Adult acute lymphoblastic leukemia at relapse. Cytogenetic, immunophenotypic, and molecular changes.
BACKGROUND
There have been published reports on cytogenetic, immunophenotypic, and molecular changes at relapse in childhood acute lymphoblastic leukemia (ALL) including lineage switch and secondary leukemia. There are limited data, however, on the cytogenetic, immunophenotypic, and molecular parameters of adult ALL at relapse. Because, as in children, the cytogenetic and/or immunophenotypic changes observed in adult ALL at relapse may have prognostic significance, the authors investigated the significance of such changes.


METHODS
Fifty-three patients with relapsed adult ALL for whom cytogenetic, immunophenotypic, and/or molecular analyses were performed at diagnosis and at relapse were studied. Changes in any of the parameters at relapse were correlated with total survival and survival from the time of relapse.


RESULTS
Of the 32 patients for whom cytogenetic studies were performed at relapse, 21 (66%) showed clonal cytogenetic changes, 40% of which were clonal evolution. None of these cases, however, showed two entirely different abnormal karyotypes at diagnosis and at relapse. The immunophenotypes showed occasional gain or loss of one or two surface markers, and the molecular genetic configurations for JH, JK, and the T-cell receptor beta were stable throughout the evolution of the disease. Patients with clonal evolution had a shorter overall survival than the rest of the group (P = 0.02). This difference, however, was not significant with respect to survival measured from the time of relapse.


CONCLUSIONS
The most frequent changes in the biologic profile of adult ALL at relapse are shifts in the karyotype, with or without clonal evolution. Clonal evolution detected at relapse is associated with a higher frequency of unfavorable karyotypes at diagnosis and with a worse overall prognosis. However, survival from the time of relapse is similar in patients with and without clonal evolution.
Chucrallah
A E
AE
Division of Laboratory Medicine, University of Texas M. D. Anderson Cancer Center, Houston 77030-4094, USA.
Stass
S A
SA
Huh
Y O
YO
Albitar
M
M
Kantarjian
H M
HM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000782:Aneuploidy; D002869:Chromosome Aberrations / Q000473:pathology; D025063:Chromosome Disorders; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D016019:Survival Analysis; D014178:Translocation, Genetic