Adult Acute Erythroid Leukemia, Adult Acute Monoblastic and Acute Monocytic Leukemia, Adult Acute Myeloid Leukemia
Conditions
Keywords
adult erythroleukemia (M6a), adult acute megakaryoblastic leukemia (M7), adult acute minimally differentiated myeloid leukemia (M0), adult acute monocytic leukemia (M5b), adult acute myeloblastic leukemia with maturation (M2), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myelomonocytic leukemia (M4)
Brief summary
RATIONALE: A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy or radiation therapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving total-body irradiation together with fludarabine, thiotepa, and antithymocyte globulin before transplant may stop this from happening. PURPOSE: This phase II trial is studying how well a donor stem cell transplant works in treating patients with acute myeloid leukemia in remission.
Detailed description
OBJECTIVES: Primary * Determine the safety and antileukemia activity of haploidentical allogeneic peripheral blood stem cell transplantation in patients with high-risk acute myeloid leukemia in first remission. Secondary * Determine the early treatment-related mortality (before day 100) of patients treated with this regimen. * Determine the incidence of acute graft-versus-host disease in patients treated with this regimen. * Determine the incidence of graft failure in patients treated with this regimen. * Correlate a mismatch in the expression of the natural killer cell inhibitory receptors CD158a and CD158b with engraftment and disease recurrence in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive a preparative regimen comprising total-body irradiation twice on day -8; fludarabine IV over 30 minutes on days -7 to -3; thiotepa IV over 2 hours twice on day -7; and antithymocyte globulin IV over 4-6 hours on days -5 to -2. Patients undergo haploidentical allogeneic peripheral blood stem cell transplantation on day 0. Patients are followed at day 100, at least monthly for 2 years, and then periodically for 3 years. PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study within 2.2 years.
Interventions
DRUGanti-thymocyte globulin
DRUGfludarabine phosphate
DRUGthiotepa
PROCEDUREbiological therapy
PROCEDUREbone marrow ablation with stem cell support
PROCEDUREchemotherapy
PROCEDUREperipheral blood stem cell transplantation
PROCEDUREradiation therapy
Sponsors
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to 59 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Morphologically confirmed acute myeloid leukemia of 1 of the following subtypes: * Acute myeloblastic leukemia (M0, M1, M2) * Acute myelomonocytic leukemia (M4) * Acute monocytic leukemia (M5) * Acute erythroleukemia (M6) * Acute megakaryocytic leukemia (M7) * Must have 1 of the following karyotypic abnormalities at the time of diagnosis: * Complex cytogenetic abnormalities (≥ 3 cytogenetic clones) * Abnormalities of chromosome 5 \[-5 or del(5q)\] * Abnormalities of the long (q) arm of chromosome 3, 9, 11, 20, or 21 * Abnormalities of the short (p) arm of chromosome 17, monosomy 7, t(9;22), or t(6;9) (8) * In morphologic first complete remission\*, as evidenced by all of the following for ≥ 4 weeks before study entry: * Absolute neutrophil count \> 1,000/mm\^3 * Platelet count \> 100,000/mm\^3 * Leukemic blasts not present in the peripheral blood * Cellularity of bone marrow biopsy \> 20% with maturation of all cell lines * Less than 5% blasts by bone marrow biopsy * No extramedullary leukemia, such as CNS or soft tissue involvement NOTE: \*Reduced hemoglobin concentration or hematocrit has no bearing on remission status * Haploidentical (3/6 or 4/6 antigen matched \[A, B, and DR\]) family donor available PATIENT CHARACTERISTICS: Age * 18 to 59 Performance status * ECOG 0-2 Life expectancy * Not specified Hematopoietic * See Disease Characteristics Hepatic * Bilirubin ≤ 2.0 mg/dL * AST \< 2 times upper limit of normal Renal * Creatinine ≤ 1.5 mg/dL Cardiovascular * Ejection fraction \> 40% by MUGA or echocardiogram * None of the following within the past 3 months: * Myocardial infarction * Significant congestive heart failure * Significant cardiac arrhythmia Pulmonary * FEV\_1 and DLCO \> 50% of predicted Immunologic * HIV negative * No active or unresolved infection * No evidence of invasive fungal infection (e.g., positive blood or deep tissue cultures or stains) Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No organ damage * No other medical problem that would preclude study participation * No other currently active tumor that would likely interfere with study treatment or that would likely compromise the patient's morbidity or mortality PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent routine use of filgrastim (G-CSF) or sargramostim (GM-CSF) to accelerate hematopoietic recovery post-transplantation Chemotherapy * More than 4 weeks since prior chemotherapy Endocrine therapy * Not specified Radiotherapy * More than 4 weeks since prior radiotherapy Surgery * Not specified
Outcome results
None listed