RESUMEN
The prognostic significance of low-hypodiploidy has not been extensively evaluated in minimal residual disease (MRD)-oriented protocols for adult acute lymphoblastic leukaemia (ALL). We analysed the outcome of hypodiploid adult ALL patients treated within Programa Español de Tratamientos en Hematología (PETHEMA) protocols. The 5-year cumulative incidence of relapse (CIR) of low-hypodiploid B-cell precursor (BCP)-ALL was significantly higher than that of high-hypodiploids (52% vs. 12%, P = 0.013). Low-hypodiploid BCP-ALL patients aged ≤35 years showed superior survival (71% vs. 21%, P = 0.026) and lower 5-year CIR (17% vs. 66%, P = 0.090) than low-hypodiploids aged >35 years. Older adults and elderly low-hypodiploid BCP-ALL patients show dismal prognosis although achieving an end-induction good MRD response.
Asunto(s)
Ploidias , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Adolescente , Adulto , Factores de Edad , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras B/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Acute erythroleukemia (AEL) is a rare disease typically associated with a poor prognosis. The median survival ranges between 3-9 months from initial diagnosis. Hypomethylating agents (HMAs) have been shown to prolong survival in patients with myelodysplastic syndromes (MDS) and AML, but there is limited data of their efficacy in AEL. We collected data from 210 AEL patients treated at 28 international sites. Overall survival (OS) and PFS were estimated using the Kaplan-Meier method and the log-rank test was used for subgroup comparisons. Survival between treatment groups was compared using the Cox proportional hazards regression model. Eighty-eight patients were treated with HMAs, 44 front line, and 122 with intensive chemotherapy (ICT). ICT led to a higher overall response rate (complete or partial) compared to first-line HMA (72% vs. 46.2%, respectively; p ≤ 0.001), but similar progression-free survival (8.0 vs. 9.4 months; p = 0.342). Overall survival was similar for ICT vs. HMAs (10.5 vs. 13.7 months; p = 0.564), but patients with high-risk cytogenetics treated with HMA first-line lived longer (7.5 for ICT vs. 13.3 months; p = 0.039). Our results support the therapeutic value of HMA in AEL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Eritroblástica Aguda/tratamiento farmacológico , Leucemia Eritroblástica Aguda/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Azacitidina/administración & dosificación , Azacitidina/análogos & derivados , Biomarcadores , Médula Ósea/patología , Análisis Citogenético , Decitabina , Femenino , Humanos , Leucemia Eritroblástica Aguda/diagnóstico , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Bendamustine is an increasingly used hybrid alkylating agent that is active in lymphoid neoplasias via a novel mechanism of action. There are some pending questions about its use in clinical practice because of its developmental features. A consensus panel of several leading Spanish hematologists with broad experience in the clinical use of bendamustine has established recommendations for the management and treatment of hematological patients with bendamustine based on available clinical data and the experience of the participants. These recommendations address the dose and treatment regimen for different clinical indications, the management of toxicity, and support therapy. This article contains the conclusions of this consensus panel, which are intended to serve as guidelines for the use of bendamustine.
Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Síndrome Linfoproliferativo Autoinmune/tratamiento farmacológico , Clorhidrato de Bendamustina/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Síndrome Linfoproliferativo Autoinmune/diagnóstico , Clorhidrato de Bendamustina/administración & dosificación , Clorhidrato de Bendamustina/efectos adversos , Conferencias de Consenso como Asunto , Manejo de la Enfermedad , Humanos , Mieloma Múltiple/diagnóstico , Guías de Práctica Clínica como AsuntoRESUMEN
The role of bosutinib as rescue treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML) patients after failing three previous tyrosine kinase inhibitors (TKIs) is currently unknown. We report here the largest series (to our knowledge) of patients treated with bosutinib in fourth-line, after retrospectively reviewing 30 patients in chronic phase, and pretreated with imatinib, nilotinib, and dasatinib. With a median follow up of 11.1 months, the probability to either maintain or improve their CCyR response was 56.6% (17/30) and 11 patients (36.7%) achieved or maintained their baseline MMR. In patients not having baseline CCyR, the probabilities of obtaining CCyR, MMR, and MR4.5 were 13, 11, and 14%, respectively. The probabilities of obtaining MMR and deep molecular response MR4.5 in patients with baseline CCyR were 40.0% (6/15) and 20.0% (3/15). At 20 months, progression-free survival was 73%. Grade 3-4 hematological toxicities were more frequent in resistant than intolerant patients (45.4 vs. 0.0%). Nonhematological toxicities were also more frequent in resistant patients, being diarrhea the most conspicuous one. Bosutinib seems to be an appropriate treatment option for patients resistant or intolerant to three prior TKI's.
