RESUMEN
Long-term outcomes following newer therapies for chronic lymphocytic leukemia (CLL) have rarely been reported. This article presents the results of the final analysis of the Polish Adult Leukemia Group PALG-CLL2 study performed 10 years from final patient enrollment. With the extended follow-up time, it was found that cladribine (2-CdA)-based combinations CMC (2-CdA, cyclophosphamide, mitoxantrone) and CC (2-CdA, cyclophosphamide) administered as first-line treatment of progressive CLL resulted in significantly longer progression-free survival, but similar overall survival compared to 2-CdA monotherapy. Furthermore, the risk of potentially fatal late adverse events including infections, autoimmune complications and, particularly, secondary neoplasms was comparable among patients treated with CMC, CC or 2-CdA. The results of our analysis support the importance of long-term outcome monitoring of randomized trials in CLL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Causas de Muerte , Cladribina/efectos adversos , Cladribina/uso terapéutico , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Humanos , Incidencia , Leucemia Linfocítica Crónica de Células B/mortalidad , Mitoxantrona/efectos adversos , Mitoxantrona/uso terapéutico , Neoplasias Primarias Secundarias , Resultado del TratamientoAsunto(s)
Antineoplásicos/uso terapéutico , Síndrome Hipereosinofílico/tratamiento farmacológico , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Benzamidas , Enfermedad Crónica , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Síndrome Hipereosinofílico/patología , Mesilato de Imatinib , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Piperazinas/administración & dosificación , Piperazinas/farmacocinética , Pirimidinas/administración & dosificación , Pirimidinas/farmacocinética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Inducción de Remisión/métodos , Estudios Retrospectivos , Esplenomegalia/etiología , Factores de Tiempo , Adulto Joven , Factores de Escisión y Poliadenilación de ARNm/genéticaAsunto(s)
Eosinófilos/metabolismo , Síndrome Hipereosinofílico/diagnóstico , Proteínas de Fusión Oncogénica/metabolismo , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Factores de Escisión y Poliadenilación de ARNm/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Recuento de Células , Movimiento Celular , Niño , Eosinófilos/inmunología , Eosinófilos/patología , Femenino , Humanos , Síndrome Hipereosinofílico/inmunología , Síndrome Hipereosinofílico/patología , Síndrome Hipereosinofílico/fisiopatología , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Esplenomegalia , Factores de Escisión y Poliadenilación de ARNm/genéticaRESUMEN
A small subgroup of patients with hypereosinophilic syndrome (HES) demonstrates imatinib-sensitive fusion transcript-the FIP1L1-PDGFRA (F/P+). These cases are currently diagnosed as chronic eosinophilic leukaemia (CEL). In this paper, we screened 77 patients to estimate the frequency of FIP1L1-PDGFRA transcript among patients with unexplained, long-term hypereosinophilia exceeding 1.5 x 10(9)/L and to analyse the clinical and serological features in F/P+ CEL population. The FIP1L1-PDGFRA chimeric protein was detectable in 16 (14 males and 2 females) out of 77 examined HES patients (20%) by RT-PCR. Two patients suffered from cough at diagnosis. Three out of 16 (18%) patients had no organ involvements, in 5-one organ was affected and in the remaining eight cases-at least two. Eosinophilic organ damage/dysfunction identified splenomegaly in the majority of studied patients. We compared clinical and serological features between CEL F/P+ (n = 16) and HES (n = 61) patients. F/P+ cases had significantly increased WBC and absolute eosinophil count (AEC) at diagnosis (p = 0.008 and 0.02), whereas platelet count was decreased in this population (p = 0.03). Serum B12 and tryptase levels were increased (p = 0.002 and 0.004) in CEL F/P+ patients when compared to HES cases whereas serum IL-5 levels were significantly increased in the latter group (p = 0.01). Male gender and splenomegaly occurred more frequent in CEL F/P+ population (p = 0.002 and 0.0007, respectively). Additionally, patients with F/P+ CEL (n = 16) were compared with F/P- CEL (n = 8). The latter group, was significantly older, had lower AEC and higher platelet count. In conclusion, significant clinical symptoms are infrequent present and splenomegaly remains the most common organ involvement in patients with CEL expressing F/P fusion transcript. Our study confirmed the long-term remission on imatinib in this patient population.
Asunto(s)
Síndrome Hipereosinofílico/genética , Proteínas de Fusión Oncogénica/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Factores de Escisión y Poliadenilación de ARNm/genética , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Benzamidas , Tos/etiología , Femenino , Hepatomegalia/etiología , Humanos , Síndrome Hipereosinofílico/sangre , Síndrome Hipereosinofílico/complicaciones , Síndrome Hipereosinofílico/tratamiento farmacológico , Síndrome Hipereosinofílico/epidemiología , Mesilato de Imatinib , Hallazgos Incidentales , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Piperazinas/uso terapéutico , Recuento de Plaquetas , Polonia/epidemiología , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , ARN Mensajero/genética , ARN Neoplásico/genética , Esplenomegalia/etiología , Adulto JovenAsunto(s)
Antineoplásicos/uso terapéutico , Síndrome Hipereosinofílico/tratamiento farmacológico , Proteínas de Fusión Oncogénica , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas , Factores de Escisión y Poliadenilación de ARNm , Adulto , Anciano , Anciano de 80 o más Años , Benzamidas , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Síndrome Hipereosinofílico/genética , Mesilato de Imatinib , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Hypereosinophilic syndrome (HES) is defined as chronic, unexplained hypereosinophilia with organ involvement. A subset of HES patients presents an interstitial deletion in chromosome 4q12, which leads to the expression of an imatinib-responsive fusion gene, FIP1L1-PDGFRA. These patients are diagnosed as chronic eosinophilic leukaemia (CEL). We treated seven CEL and HES patients, six of which expressed FIP1L1-PDGFRA, with imatinib using initial daily doses ranging from 100 to 400 mg. In a remission maintenance phase, the patients were treated with imatinib once weekly. All imatinib-treated patients achieved a complete haematological remission (CHR), and five of the six patients with FIP1L1-PDGFRA expression exhibited molecular remission. The decreased imatinib doses were as follows: 200 mg/week in three patients, 100 mg/week in two patients and 100 mg/d in the remaining two patients. For remission maintenance, imatinib doses were set at 100 mg/week in five patients and 200 mg/week in two patients. At a median follow-up of 30 months all patients remained in CHR and FIP1L1-PDGFRA expression was undetectable in five of the six FIP1L1-PDGFRA-expressing patients. These data suggest that a single weekly dose of imatinib is sufficient to maintain remission in FIP1L1-PDGFRA- positive CEL patients.