Evaluation for the Development of 11q23 Rearrangements in Lymphoma Patients Treated with a High Dose VP-16 and Cyclophosphamide Salvage Regimen

Abstract

Patients with relapsed or refractory lymphoma often require treatment with aggressive chemotherapy. At McGill University, a combination of high dose VP-16 and cyclophosphamide (VP-CY) is commonly used as a salvage regimen. In recent years, cytogenetic abnormalities of the long arm of chromosome 11 at band 23 (11q23) have been linked to the use of VP-16, and may be associated with secondary myelodysplastic syndrome or acute leukemia. Therapy related 11q23 anomalies have not been widely studied in lymphoma patients. We have identified and reviewed the course of 107 patients who have been treated with VP-CY. Thirty-five patients remain alive and 21 consented to participate in our study. Patient bone marrows were studied morphologically, cytogenetically and molecularly, to identify any new changes that may have developed over the course of their treatment, with a special emphasis on the search for 11q23 rearrangements. Mean time between VP-CY treatment and marrow evaluation was 3.6 years. Of the 21 patients, 5 had Hodgkin's disease (HD) and 16 had non Hodgkin's lymphoma (NHL). They received a total of 30 cycles of VP-CY. Response rate was 100%, with 16 complete and 5 partial responses. Eighteen patients later underwent autologous stem cell transplantation. At the time of study, 19 of the patients were disease free and 2 were in relapse. On morphological analysis, 12 marrows appeared normal and 6 showed mild dyserythropoiesis. Standard cytogenetics was done to examine for any new chromosomal translocations or deletions. All cytogenetic studies yielded normal results. Molecular analysis by Southern blot was done on 15 patients in a search for 11q23 rearrangements, including the partial tandem duplication of ALL-1. All molecular studies were normal. We conclude that the use of VP-CY, given in our treatment schedule, does not appear to be associated with an increased risk of developing 11q23 rearrangements.