title: Impact of cytogenetics on the outcome of adult acute lymphoblastic leukemia: results of Southwest Oncology Group 9400 study.
abstract: We examined the prognostic impact of cytogenetics on the outcome of 200 acute lymphoblastic leukemia (ALL) patients 15 to 65 years of age enrolled in Southwest Oncology Group (SWOG)-9400 study. Evaluable cytogenetics or fluorescence in situ hybridization studies were available in 140 (70%) patients. Four karyotype categories (normal [n = 31, 22%], t(9;22)/BCR/ABL1 [n = 36, 26%], other unfavorable [-7, +8, or 11q23 rearrangement, n = 19, 13%], and miscellaneous [n = 54, 39%]) and the biologically and clinically relevant ALL ploidy subgroups were prospectively defined. Overall survival (OS) decreased significantly with increasing age (P = .009) and varied with karyotype category (P < .001). OS was worst for t(9;22)/BCR/ABL1 followed by other unfavorable karyotypes, with hazard ratios (HR) of 3.45 (95% confidence interval [CI], 1.88-6.31) and 2.14 (95% CI, 1.04-4.04), respectively, compared with normal diploid group. OS of the miscellaneous group was similar to that of the normal diploid group (HR = 0.82; 95% CI, 0.44-1.53). Relapse-free survival (RFS) was not significantly associated with age (P = .30) but was heterogeneous among karyotype categories (P < .001) primarily because of poor RFS in t(9;22)/BCR/ABL1 (HR = 3.49; 95% CI, 1.80-6.75) compared with the normal diploid group. After accounting for the variation among karyotype groups, age was not a significant prognostic factor for OS or RFS, highlighting cytogenetics as the most important prognostic factor in adult ALL. This trial was registered at www.ClinicalTrials.gov as #NCT00002665.
authors.affiliation: Division of Hematology and Hematopoietic Cell Transplantation, Department of Cytogenetics, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA 91010, USA. vpullarkat@coh.org
authors.forename: Vinod
authors.initials: V
authors.lastname: Pullarkat
authors.forename: Marilyn L
authors.initials: ML
authors.lastname: Slovak
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Kopecky
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D003582:Cytogenetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D011003:Ploidies; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents