Patterns Of Relapse After Salvage Autologous Hematopoietic Cell Transplantation For Hodgkin'S Lymphoma: Should Sites Of Relapse Relative To Initially Involved Sites Be Used To Guide Indications For Peritransplant Radiation Therapy

The utilization of radiotherapy (RT) in the upfront management of Hodgkin’s Lymphoma (HL) is declining in favor of chemotherapy alone favoring patterns of relapse towards initially involved sites. For patients suffering relapsed/refractory HL, autologous Hematopoietic Cell Transplantation (auto-HCT) is the preferred method of salvage therapy, where-in the role of peritransplant RT is controversial and based primarily on data formulated in subsets receiving RT as a component of upfront therapy. We aimed to assess patterns of relapse in patients undergoing salvage auto-HCT for relapsed HL with the hypothesis that patients suffering relapse at initially involved sites are at increased risks of relapse post-auto-HCT that may help guide the application of peritransplant RT. A retrospective review of 41 patients undergoing auto-HCT from 2002-2017 for relapsed or refractory HL. Three patient received peritransplant RT to a median dose of 32.5Gy. Site of relapse at time of auto-HCT and subsequent relapse were compared to sites of involvement at diagnosis using follow-up imaging (PET/CT). Relapse and overall survival were calculated from the date of auto-HCT using the Kaplan Meier method with multivariate analysis completed using Cox multivariate analysis. The median follow-up was 39 months for all patients [Interquartile Range (IQR): 18-68 months] and 48 months for surviving patients (IQR: 29-84 months). Median age at auto-HCT was 35 years (IQR: 26-50 years), stage at relapse was I-II in 49%. For upfront therapy, 81% of patients received chemotherapy alone, predominately with ABVD to a median of 6 cycles. Twenty-three patients (56%) suffered relapse following auto-HCT at a median time to relapse of 8.8 months (IQR: 3.2-12.3) with a 5-year risk of relapse of 56% (95%CI: 40-72%). Of those patients with relapse, 37% were in sites involved prior to auto-HCT, of which 86% were similarly involved at initial diagnosis and only 8% of which had RT as a part of upfront therapy. On univariate analysis, there was no difference in relapse after auto-HCT by refractory versus relapsed HL, B-symptoms at diagnosis, use of RT as part of upfront therapy or peritransplant, age at diagnosis or relapse, response to salvage chemotherapy prior to auto-HCT or stage at diagnosis or relapse. However, pre-auto-HCT relapse at an initially involved site trended toward significance for higher rates of relapse post-auto-HCT at 68% at 5-years (95%CI: 49-87%) compared to relapse at initially uninvolved sites 30% (95%CI: 8-58%), p =0.06. By multivariate analysis, initial sites of disease were more likely to be involved at relapse after auto-HCT, HR 5.85 95%CI 1.10-31.0, p =0.04. Post-auto-HCT relapse of HL are likely to occur early in initially involved sites of disease and site of relapse at an initially involved site represent an area where additional studies are needed to clarify the role of peritransplant RT.