Validation of the NCCN-IPI in both de novo and transformed diffuse large B cell lymphoma

The International Prognostic Index (IPI) is a clinical prognostic tool used for more than 20 years in the risk stratification of patients with de novo diffuse large B cell lymphoma (DLBCL) who received anthracycline-based chemotherapy with curative intent. [1] Since the addition of rituximab (R) to CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, patients with DLBCL have experienced a significant improvement in survival. [2–4] Consequently, the IPI [5] and the revised IPI [6] have each been validated to be relevant in the R-chemotherapy era; however, neither is able to identify patients with an overall survival of <50%. [5] The National Comprehensive Cancer Network (NCCN) pooled 1650 patients from seven cancer centers across the United States and developed the NCCN-IPI. [7] The NCCN-IPI used an incremental scoring system for age and extent of LDH elevation and specified extranodal sites associated with poorer prognosis. The NCCN was able to identify a highrisk cohort with a five-year overall survival (OS) of 33%. Historically, only patients with de novo disease were included in the studies that developed prognostic scores in DLBCL. The NCCN-IPI applicability to histologically transformed large B cell lymphomas is neither currently known, nor is there a specific prognostic tool for the setting of transformed lymphoma. We previously demonstrated comparable survivals between transformed and non-transformed lymphomas. [8] Using the same database, and with updated survival data, the objective of this current research was to validate the NCCN-IPI and to test its utility in the setting of DLBCL transformed from indolent lymphomas. The methods for identifying de novo and transformed large B cell lymphomas have been previously described. [8] In brief, all electronic chemotherapy records of R-CHOP chemotherapy dispensed between July 2001 and December 2010 at our institution were identified. Patients treated for de novo DLBCL or transformed histologies were included. R-CHOP was the only treatment offered to patients with transformed histology at our institution. The definition of transformation was primarily based on biopsy as previously described [8] and included transformation at time of diagnosis if both indolent and aggressive histologies were present in the same biopsy sample. Discordant histologies at different sites at the time of diagnosis were not considered as transformed DLBCL. Baseline characteristics were obtained for patients with de novo and transformed DLBCL and are described as medians and ranges for continuous variables and as proportions for categorical variables. IPI and NCCN-IPI scores were assigned to all patients. Continuous variables were compared by Wilcoxon rank-sum test and categorical variables by the Fisher exact test. Kaplan–Meier OS and progression-free survival (PFS) curves were generated according to the IPI and NCCN-IPI and compared using the log rank test. The generalized R statistic and Akaike’s Information Criterion (AIC) were used to assess which covariate (NCCN-IPI or IPI) was more strongly associated with OS and PFS. A smaller AIC or larger R is indicative that the model with such covariate has better goodness-of-fit and has a stronger association with the outcome. This database study was REB approved. Our cohort consisted of 316 patients, 257 with de novo DLBCL, and 59 transformed from indolent non-Hodgkin lymphomas. The median age was 64 years (IQR 54–73) and 53.8% were male. Stage III–IV disease was found in 69% of patients and 19% had decreased performance status (ECOG 2). The majority (63%) of preceding indolent histologies were follicular lymphoma followed by marginal zone (24%), as well as seven patients with chronic lymphocytic lymphoma and one with lymphoplasmacytic lymphoma. Fifty transformed patients (85%) were chemotherapy-na€ıve for their indolent lymphoma, and 13 (22%) had received prior radiation therapy. Nine patients were previously treated with chemo-therapy including