Patterns of Failure and Survival Outcomes after Total Lymphoid Irradiation and High-Dose Chemotherapy with Autologous Stem Cell Transplantation for Relapsed or Refractory Classical Hodgkin Lymphoma

Purpose: The patterns of failure and long-term outcomes of patients with relapsed or refractory classical Hodgkin lymphoma treated with total lymphoid irradiation (TLI) and high-dose chemotherapy followed by autologous stem cell transplantation (aSCT) are reported. Methods and Materials: Patients with biopsy-proven primary refractory or relapsed classical Hodgkin lymphoma who received salvage chemotherapy and accelerated hyperfractionated TLI before high-dose chemotherapy and aSCT were included. Patterns of failure were delineated after fusing pretransplant planning computed tomography to the scan reporting the first failure. Survival rates were computed using the Kaplan-Meier method. Multivariate analysis using proportional hazards regression was done to determine prognostic factors for overall survival (OS) and progression-free survival (PFS). Results: Between 1993 and 2016, 89 patients underwent salvage treatments. Twenty patients failed at a median of 6.1 months after aSCT. Posttreatment scans were available for 16 patients who failed in a combined 43 different sites, 11 of which were extranodal. Patients failed at multiple sites, mostly within radiation fields. The 5-, 10-, and 15-year OS rates were 72.8%, 68.0%, and 58.3%; PFS rates were 73.3%, 68.5%, and 58.7%; event-free survival rates were 72.3%, 67.5%, and 57.8% respectively. The 5- and 10- year actuarial local control rates were both 77.6%. Complete response (CR) to salvage chemotherapy was associated with statistically significant improvements in OS and PFS. Eight patients developed secondary malignancies; 5 were hematologic and 3 were solid tumors. Conclusions: Most failures were within the irradiated volume, which reflects the treatment-resistant disease biology. As part of a conditioning regimen, TLI yields good survival outcomes, particularly in patients achieving CR before transplant. However, need for RT in this setting should be assessed and new strategies should be developed to combat the treatment-resistant biology, especially in patients with less than CR after salvage chemotherapy.