Differential Impact of Relative Dose-Intensity Reductions in Diffuse Large B-Cell Lymphoma Treated with R-CHOP21 or R-CHOP14.

DLBCL is an aggressive lymphoma treated with R-CHOP. Recently, attempts have been made to improve the outcome by increasing both dose-density and intensity but there have been no benefits in terms of survival. When treating malignancies RDI is important to consider but there is little published information on DLBCL. The purpose of this study was to analyze the differential prognostic impact of RDI in two cohorts of DLBCL patients treated with R-CHOP21 or R-CHOP14. From January 2001 to August 2013 we included DLBCL patients homogenously treated with R-CHOP21 or R-CHOP14, with or without radiotherapy, at University Hospital Son Espases, Hospital Son Llatzer of Palma and Hospital del Mar of Barcelona (N = 157). In order to avoid selection bias the patients were retrospectively identified from the Pathology Department and Pharmacy registries. Median follow-up was 68 months. There was no difference in the response or survival between the two cohorts. In the R-CHOP21 group, both a reduction higher than 15% in RDI (RR 7.41) and R-IPI (RR 2.99) were independently associated with OS. However, a reduction higher than 15% in RDI (RR 4.41) was only noted for PFS. In the R-CHOP14 group, NCCN-IPI (RR 7.09) and B-symptoms (RR 5.37) for OS; AA stage III-IV (RR 6.26) and bulky disease (RR 4.05) for PFS. There was a trend towards a higher rate of RDI reduction observed in the R-CHOP14 group but it only made an impact in the R-CHOP21 group. We conclude that R-CHOP21 and R-CHOP14 are equivalent regimens in terms of response and survival, but only if RDI reductions are avoided. For patients receiving R-CHOP21 we recommend using clinical and support measures in order to avoid RDI reductions.

Gemcitabine and oxaliplatinum: an effective regimen in patients with refractory and relapsing Hodgkin lymphoma.

BACKGROUND: Most Hodgkin lymphomas (HL) can be cured with current strategies. However, one-third of the cases do not respond or relapse and need salvage regimens. We report the results of a retrospective study using the gemcitabine and oxaliplatinum (GemOx) regimen. METHODS: Patients who relapsed or failed to achieve complete response were eligible and received GemOx salvage therapy. To avoid selection bias and thus to overcome the retrospective nature of the study, all treated patients were included from the pharmacy database. RESULTS: Between 2003-2013, 24 HL patients - relapsing (number [n]=12) or refractory (n=12) - were included, receiving a total of 26 induction treatments with GemOx. Mean previous regimens were 2.38 (42% relapsing after autologous transplantation). Median follow-up was 37 months, and 71% responded (38% of patients achieved complete response). The factors related to better progression-free survival were: B symptoms; response to GemOx; and consolidation with stem cell transplantation. Grades 1 and 2 neurological toxicity was present in 17% of patients. Hematological toxicity was common, with grades 3 and 4 neutropenia (25%) and thrombocytopenia (34%) observed. Progression-free survival was better in patients consolidated with stem cell transplantation. The peripheral blood stem cell collection after GemOx was successful for all candidates. CONCLUSION: 1) The GemOx regimen is effective in relapsed or refractory HL with manageable toxicity. 2) No mobilization failures were observed. 3) Consolidation after response is needed. 4) Its efficacy and favorable toxicity profile might make multiple administrations possible in several recurrences in HL.

Resultados del tratamiento con 2-clorodesoxiadenosina en la histiocitosis de células de Langerhans resistente o en recaída. Estudio de 9 pacientes / Results of treatment with 2-chlorodeoxyadenosine in refractory or relapsed Langerhans cell histiocytosis. Study of 9 patients

FUNDAMENTO: Analizar los resultados del tratamiento con 2-clorodesoxiadenosina (2CdA) en 9 pacientes diagnosticados de histiocitosis de células de Langerhans (HCL) multisistémica, refractaria o en recaída, atendidos en 8 hospitales españoles entre 1993 y 1999. PACIENTES Y MÉTODO: Se recogieron los siguientes datos de los 9 pacientes: edad, sexo, afección orgánica por la HCL, tratamiento inicial y respuesta al mismo, dosis, número de ciclos y forma de administración de la 2CdA, respuesta al tratamiento con 2CdA, toxicidad, supervivencia libre de enfermedad y supervivencia global. RESULTADOS: La edad mediana era de 25 años (límites, 6-63). Todos ellos presentaban afección multiorgánica por la HCL, con disfunción grave de órganos en 4 casos. La 2CdA se administró como tratamiento de segunda línea en 7 casos y de tercera línea en dos. La dosis de 2CdA fue de 0,1 mg/kg y día durante 5 días en la mayoría de los pacientes, con un intervalo de 4 semanas entre los ciclos. Hubo respuesta completa (RC) en dos casos y parcial (RP) en 4 (respuesta global del 66 por ciento). La principal toxicidad fue la hematológica, con neutropenia de grado superior a 2 en 5 casos y trombocitopenia mayor de 2 en 5. Cuatro pacientes presentaron infecciones, con evolución fatal en uno de ellos. Tras una mediana de seguimiento de 8 meses (intervalo, 2-17), dos enfermos se hallan en RC (12 meses en ambos), 4 en RP (intervalo, 2-12 meses) y uno con enfermedad activa (17 meses). Los dos restantes fallecieron por progresión de la enfermedad y sepsis por Aspergillus spp., respectivamente. Las probabilidades actuariales de supervivencia libre de enfermedad y supervivencia global al año fueron del 58 por ciento (intervalo de confianza [IC] del 95 por ciento, 38-78 por ciento) y del 71 por ciento (IC del 95 por ciento, 54-88 por ciento), respectivamente. CONCLUSIONES: La 2CdA es un fármaco eficaz en pacientes con HCL refractaria o en recaída, y su efecto tóxico principal es la mielodepresión. La utilidad de la 2CdA, aislada o en combinación con otros fármacos, en pacientes con HCL multisistémica, refractaria o en recaída, debe demostrarse en estudios controlados (AU)