Predictors of delay in diagnosis and treatment in diffuse large B-cell lymphoma and impact on survival.

There is a paucity of data on the impact of diagnostic and treatment delays on outcomes in haematological malignancies, particularly in patients with diffuse large B-cell lymphoma (DLBCL). Our database of patients treated for DLBCL between 2002 and 2010 was interrogated. Univariate and multivariate analyses were performed to determine the relationship between sociodemographic or disease-specific variables and delays. Cox Regression analysis was used to discern the impact of delays on survival. Patients (n = 278) waited a median of 4 weeks before seeking medical attention. It took a median of 8 weeks for a non-haematology physician to diagnose DLBCL and refer to a haematologist. A median of 3 weeks elapsed between specialist consultation and chemotherapy initiation. In multivariate logistic regression analysis, bone marrow involvement [odds ratio (OR) = 0·41, P = 0·018], Charlson comorbidity index (OR = 1·42, P = 0·017) and urgent inpatient chemotherapy (OR = 0·40, P = 0·012) were associated with diagnostic delays >6 weeks. Lack of pathological diagnosis at the time of haematology referral was the only factor that independently predicted for treatment delays >4 weeks (OR = 8·25, P < 0·01). Diagnostic or treatment delays did not impact survival or progression-free survival. In conclusion, selected disease and patient-related factors are associated with delays in management of DLBCL, but do not impact outcomes.

Survival of patients with transformed lymphoma in the rituximab era.

In the pre-rituximab era, transformation of indolent B-cell lymphoma to diffuse large B-cell lymphoma (DLBCL) was associated with an extremely poor outcome and a median post-transformation survival ranging from 1 to 2 years. We evaluated the impact of rituximab-cyclophosphamide, adriamycin, vincristine, prednisone (R-CHOP) on the survival outcomes of transformed lymphoma compared with de novo DLBCL. Between 2002 and 2010, 317 DLBCL patients who were consecutively diagnosed and treated with R-CHOP were identified at our institution. Patients with transformed lymphoma were included if they had not previously received R-CHOP. Patient characteristics, treatment, and outcome data were retrospectively collected. Sixty patients (19 %) had transformed lymphoma of which 37 (62 %) had transformed from follicular lymphoma, 50 (83 %) were chemotherapy naïve, and 58 (96 %) were rituximab naïve at the time of treatment. With a median follow-up of 31.4 months, 231 patients achieved either complete response or complete response unconfirmed (73 %) with no significant difference between de novo DLBCL (n = 192, 75 %) and the transformed group (n = 39, 65 %) (P = 0.25). Six patients (15 %) relapsed in the transformed group at a median time to relapse of 29.3 months. The 2-year and 5-year overall survivals for all patients were 82 and 72 %, respectively. The overall and progression-free survivals for transformed lymphoma and de novo DLBCL were not statistically different (P = 0.45 and P = 0.38, respectively). With R-CHOP chemotherapy, the prognosis of transformed lymphoma in patients with minimal chemotherapy exposure for indolent disease is similar to that of de novo DLBCL.

Impact of central nervous system (CNS) prophylaxis on the incidence and risk factors for CNS relapse in patients with diffuse large B-cell lymphoma treated in the rituximab era: a single centre experience and review of the literature.

Central nervous system (CNS) prophylaxis for diffuse large B-cell lymphoma (DLBCL) is controversial with even less evidence in the era of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. We reviewed the impact of CNS prophylaxis in DLBCL patients treated with R-CHOP at a tertiary care centre over a 7-year period. CNS prophylaxis was recommended for 'higher risk' patients and consisted of intrathecal methotrexate and/or high-dose methotrexate. Of 214 patients 12·6% received CNS prophylaxis. With a median follow-up of 27 months, eight patients (3·7%) developed CNS relapse (75% isolated to the CNS and 62·5% as parenchymal brain disease) at a median time of 17 months. Patients who did not receive CNS prophylaxis had lower events (2·7%) than those who did (11·1%). Half of the CNS relapses occurred in testicular lymphoma patients, 75% of whom had received CNS prophylaxis. In multivariate analysis, testicular involvement was the only significant prognostic factor for CNS relapse (hazard ratio 33·5, P < 0·001). In conclusion, CNS relapse in DLBCL appears to present as a later, more isolated parenchymal event and at a lower rate in the rituximab era compared with historical data. R-CHOP may negate the need for CNS prophylaxis with the exception of testicular lymphoma.