Asunto(s)
Compuestos de Anilina/uso terapéutico , Antineoplásicos/uso terapéutico , Ensayos de Uso Compasivo , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Nitrilos/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinolinas/uso terapéutico , Adulto , Anciano , Benzamidas/uso terapéutico , Dasatinib , Resistencia a Antineoplásicos , Femenino , Humanos , Mesilato de Imatinib , Leucemia Mieloide de Fase Crónica/enzimología , Leucemia Mieloide de Fase Crónica/mortalidad , Leucemia Mieloide de Fase Crónica/patología , Masculino , Persona de Mediana Edad , Piperazinas/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/metabolismo , Pirimidinas/uso terapéutico , Estudios Retrospectivos , España , Análisis de Supervivencia , Tiazoles/uso terapéuticoRESUMEN
Bacteremia is the most frequent infectious complication during neutropenia in patients receiving autologous hematopoietic stem cell transplantation (ASCT). The objective of this study was to analyze the incidence, characteristics, risk factors, and outcome of bacteremia during the early period after ASCT. A total of 720 patients undergoing ASCT in two observational prospective consecutive multicenter studies of the Programa Español para el Tratamiento de las Hemopatías group were analyzed. Bacteremia occurred in 20 % of patients. Coagulase-negative Staphylococcus was the most frequent (66 %) among the gram-positive agents and Escherichia coli (49 %) among the gram-negative agents. Multivariate analysis showed that the length of neutropenia <1 × 10(9)/L (more than 9 days) [relative risk (RR) of 2.6, p < 0.001] was the sole risk factor for overall bacteremia. We identified the length of neutropenia <1 × 10(9)/L (more than 9 days) (RR 4.98, p < 0.001) and the use of prophylactic fluoroquinolones (RR 0.46, p < 0.01) as specific risk factors for gram-negative bacteremia. Risk factors for gram-positive bacteremia were the use of total parenteral nutrition (RR 1.92, p < 0.01) and deep neutropenia (<0.1 × 10(9)/L), with duration over 5 days (RR 1.67, p < 0.027). Bacteremia showed an increased morbidity with no impact on neither overall nor infectious related mortality. The identification of such risk factors may be helpful to implement prophylactic and therapeutic risk-adapted strategies to reduce the incidence of bacteremia in ASCT.
Asunto(s)
Antibacterianos/administración & dosificación , Bacteriemia , Fluoroquinolonas/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Neoplasias/terapia , Neutropenia , Adolescente , Adulto , Anciano , Autoinjertos , Bacteriemia/epidemiología , Bacteriemia/etiología , Bacteriemia/prevención & control , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neutropenia/epidemiología , Neutropenia/etiología , Neutropenia/microbiología , Neutropenia/terapia , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
Few studies have examined the outcome of large numbers of patients with the microgranular variant (M3V) of acute promyelocytic leukemia (APL) in the all-trans retinoic acid era. Here, the outcome of 155 patients treated with all-trans retinoic acid-based therapy on 3 clinical trials, North American Intergroup protocol I0129 and Programa para el Estudio de la Terapéutica en Hemopatía Maligna protocols LPA96 and LPA99, are reported. The complete remission rate for all 155 patients was 82%, compared with 89% for 748 patients with classical M3 disease. The incidence of the APL differentiation syndrome was 26%, compared with 25% for classical M3 patients, and the early death rate was 13.6% compared with 8.4% for patients with classical M3 morphology. With a median follow-up time among survivors of 7.6 years (range 3.6-14.5), the 5-year overall survival, disease-free survival, and cumulative incidence of relapse for patients with M3V were 70%, 73%, and 24%, respectively. With a median follow-up time among survivors of 7.6 years (range 0.6-14.3), the 5-year overall survival, disease-free survival, and cumulative incidence of relapse among patients with classical M3 morphology were 80% (P = .006 compared with M3V), 81% (P = .07), and 15% (P = .005), respectively. When outcomes were adjusted for the white blood cell count or the relapse risk score, none of these outcomes were significantly different between patients with M3V and classical M3 APL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Lactante , Leucemia Promielocítica Aguda/clasificación , Masculino , Persona de Mediana Edad , Inducción de Remisión , Tasa de Supervivencia , Resultado del Tratamiento , Tretinoina/administración & dosificación , Adulto JovenRESUMEN
