Diffuse Large B-cell Lymphoma (DLBCL) is the commonest subtype of Non-Hodgkin Lymphoma (NHL). Staging bone marrow (BM) biopsies in NHL are conventionally examined using histology alone, although the use of immunophenotyping to aid diagnosis is increasing. This study addresses the clinical impact of routine use of flow cytometry (FL) and immunohistochemistry (IHC) in 156 histologically proven DLBCL cases at initial diagnosis. The median age of the patient cohort was 62 years (range 20–86 years) and the gender ratio was 1.53 in favor of males. Nine patients were treated with palliative intent and were excluded from all survival analyses. The rest were treated with anthracycline based chemotherapy regimens; 36 patients received concomitant Rituximab. Median overall survival (OS) was 6.1 years (95% CI: 3.8, 8.4). Histological involvement was noted in 30 cases (19.2 %) using standardized Cheson criteria [
Cheson BD, Horning SJ, Coiffier B et al. J Clin Oncol 1999; 17:1244
]. FL and IHC (using T-cell, B-cell, and light chain markers) detected an additional 17 cases (10.9%) each with 4 cases detected by both methods. Thirty (19.2 %) patients were upstaged to stage IV with the use of these investigations (stage I: 6, stage II: 12, stage III: 12). Kaplan Meier curves demonstrated that positivity on FL, IHC and both (FL + IHC) resulted in a significantly worse OS and progression free survival (PFS) compared to negative cases. Cox proportional hazards models were used to determine the additional benefit of FL and IHC in predicting OS over histological involvement, after adjusting for age, performance status and use of Rituximab. The first analysis compared FL with histology and showed that FL added significant independent prognostic value [Histology: HR = 2.1, 95% CI 1.0, 4.3, p=0.05; FL: HR = 2.0, 95% CI 1.0, 3.8, p=0.04]. The second analysis compared histology with IHC and showed that the two had co linearity in their prediction of survival with IHC adding significantly more than histology alone [Histology: HR = 1.3, 95% CI 0.5, 3.0, p=0.6; IHC: HR = 2.3, 95% CI 1.1, 5.0, p = 0.03]. In the final model, we examined the interactive effect of FL and IHC over and above histological diagnosis and found the interaction to be the stronger predictor of OS [Histology: HR = 1.8, 95% CI 0.8, 3.7, p =0.1; FL/IHC: HR = 2.7, 95% CI 1.2, 6.2, p=0.02]. In conclusion, our results show that FL and IHC performed routinely can improve detection of BM involvement in DLBCL and upstage ~20 % patients to stage IV disease. We found that FL added significant independent prognostic value while IHC showed greater co linearity with routine histological diagnosis. The interactive effect of FL/IHC had additional benefit over routine histology in predicting survival. These results suggest that staging BM in DLBCL should have FL and IHC performed routinely at initial diagnosis.
Disclosures: No relevant conflicts of interest to declare.
