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 µmol/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.