Abstract
BackgroundPrimary refractory disease is a main challenge in the management of non-Hodgkin’s Lymphoma (NHL). This survey was performed to define the rate of refractory disease to first-line therapy in B and T-cell NHL subtypes and the long-term survival of primary refractory compared to primary responsive patients.MethodsMedical records were reviewed of 3,106 patients who had undergone primary treatment for NHL between 1982 and 2012, at the Hematology Centers of Torino and Bergamo, Italy. Primary treatment included CHOP or CHOP-like regimens (63.2%), intensive therapy with autograft (16.9%), or other therapies (19.9%). Among B-cell NHL, 1,356 (47.8%) received first-line chemotherapy with rituximab. Refractory disease was defined as stable/progressive disease, or transient response with disease progression within six months.ResultsOverall, 690 (22.2%) patients showed primary refractory disease, with a higher incidence amongst T-cell compared to B-cell NHL (41.9% vs. 20.5%, respectively, p<0.001). Several other clinico-pathological factors at presentation were variably associated with refractory disease, including histological aggressive disease, unfavorable clinical presentation, Bone Marrow involvement, low lymphocyte/monocyte ration and male gender. Amongst B-cell NHL, the addition of rituximab was associated with a marked reduction of refractory disease (13.6% vs. 26.7% for non-supplemented chemotherapy, p<0.001). Overall, primary responsive patients had a median survival of 19.8 years, compared to 1.3 yr. for refractory patients. A prolonged survival was consistently observed in all primary responsive patients regardless of the histology. The long life expectancy of primary responsive patients was documented in both series managed before and after 2.000. Response to first line therapy resulted by far the most predictive factor for long-term outcome (HR for primary refractory disease: 16.52, p<0.001).ConclusionChemosensitivity to primary treatment is crucial for the long-term survival in NHL. This supports the necessity of studies aimed to early identify refractory disease and to develop different treatment strategies for responsive and refractory patients.
Highlights
Despite improvements in the efficacy of the available treatments, there is a variable proportion of non-Hodgkin’s Lymphoma (NHL) patients displaying very poor or transient response to primary treatment. [1,2,3] These patients have primary refractory disease
Primary refractoriness remains a challenge in the management of malignant lymphoma. [4,5] several studies are investigating molecular markers that may be associated with refractory disease. [6,7,8,9,10,11] These markers might allow for early diagnosis, as well as the identification of novel therapeutic targets. [12,13,14] alternative treatment options are sought in order to improve the usually poor outcome for refractory lymphoma patients. [15,16,17]
The rate of response to first line therapy could be properly determined in 3,106 patients
Summary
Despite improvements in the efficacy of the available treatments, there is a variable proportion of non-Hodgkin’s Lymphoma (NHL) patients displaying very poor or transient response to primary treatment. [1,2,3] These patients have primary refractory disease. Response to primary treatment has relevant clinical implications, there are several open issues regarding primary refractory disease It has to be determined: (i) the real proportion of refractory patients amongst the various lymphoma subgroups; (ii) the influence of the presently available treatments on the rate of refractory disease; (iii) the actual long-term survival of primary responsive compared to primary refractory patients. To address these issues, we performed a long-term, retrospective survey on 3,106 NHL patients that had been managed over the last three decades. This survey was performed to define the rate of refractory disease to first-line therapy in B and T-cell NHL subtypes and the longterm survival of primary refractory compared to primary responsive patients
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