CYTOGENETIC CORRELATION WITH DISEASE STATUS AND TREATMENT OUTCOME IN ADVANCED-STAGE LEUKEMIA POST BONE-MARROW TRANSPLANTATION - A SOUTHWEST-ONCOLOGY-GROUP STUDY (SWOG-8612)

A retrospective cytogenetic study was performed to determine whether n onrandom chromosome aberrations were related to the outcome of marrow transplantation for advanced stage acute leukemia (AL) and chronic mye logenous leukemia (CML). The patients were registered on SWOG-8612, a randomized comparison of busulphan and cyclophosphamide (BU/CY) to fra ctionated total body irradiation and etoposide (FTBI/VP16) as preparat ory regimens for allogeneic bone marrow transplant (BMT). Plume K. G., Kopecky K. J., Henslee-Downey J. P., Forman S. J., Stiff P. J., Le Ma istre C. F. and Appelbaum F. R. (1987) Blood 81, 2187. Pretreatment cy togenetic studies were available for 90 (78%) of the 115 patients who proceeded to BMT. Patients were categorized by diagnosis (ALL/AML/CML) , disease status ['good' risk=second complete remission (CR2) or CML-a ccelerated phase (AP); 'poor' risk=third complete remission (CR3), ind uction failure, florid relapse or CML-blast phase (BP)] and cytogeneti c status (favorable = normal cytogenetics in AL or Philadelphia chromo some positive (Ph+) standard or variant translocation as the sole find ings in CML; unfavorable = all other cytogenetic aberrations). Chromos omal aberrations observed in the unfavorable category included -7, t(9 ;22) in AL, t(8;21) in association with complex karyotypes, t(6;9), de l(9q), t/del(11q), t(1;19), hypotetraploidy, and complex karyotypes (> 3 cytogenetic anomalies). Unfavorable cytogenetic status was significa ntly more frequent among patients with 'poor' risk clinical disease st atus (P<0.0001). In multivariate analysis, disease-free survival (DFS) was significantly poorer for patients with unfavorable cytogenetic st atus (P = 0.002) but not significantly related to disease status (P = 0.43). These data indicate that certain secondary chromosome aberratio ns [+8,i(17q), duplication of Ph] should be reclassified as relatively favorable predictors of successful BMT in CML and, therefore, be sepa rated from the unfavorable cytogenetic aberrations characteristic of d rug resistant disease [-7, inv(3), complex karyotypes]. The limited nu mber of patients precluded definitive assessment of the prognostic sig nificance of specific cytogenetic aberrations for any single diagnosis . Nevertheless, these findings suggest that cytogenetic status may be an important and independent factor in predicting outcome following al logeneic bone marrow transplantation.