Acute Lymphoblastic Leukemia Treated With Modified Hyper C-VAD Protocol In Iran

Relapse and mortality remains high in Acute Lymphoblastic Leukemia (ALL) with reported 5-year survival less than 39%. Bone marrow transplant (BMT) has been offered to some patients; however, 70% of patients do not have a donor-matched sibling and transplant beds are limited in Iran. We treated a cohort of 251 patients by inducing a remission and then treating with Hyper-CVAD rather than treating with Hyper-CVAD at induction and examined survival compared to reports in the literature.

We conducted a retrospective review of survival of 251 treated with a modified protocol of Hyper-CVAD between 2005 and 2012. The treatment protocol used 4-week induction regimen with Vincristine, Daunorubicin, and Dexamethasone. BCR-ABL positive patients also received daily Imatinib. Intrathecal methotrexate and cytarabine were given to patients with brain involvement. Remission was evaluated by a bone marrow biopsy and aspiration. If patient had T-Cell ALL then we add cyclophosphamide to the induction regimen. Hyper-CVAD treatment was initiated two weeks after last dose of Vincristine. Any patient with brain or bone involvement received radiotherapy post induction. BMT was offered to all BCR-ABL positive patients or those who had a suitable donor. All patients in complete remission received monthly vincristine prednisone for 5 days ,6- mercaptopurine every night and methotrexate every week up to 30 months .Patient with persistent liver enzyme elevation received cyclophosphamide instead of methotrexate.

The mean age was 26 (range 14 to 70). The cohort included patient with T ALL (11%), Burkitt’s type ALL (15%), Pre-B ALL (67%), Pro-B ALL (4%) and BCR-ABL (3%). Sixteen patients died during the first month. Mortality increased to 45 patients at the end of six months. Relapse was the main cause of death. BMT was conducted after complete second remission and suitable patient with BCR-ABL positive patients on 13 occasions but none survived. At 5 years of follow up 129 patients were alive (50.1% survival).

Our patients experienced an improved survival compared to reports in the literature and many did not have complication of radiotherapy. A modified Hyper-CVAD protocol should be the subject of further investigation for the treatment of ALL.

No relevant conflicts of interest to declare.