Impact of Revised International Working Group Criteria on Lymphoma Patients Undergoing Autologous Stem Cell Transplantation.

Background: Fluoro-Deoxyglucose Positron Emission Tomography (PET) has shown to be more accurate than conventional CT imaging for lymphoma restaging after chemotherapy. This led to recent modifications of the International Working Group Criteria (IWC) that integrate FDG-PET in the standard assessment of response to lymphoma therapy (Cheson, 2006). PET also appears to have predictive value in patients (pts) with chemosensitive relapsed or primary refractory Hodgkin lymphoma (HL) and aggressive non-Hodgkin lymphoma (NHL) undergoing high-dose chemotherapy followed by autologous stem cell transplantation (ASCT).

Methods: To assess the impact of the revised IWC on assessment of chemosensitive disease and response assessment after ASCT, we performed a retrospective analysis of 53 pts with relapsed or refractory lymphoma planned for ASCT between 1998 and 2006, and reviewed clinical, CT, PET, and PET/CT studies. Whole-body FDG-PET scans performed after salvage (n=36) and after transplant (n=38) were utilized to compare conventional and revised IWC following salvage therapy and following ASCT. Visual analysis and lymph node/mass measurements were obtained for each CT scan and standardized uptake value (SUV) of lesions for attenuation-corrected PET scans. Overall survival (OS) for pts stratified by IWC response category were compared. Univariate and multiple variable logistic regression models were used to assess revised and conventional IWC compared with other predictive factors for one-year and two-year OS.

Results: 53 pts (35 with HL 18 with NHL) received salvage therapy with: RICE/ICE (n=30), ESHAP (n=5), and other regimen (n=18). Responsive disease to salvage chemotherapy was noted in 18 of 41 pts (9 CR, 8 CRu, 1 PR) assessed by conventional IWC and in 21 of 36 pts (16 CR, 5 PR) assessed using revised IWC. In 30 pts assessed by both methods, most pts had concordance, but 3 pts coded as stable disease by conventional IWC had progression and 2 others were determined to be in CR when PET findings were included. 47 pts proceeded to ASCT [HL (n=33), DLCL (n=12), ALCL (n=2)]. Median OS for pts achieving CR by revised IWC prior to ASCT was 25 months (range 5–50 months) compared with 12.5 months (1–63) for those who did not. In univariate models and after controlling for lymphoma histology (HL vs. NHL), age (<50 vs. >50), stage (I/II vs. III/IV), achieving revised IWC CR prior to ASCT was associated with improved likelihood of one-year (OR 15.7 adjusted, p = 0.023) and two-year survival (OR 10.4, p = 0.012); whereas conventional IWC CR was less strongly predictive of survival: one-year (OR 6.2 adjusted, p = 0.049), two-year (OR 3.9, p = 0.077) and only a significant predictor for one-year OS. Following ASCT, CR was achieved in 65% of pts at 3 months and 62% at 12 months by revised IWC.

Discussion: Revised IWC provides a method for lymphoma response assessment that has similar operating characteristics to conventional IWC in pts with relapse/refractory lymphoma without the ambiguity of unconfirmed CRs and stratifies patients into categories that are predictive of OS. Utilizing revised IWC following salvage therapy appears to offer superior prognostic ability for determining which relapsed/refractory lymphoma patients should receive ASCT. Larger retrospective and randomized studies are needed to confirm this finding.