DV-ICE, intensive induction and early transplantation for adult patients with acute lymphoblastic leukemia: a phase II study

Authors


Jakob R. Passweg, MS, Medecin-Chef de Service, Service d’Hématologie, Departement Medecine Interne, Hôpitaux Universitaires de Geneve, Rue Micheli-du-Crest 24, 1211 Geneva 14, Switzerland. Tel: +41223723958; Fax: +4122-3727288; e-mail: jakob.passweg@hcuge.ch

Abstract

Objectives:  Eighty percent of adult patients with acute lymphoblastic leukemia (ALL) achieve a complete remission (CR) but only 30–40% are long term survivors. Best treatment strategies remain to be defined. The role of induction intensity, first remission hematopoietic stem cell transplantation (HSCT) and maintenance chemotherapy continues to be discussed. We tested a strategy of high intensity treatment of short duration followed by HSCT.

Patients and methods:  This prospective phase II study used induction with DV-ICE followed by immediate allogeneic or autologous HSCT (depending on donor availability) without additional consolidation or maintenance treatment. DV-ICE consisted of dexamethasone, vincristine, idarubicin, etoposide, and conventional dose cytosine arabinoside; HSCT was planned immediately if CR was achieved or after an additional course of intermediate high dose cytosine arabinoside and etoposide for patients with induction failure. A total of 42 consecutive patients between 17 and 67 yr of age (median 43 yr) were enrolled. Of the 42 patients, 57% were male, 76% had B-lineage ALL, 19% T-lineage ALL and two patients biphenotypic ALL. 29% were Ph+; 7% had 11q23 and 45% had a normal karyotype. CNS involvement was found in three patients.

Results:  Thirty-three patients (79%) achieved a CR, 24 patients after induction I or II and nine patients after rescue HSCT. 31 patients received a HSCT (seven autologous and 24 allogeneic). 11 patients did not receive a HSCT because of early death in nine (treatment toxicity in five, refractory disease in four), one patient refused transplantation, one patient was not suitable. Disease-free survival (DFS) of the entire cohort was 46% (95% CI ±16%) at 1 yr and 16% (±13%) at 5 yr. Overall survival (OS) was 63% (±15%) at 1 yr and 23% (±15%) at 5 yr, with a median follow-up of surviving patients of 55 (4–136) months. Neither disease subtype, cytogenetic abnormalities nor patient age or gender was significantly associated with survival.

Conclusions:  Intensive induction using DV-ICE followed by early transplantation without treatment beyond 4 months failed to improve outcome compared with standard treatment.

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