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Current Issues in Adult AML

The Role of Cytogenetics in the Treatment of AML

Estey spacer
Elilu H. Estey, MD
Professor of Medicine,
University of Texas,
M.D. Anderson Cancer Center

The prognosis of adults with AML in first complete remission (CR) varies considerably.1 It is important to understand what dictates these prognoses in order to be able to assign appropriate therapy to patients. The table below demonstrates this by presenting cytogenetics in patients entering CR at The University of Texas M.D. Anderson Cancer Center between January 1, 1986 and July 1, 1992, and the percent of these patients who remained alive in first CR for at least 2 years. Our data show the likelihood of relapse declines significantly after 2 years in remission, so that patients who are still in remission at 2 years can realistically be considered to be potentially cured.

Presenting cytogenetics and disease-free survival
for patients with AML entering CR

Cytogenetic group Patients Median duration
disease-free
survival
Patients achieving CR
still alive in CR
at 2 years
Favorable prognosis inv(16)
t(15;17)
t(8;21)
22
29
23
70 mo
67 mo
160 mo
50%
38%
58%
Intermediate prognosis normal 125 46 mo 23%
Poor prognosis abnormal
+8
-5/-7
other abnormalities
19
17
21
52
40 mo
10 mo
10 mo
32 mo
13%
20%
0
18%

It can be seen that patients with a pericentric inversion of chromosome 16, known as inv(16), or with a translocation between chromosomes 15 and 17, known as t(15;17), or with a translocation between chromosomes 8 and 21, known as t(8;21), have relatively favorable prognoses. In contrast, patients with other abnormalities, especially those involving chromosomes 5 and/or 7, have worse prognoses. The prognoses of patients with a normal karyotype is intermediate.

Patients whose outcomes are illustrated above were treated primarily with high-dose cytarabine (Ara-C) combined with either anthracyclines or fludarabine. The results indicate that this therapy produces acceptable outcomes only in patients with inv(16) and t(15;17). Indeed, data indicate that high-dose Ara-C produces results superior to conventional-dose Ara-C in patients with inv(16).2 In contrast, patients with t(15;17), the hallmark of acute promyelocytic leukemia, benefit more from anthracyclines than high-dose Ara-C.2 These results suggest cytogenetics can divide AML into different diseases, each characterized by a different response to conventional treatment and possibly by different optimal treatments, as in the case of inv(16) and t(15;17).

Conclusions

  • Presenting cytogenetics is the most useful guide available for the purposes of planning AML treatment in remission.
  • Based on the tenet that therapy should be commensurate with prognosis:
    • the approximately 10% to 15% of patients with AML in first remission who present with inv(16) or t(15;17) karyotypes are appropriate candidates for conventional-type chemotherapy.
    • the remaining 85% to 90% of patients are appropriate candidates for investigational therapies-allogeneic and autologous bone marrow transplantation, as well as novel approaches to chemotherapy (eg, use of cytokines to sensitize leukemia cells, or new drugs, and immunotherapy).
  • In the future, more sensitive techniques will allow cytogenetic classification of more patients in remission as well as identification of cytogenetic abnormalities before morphologic relapse is evident, permitting treatment to be changed before relapse has occurred.

References

  1. Estey EH, Kantarjian H, Keating MJ. Therapy for acute myeloid leukemia. In: Hoffman R, Benz E, Shattel S, Furce B, Cohen M, eds. Hematology, Basic Principles and Practice. 2nd ed. New York, NY: Churchill Livingstone Publishers; 1995: chap 65.
  2. Ghaddar HM, Plunkett W, Kantarjian HM. Long-term results following treatment of newly-diagnosed acute myelogenous leukemia with continuous-infusion high-dose cytosine arabinoside. Leukemia. 1994; 8: 1269-1274.


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