Therapy Related Acute Myelogenous Leukemia and Myelodysplastic Syndrome in Patients with Acute Lymphoblastic Leukemia Treated with the Hyper-CVAD Regimen.

Secondary malignancies including myeloid neoplasms occur infrequently in patients with acute lymphoblastic leukemia (ALL). This has been well documented in the pediatric population but not for the adult patients. We have reviewed retrospectively 641 patients with de novo ALL, treated with the hyper-CVAD regimen or its variants, at M D Anderson Cancer Center from 1992 to 2007. Fourteen patients (2.18%, 7 female, 7 male) developed secondary acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Six patients had AML and 8 MDS. Median age at the time of ALL diagnosis was 52 years (range, 23 – 66). Cytogenetics at ALL diagnosis was diploid in 10, pseudo-diploid with −2 in 1, t(9;22) in 1, and unavailable in 2 patients. Frontline therapy included hyper-CVAD in 7, hyper-CVAD with rituximab in 6, and hyper-CVAD with imatinib in 1 patient. Karyotype at the time of AML/MDS diagnosis was −5, −7 in 8 patients, diploid in 1, miscellaneous in 1, inv(11) in 1, t(4;11) in 1, and unavailable in 2. Secondary AML/MDS developed at a median of 31 months (range, 11 – 74) after the start of ALL therapy. Treatment for the secondary AML and MDS was varied and included cytarabine plus anthracycline based regimens for AML and high risk MDS. One patient with MDS received arsenic trioxide, 1 clofarabine, and 1 decitabine. The response rate to treatment for AML/MDS was complete remission (CR) in 2, partial remission in 6 and no response in 6 patients. Five patients (all MDS) underwent an allogeneic stem cell transplant and all but one died at a median of 3 months (range, 0.5 – 11) after the transplant. One patient is alive and in CR 14 months after a haplo-identical sibling transplant; 2 other patients are alive 3.5 and 4 months after the diagnosis of MDS. The median overall survival after the diagnosis of secondary AML and MDS is 8.3 months (range 3.5+ to 18.5+). We conclude that secondary AML and MDS occur infrequently (2.18%) in adult patients with de novo ALL treated with the hyper-CVAD regimens and response to their subsequent therapy is poor.