A Randomized Trial of Sirolimus-Based Graft Versus Host Disease Prophylaxis After Hematopoietic Stem Cell Transplantation in Relapsed Acute Lymphoblastic Leukemia

Inclusion Criteria:

- Histologically or cytologically confirmed acute lymphoblastic leukemia (ALL)* in
second complete remission (CR2) (M1 bone marrow, < 5% blasts by morphology) meeting
the following criteria:

- Eligible for matched sibling transplantation AND intermediate-risk disease
meeting 1 of the following criteria:

- B-lineage ALL in CR2 after a late first bone marrow (BM) relapse (≥ 36
months after the initiation of primary chemotherapy) with or without
associated extramedullary disease

- B-lineage ALL in CR2 after a very early isolated extramedullary relapse**

- Eligible for other related donor, unrelated donor, or matched sibling
transplantation AND high-risk disease meeting 1 of the following criteria:

- In CR2 after an early first BM relapse (< 36 months from initiation of
primary chemotherapy)

- T-lineage ALL in CR2 after a first BM relapse occurring at any time after
initiation of primary chemotherapy

- Philadelphia chromosome-positive ALL in CR2 after a first BM relapse
occurring at any time after the initiation of primary chemotherapy

- T-lineage ALL in CR2 after a very early isolated extramedullary relapse**

- Enrolled on an appropriate COG relapsed ALL clinical trial meeting 1 of the following
criteria:

- Must proceed directly to transplantation after completing the required study
therapy (i.e., 1 induction course and 2 consolidation courses)

- Patients not on a COG relapsed ALL clinical trial are eligible provided they
have received ≥ 1 round of re-induction lasting 4-6 weeks and 1 round of
intensive consolidation chemotherapy lasting 3-6 weeks

- No B-cell ALL L3 morphology with evidence of myc translocation by molecular or
cytogenetic technique

- No Down syndrome

- No evidence of active CNS or other extramedullary disease (i.e., no CNS2)

- Karnofsky performance status (PS) 60-100% (for patients > 16 years of age) OR Lansky
PS 60-100% (for patients ≤ 16 years of age)

- Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by
radionuclide angiogram

- ALT or AST < 5 times upper limit of normal

- Bilirubin < 2.5 mg/dL (unless an increase is attributable to Gilbert's syndrome)

- Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min

- FEV_1 ≥ 60% by pulmonary function tests (PFTs)

- FVC ≥ 60% by PFTs

- DLCO ≥ 60% by PFTs

- For children who are unable to cooperate for PFTs all of the following criteria must
be met:

- No evidence of dyspnea at rest

- No exercise intolerance

- No requirement for supplemental oxygen therapy

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No HIV or uncontrolled fungal, bacterial, or viral infection

- Fungal infection acquired during induction therapy allowed provided there is a
significant response to antifungal therapy with minimal or no evidence of
disease by CT scan

- Other concurrent immunosuppressants allowed

- No prior allogeneic or autologous stem cell transplantation

- No prior or concurrent voriconazole unless prior voriconazole therapy is completed or
a different agent is substituted for voriconazole prior to study entry

- No concurrent grapefruit juice during sirolimus administration