This is a randomized phase-2 trial aimed to compare consolidation vs. maintenance in untreated patients with follicular lymphoma (FL) responding to induction. 146 patients were enrolled from 25 Spanish institutions (ZAR2007; ClinicalTrials.gov #NCT00662948). Patients in PR or CR/CR[u] after R-CHOP were randomized 1:1 to 90Y-ibritumomab-tiuxetan 0.4 mCi/kg (arm A) vs. rituximab 375 mg/m2 every 8 weeks for 2 years (arm B). After a median follow-up of 10.55 years, 53 patients eventually progressed with a 10-year PFS of 50% vs. 56% for patients in arm A and B, respectively (HR = 1.42; p > 0.1). No significant differences were seen in OS (10-year OS 78% vs. 84.5%; HR = 1.39, p > .1). Patients receiving 90Y-ibritumomab-tiuxetan showed higher incidence of second neoplasms than those in arm B (10-year cumulative incidence 18.5 vs. 2%, respectively; p = .038). In conclusion, in FL patients responding to R-CHOP, no significant differences were found between consolidation and maintenance, although with higher late toxicity for consolidation.
Asunto(s)
Linfoma Folicular , Anticuerpos Monoclonales , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Supervivencia sin Enfermedad , Estudios de Seguimiento , Humanos , Linfoma Folicular/diagnóstico , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/etiología , Radioinmunoterapia/métodos , Rituximab/efectos adversos , Resultado del Tratamiento , Radioisótopos de Itrio/uso terapéuticoRESUMEN
Differentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all-trans retinoic acid (ATRA). Detailed knowledge about DS has remained limited. We present an analysis of the incidence, characteristics, prognostic factors, and outcome of 739 APL patients treated with ATRA plus idarubicin in 2 consecutive trials (Programa Español de Tratamientos en Hematología [PETHEMA] LPA96 and LPA99). Overall, 183 patients (24.8%) experienced DS, 93 with a severe form (12.6%) and 90 with a moderate form (12.2%). Severe but not moderate DS was associated with an increase in mortality. A bimodal incidence of DS was observed, with peaks occurring in the first and third weeks after the start of ATRA therapy. A multivariate analysis indicated that a WBC count greater than 5 x 10(9)/L and an abnormal serum creatinine level correlated with an increased risk of developing severe DS. Patients receiving systematic prednisone prophylaxis (LPA99 trial) in contrast to those receiving selective prophylaxis with dexamethasone (LPA96 trial) had a lower incidence of severe DS. Patients developing severe DS showed a reduced 7-year relapse-free survival in the LPA96 trial (60% vs 85%, P = .003), but this difference was not apparent in the LPA99 trial (86% vs 88%).
Asunto(s)
Antraciclinas/uso terapéutico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/patología , Tretinoina/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Supervivencia sin Enfermedad , Quimioterapia Combinada , Femenino , Humanos , Leucemia Promielocítica Aguda/complicaciones , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Factores de Riesgo , Síndrome , Factores de TiempoRESUMEN
Chronic Lymphocytic Leukemia (CLL) is the most prevalent leukemia in Western countries and is notable for its variable clinical course. This variability is partly reflected by the mutational status of IGHV genes. Many CLL samples have been studied in recent years by next-generation sequencing. These studies have identified recurrent somatic mutations in NOTCH1, SF3B1, ATM, TP53, BIRC3 and others genes that play roles in cell cycle, DNA repair, RNA metabolism and splicing. In this study, we have taken a deep-targeted massive sequencing approach to analyze the impact of mutations in the most frequently mutated genes in patients with CLL enrolled in the REM (rituximab en mantenimiento) clinical trial. The mutational status of our patients with CLL, except for the TP53 gene, does not seem to affect the good results obtained with maintenance therapy with rituximab after front-line FCR treatment.
