A Comparative Study Of Fludarabine-based Versus CHOP-like Regimens In Untreated Primary Indolent Lymphoma

Objective:This study compared the efficacy and safety of fludarabine-including regimens with CHOP-like regimens (cyclophosphamide doxorubicin, vincristine and prednisone) with or without rituximab as front-line chemotherapy in patients with primary indolent non-Hodgkins’lymphoma.Methods:Previously untreated patients with indolent lymphomas in Tianjin Medical University Cancer Institute Hospital and Chinese PLA General Hospital (301Hospital) from2007to2012were enrolled retrospectively. The criteria for eligibility includes:1) Diagnosis by biopsy and immunophenotypical analysis approved by WHO criteria for indolent lymphoma;2) Complete clinical records;3) Acception of standardized treatment:4-8cycles of fludarabin-based combination chemotherapy scheme and CHOP sample solution, with or without rituximab. Collecting clinical data and follow-up of the patients’cases enrolled, including stage, chemotherapy response, adverse reaction and survival analysis related indicators. Then we analyze the relevance between stage, chemotherapy response, adverse reaction and adverse reaction with application of statistical methods.Results:1.103patients with indolent lymphomas were evaluated retrospectively. Among them,53patients received CHOP or CHOP-like regimen (CHOP group) and54patients received fludarabine-based regimen (FLU group). No significant difference was found between the groups in terms of age, sex, Ann Arbor-Cotwolds stage, B-symptom, exnodal involvement, LDH level, ECOG scoring and the rate of patients receiving combination chemotherapy of rituximab.2. The FLU group had similar response compared CHOP group (OR rate:96.3%vs86.8%, P=0.093; CR rate:68.5%vs67.9%, P=0.947). There were median follow-up of26months (range2-66months), overall3-year PFS and3-year OS were68.0%and78.8%, respectively. The FLU group had a significantly better3-year PFS (75.8%vs61.0%; P=0.011), but no significant differences were observed in the 3-year OS between the two groups (82.1%vs74.8%; P=0.209).3. Most common adverse effects occurred were Ⅲ-Ⅳ grade myelosuppression, infection and gastrointestinal reaction. FLU group was associated with a higher occurrence of adverse effect (infection:27.8%vs5.7%, P=0.002; III-IV grade myelosuppression:42.6%vs7.5%, P＜0.000).4. Factors related to infection in univariate logistic regression includes the following:age over60years old, aggressive Ann Arbor-Cotwolds stage, the presence of Ⅲ-Ⅳ grade myelosuppression and the combination chemotherapy of rituximab. Factors identified in the multivariable logistic regression as being independently associated with infection were age over60years and presence of grade Ⅲ-Ⅳ myelosuppression. Univariate analysis showed the choice of chemotherapy varied the ocuruncy of Ⅲ-Ⅳ grade myelosuppression, and in the multivariable logistic regression analysis, patients who received a fludarabine-based regimen or presented with B symptom significantly related to myelosuppression.Conclusion:1. This trial showed that fludarabine-based regimen had a similar CR rate, OR rate and outcome compared with CHOP-like regimen, except a superior PFS. However, a higher rate of adverse effect was found in fludarabine-based regimen.2. The use of fludarabine was associated with a higher incidence of bone marrow suppression, which indicates anti-infection treatment was necessary after fludarabine therapy.