A Follow-up Review of Fludarabine-cytabarine-melphalan combination - a novel high-dose chemotherapy conditioning regime for autologous peripheral blood stem cell

transplant in lymphoma
Yong Khee Guan, Tee Chuan Ong, Kian Meng Chang, Muhd Zanapiah Zakaria, Jay Suriar Rajasuriar, Jerome Tan, Sen Mui Tan, Ahlam Naila Kori, Xavier Sim. Hospital Ampang (Ampang, MY)

Background: Fludarabine-Cytabarine-Melphalan combination(FLAM) is a novel combination chemotherapy which theoretically has the advantage of being able to provide Central Nervous System penetration(high dose cytarabine) as well as 2 non-cross resistant chemotherapy drugs(Fludarabine and Melphalan) that is lympholytic and to whom many patients were previously unexposed. This is a follow-up review of the cohort presented in 2011 EBMT poster presentation. Methods: Selected patients with prior autologous peripheral blood stem cells collected(chemotherapy GCSF mobilisation) were treated in Hospital Ampang from June 2011 till October 2012 with IV Fludarabine 30mg/m^2 for 5 days, IV Cytarabine 2000mg/m^2 over 2 hours for 5 days, IV Patients Characteristics (n=39) Melphalan 140mg/m^2 for 1 day before autologous stem cell reinfusion. Most of the patient received GCSF from D3 onwards until engraftment. Patients were monitored in the ward until stable engraftment. Demographic data, disease and remission status and chemotherapy toxicity, engraftment details and follow-up data were collected. Results: There were a total of 39 patients treated. 9(23.1%) had Hodgkin Lymphoma, 30(76.9%) had Non-Hodgkin's Lymphoma in which 23(59%) had B cell lymphoma and 7(17.9%) had T cell lymphoma. The main diagnosis was DLBCL(n=19,48.7%).

Median Age Gender Male Female Diagnosis Hodgkin Lymphoma LYMPHOCYTE RICH CLASSIC HD - 1(2.6%) MIXED CELLULARITY - 1(2.6%) NODULAR SCLEROSIS - 5(12.8%) UNCLASSIFIABLE CLASSIC HD - 2(5.1%) B Cell - 23(59%) B CELL CLL/SLL 1(2.6%) DIFFUSE LARGE B CELL - 19(48.7%) FOLLICULAR LYMPHOMA GRADE 2 1(2.6%) MANTLE CELL LYMPHOMA - 2(5.1%) T Cell 7(17.9%) ANGIOIMMUNOBLASTIC T CELL LYMPHOMA 1(2.6%) ALC LYMPHOMA(T AND NULL CELL TYPE) 2(5.1%) ENTEROPATHIC TYPE INTESTINAL T CELL 1(2.6%) PRIMARY CUTANEOUS CD30 +VE T CELL 1(2.6%) SUBCUTANEOUS PANNICULITIS -LIKE 1(2.6%) T CELL PROLYMPHOCYTIC LEUKEMIA 1(2.6%) Disease Status at Transplant Complete Remission 1 Complete Remission > 1 Partial Response Primary Refractory Relapsed Refractory

39.25 years 29(74.4%) 10(25.6%)

9(23.1% of total)

NonHodgkin Lymphoma

30(76.9% of total)

10(25.6%) 6(15.4%) 14(35.9%) 1(2.6%) 8(20.5%)

57.9% had no significant oral mucositis. There was only 1(2.6%) patient with grade 3 oral mucositis, 4(10.5%) with grade 2 mucositis, 11(28.9%) with grade 1 mucositis. No grade 3 or grade 4 renal or liver toxicity was noted. Median autologous stem cell dose was 3.95 x 10^6 CD34/kg. Median day of neutrophil engraftment was D+10 and median day of platelet engraftment was D+11. There were 1 early treatment related mortality (TRM)(2.6%) due to sepsis and 3(7.7%) late TRM due to infections. Median follow-up was 7 months. 8 patients progressed or relapsed (at median of 3 months) contributing to 5 relapsed-related death. Progression free survival at 1 year was 74.3%.

Conclusions The selected cohort was a high risk cohort where 23% of the patients were frank refractory patients and 36% of patients were not in CR. FLAM is a feasible and effective high dose chemotherapy regime that could be used in combination of autologous stem cell rescue even in this cohort of high risk patients. Early TRM was acceptable and complications appeared manageable. Engraftment rates were comparable with other regimes. Longer term follow-up data is required.