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


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.
Dudler
Christine
C
University of Basel, University Hospital, Switzerland.
Bargetzi
Mario
M
Tichelli
André
A
Gratwohl
Alois
A
Passweg
Jakob R
JR
Wernli
Martin
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D057239:Early Termination of Clinical Trials; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000009:adverse effects; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D010865:Pilot Projects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D011446:Prospective Studies; D017211:Treatment Failure; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
D003561:Cytarabine; D014750:Vincristine; D005047:Etoposide; D003907:Dexamethasone; D006854:Hydrocortisone; D008727:Methotrexate; D015255:Idarubicin