Asunto(s)
Ciclofosfamida/administración & dosificación , Regulación Leucémica de la Expresión Génica , Inmunoterapia/métodos , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/terapia , Mutación , Rituximab/administración & dosificación , Vidarabina/análogos & derivados , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Análisis Mutacional de ADN , Femenino , Genómica , Humanos , Masculino , Persona de Mediana Edad , Empalme del ARN , Vidarabina/administración & dosificaciónRESUMEN
BACKGROUND AND AIM: Flow cytometry (FCM) analysis of cerebrospinal fluid (CSF) is more sensitive than conventional cytology (CC) for diagnosis of lymphomatous meningeosis, but the clinical significance of occult central nervous system (CNS) disease (positive FCM with negative CC) remains unknown. PATIENTS AND METHODS: CSF samples from 105 patients with newly diagnosed aggressive lymphomas at high risk of CNS involvement were prospectively studied by both CC and FCM, and results were correlated with cumulative incidence of CNS relapse and overall survival (OS). Patients were divided into three groups: 1) patients without CNS involvement (CC-/FCM-; n=83); 2) individuals with occult CNS disease (FCM+/CC-; n=15); and 3) cases with CNS disease (CC+/FCM+; n=7). RESULTS: Six cases showed CNS relapse or progression: two in Group 1 (2.4%), two in Group 2 (13%) and two in Group 3 (28.5%) (Group 2 vs. 1, P=0.04; Group 3 vs. 1, P<0.001). Patients from Groups 2 (P=0.05) and 3 (P<0.001) also showed a higher cumulative incidence of CNS relapse than those from Group 1. Significant differences were observed in OS between FCM-/CC- and FCM+/CC+ cases (P=0.02), while patients with occult CNS disease (FCM+/CC-) displayed intermediate OS rates, although differences did not reach statistical significance. CONCLUSIONS: The presence of occult CNS involvement at diagnosis in patients with NHL at high risk of CNS disease is associated with a higher probability of CNS relapse.
Asunto(s)
Neoplasias del Sistema Nervioso Central/líquido cefalorraquídeo , Neoplasias del Sistema Nervioso Central/diagnóstico , Citometría de Flujo/métodos , Linfoma no Hodgkin/líquido cefalorraquídeo , Linfoma no Hodgkin/diagnóstico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades del Sistema Nervioso Central/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso Central/complicaciones , Enfermedades del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/complicaciones , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/patología , Femenino , Humanos , Linfoma no Hodgkin/complicaciones , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/patología , Masculino , Microscopía/métodos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Recurrencia , Factores de Riesgo , RituximabRESUMEN
BACKGROUND: Between 30% and 60% of patients with thrombotic thrombocytopenic purpura (TTP) relapse and mortality remains at 15-20%. Limited clinical data suggest that the administration of anti-CD20 antibody (rituximab) may be useful in preventing acute refractory and chronic relapsing TTP. DESIGN AND METHODS: We studied the clinical response to rituximab in 24 adult patients (median age 42 years, range 24-72 years) from 15 Spanish centers with an acute refractory (14 patients) or acute relapsing (10 patients) episode of idiopathic TTP. On admission, every patient received daily plasma exchange (PE). Rituximab was administered at a dose of 375 mg/m(2) weekly for a median of 13 days (range 0-57 days) after starting PE for a median of 4 doses (range 1-8 doses). RESULTS: No severe acute or delayed toxicity was observed in the patients treated with rituximab. Three (12.5%) patients died because of TTP-related causes. The remaining 21 (87.5%) patients achieved complete remission in a median of 21 days (range 2-35 days) after initiating rituximab. After a median follow-up of 30 months (range 7.5-74 months), 18 patients are in remission and 3 patients have relapsed at 7, 29, and 29 months. CONCLUSIONS: Rituximab appears to be a safe, effective therapy and has a high response rate for the treatment of acute refractory or relapsing idiopathic TTP in adult patients.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Terapia Recuperativa/métodos , Adulto , Anciano , Evaluación de Medicamentos , Humanos , Persona de Mediana Edad , Intercambio Plasmático , Púrpura Trombocitopénica Trombótica/terapia , Estudios Retrospectivos , Rituximab , España , Resultado del Tratamiento , Adulto JovenRESUMEN
