pharmacologic pretransplant immunosuppression (ptis) + reduced toxicity conditioning (rtc) allogeneic stem cell transplantation in inherited hematologic disorders

Conditions: Stem Cell Transplantation

Summary: to assess the outcomes of nrm when administering pharmacologic pretransplant immunosuppression (ptis) followed by pretransplant reduced toxicity conditioning (rtc) and an allogeneic stem cell transplant (allo-sct) and post-transplant graft-versus-host disease prophylaxis based on post-transplant cyclophosphamide (pt-cy) in patients with inherited blood disorders.

objectives primary: to estimate the 100-day non-relapse mortality (nrm) rate when administering pharmacologic pretransplant immunosuppression (ptis) followed by pretransplant reduced toxicity conditioning (rtc) and an allogeneic stem cell transplant (allo-sct) and post-transplant graft-versus-host disease prophylaxis based on post-transplant cyclophosphamide (pt-cy) in patients with inherited blood disorders. secondary outcomes include the following: i. immune reconstitution ii. infectious complications iii. quality of life (qol) at 3 months,100 days, and 1 year post-transplant iv. os, efs, and grfs v. incidence of agvhd at day 100. vi. rate of chronic gvhd within the first-year post transplantation. vii. rate of graft failure

Eligibility criteria:
inclusion criteria: 1. the first six patients will be ages \>12 years old and \<35 years old. thereafter in a second stage, patients ages 2 to 50 years old will be included. 2. patient with a matched related donor or who has a related haploidentical donor identified. 3. performance score of at least 70 by karnofsky or 0 to 1 by ecog (age \> 12 years), or zubrod or lansky play performance scale of at least 70 (age \<12 years). 4. adequate major organ system function as demonstrated by: 1. serum creatinine clearance equal or more than 50 ml/min (calculated with cockroft-gault formula). 2. bilirubin equal or less than 1.5 mg/dl except for gilbert's disease. alt and/or ast equal or less than 3x institutional uln. conjugated (direct) bilirubin less than 2x upper limit of normal. 3. left ventricular ejection fraction equal or greater than 50%. 4. diffusing capacity for carbon monoxide (dlco) equal or greater than 50% 5. predicted, corrected for hemoglobin. for children \ 92% on room air by pulse oximetry. 5. patient or the patient's legal representative, parent(s) or guardian should be able to provide written informed consent. assent of a minor if participant's age is at least seven and less than eighteen years. 6. sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the investigator. exclusion criteria: 1. hiv positive; active hepatitis b or c. 2. uncontrolled infections. 3. liver cirrhosis. however mild fibrosis will be allowed i.e. fine reticulin or grade 1, with bridging fibrosis. 4. cns involvement within 3 months. 5. positive pregnancy test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization. 6. inability to comply with medical therapy or follow-up. 7. will restrict eligibility to a maximum bmi of ≤40 8. patient with a known history of allergic reactions to any constituents of the cell product, including a known history of allergic reactions to dmso. 9. prior allo-sct 10. other active malignancy/cancer diagnosis in remission for at least 2yrs. malignancies not being excluded are as follows: ductal carcinoma in situ (dcis), basal cell carcinoma (bcc), cervical intraepithelial neoplasia (cin)