A white blood cell index as the main prognostic factor in t(8;21) acute myeloid leukemia (AML): a survey of 161 cases from the French AML Intergroup

Abstract

While the t(8;21) translocation is one of the most recurrent chromosomal abnormalities in acute myeloid leukemia, prognostic studies have been hampered by the relatively few number of patients reported. We thus performed a large retrospective study in 161 adults and children with t(8;21) acute myeloid leukemia, all prospectively enrolled in 6 different trials conducted in France between 1987 and 1998 (median follow-up 4.9 years). Prognostic studies were performed in the 154 patients who achieved a complete remission. Individual data were registered, including sex, age, blood and marrow counts, extramedullary disease, and cytogenetics. The value of allogeneic stem cell transplantation versus chemotherapy as postremission therapy was evaluated according to the intent-to-treat principle. Estimated 5-year disease-free survival (DFS) and overall survival were 52% and 59%, respectively. Outcome was not significantly better in patients from the stem cell transplantation group (estimated 5-year DFS and survival, 56% vs 52% and 67% vs 57%; P ‫؍‬ .55 and .64, respectively). White blood cell count (WBC) was the only identified prognostic factor. To further take into account the spontaneous differentiation potential of the leukemic clone, a WBC index was derived as the product of WBC by the ratio of marrow blast. This WBC index was a more powerful factor than the original WBC, allowing us to distinguish 3 subgroups of patients with different outcomes (low index, < 2.5; intermediate index, 2.5-20; high index, 20 or more). In multivariate analysis, the WBC index was the only prognostic factor for DFS (P ‫؍‬ .003), complete remission duration (P ‫؍‬ .002), and overall survival (P ‫؍‬ .04). (Blood. 2002;99:3517-3523)

Acute myeloid leukemia harboring t(8;21)(q22;q22): a heterogeneous disease with poor outcome in a subset of patients unrelated to secondary cytogenetic aberrations

“…These results are in keeping with the observations by other investigators who had 4100 cases in their respective study series. 5,12,13,15 These series demonstrated no deleterious effect of loss of a sex chromosome or del(9q) on the outcome of patients with t(8;21). The strength of our series is that the large majority of newly diagnosed patients were treated similarly in a single institution instead of multiple different protocols as in earlier large series, allowing us to assess the prognostic factors across different subgroups despite the relatively small cohort size.…”

“…Among these are certain secondary cytogenetic aberrations, leukocytosis, CD56 expression and extramedullary manifestations. Review of the literature found that some suggested indicators, most notably CD56 9 and extramedullary involvement, 10 were identified in a single or relatively small studies; others were based on the patients treated with different protocols [11][12][13][14] or included secondary leukemia, 15 rendering it difficult to compare and draw consistent conclusions. This is particularly true regarding implications of additional cytogenetic aberrations.…”

Allogeneic stem cell transplantation in second rather than first complete remission in selected patients with good-risk acute myeloid leukemia

“…8,9 The French AML Intergroup has recently reported the results of two large retrospective studies conducted in patients with t(8;21) and inv(16) AML, which both confirm this observation in patients with core binding factor (CBF) AML. 10,11 No controlled study has, however, formally compared SCT in second vs first CR in selected AML patients. There is consequently no consensus on the appropriate group of patients in whom SCT might be safely delayed in second CR.…”

Prognostic value of real-time quantitative PCR (RQ-PCR) in AML with t(8;21)

“…Initial features such as a high initial white blood cell count (WBC), WBC index, CD56 expression, del (9q) in addition to t(8;21) or extramedullary disease have been associated with an increased risk of relapse. [5][6][7][8][9] We previously reported that with a qualitative RT-PCR method, a good correlation was found between rapid negativation of PCR results during treatment and absence of subsequent relapse. 10 Several studies strongly suggest that quantitative PCR (RQ-PCR) methods of minimal residual disease (MRD) detection might improve the predictive results of qualitative PCR techniques in acute leukemia.…”