We analyzed the efficacy of imipenem/cilastatin alone (group I, 197 patients) or in combination with a glycopeptide (group I + G, 231 patients) as first-line antibiotic therapy for 2 consecutive cohorts of autologous stem cell transplantation (ASCT) recipients with febrile neutropenia. From June 2001 to June 2002, patients received imipenem/cilastatin (500 mg/6 hours), and from July 2002 to December 2003, they received imipenem/cilastatin as for group I plus a glycopeptide (vancomycin, 1 g/12 hours or teicoplanin, 400 mg/day). Fever of unknown origin accounted for 33.5% of episodes (66 patients) in group I and 50% of episodes (116 patients) in group I + G (P = .005). Bacteremia occurred in 55 patients (28%) in group I and in 51 patients (22%) in group I + G (P = .16). Resolution of fever without modification of the therapy regimen was observed in 108 patients (55%) and 159 patients (69%) in groups I and I + G, respectively (P = .003). The median interval to defervescence (4 days) and overall mortality were similar between groups. Inclusion of a glycopeptide in the initial antibiotic regimen for febrile neutropenia results in a higher success rate without modifying the regimen. However, glycopeptide inclusion does not improve the interval to defervescence or mortality rate.
Asunto(s)
Antibacterianos/administración & dosificación , Bacteriemia/tratamiento farmacológico , Cilastatina/administración & dosificación , Glicopéptidos/administración & dosificación , Imipenem/administración & dosificación , Neutropenia/tratamiento farmacológico , Inhibidores de Proteasas/administración & dosificación , Trasplante de Células Madre , Adolescente , Adulto , Anciano , Bacteriemia/mortalidad , Supervivencia sin Enfermedad , Femenino , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Neutropenia/mortalidad , Estudios Retrospectivos , España , Tasa de Supervivencia , Teicoplanina/administración & dosificación , Trasplante Autólogo , Vancomicina/administración & dosificaciónRESUMEN
BACKGROUND: The prevalence of and risk factors for central nervous system recurrence in patients with acute promyelocytic leukemia are not well established and remain a controversial matter. DESIGN AND METHODS: Between 1996 and 2005, 739 patients with newly diagnosed acute promyelocytic leukemia enrolled in two consecutive trials (PETHEMA LPA96 and LPA99) received induction therapy with all-trans retinoic acid and idarubicin. Consolidation therapy comprised three courses of anthracycline monochemotherapy (LPA96), with all-trans retinoic acid and reinforced doses of idarubicin in patients with an intermediate or high risk of relapse (LPA99). Central nervous system prophylaxis was not given. RESULTS: Central nervous system relapse was documented in 11 patients. The 5-year cumulative incidence of central nervous system relapse was 1.7% (LPA96 3.2% and LPA99 1.2%; p=0.09). The cumulative incidence was 0%, 0.8%, and 5.5% in low-, intermediate-, and high-risk patients, respectively. Relapse risk score (p=0.0001) and the occurrence of central nervous system hemorrhage during induction (5-year cumulative incidence 18.7%, p=0.006) were independent risk factors for central nervous system relapse. CONCLUSIONS: This study shows a low incidence of central nervous system relapse in patients with acute promyelocytic leukemia following therapy with all-trans retinoic acid and anthracycline without specific central nervous system prophylaxis. Central nervous system relapse was significantly associated with high white blood cell counts and prior central nervous system hemorrhage, which emerged as independent prognostic factors.
