Total-Body Irradiation and Chemotherapy Followed By Donor Bone Marrow Transplant in Treating Young Patients With Hematologic Cancer

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.

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