Safety Study of Bone Marrow Transplant Using Mismatched Tissue Followed by Chemotherapy
Condition: MDS; Leukemias; Lymphomas
MeSH terms: Lymphoma; Leukemia
Intervention: Busulfan; Cyclophosphamide; Total body irradiation
Intervention description: Participant will receive Busulfan injections, 4 times a day for 4 days with dilantin prophylaxis (in patients 10 years of age or older). Busulfan levels in the blood will be measured and dose adjusted, if needed.; Patient will receive Cy by IV once a day for 2 days.; Patients will receive TBI once a day for 4 days.
Intervention MeSH terms: Cyclophosphamide; Busulfan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 107.0
Sex: All
Minimum age: 6 Months
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Leukemia; Lymphoma; Hematologic malignancies; ALL; AML; MDS; Transplantation; Mismatched; Haploidentical; Busulfan; Cyclophosphamide; Cellcept; Tacrolimus; TBI; CMMOL; CML; JMML

Summary:

      The purpose of this study is to see if giving high dose chemotherapy and total body
      irradiation before and repeating high dose chemotherapy after a bone marrow transplant could
      reduce the incidence of graft rejection and disease for patients with blood cancers
    

Eligibility criteria:

        Inclusion Criteria:

          -  Acute lymphocytic leukemia in high risk CR1

          -  Acute myeloid leukemia in CR1

          -  Therapy-related AML

          -  RAEB with >5% and <20% bone marrow blasts

          -  Chronic myelogenous leukemia beyond 1st chronic phase; Patients cannot be in blast
             crisis

          -  CMMoL

          -  JMML

          -  Chemotherapy-resistant Hodgkins Lymphoma or intermediate or high grade Non-Hodgkins
             lymphoma (Less than a PR after standard or salvage chemotherapy)

          -  Mantle cell lymphoma: chemotherapy refractory (Less than a PR after standard or
             salvage chemotherapy) or patients beyond CR1 with chemosensitive disease

          -  Follicular Lymphoma, Grade 3

          -  Transformed indolent lymphomas

        Exclusion Criteria:

          -  Poor cardiac function: left ventricular ejection fraction <45% as determined by MUGA
             or ECHO. For pediatric patients LVEF <45% or a shortening fraction below normal limits
             for age.

          -  Poor pulmonary function: FEV1 and FVC <50% predicted for patients who have not
             received thoracic or mantle irradiation. For patients who have received thoracic or
             mantle irradiation, FEV1 and FVC <70% predicted or DLCO < 50 of predicted. For
             children unable to perform PFTs because of developmental stage pulse oximetry < 85% on
             RA

          -  Poor liver function: bilirubin >2 mg/dl (not due to hemolysis, Gilbert's or primary
             malignancy)

          -  Poor renal function: Creatinine >2.0mg/dl or creatinine clearance

          -  HIV-positive

          -  Positive leukocytotoxic crossmatch

          -  Women of childbearing potential who currently are pregnant or who are not practicing
             adequate contraception

          -  Uncontrolled viral, bacterial, or fungal infections Patients with symptoms consistent
             with RSV, influenza A, B, or parainfluenza at the time of enrollment will be assayed
             for the above viruses and if positive are not eligible for the trial until they are no
             longer symptomatic (patients may have continued assay positivity for a period of time
             post resolution of symptoms secondary to the nature of the assay.

          -  Indolent lymphomas (Follicular Grade 1 and 2, marginal zone, chronic lymphocytic
             leukemia, small lymphocytic lymphoma, MALT)