Asunto(s)
Antibióticos Antineoplásicos/agonistas , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Idarrubicina/administración & dosificación , Leucemia Promielocítica Aguda/tratamiento farmacológico , Tretinoina/administración & dosificación , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Factores de RiesgoRESUMEN
BACKGROUND: The role of re-treatment with rituximab in aggressive B-cell lymphomas still needs to be defined. This study evaluated the influence of prior exposure to rituximab on response rates and survival in patients with diffuse large B-cell lymphoma treated with rituximab plus etoposide, cytarabine, cisplatinum and methylprednisolone (R-ESHAP). DESIGN AND METHODS: We retrospectively analyzed 163 patients with relapsed or refractory diffuse large B-cell lymphoma who received R-ESHAP as salvage therapy with a curative purpose. Patients were divided into two groups according to whether rituximab had been administered (n=94, "R+" group) or not (n=69, "R-" group) prior to R-ESHAP. RESULTS: Response rates were significantly higher in the R- group in the univariate but not in the multivariate analysis. In the analysis restricted to the R+ group, we observed very low complete remission and overall response rates in patients with primary refractory disease (8% and 33%, respectively), as compared to those in patients who were in first partial remission (41% and 86%) or who had relapsed disease (50% and 75%) (p<0.01 in both cases). Overall, 60% and 65% of patients in the R+ and R- groups, respectively, underwent stem-cell transplantation after the salvage therapy. With a median follow-up of 29 months (range, 6-84), patients in the R+ group had significantly worse progression-free survival (17% vs. 57% at 3 years, p<0.0001) and overall survival (38% v 67% at 3 years, p=0.0005) than patients in the R- group. Prior exposure to rituximab was also an independent adverse prognostic factor for both progression-free survival (RR: 2.0; 95% CI: 1.2-3.3, p=0.008) and overall survival (RR: 2.2; 95% CI: 1.3-3.9, p=0.004). CONCLUSIONS: R-ESHAP was associated with a high response rate in patients who were not refractory to upfront rituximab-based chemotherapy. However, the survival outcome was poor for patients previously exposed to rituximab, as compared to in those who had not previously been treated with rituximab.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Terapia Recuperativa/métodos , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Cisplatino/administración & dosificación , Citarabina/administración & dosificación , Dexametasona/administración & dosificación , Etopósido/administración & dosificación , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Rituximab , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: Central nervous system (CNS) involvement in patients diagnosed with acute leukemias (AL) is an uncommon complication with poor prognosis. The indication and the schedules of prophylaxis and treatment of CNS involvement in AL are not homogenous among countries and within the same country. The aim of this prospective longitudinal study was to analyze and report the practice of CNS prophylaxis and treatment in patients with AL in Spain. PATIENTS AND METHOD: Prospective study conducted from June 2005 to June 2006. Adult patients (> or = 18 yr.) diagnosed with AL who received CNS prophylaxis or treatment were consecutively included through online registration. RESULTS: 265 patients from 32 hospitals were included. Mean (standard deviation) age was 44 (16) yr. and 133 (50%) were males. For acute lymphoblastic leukemia patients (n = 158), CNS therapy was given to 12 cases (10 at diagnosis and 2 at relapse) and consisted of triple intrathecal therapy (TIT, methotrexate, cytarabine and hydrocortisone) in 11 and liposomal depot cytarabine in one. CNS prophylaxis (n = 146) consisted of TIT in 135 cases, intrathecal methotrexate in 7, intrathecal cytarabine in 2 and intrathecal liposomal depot cytarabine in 2. No cranial irradiation either for prophylaxis or therapy was given in any case. In acute myeloblastic leukemia patients (n = 107), CNS therapy was administered to 17 cases (9 at diagnosis and 8 at relapse). Intrathecal therapy consisted of TIT in 11, intrathecal liposomal depot cytarabine in 5 and intrathecal cytarabine in one. One patient also received craniospinal irradiation. CNS prophylaxis (n = 90) consisted of TIT in 68 cases and intrathecal methotrexate in 22. CONCLUSIONS: In Spain, the patterns of CNS prophylaxis and therapy for AL are homogeneous. TIT was the most frequent schedule for CNS prophylaxis and therapy. The lack of use of cranial or craniospinal irradiation and the administration of new drugs (i.e.: liposomal depot cytarabine) for CNS therapy and prophylaxis is of note.
