Do two cycles of stem cell therapy lead to longer progression free survival in relapsed or refractory HL patients?

This study determined if progression-free survival (time from treatment before disease progression) could be improved in patients with relapsed or refractory Hodgkin’s lymphoma (HL) who received two cycles (tandem) of autologous hematopoietic stem cell transplantation (AHSCT). This study concluded that tandem AHSCT appears effective in treating refractory HL patients with poor prognosis after one AHSCT cycle.

Autologous hematopoietic stem cell transplantation (AHSCT) is the standard of care for patients with relapsed or primary refractory (no remission after chemotherapy) HL. Primary refractory disease is one of the main risk factors for a poor prognosis. For these patients, progression-free survival (time from treatment before disease progression) at 5 years is less than 30%.

Approximately 50% of patients with chemotherapy-sensitive HL are cured with AHSCT therapy. Unfortunately, post-AHSCT relapse is a major cause of treatment failure. Whether two cycles of AHSCT therapy improves outcomes for poor risk HL patients remains to be determined. 

This study involved 89 patients with relapsed or refractory HL. 91% of patients had NSCHL (nodular sclerosis classical Hodgkin’s lymphoma). 83% of patients had stage 3 or 4 disease. 53% of patients had primary refractory disease. 81% of patients had disease that did not respond to salvage chemotherapy. All patients received one cycle of AHSCT therapy and 82 patients completed both cycles. Cycle 1 AHSCT was melphalan (Alkeran) and stem cell infusion. Cycle 2 AHSCT was etoposide (Etopophos) and cyclophosphamide (Cytoxan) with either total body irradiation or carmustine (BCNU), and stem cell infusion. CT scans were used to determine response to therapy. Patients were followed for an average of 6.2 years.

At follow-up, the overall response rate (tumor shrinking or disappearance) was 36%, with 5% of patients having disease progression. Progression-free survival was 63% at 2 years and 55% at 5 years. Overall survival (time from treatment to death of any cause) was 91% at 2 years and 84% at 5 years.

78.6% of patients reported severe (grade 4) side effects. 98.6% of these were blood-based side effects. Other effects included febrile neutropenia (fever associated with low white blood cell count), low phosphate in the blood, nausea, mouth sores, and loss of appetite.

This study concluded that tandem AHSCT appears effective in treating refractory HL patients with poor prognosis after only one AHSCT cycle.

This study only included 89 eligible patients out of 98 patients who enrolled, which is a small sample size. These results need to be confirmed in a larger randomized clinical trial. Because FDG-PET-CT scan data was unavailable, the number of refractory patients (53%) in this study may be overestimated. The response rate after two AHSCT cycles may also be underestimated. This study also has selection bias because research centers only enrolled high-risk patients.

If you have relapsed or refractory HL, talk to your care team about undergoing two cycles of AHSCT therapy.