Tacrolimus and Methotrexate With or Without Sirolimus in Preventing Graft-Versus-Host Disease in Young Patients Undergoing Donor Stem Cell Transplant for Acute Lymphoblastic Leukemia in Complete Remission

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: * Intermediate risk relapsed ALL in CR2 (may receive matched sibling transplantation only) 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 (\<18 months from the initiation of primary chemotherapy) * High risk relapsed ALL in CR2 (may receive other related donor, unrelated donor, or matched sibling transplantation) 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 (\<18 months from the initiation of primary chemotherapy) * High risk de novo ALL in CR1 (may receive matched sibling, other related/unrelated BM/PBSC or unrelated CB transplantation) meeting 1 of the following criteria: * Patients with the presence of t(9;22) translocation (Ph+) detected by cytogenetic or PCR analysis at initial diagnosis. For patients on AALL0622, the criteria for transplant are 1) any patient with Ph+ ALL with an available matched sibling donor or 2) any patient with Ph+ ALL that is defined as high risk (MRD \> 1% Day 29 or MRD \> 0.01% end-Consolidation Block 2) with any available donor, related or unrelated. Patients enrolled on AALL0622 are only eligible if they follow this algorithm. * Patients with the presence of extreme hypodiploidy (\< 44 chromosomes or DNA index of \< 0.81) detected by cytogenetic/ploidy analysis at initial diagnosis. * Patients with the presence of 11q23 (MLL) rearrangements detected by cytogenetic or PCR analysis at initial diagnosis who are slow early responders (M2/M3 at Day 14 or MRD \> 0.1% at Day 29). * Enrolled on an appropriate COG relapsed ALL clinical trial after completing the required study therapy (i.e., minimum 1 re-induction course (4-6 weeks) and 1 round of intensive consolidation chemotherapy (3-6 weeks). Patients with high risk ALL in CR1 are eligible as soon as they have achieved a CR. * 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