Abstract
Background: gene profiling (GEP) revealed the main two types of DLBCL [the germinal center B-cell (GCB) and the non-germinal center or Activated B-cell lymphoma(ABC)]. Immuno-histochemistry plays an important role in differentiating between the two types using several algorithms, however, Hans algorithm and the improved Hans are considered the more reliable. Patients with GCB are still doing well in the era of type I and II anti-CD20, however, ACB patients are experiencing bad prognosis with shorter progression free and overall survival rates, therefore, we have developed a high-dense high intense protocol to treat those population with ABC. Aims: the study aims at evaluating a new dose intense chemotherapy in patients with ABC lymphoma with end points including progression free and overall survival Methods: this is a multicenter study Al Bairouni university cancer center in Damascus, Syria between 2013 and 2015 where we recruited 122 patients having ABC DLBCL confirmed by immuno-histochemistry using the improved Hans algorithm. Patients received a dose dense protocol as follows: (Rituximab 375 mg/m2 with Doxorubicin 75 mg/m2, Cyclophosphamide 1200 mg/m2, Etopdside 300 mg/m2 and Prednisolone 1 mg/kg for 5 days) repeated every 21 days for 6 cycles with 5 days G-csf support. Then partial and complete responders were given (Ifosfamide 4 gr/m2 day 1–3 + Cisplatine 40 mg/m2 day 1–3) for 4 cycles repeated every 15 days with 4 days G-csf support. Lenalidomide 10 mg/d was given upfront lasting for 1 year. End-points were progression free survival and overall survival at 5 years. Results: overall response rate (ORR) was documented in 118 patients (96.7%) (92 complete responders and 26 partial responders). 10 patients progressed at different stages of follow up with a progression free survival (PFS) of 88.6% (95% CI 83–94). However, 113 patients were found to still alive at 5 years with an overall survival (OS) rate of 92.6 (95% CI 86–97). In spite of G-csf support, neutropenia of different grades was documented in 23 patients (18.8%). Acute and transient renal failure was observed and managed in 15 patients (12.2%) mainly in the first 6 cycles. Other side effects were manageable. Summary/Conclusion: ABC forms a special entity of DLBCL carrying a bad prognosis compared with GCB subtype. Progress was made using the R-CHOP, however, results were still poor until the addition of Ibrutinib, Lenalidomide or Bortezomib to R-CHOP in different trials which improved OS to exceed 90%. In this study, we present a dose intense protocol conferring a good PFS and OS rates with acceptable toxicity profile. However, a big randomized trials including both ABC and GCB patients in order to identify factors having bad impact on progression.
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