Correspondence

Secondary Acute Myeloid Leukemia after Treatment of Acute Monoblastic Leukemia

N Engl J Med 2000; 343:1897-1898December 21, 2000

Article

To the Editor:

Secondary cancer is an important complication of the treatment of childhood cancer. The occurrence of secondary acute myeloid leukemia (AML) after successful treatment of a variety of tumors1-3 generally carries a poor prognosis. We report a case of secondary AML that followed treatment for acute monoblastic leukemia.

A 21-year-old woman had been treated when she was 18 years old for acute monoblastic leukemia subtype M5a according to the French–American–British (FAB) classification with cytarabine (cumulative dose, 36.2 g per square meter of body-surface area), etoposide (795 mg per square meter), thioguanine (2.58 g per square meter), doxorubicin (120 mg per square meter), vincristine (6 mg per square meter), idarubicin (36 mg per square meter), mitoxantrone (20 mg per square meter), cyclophosphamide (1 g per square meter), and prednisone (1.12 g per square meter), followed by standard maintenance therapy for one year with subcutaneous cytarabine, oral thioguanine, and prophylactic cranial irradiation (18 Gy) plus four doses of intrathecal cytarabine. Three years after the first diagnosis she presented with signs of acute leukemia. A bone marrow aspirate contained 88 percent blast cells of FAB subtype M2 with Auer rods. She received a continuous infusion of cytarabine (500 mg per square meter per day for four days), liposomal daunorubicin (60 mg per square meter per day for three days), and intrathecal cytarabine (40 mg), followed by cytarabine (3 g per square meter every 12 hours for six days), mitoxantrone (10 mg per square meter for two days), and intrathecal cytarabine (40 mg). Despite further treatment with thioguanine (60 mg per square meter per day), vincristine (1.5 mg per square meter per day for 3 days), cytarabine (75 mg per square meter per day for 12 days), liposomal daunorubicin (35 mg per square meter per day for 3 days), and prednisone (40 mg per square meter per day), the patient died of progressive leukemia.

Although relapse of acute monoblastic leukemia would have been the obvious diagnosis, a diagnostic workup revealed AML, in which the leukemic cells contained Auer rods and myeloperoxidase, but not nonspecific esterase. Flow-cytometric analysis disclosed the strong expression of early myeloid markers (CD13 and CD33) but not CD7, CD4, or CD56, markers that were present in the initial population of monoblasts. In contrast to the initial acute monoblastic leukemia, which had the characteristic t(9;11) translocation, the second leukemia contained two clones with distinctive karyotypes. Both clones displayed the unbalanced dicentric translocation t(5;17)(q11;p11). In addition, clone 1 had an unbalanced translocation t(9;19) in combination with a partial monosomy 16 with an acentric fragment of chromosome 16. In contrast, clone 2 had the unbalanced translocation t(16;19) and monosomy 8 and 10.

In our patient, the cytogenetic finding of the dicentric deletion of chromosomes 5q and 17p suggests a treatment-induced secondary AML,4,5 but there are also some unusual cytogenetic findings, such as monosomy 8 and 10. In conclusion, in patients thought to have relapsed AML, particularly those with a “phenotype switch,” another diagnostic workup is warranted to avoid erroneous classification. Such patients might have a particularly poor prognosis, requiring novel therapeutic approaches.

Christian Kebelmann-Betzing, M.D.
Karlheinz Seeger, M.D., Ph.D.
Andreas Kulozik, M.D., Ph.D.
Günter Henze, M.D.
Humboldt University, D-13353 Berlin, Germany

Thomas Liehr, M.D.
Anita Heller
Friedrich Schiller University, D-07743 Jena, Germany

Andrea Teigler-Schlegel, Ph.D.
Justus Liebig University, D-35392 Giessen, Germany

5 References

1. 1

   Kreissman SG, Gelber RD, Cohen HJ, Clavell LA, Leavitt P, Sallan SE. Incidence of secondary acute myelogenous leukemia after treatment of childhood acute lymphoblastic leukemia. Cancer 1992;70:2208-2213
   CrossRef | Web of Science | Medline

2. 2

   Orlandi E, Lazzarino M, Bernasconi P, Astori C, Bernasconi C. Secondary acute myeloid leukemia following treatment with VP16-containing regimens for non-Hodgkin's lymphoma. Haematologica 1998;83:758-759
   Web of Science | Medline

3. 3

   Valagussa P, Bonadonna G. Hodgkin's disease and the risk of acute leukemia in successfully treated patients. Haematologica 1998;83:769-770
   Web of Science | Medline

4. 4

   Le Beau MM, Espinosa R III, Neuman WL, et al. Cytogenetic and molecular delineation of the smallest commonly deleted region of chromosome 5 in malignant myeloid diseases. Proc Natl Acad Sci U S A 1993;90:5484-5488
   CrossRef | Web of Science | Medline

5. 5

   Merlat A, Lai JL, Sterkers Y, et al. Therapy-related myelodysplastic syndrome and acute myeloid leukemia with 17p deletion: a report on 25 cases. Leukemia 1999;13:250-257
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   DR Barnard, WG Woods. (2005) Treatment-related myelodysplastic syndrome/acute myeloid leukemia in survivors of childhood cancer – An update. Leukemia & Lymphoma 46:5, 651-663
   CrossRef