Sirolimus & Mycophenolate Mofetil as GVHD Prophylaxis in Myeloablative, Matched Related Donor HCT

• Grade III-IV acute GVHD [ Time Frame: 100 days post transplant ] [ Designated as safety issue: Yes ]
• Pharmacokinetics of MMF [ Time Frame: completion of study- at 2-3 years after institution ] [ Designated as safety issue: No ]
• Veno-occlusive Disease Incidence of Infection CMV reactivation [ Time Frame: 100 days ] [ Designated as safety issue: No ]
• Chronic GVHD Disease-free and Overall Survival [ Time Frame: approximately 1-2 years after completion of the study ] [ Designated as safety issue: No ]
• Time to neutrophil and platelet engraftment Thrombotic microangiopathy Severity of Mucositis [ Time Frame: 100 days post-transplant per patient Thrombotic microangiopathy- as it occurs and/or 100 days post-transplant Mucositis- first 3 weeks post-transplant per patient; all patients - reviewed at completion of trial ] [ Designated as safety issue: Yes ]

• Grade III-IV acute GVHD [ Time Frame: D100 post-transplan ] [ Designated as safety issue: Yes ]
• Pharmacokinetics of MMF [ Time Frame: completion of study- at 2-3 years after institution ] [ Designated as safety issue: No ]
• Veno-occlusive Disease Incidence of Infection CMV reactivation [ Time Frame: VOD- ] [ Designated as safety issue: No ]
• Chronic GVHD Disease-free and Overall Survival [ Time Frame: approximately 1-2 years after completion of the study ] [ Designated as safety issue: No ]
• Time to neutrophil and platelet engraftment Thrombotic microangiopathy Severity of Mucositis [ Time Frame: Time to neutrophil and platelet engraftment: D100 post-transplant per patient Thrombotic microangiopathy- as it occurs and/or D100 post-transplant Mucositis- first 3 weeks post-transplant per patient; all patients - reviewed at completion of trial ] [ Designated as safety issue: Yes ]

GVHD prophylaxis of sirolimus and mycophenolate mofetil for patients undergoing matched related allogeneic transplant for acute and chronic leukemia, MDS, high risk NHL and HL

• Drug: Sirolimus
  12 mg loading dose, 4 mg QD, PO
  Other Names:

  • rapamycin
  • Rapamune
• Drug: Mycophenolate Mofetil
  15 mg/kg TID, IV or PO
  Other Name: MMF
• Drug: Carmustine
  15 mg/kg, IV
  Other Name: BCNU
• Drug: VP-16
  60 mg/kg, IV
  Other Names:

  • Vmw65
  • α-TIF
  • Trans Inducing Factor
• Drug: cyclophosphamide
  100-120 mg/kg, IV
  Other Names:

  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune
  • cytophosphane

Inclusion Criteria:

• Disease Categories (participants will have one of the following)

  • AML, age 2 - 60 years beyond 2nd remission or relapsed/refractory disease
  • AML, age 51-60 years of age, in first or subsequent remission or relapsed/refractory disease
  • AML with multilineage dysplasia
  • ALL, age 2 - 60 years beyond 2nd remission or relapsed/refractory disease
  • ALL, age 51 - 60 years in first or subsequent remission or relapsed/refractory disease
  • CML Beyond 2nd chronic phase or in blast crisis
  • MDS; Includes World Health Organization classifications of refractory anemia with excess blasts-1 (RAEB-1), RAEB-2 and therapy-related MDS
  • Myeloproliferative disorders; MDS with poor long-term survival including myeloid metaplasia and myelofibrosis
  • High risk NHL in first remission
  • Relapsed or refractory NHL
  • HL beyond first remission
• Males and females of any ethnic background 2 - 60 years of age
• Karnofsky Performance Status >= 70% or Lansky performance status > 70% for patients < 16 years of age.

• Matched related donor identified

  • 6/6 HLA-A, B and DRB1
• Willingness to take oral medications during the transplantation period
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Prior myeloablative allogeneic or autologous HCT
• HIV infection
• Pregnant or lactating females
• Evidence of uncontrolled active infection

• Organ Dysfunction

  • Serum creatinine > 1.5 mg/dL or 24 hour creatinine clearance < 50 ml/min
  • Direct bilirubin, ALT or AST > 2 x ULN
  • In adults DLCO < 60% predicted and in children room air oxygen saturation < 92%
  • In adults, left ventricular ejection fraction < 45% and in children, shortening fraction < 26%
• Fasting Cholesterol > 300 mg/dL or Triglycerides > 300 mg/dL while on lipid-lowering agents.
• Patients receiving investigational drugs unless cleared by the PI.
• Patients with prior malignancies except basal cell carcinoma or treated carcinoma in-situ. Cancer treated with curative intent > 5 years will be allowed. Cancer treated with curative intent <= 5 years will not be allowed with PI approval.