Adult acute lymphoblastic leukemia at relapse. Cytogenetic, immunophenotypic, and molecular changes

Abstract

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. Cancer 1995;76:985–91.

Relapsed childhood high hyperdiploid acute lymphoblastic leukemia: presence of preleukemic ancestral clones and the secondary nature of microdeletions and RTK-RAS mutations

“…This is not unexpected considering that several previous studies, using conventional chromosome banding techniques, have shown increased numbers of structural chromosome abnormalities in ALL, including high hyperdiploid cases, at relapse. [22][23][24][25][26][27] Using SNP array analysis, Mullighan et al 12 also observed significantly higher frequencies of deletions in relapse samples. In this study, most RTK-RAS mutations were detected at relapse.…”

A rare case of Acute Lymphocytic Leukemia (ALL) presenting with double Philadelphia chromosome: relapse or secondary leukemia?

“…Clonal evolution is not the only cytogenetic observation at relapse; some cases show entirely different karyotypes, thereby raising the possibility of secondary leukemia (Raimondi SC, 1993). Chucrallah et al (1995) analyzed 32 relapsed adult ALL patients and found that nine (28%) had clonal evolution, 12 (37%) had a different karyotype, and 11 (34%) had an unchanged karyotype.…”

Immunologic monitoring in adults with acute lymphoblastic leukemia

“…Two major pitfalls have the potential to reduce the value of flow-cytometry immunophenotypic detection of MRD: the absence of leukemia-specific antigens and the existence of phenotypic changes at relapse that could induce false-negative results [4][5][6][7][8][32][33][34][35]. However, immunophenotypic detection of MRD is possible in acute leukemia because the neoplastic cells frequently express aberrant or unusual phenotypes.…”

“…In addition, such abnormal or infrequent antigenic patterns remain relatively stable during the course of the disease [22,36]. Although phenotypic changes have been shown to occur at high frequencies (20%-70%) in acute leukemia they are less freqent in ALL than in acute myeloid leukemia, and most of these changes involve individual antigens that are associated with maturation [32][33][34][35][36]. In our experience, changes affecting aberrant phenotypes were much less frequent, and at least one of the aberrations detected at diagnosis remained stable at relapse.…”

“…In addition, apparent but not real antigenic changes may be related to technical questions (ie, use of different fluorochrome-conjugated reagents or monoclonal antibody clones) or to biologic variability due to the presence of several blast cell populations-some of them very small-that could exist in ALL (25% of patients) [37]. It is also important to consider that the immunophenotype of blast cells at relapse is frequently more immature than it was at diagnosis [32][33][34][35]. Therefore, special attention should be paid to the more immature blast cell subpopulations found at diagnosis during follow-up analysis of these patients once they are in mCR.…”