Targeted Oral Busulfan (BU)/Cyclophosphamide (CY)/VP-16 and Autologous Stem Cell Transplant (ASCT) for Hodgkin's (HL) and Non-Hodgkin's Lymphoma (NHL) Results in Excellent 5-Year Survival and Low Treatment-Related Mortality: Ten-Year Single Center Experience of 246 Consecutively Treated Patients

Targeted Oral Busulfan (BU)/Cyclophosphamide (CY)/VP-16 and Autologous Stem Cell Transplant (ASCT) for Hodgkin's (HL) and Non-Hodgkin's Lymphoma (NHL) Results in Excellent 5-Year Survival and Low Treatment-Related Mortality: Ten-Year Single Center Experience of 246 Consecutively Treated Patients.

High-dose chemotherapy with ASCT has been a standard component of therapy for patients with HL and NHL for decades, however there are no randomized data supporting the superiority of any specific high-dose regimen. A recent retrospective CIBMTR analysis has suggested a potential benefit of BCNU-based regimens in patients with HL (Chen et al. Biol Blood Marrow Transplant 2015; 21:1046-1053).� We present long-term outcome data for 246 consecutive HL and NHL patients receiving ASCT at a single institution between July 2004 and December 2014.� All patients received a preparative regimen consisting of targeted oral BU (days -8 to -4, AUC targeted to 1200 �mol/L), CY (60mg/kg/d x 2 days, day -3, -2) and VP-16 (10mg/kg/d x 3 days, days -4, -3, -2).� All treatment and post-transplant care was planned to be delivered in the outpatient setting, and patients were admitted only for complications more safely managed in the inpatient setting.� The treatment cohort included 80 HL and 166 NHL (including 77 diffuse large B cell [DLBCL], 28 follicular [FL], 29 mantle cell [MCL], 27 T cell [TCL] lymphoma) patients, median age 50 [19, 71] (HL 33 [19, 67], NHL 54 [20, 71]).� CIBMTR risk group was low (CR1), intermediate (chemosensitive relapsed or resistant disease), or high (chemorefractory) in 62 (25%), 158 (64%), and 26 (11%) respectively (8%, 70%, 22% for HL; 34%, 61%, 5% for NHL).� Median follow-up for surviving patients was 64 months [6, 132].� �Non-relapse mortality (NRM) by 100 days post-transplant occurred in one patient (0.4%) and one-year NRM was 0% and 3% for HL and NHL respectively.� In NHL patients, 5-year OS for low, intermediate, and high CIBMTR� disease risk patients was 86%, 74%, and 25%; corresponding 5-year DFS was 68%, 52%, and 25% respectively (figure 1).� Five-year OS, DFS, and relapse was 77%, 59%, and 34% for DLBCL; 83%, 71%, and 20% for MCL; 76%, 48%, and 52% for FL; 70%, 48%, and 45% for TCL patients.� In HL patients, 5-year OS for low, intermediate, and high CIBMTR disease risk patients was 100%, 82%, and 72%; corresponding 5-year DFS was 67%, 58%, and 17%; and relapse was 33%, 40%, and 83% respectively.� Multivariate analysis demonstrated two factors that predicted inferior overall survival:� age ≥55 years [HR 2.16, p=0.003], CIBMTR risk group (high vs intermediate/low) [HR 2.31, p=0.017].� High CIBMTR risk status was also a risk factor for DFS [HR 3.49, p<0.001] and relapse [3.65, p<0.001].� In summary, targeted oral Bu/Cy/VP-16 and ASCT results in low NRM and excellent long-term survival in patients with NHL and HL. �Although CIBMTR high risk patients, defined by chemoresistance prior to ASCT, do not appear to benefit significantly from this approach, high-risk HL patients maintain a favorable outcome despite a high incidence of post-transplant relapse.