicos/efectos adversos , Fallo Renal Crónico/inducido químicamente , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/efectos adversos , Pirimidinas/efectos adversos , Lesión Renal Aguda/fisiopatología , Adulto , Factores de Edad , Antineoplásicos/administración & dosificación , Benzamidas , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Mesilato de Imatinib , Fallo Renal Crónico/fisiopatología , Leucemia Mielógena Crónica BCR-ABL Positiva/fisiopatología , Masculino , Persona de Mediana Edad , Piperazinas/administración & dosificación , Pirimidinas/administración & dosificación , Adulto JovenRESUMEN
Imatinib mesylate (IM) is now first-line treatment for CML. To study the results of treatment with IM after IFN failure/intolerance versus allogeneic BMT (allo-BMT), we retrospectively analyzed 264 patients treated for CML in first chronic phase in three different institutions. Over a 6-year period (2001-2006), 174 patients received IM after failure of or intolerance to IFN. During the same period of time, 90 patients received an allo-BMT from an HLA-matched sibling (n=83) or an unrelated donor (n=7). The IM group was older (41 versus 33 years, P<0.001). Five-year EFS was 62% among patients receiving IM and 52% among patients undergoing allo-BMT (P=0.0002). OS at 5 years was 93% for IM-treated patients and 59% for patients undergoing allo-BMT (P<0.0001). Allo-BMT cannot be considered as first-line treatment for CML patients in first chronic phase.