Asunto(s)
Neoplasias del Sistema Nervioso Central/prevención & control , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Sistema de Registros , Adolescente , Adulto , Antiinflamatorios/administración & dosificación , Antimetabolitos Antineoplásicos/administración & dosificación , Citarabina/administración & dosificación , Quimioterapia Combinada , Femenino , Humanos , Hidrocortisona/administración & dosificación , Inyecciones Espinales , Liposomas , Estudios Longitudinales , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Estudios Prospectivos , EspañaRESUMEN
BACKGROUND AND OBJECTIVE: Central nervous system (CNS) involvement in patients diagnosed with non-Hodgkin's lymphoma (NHL) or other lymphoproliferative disorders is an infrequent complication with a poor prognosis. The prophylaxis and treatment of CNS involvement in these patients are not homogenous. The aim of this prospective longitudinal study was to report the current practice of CNS prophylaxis and treatment in patients with lymphoproliferative disorders in Spain. METHODS: Prospective study conducted from June 2005 to June 2006. Adult patients (> or = 18 yr) diagnosed with NHL or other lymphoproliferative disorders who received CNS prophylaxis or treatment were consecutively included through online registration. RESULTS: 228 patients from 33 hospitals were included. The mean (SD) age was 52 (16) yr and 144 (63%) were males. CNS therapy was given to 41 cases and consisted of triple intrathecal (IT) therapy (TIT, methotrexate, cytarabine and hydrocortisone) in 22, liposomal depot cytarabine in 18 and methotrexate in one. In addition, 4 patients received cranial radiotherapy. CNS prophylaxis (n = 187) consisted of TIT (166 cases), IT methotrexate (17), IT liposomal depot cytarabine (3) and IT cytarabine (1), whereas cranial or craniospinal radiotherapy was administered to 2 patients. The main reasons for CNS prophylaxis cited by the investigators included extranodal involvement (89 patients), raised serum lactate dehydrogenase level (87), IPI score > 2 (62), bulky mass (43), extranodal involvement in more than one organ (33), age over 60 yr (28) and human immunodeficiency virus infection (13). CONCLUSIONS: The results of this study point out the generalized use of TIT therapy both for CNS prophylaxis and therapy in patients with lymphoproliferative disorders in Spain. The introduction of the new formulations of drugs, especially liposomal depot cytarabine for CNS involvement, and the scarce use of radiotherapy are also of note. Similar to other studies, the absence of homogeneous criteria for CNS prophylaxis is of note.
Asunto(s)
Neoplasias del Sistema Nervioso Central/prevención & control , Linfoma no Hodgkin/terapia , Neoplasias del Sistema Nervioso Central/etiología , Neoplasias del Sistema Nervioso Central/terapia , Femenino , Humanos , Linfoma no Hodgkin/complicaciones , Masculino , Estudios Prospectivos , EspañaRESUMEN
Intrathecal (IT) depot liposomal cytarabine is useful in solid tumors or lymphomatous meningitis, but has scarcely been used in central nervous system (CNS) involvement in acute leukemia. We report the results of compassionate therapy with IT depot liposomal cytarabine in 10 patients with acute myeloid leukemia with CNS involvement. Five of 6 cases receiving this drug as the only IT therapy and the remaining 4 receiving it as adjuvant therapy to other CNS-directed therapies showed clearance of cerebrospinal fluid blast cells, with sustained response in 5 and mild side effects. Systemic therapy was given concomitantly in all cases, with high-dose cytarabine in 6. Clinical trials should establish the role of IT liposomal cytarabine in leukemic meningitis.
