BuCy Provides Equivalent Outcomes to VCyTBI as Conditioning Prior to Auto-SCT in Patients with Relapsed/Refractory NHL and Is a Valuable Option in Older (≥60 years) Patients.

Cyclophosphamide+total body irradiation +/− etoposide (CyTBI+/−V) is a standard conditioning regimen prior to auto-SCT for NHL patients. However, TBI-based dose intensive therapy is often contraindicated in older patients, or those with prior radiation. We performed a single-institution Phase II non-randomized prospective study of VCyTBI vs. Busulfan+Cy (BuCy) to determine if BuCy provides comparable disease control to standard dose intensive therapy with VCyTBI. BuCy was used in patients ≥60 years and when TBI was contraindicated. Seventy-five relapsed or refractory NHL patients underwent auto-SCT at Roswell Park Cancer Institute from 8/92 to 7/05. All patients were treated on a single IRB-approved protocol with standard eligibility criteria including age ≥18 and ≤70, adequate cardiac, pulmonary, hepatic and renal function and KPS ≥70. All patients signed informed consent and were followed prospectively. All data have been de-identified. Survival status for all patients was updated through 8/1/08. VCyTBI (N=47) consisted of V 1800 mg/m² 26-hour continuous iv infusion on day -5, Cy 60 mg/kg day -4 (12 patients received 180 mg/kg total dose), and TBI 200 cGy on days -3, -2, and -1 for total dose of 1000 cGy (8 patients received 1200 cGy). BuCy (N=28) consisted of iv Bu 0.8 mg/kg every 6 hours on days -7, -6, -5, -4 (total 12.8mg, one patient received oral Bu total dose 16 mg/kg) and Cy 60 mg/kg on days -3 and -2 (total 120 mg/kg, one patient received total dose 200 mg/kg). Eight patients received iv Bu without dose adjustment and 19 received iv Bu with dose adjusted to maintain a steady state level between 600– 900 ng/ml. Stem cells were re-infused on day 0. Patients received peripheral blood stem cells (n=53), bone marrow (n=14) or both (n=8). The median age was significantly higher in the BuCy compared to the VCyTBI group (61.5 vs 53 years, p=0.0002), and there were fewer patients with a KPS of 90–100 in the VCyTBI group (75% vs 93%, p=0.07). There were no significant differences on the following patient characteristics by BuCy vs VCyTBI: gender, disease risk, stem cell source, histology (diffuse, follicular, mantle, other), or remission status at SCT. Treatment-related mortality at day+100 post-auto SCT was very low in both groups: 0% in BuCy and 2% in VCyTBI. However, 3 patients in the VCyTBI group and none in the BuCy group developed AML at 1.3, 1.8 and 6.5 years post-auto-SCT. At a median follow-up of 4.6 years, the 5-year progression-free survival for BuCy and VCyTBI was 32% (95% CI 14–50%) and 24% (95% CI, 11–39%, P>0.8), respectively. The 5-year overall survival for BuCy and VCyTBI was 46% (95% CI 25– 64%) and 49% (95% CI 33–64%, P>0.7), respectively. Multivariate analysis controlling for age and KPS at BMT also demonstrated no significant difference between BuCy and VCyTBI for either progression-free (RR=0.9, 95% CI 0.5–1.8) or overall (RR=0.7, 95% CI 0.3–1.6) survival. This is the largest reported study evaluating the efficacy of BuCy as alternative conditioning for auto-SCT in relapsed/refractory NHL. BuCy provides equivalent survival outcomes to VCyTBI as conditioning for auto-SCT in NHL patients. Based on these results, our practice continues to use BuCy for NHL patients ≥60 years.