Nonmyeloablative Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease and Beta-thalassemia in People With Higher Risk of Transplant Failure

This is an interventional treatment trial for Sickle Cell Disease focused on measuring Sickle Cell Disease, Allogeneic Hematopoietic Stem Cell Transplant, Pentostatin (Nipent), Cyclophosphamide, Alemtuzumab (Campath) Read More

-INCLUSION CRITERIA- recipients (must fulfill one disease category in 1 and all of 2)

1. Disease specific

   Patients with severe sickle cell disease (not limited to Hb SS, SC, or S beta-thal) at high risk for disease-related morbidity or mortality, defined by having severe end-organ damage (A, B, C, D, or E) or potentially modifiable complication(s) not ameliorated by hydroxyurea or sickle specific therapy (F):

   --A. Stroke defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI or cerebral arteriopathy requiring chronic transfusion therapy; OR

   --B. Sickle cell-related renal insufficiency defined by a creatinine level greater than or equal to 1.5 times the upper limit of normal and kidney biopsy consistent with sickle cell nephropathy OR nephrotic syndrome OR creatinine clearance less than < 50mL/min OR requiring peritoneal or hemodialysis; OR

   --C. Tricuspid regurgitant jet velocity (TRV) of greater than or equal to 2.5 m/s 40, 41 at baseline; OR

   --D. Recurrent priapism defined as at least 2 episodes of an erection lasting >4 hours involving the corpora cavernosa and corpus spongiosa; OR

   --E. Sickle hepatopathy defined as EITHER ferritin >1000mcg/L OR direct bilirubin >0.4 mg/dL at baseline

   --F. Any one of the below complications:

   ---Complication/ Eligible for hydroxyurea*/ Eligible for HSCT

   ----Vaso-occlusive crises/ At least 3 hospital admissions in the last year/ More than one hospital admission in the last year while on therapeutic dose of hydroxyurea or sickle cell therapy

   • Acute chest syndrome/ 2 prior ACS/ any ACS while on hydroxyurea
   • Osetonecrosis of 2 or more joints/ And significantly affecting their quality of life by Karnofsky score 50-60/ And on hydroxyurea where total hemoglobuin increases less than 1 g/dL or fetal hemoglobin increases less than 2.5 times the baseline level

   • Red cell alloimmunization/ Transfusion dependent/ Total hemoglobin increases less than 1g/dL while on hydroxurea

     2. Patients with beta-thalassemia who have grade 2 or 3 iron overload, determined by the presence of 2 or more of the following:

     -- portal fibrosis by liver biopsy

     • inadequate chelation history (defined as failure to maintain adequate compliance with chelation with deferoxamine initiated within 18 months of the first transfusion and administered subcutaneously for 8-10 hours at least 5 days each week)
     • hepatomegaly of greater than 2cm below the costochondral margin

   Non-disease specific:

   -Age greater than or equal to 4 years

   -6/6 HLA matched family donor available

   • Ability to comprehend and willing to sign an informed consent
   • Negative beta-HCG, when applicable

   EXCLUSION CRITERIA -recipient (any of the following would exclude the subject from participating)

   -ECOG performance status of 3 or more

   -Evidence of uncontrolled bacterial, viral, or fungal infections (currently taking medication and progression of clinical symptoms) within one month prior to starting the conditioning regimen. Patients with fever or suspected minor infection should await resolution of symptoms before starting the conditioning regimen.

   -Major anticipated illness or organ failure incompatible with survival from PBSC transplant

   -Pregnant or lactating

   INCLUSION CRITERIA -donor

   -6/6 HLA matched family donor deemed suitable and eligible, and willing to donate, per clinical evaluations who are additionally willing to donate blood for research. Matched related donors will be evaluated in accordance with existing Standard NIH Policies and Procedures for determination of eligibility and suitability for clinical donation. Note that participation in this study is offered to all matched related donors, but is not required for a donor to make a stem cell donation, so it is possible that not all related donors will enroll onto this study.

   EXCLUSION CRITERIA -donor

   -None