RESUMEN
BACKGROUND: Immunoglobulin replacement therapy is recommended in case of severe hypogammaglobulinemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the supposed increased risk of infection in case of hypogammaglobulinemia has not been confirmed in allo-HSCT. In this study, we assessed the relationship between the gamma globulin level and the risk of infection during the 100 days following the allo-HSCT. METHODS: We gathered the weekly laboratory tests from day 7 to day 100 of 76 allograft patients, giving a total of 1 044 tests. 130 infections were documented clinically, by imaging, or microbiologically. RESULTS: Average gamma globulin levels between D-7 and D100 did not differ between patients with or without infection (642 ± 232 and 671 ± 246 mg/dL, respectively, P = .65). Gamma globulin level <400 mg/dl was not associated with the occurrence of infection between the test studied and the next one (aOR 1.33 [0.84-2.15], P = .24). The gamma globulin level was not predictive of bacterial or fungal infections (AUC 0.54 [95%CI: 0.47-0.61]) nor of viral reactivations (AUC 0.51 [95%CI: 0.43-0.60]). CONCLUSIONS: This confirmed that the humoral deficiency is a minor part of the immune deficiency in the 100 days post-transplant. This questions the relevance of the indications of immunoglobulin substitution during this period.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Inmunoglobulinas Intravenosas/uso terapéutico , Síndromes de Inmunodeficiencia/terapia , Leucemia/terapia , Linfoma/terapia , Síndromes Mielodisplásicos/terapia , Infecciones Oportunistas/diagnóstico , Anciano , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/inmunología , Infecciones Bacterianas/microbiología , Ciclosporina/administración & dosificación , Ciclosporina/efectos adversos , Femenino , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/patología , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Síndromes de Inmunodeficiencia/etiología , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/patología , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Leucemia/inmunología , Leucemia/patología , Linfoma/inmunología , Linfoma/patología , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/efectos adversos , Micosis/diagnóstico , Micosis/inmunología , Micosis/microbiología , Agonistas Mieloablativos/uso terapéutico , Síndromes Mielodisplásicos/inmunología , Síndromes Mielodisplásicos/patología , Infecciones Oportunistas/inmunología , Infecciones Oportunistas/microbiología , Infecciones Oportunistas/virología , Pronóstico , Curva ROC , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo , Activación Viral/efectos de los fármacos , gammaglobulinas/metabolismoRESUMEN
PURPOSE: Cytarabine, a key chemotherapy agent for acute myeloid leukemia (AML) treatment, is deaminated into inactive uracil-arabinoside by cytidine deaminase. This deamination leads to samples stability issues with respect to clinical pharmacokinetic trials. The aim of our study was to study in vitro cytarabine stability in blood samples obtained from AML patients. METHODS: Cytarabine quantification was performed using a fully validated LC/MS/MS method. In vitro cytarabine stability was assessed at room temperature over 24 h in samples coming from 14 AML patients and 7 control patients (CTRL) with no hematological malignancy. In vitro concentrations versus time data were analyzed using a noncompartmental approach. RESULTS: Cytarabine in vitro area under the curve (AUCIVlast) was 22-fold higher in AML samples as compared to CTRL samples (AML mean (standard deviation (SD)), 51,829 (27,004) h ng/mL; CTRL mean (SD), 2356 (1250) h ng/mL, p = 0.00019). This increase was associated with a prolonged in vitro degradation half-life (t1/2IVdeg AML mean (SD), 15 (11.8) h; CTRL mean (SD), 0.36 (0.37) h, p = 0.0033). Multiple linear regression analysis showed that AML diagnosis significantly influenced t1/2IVdeg and AUCIVlas relationship. CONCLUSION: Cytarabine stability is higher in AML than in CTRL samples. The absence of correlation between t1/2IVdeg and AUCIVlast in AML samples suggests that in vitro cytarabine degradation in AML is complex. These results open perspectives including the evaluation of the clinical relevance and the involved molecular mechanisms.
