Researchers from the Memorial Sloan-Kettering Cancer Center have reported that accelerated involved field fractionated radiotherapy (IFRT) followed by total lymphoid irradiation (TLI) prior to autologous stem cell transplantation (ASCT) is effected therapy for previously unirradiated patients with refractory or relapsed Hodgkin’s lymphoma (HL). The details of this study were presented at the Joint ECCO 15 – 34^th ESMO Multidisciplinary Congress in Berlin, September 20-24, 2009.[1]

ASCT has been the treatment of choice for patients with responsive relapse of HL for two decades or more. A previous study by the German Hodgkin's Lymphoma Study Group (GHSG) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation (EBMT) evaluated ASCT intensive chemotherapy without stem cell support. This study showed that patients receiving ASCT had a lower relapse rate than observed with conventional treatment. An Italian randomized trial showed an event-free survival of 63% for patients with HL transplanted at first recurrence, 50% for those transplanted beyond first relapse, and 33% for those with refractory disease. There is some evidence that the use of peripheral blood stem cells (PBSC) rather than bone marrow has further improved the results of ASCT for HL. Although ASCT may represent the best therapy for relapsed and refractory patients with HL, the optimal treatment regimen remains to be determined.

One of the more common treatment regimens used prior to ASCT for patients with HL and non-Hodgkin’s lymphoma (NHL) is high-dose cyclophosphamide and etoposide preceding or following high-dose total body irradiation (TBI). Some researchers have argued that TBI is unnecessary and can be substituted by IFRT and TLI. For example, researchers from Northwestern University have reported that 63% patients with refractory or relapsed HL become long-term disease-free survivors following a regimen of TLI, chemotherapy, and ASCT.

The current study reports outcomes of 186 previously unirradiated patients with relapsed or refractory HL who received a TLI-based regimen prior to ASCT. Patients in this study were treated between 1985 and 2008. Fifty-three percent had primary refractory disease, and 47% relapsed after a complete response (CR). After salvage chemotherapy patients were treated with accelerated IFRT to sites of disease followed by TLI and high-dose chemotherapy with etoposide and cyclophosphamide. These researchers made the following observations:

• 5- and 10-year overall survivals were 68% and 56%, respectively.
• 5- and 10-year event-free survivals were 62% and 56%, respectively.
• 5- and 10-year HL-related deaths were 21% and 29%, respectively.
• 62% of patients were alive and free of disease at last follow-up.
• Patients who achieved a CR to salvage therapy had improved outcomes.
• Primary refractory disease and extranodal disease predicted for poor outcomes.
• Introduction of peripheral blood stem cells in 1995 was associated with improved OS (P=0.06).
• Early mortality decreased over time with only one death since 1998 (1.2%).

Comments: These data confirm the long-term benefits of ASCT for patients with relapsed or refractory HL. They also suggest that TBI is not essential for cure, and patients can be treated with less RT.

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