RESUMEN
The value of prophylactic donor lymphocyte infusion (pDLI) is unclear and differs among diseases and transplantation protocols. Experience with this approach in patients with acute leukemia undergoing hematopoietic cell transplantation (HCT) with an alemtuzumab-incorporating conditioning protocol is lacking. We conducted a single-center prospective study to investigate the applicability and efficacy of prophylactic donor lymphocyte infusion (pDLI) in patients with leukemia undergoing HCT with a low-dose alemtuzumab-containing conditioning regimen. Inclusion criteria were high-risk acute myelogenous leukemia, acute lymphoblastic leukemia, or increasing mixed chimerism. All patients included were tapered off of immunotherapy. Exclusion criteria were a history of ≥ grade II or active graft-versus-host disease (GVHD). Of the 56 consecutive patients who underwent HCT with an alemtuzumab-containing regimen, 15 patients (8 with acute myelogenous leukemia and 7 with acute lymphoblastic leukemia) met the study inclusion criteria and received prophylactic DLI (total of 45 infusions) from 7 sibling donors and 8 unrelated donors. The first infusion was given at a median of 162 days posttransplantation. The median number of DLIs was 3, and the median cumulative CD3(+) cell dose was 2 × 10(6)cells/kg. Six of the 8 patients (75%) who received pDLI while in mixed chimerism converted to stable, complete donor chimerism. Some 47% of DLI recipients developed GVHD (4 acute GVHD and 3 with chronic GVHD) after a median cumulative dose of 2 × 10(6) CD3(+) cells/kg. After a median follow-up of 575 days, 11 (73%) pDLI recipients were alive. All 4 deaths were due to GVHD-related causes. None of the patients who received pDLIs relapsed. Patients with leukemia who received low-dose pDLI after conditioning with alemtuzumab are at low risk for relapse; however, this approach is associated with a relatively high incidence of severe GVHD.
Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Transfusión de Linfocitos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Hermanos , Acondicionamiento Pretrasplante , Donante no Emparentado , Adulto , Alemtuzumab , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos/efectos adversos , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Trasplante HomólogoRESUMEN
BACKGROUND: Postremission therapy is critical in maintaining complete remission (CR) in patients with de novo acute myelogenous leukemia (AML). The aim of this trial was to compare allogeneic stem cell transplantation (SCT), high-dose cytarabine (ara-C; HiDAC), and autologous SCT as postremission therapy in patients with de novo AML. METHODS: One hundred twenty patients age = 60 years with previously untreated AML (non-M3) and a performance status score of = 2 received induction therapy with 3 days of idarubicin and 7 days of ara-C (IA). Patients in CR received one course of HiDAC. Subsequently, patients age = 50 years with available HLA-compatible donors were assigned to receive allogeneic SCT; patients with "favorable" cytogenetics received a second course of HiDAC; and all others were randomized to a second course of HiDAC or autologous SCT. RESULTS: The IA combination induced CR in 99 patients (82.5%). With a median follow-up of 43 months (range, 18-64 years), the 3-year survival and failure-free survival (FFS) rates were 47% and 45%, respectively. The factors associated with longer survival were those identified for CR (i.e., age and cytogenetics). Forty-nine patients (49%) received the assigned postremission therapy. Fifteen patients underwent allogeneic SCT. Nineteen patients underwent autologous SCT and 15 patients received a second course of HiDAC, after randomization. In the allogeneic SCT group, both the 3-year survival and the FFS rates were 73%. In the autologous SCT and HiDAC groups, the 3-year survival rates were 58% and 46%, respectively (P = 0.80), and the 3-year FFS rates were 42% and 33%, respectively (P = 0.83). CONCLUSIONS: The three postremission treatment groups had comparable survival. Allogeneic SCT is associated with a prolonged FFS.
Asunto(s)
Citarabina/administración & dosificación , Leucemia Mieloide Aguda/terapia , Trasplante de Células Madre , Adolescente , Adulto , Esquema de Medicación , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Inducción de Remisión , Análisis de Supervivencia , Acondicionamiento Pretrasplante , Trasplante Autólogo , Trasplante Homólogo , Resultado del TratamientoRESUMEN
The multidrug resistance (MDR) transporter-proteins P-glycoprotein (Pgp), multidrug resistance protein (MRP) and lung resistance protein (LRP) have been associated with treatment failure. The aim of this study was to investigate prospectively the clinical significance of expression and function of the MDR proteins, considering other prognostic factors, such as age, immunophenotype, and cytogenetics. Mononuclear cells of peripheral blood or bone marrow from 61 patients with de novo acute myelogenous leukemia (AML) were analyzed. The monoclonal antibodies JSB1, MRPm6 and LRP56 were used for expression studies. Accumulation and retention studies were performed using the substrates Daunorubicin, Calcein-AM, Rhodamine-123 and DiOC(2) in the presence or absence of the modifiers Verapamil, Genistein, Probenecid, BIBW22S and PSC833. Induction treatment consisted of a 3+7 combination of Ida/Ara-C for patients < or = 60 years of age and a 3+5 Ida/VP-16 combination per OS for patients >60. MDR function was expressed as the ratio of mean fluorescence intensity substrate in the presence of modifier over the substrate alone (resistance index, RI). Patients with advanced age, low CD15 expression and high RI for accumulation of DiOC(2) in the presence of BIBW22S had significantly lower complete remission (CR) rates. No factor was prognostic for event-free survival analysis, which was limited to remitters only. Overall survival was shorter in patients with advanced age, poor prognosis cytogenetics, high CD7 expression, and high RI for Daunorubicin efflux modulated by Verapamil. These results suggest that MDR transporter-proteins have a limited role in the treatment failure of patients treated with Idarubicin-based regimens.