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 non-random chromosome aberrations were related to the outcome of marrow transplantation for advanced stage acute leukemia (AL) and chronic myelogenous leukemia (CML). The patients were registered on SWOG-8612, a randomized comparison of busulphan and cyclophosphamide (BU/CY) to fractionated total body irradiation and etoposide (FTBI/VP16) as preparatory regimens for allogeneic bone marrow transplant (BMT). Blume K. G., Kopecky K. J., Henslee-Downey J. P., Forman S. J., Stiff P. J., Le Maistre C. F. & Appelbaum F. R. (1987) Blood 81, 2187. Pretreatment cytogenetic 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-accelerated phase (AP); 'poor' risk = third complete remission (CR3), induction failure, florid relapse or CML-blast phase (BP)] and cytogenetic status (favorable = normal cytogenetics in AL or Philadelphia chromosome positive (Ph+) standard or variant translocation as the sole findings in CML; unfavorable = all other cytogenetic aberrations). Chromosomal aberrations observed in the unfavorable category included -7, t(9;22) in AL, t(8;21) in association with complex karyotypes, t(6;9), del(9q), t/del(11q), t(1;19), hypotetraploidy, and complex karyotypes (> 3 cytogenetic anomalies). Unfavorable cytogenetic status was significantly more frequent among patients with 'poor' risk clinical disease status (P < 0.0001). In multivariate analysis, disease-free survival (DFS) was significantly poorer for patients with unfavorable cytogenetic status (P = 0.002) but not significantly related to disease status (P = 0.43). These data indicate that certain secondary chromosome aberrations [+8,i(17q), duplication of Ph] should be reclassified as relatively favorable predictors of successful BMT in CML and, therefore, be separated from the unfavorable cytogenetic aberrations characteristic of drug resistant disease [-7, inv(3), complex karyotypes]. The limited number of patients precluded definitive assessment of the prognostic significance 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 allogeneic bone marrow transplantation.
Slovak
M L
ML
Department of Cytogenetics, City of Hope National Medical Center, Duarte, CA, USA.
Kopecky
K J
KJ
Wolman
S R
SR
Henslee-Downey
J P
JP
Appelbaum
F R
FR
Forman
S J
SJ
Blume
K G
KG
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000628:therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome