Myelodysplastic Syndrome Clinical Trial
Total-Body Irradiation and Chemotherapy Followed By Donor Bone Marrow Transplant in Treating Young Patients With Hematologic Cancer
Summary
RATIONALE: Giving chemotherapy and total body irradiation before a donor bone marrow transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin and removing the T cells from the donor cells before transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well total-body irradiation and chemotherapy followed by T-cell depleted donor bone marrow transplant works in treating young patients with hematologic cancer.
Full Description
OBJECTIVES:
Determine the efficacy of hyperfractionated total body irradiation, thiotepa, and cyclophosphamide followed by T-cell-depleted allogeneic bone marrow transplantation in children with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, or myelodysplastic syndromes.
Correlate the progenitor cell dose and dose of clonable T cells with the incidence and quality of engraftment, extent of chimerism, incidence and severity of acute and chronic graft-versus-host disease, characteristics of hematopoietic and immunologic reconstitution, and overall and disease-free survival at 2 years in patients treated with this regimen.
OUTLINE: Patients undergo total body irradiation three times daily on days -9 to -7 and twice on day -6. Patients receive thiotepa IV over 4 hours on days -5 and -4 and cyclophosphamide IV over 30 minutes on days -3 and -2. Patients who cannot receive cyclophosphamide, due to prior hemorrhagic cystitis or exposure to high-dose cyclophosphamide or ifosfamide, receive fludarabine IV over 30 minutes on days -5 to -1. Patients planning to receive family member HLA-mismatched or unrelated bone marrow transplantation receive horse anti-thymocyte globulin IV once daily on days -5 and -4. Patients undergo allogeneic T-cell-depleted bone marrow transplantation on day 0. Patients receive filgrastim (G-CSF) IV every 12 hours beginning on day 7 and continuing until blood counts recover.
Patients are followed every 2-4 weeks for the first 100 days post-transplantation, every 6 weeks for 6 months, every 3 months for 1 year, and then every 3-6 months until 2 years post-transplantation.
PROJECTED ACCRUAL: A total of 50 patients (25 with HLA 6/6 antigen-matched related donors and 25 with HLA 5/6 antigen-matched related donors or HLA 5/6 or 6/6 antigen-matched unrelated donors) will be accrued for this study within 3 years.
Eligibility Criteria
DISEASE CHARACTERISTICS:
One of the following diagnoses:
Histologically confirmed good-risk acute myeloid leukemia (AML) in first remission with an HLA-compatible related donor
Ineligible for unrelated bone marrow transplantation unless failed first-line induction chemotherapy or have molecular evidence of disease at time of transplantation
Histologically confirmed high-risk AML in first remission
High risk defined by cytogenetics, biphenotypic and undifferentiated leukemia phenotype, secondary AML, or AML after myelodysplastic syndromes (MDS)
Eligible for related or unrelated donor transplantation
Histologically confirmed acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) in first remission with high risk for relapse or in second or third remission
High risk for relapse defined by hypodiploidy, pseudodiploidy with translocations t(9;22) or infant t(4;11), or failure to achieve remission after four weeks of induction therapy
Eligible for related or unrelated donor transplantation
Histologically confirmed chronic myelogenous leukemia (CML) in at least first chronic phase or acceleration with an HLA-compatible related donor
Histologically confirmed CML in first chronic phase if failed conventional therapy or in at least second chronic phase or acceleration with an HLA-compatible unrelated donor
Histologically confirmed non-Hodgkin's lymphoma beyond first complete remission or primary induction failure and tumors that are chemosensitive defined as at least 50% reduction in mass size
Eligible for related or unrelated donor transplantation
Histologically confirmed MDS with intermediate or high-risk disease defined by International Prognostic Scoring System and paroxysmal nocturnal hematuria
Eligible for related or unrelated donor transplantation
Treatment-related MDS or leukemia allowed if primary malignancy (e.g., neuroblastoma or Ewing's sarcoma) at low risk of recurrence
No AML, ALL, or LL in relapse or greater than third remission
No CML in blast crisis defined as more than 30% blasts plus promyelocytes
No active CNS involvement
History of leukemia cutis allowed
HLA compatible donor available
5/6 or 6/6 HLA antigen matched related or unrelated
PATIENT CHARACTERISTICS:
Age:
18 and under
Performance status:
Karnofsky 70-100% OR
Lansky 50-100%
Life expectancy:
Not specified
Hematopoietic:
See Disease Characteristics
Hepatic:
Bilirubin no greater than 2.5 times upper limit of normal (ULN)
AST no greater than 3 times ULN (unless liver involvement is present)
Renal:
Creatinine normal OR
Creatinine clearance greater than 60 mL/min
Cardiovascular:
LVEF at least 50% at rest (if less than 50% at rest, must increase with exercise)
Pulmonary:
Asymptomatic with no prior risk features OR
DLCO greater than 40% predicted (corrected for hemoglobin) if symptomatic
Other:
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
HIV I/II negative
No uncontrolled viral, bacterial, or fungal infection
No known hypersensitivity to bovine proteins
PRIOR CONCURRENT THERAPY:
Biologic therapy:
See Disease Characterisitics
Chemotherapy:
See Disease Characteristics
Endocrine therapy:
Not specified
Radiotherapy:
No prior radiotherapy that would preclude total body irradiation dose
Surgery:
Not specified
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There is 1 Location for this study
New York New York, 10021, United States
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