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Antimetabolitos Antineoplásicos/administración & dosificación , Citarabina/administración & dosificación , Leucemia Mieloide Aguda , Infiltración Leucémica/tratamiento farmacológico , Meninges/patología , Adulto , Femenino , Humanos , Inyecciones Espinales , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Infiltración Leucémica/complicaciones , Liposomas , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , España , Reino UnidoRESUMEN
PURPOSE: To analyze the simultaneous combination of all-trans retinoic acid (ATRA) and anthracycline monochemotherapy for children with acute promyelocytic leukemia (APL). PATIENTS AND METHODS: Since November 1996, 66 children (younger than 18 years) with genetically proven APL received induction therapy with ATRA and idarubicin. Consolidation therapy consisted of three courses of anthracycline monochemotherapy. After November 1999, patients with intermediate and high risk of relapse received consolidation therapy with ATRA and slightly reinforced doses of idarubicin. Maintenance therapy consisted of ATRA and low-dose mercaptopurine and methotrexate. RESULTS: Thirty-nine girls (59%) and 27 boys (41%) were included in this study. The WBC count at presentation was more than 10 x 10(9)/L in 26 patients (39%). Sixty-one children (92%) achieved complete remission (CR). Early deaths from hemorrhage and retinoic acid syndrome occurred in three patients and two patients, respectively. Toxicity was manageable during consolidation and maintenance therapy. No deaths in CR, clinical cardiomyotoxicity, or secondary malignancy occurred. Two patients had molecular persistence at the end of consolidation. Three clinical relapses and two molecular relapses were also observed. Apart from one molecular relapse, all these events occurred among children with hyperleukocytosis. The 5-year cumulative incidence of relapse was 17%, whereas disease-free and overall survival rates were 82% and 87%, respectively. CONCLUSION: A high incidence of hyperleukocytosis in children with APL was confirmed. Besides low toxicity and a high degree of compliance, a risk-adapted therapy combining ATRA and anthracycline monochemotherapy showed an antileukemic efficacy comparable to those previously reported with other chemotherapy combinations in children.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adolescente , Antraciclinas/administración & dosificación , Niño , Preescolar , Femenino , Humanos , Idarrubicina/administración & dosificación , Incidencia , Leucemia Promielocítica Aguda/epidemiología , Masculino , Mercaptopurina/administración & dosificación , Metotrexato/administración & dosificación , Pronóstico , Inducción de Remisión , Factores de Riesgo , Tasa de Supervivencia , Tretinoina/administración & dosificaciónRESUMEN
Waldenström's macroglobulinemia (WM) is a lymphoid malignancy characterized by infiltration, mainly of the bone marrow and lymph nodes, by small mature lymphocytes showing plasmacytoid differentiation, associated with an IgM monoclonal band, and, in general, a low degree of aggressiveness. We present the first case reported in the Spanish literature of interstitial lung disease presenting as MW and we review the literature.
Asunto(s)
Enfermedades Pulmonares Intersticiales/etiología , Macroglobulinemia de Waldenström/complicaciones , Anciano , Humanos , Masculino , Macroglobulinemia de Waldenström/diagnósticoRESUMEN
PURPOSE: We analyzed the incidence, risk factors, and outcome of therapy-related myeloid neoplasms (t-MNs) in patients with acute promyelocytic leukemia (APL) in first complete remission (CR). PATIENTS AND METHODS: From 1996 to 2008, 1,025 patients with APL were enrolled onto three sequential trials (LPA96, LPA99, and LPA2005) of the Programa Español para el Tratamiento de Enfermedades Hematológicas and received induction and consolidation therapy with all-trans-retinoic acid (ATRA) and anthracycline-based chemotherapy. RESULTS: Seventeen of 918 patients who achieved CR developed t-MN (10 with < 20% and seven with > or = 20% of bone marrow blasts) after a median of 43 months from CR. Partial and complete deletions of chromosomes 5 and 7 (nine patients) and 11q23 rearrangements (three patients) were the most common cytogenetic abnormalities. Overall, the 6-year cumulative incidence of t-MN was 2.2%, whereas in low-, intermediate-, and high-risk patients, the 6-year incidence was 5.2%, 2.1%, and 0%, respectively. Multivariate analysis identified age more than 35 years and lower relapse risk score as independent prognostic factors for t-MN. The median overall survival time after t-MN was 10 months. CONCLUSION: t-MN is a relatively infrequent, long-term, and severe complication after first-line treatment for APL with ATRA and anthracycline-based regimens. Therapeutic strategies to reduce the incidence of t-MN are warranted.