Secondary acute myeloid leukemia in children with acute lymphoblastic leukemia treated with etoposide. 1993

N J Winick, and R W McKenna, and J J Shuster, and N R Schneider, and M J Borowitz, and W P Bowman, and D Jacaruso, and B A Kamen, and G R Buchanan
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063.

OBJECTIVE To describe the occurrence of secondary acute myeloid leukemia (AML) in children with acute lymphoblastic leukemia (ALL) treated with etoposide (VP-16). METHODS Two hundred five consecutive children with early B-lineage ALL were treated according to the Dallas/Fort Worth (DFW) protocol between January 1986 and July 1, 1991. Therapy included a four-drug induction followed by consolidation and continuation phases of nightly oral mercaptopurine (6-MP) and repetitive courses of divided-dose oral methotrexate (dMTX) and asparaginase (L-asp). Three doses of VP-16 and cytarabine (Ara-C) were given during consolidation and later, during continuation, two doses were given 3 to 4 days apart, every 9 weeks. Intrathecal (IT) chemotherapy was given throughout the treatment period. RESULTS Two hundred three of the 205 patients entered remission. Only eight of these 203 children have had a bone marrow relapse (ALL). However, 10 other children have developed secondary AML 23 to 68 months following the diagnosis of ALL. Overall event-free survival (EFS) at 4 years is 79.3% +/- 5.1%, with a risk of secondary AML at 4 years of 5.9% +/- 3.2%. CONCLUSIONS This experience provides strong evidence for a link between epipodophyllotoxin therapy and secondary AML since none of these children received alkylating agent therapy or irradiation. This serious complication raises concern as to the appropriate use of epipodophyllotoxins in the treatment of childhood ALL.

UI MeSH Term Description Entries
D007223 Infant A child between 1 and 23 months of age. Infants
D007951 Leukemia, Myeloid Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites. Granulocytic Leukemia,Leukemia, Granulocytic,Leukemia, Myelocytic,Leukemia, Myelogenous,Myelocytic Leukemia,Myelogenous Leukemia,Myeloid Leukemia,Leukemia, Monocytic, Chronic,Monocytic Leukemia, Chronic,Chronic Monocytic Leukemia,Chronic Monocytic Leukemias,Granulocytic Leukemias,Leukemia, Chronic Monocytic,Leukemias, Chronic Monocytic,Leukemias, Granulocytic,Leukemias, Myelocytic,Leukemias, Myelogenous,Leukemias, Myeloid,Monocytic Leukemias, Chronic,Myelocytic Leukemias,Myelogenous Leukemias,Myeloid Leukemias
D008297 Male Males
D012008 Recurrence The return of a sign, symptom, or disease after a remission. Recrudescence,Relapse,Recrudescences,Recurrences,Relapses
D001853 Bone Marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Marrow,Red Marrow,Yellow Marrow,Marrow, Bone,Marrow, Red,Marrow, Yellow
D002051 Burkitt Lymphoma A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative. African Lymphoma,Burkitt Cell Leukemia,Burkitt Tumor,Lymphoma, Burkitt,Burkitt Leukemia,Burkitt's Leukemia,Burkitt's Lymphoma,Burkitt's Tumor,Leukemia, Lymphoblastic, Burkitt-Type,Leukemia, Lymphocytic, L3,Lymphocytic Leukemia, L3,Burkitts Leukemia,Burkitts Lymphoma,Burkitts Tumor,L3 Lymphocytic Leukemia,L3 Lymphocytic Leukemias,Leukemia, Burkitt,Leukemia, Burkitt Cell,Leukemia, Burkitt's,Leukemia, L3 Lymphocytic,Lymphoma, African,Lymphoma, Burkitt's,Tumor, Burkitt,Tumor, Burkitt's
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D005047 Etoposide A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. Demethyl Epipodophyllotoxin Ethylidine Glucoside,Celltop,Eposide,Eposin,Eto-GRY,Etomedac,Etopos,Etoposide Pierre Fabre,Etoposide Teva,Etoposide, (5S)-Isomer,Etoposide, (5a alpha)-Isomer,Etoposide, (5a alpha,9 alpha)-Isomer,Etoposide, alpha-D-Glucopyranosyl Isomer,Etoposido Ferrer Farma,Exitop,Lastet,NSC-141540,Onkoposid,Riboposid,Toposar,VP 16-213,VP-16,Vepesid,Vépéside-Sandoz,Eto GRY,Etoposide, alpha D Glucopyranosyl Isomer,NSC 141540,NSC141540,Teva, Etoposide,VP 16,VP 16 213,VP 16213,VP16,Vépéside Sandoz,alpha-D-Glucopyranosyl Isomer Etoposide
D005260 Female Females

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