NEW YORK (Reuters Health) – Reducing exposure to alkylating agents in patients with Hodgkin lymphoma is key to reducing the risk of developing therapy-related acute myeloid leukemia or myelodysplastic syndrome (t-AML/MDS), reports a group from Stanford University, California.

The finding emerged from an analysis of outcomes in three groups of clinical trials conducted between 1974 and 2003 involving a total of 754 patients with Hodgkin lymphoma (HL). “Successive generations of HL treatments at Stanford, specifically the Stanford V regimen, demonstrate a significantly lower risk of t-AML/MDS without compromising efficacy, which was one of the important goals in the development of the latter regimen,” the researchers report in the Journal of Clinical Oncology online January 7.

Dr. Ranjana H. Advani and colleagues explain that, compared to earlier chemotherapy regimens, the Sanford V regimen reduced the dose of nitrogen mustard by 75%-83% and omitted procarbazine and melphalan, resulting in notably lower exposure to alkylating agents. Specifically, the regimen includes mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone, given for 8 to 12 weeks depending on stage

Earlier regimens consisted of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or procarbazine, mechlorethamine, and vinblastine (PAVe) in trials conducted between 1974 and 1980; in the period 1981-1989, chemotherapy consisted of MOPP or PAVe, as well as vinblastine, bleomycin, and methotrexate (VBM), or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). The most recent trials (1989-2003) used either the Stanford V regimen or VbM, i.e., VBM with a reduced dose of bleomycin.

The incidence of therapy-related AML/MDS in the two earlier eras was 5.7% and 5.2%, respectively, whereas in the most recent trials it was just 0.3%, the team reports.

In the latter instance, that figure represents just one patient who developed therapy-related AML/MDS after salvage therapy because of relapse; there were no cases after primary therapy.

Discussing the findings, Dr. Advani and colleagues note that the prognosis for therapy-related AML/MDS is “dismal,” so reducing this risk is imperative. “Current ongoing adaptive strategies based on interim positron emission tomography imaging to evaluate early response to treatment may allow for selection of patients so that AA (alkylating agent) exposure can be limited to those with high-risk disease.”

SOURCE: Risk of Therapy-Related Secondary Leukemia in Hodgkin Lymphoma: The Stanford University Experience Over Three Generations of Clinical Trials
J Clin Oncol 2013;30.