Treatment of Children With Down Syndrome (DS) and Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), and Transient Myeloproliferative Disorder (TMD): A Phase III Group-Wide Study
Treatment of Children With Down Syndrome (DS) and Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), and Transient Myeloproliferative Disorder (TMD): A Phase III Group-Wide Study
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
PURPOSE: Phase III trial to study the effectiveness of combination chemotherapy in treating children who have Down syndrome and myeloproliferative disorder, acute myelogenous leukemia, or myelodysplastic syndrome.
OBJECTIVES:
OUTLINE: This is a multicenter study.
Patients who achieve remission after induction therapy receive 2 courses of intensification therapy, for approximately 4 months. During the first course, patients receive cytarabine IV over 3 hours twice daily on days 0, 1, 7, and 8. Patients also receive asparaginase intramuscularly on days 1 and 8. The second course of therapy comprises CNS prophylaxis. Patients with no CNS disease at diagnosis or whose CNS disease resolved by day 7 of induction therapy receive cytarabine IT on days 0, 7, and 14. Patients with persistent CNS disease on day 7 of induction therapy receive cytarabine IT, hydrocortisone IT, and methotrexate IT on days 0, 7, and 14.
Patients are followed monthly for 18 months, every 3 months for 1 year, every 6 months for 2.5 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 70 patients with acute myeloid leukemia or myelodysplastic syndromes will be accrued for this study within 3.2 years. A total of 88 patients with transient myeloproliferative disorder who enter remission will be accrued for this study within 5 years.
DISEASE CHARACTERISTICS:
Cytogenetically proven Down Syndrome (constitutional trisomy 21) with transient myeloproliferative disorder (TMD), myelodysplastic syndromes (MDS), or acute myelogenous leukemia (AML)
Group I:
Diagnosis of TMD in patients no older than 90 days at initial presentation
Must have nonerythroid blasts (any amount) in the peripheral blood and one of the following:
Histologically or cytologically proven TMD with blasts in an affected organ or in fluid (pericardial, pleural, or peritoneal)
Bone marrow aspirate is required
Group II (closed to accrual as of 6/24/04):
Diagnosis of MDS or AML (except M3 subtype) in patients older than 90 days with more than 29% blasts in bone marrow (with or without history of TMD), or any of the following histologies:
Refractory anemia (RA)
RA with excess blasts (RAEB)
RAEB in transformation
RA with ringed sideroblasts (RARS)
Primary cytopenia (later confirmed by bone marrow aspirate as due to marrow hypoplasia) defined by one or more of the following:
The following diagnoses will be observed only:
Granulocytic sarcoma (chloroma), with or without bone marrow involvement, allowed
PATIENT CHARACTERISTICS:
Age:
Performance status:
Life expectancy:
Hematopoietic:
Hepatic:
Renal:
Cardiovascular:
PRIOR CONCURRENT THERAPY:
Biologic therapy:
Chemotherapy:
Endocrine therapy:
Radiotherapy:
Surgery:
Other:
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