stem cell transplant in sickle cell disease and thalassemia

Conditions: Sickle Cell Disease; Beta Thalassemia

Summary: the primary purpose of this study is to see if giving lower doses of chemotherapy (moderately ablative) will result in successful bone marrow replacement without as severe side-effects but with permanent control of the disease. patients will receive a chemotherapy regimen with busulfan, fludarabine, and alemtuzumab followed by an infusion of stem cells, either from a family-related or cord-blood matched donor.

sickle cell disease is a genetic disorder in which a mutation in the beta chain of human hemoglobin results in abnormal blood hemoglobin, causing red blood cells to sickle under stress with resulting symptoms including severe pains and strokes. beta thalassemia is another genetic disorder in which there are abnormal beta hemoglobin chains, causing anemia. in both disorders, frequent red blood cell transfusions may be required to sustain life, but these often result in complications including multiple hospitalizations, iron overload, or bacterial or viral infections such as hepatitis. standard drugs and therapies used in the treatment of sickle cell disease and/or beta thalassemia provide only supportive care, and may result in long-term side effects, and inadequate control of the disease process. bone marrow transplant has been increasingly used for the long-term treatment and cure of sickle cell disease and beta thalassemia. although, not without acute and potential long term side effects, this alternative offers long term control and potential cure of the disease. most of the side effects seen with bone marrow transplant are directly related to the high intensity of chemotherapy used (ablative).

Eligibility criteria:
inclusion criteria: sickle cell disease: * diagnosis of homozygous hemoglobin s disease or heterozygous hemoglobin sickle cell (sc) or s 0/+ thalassemia, or sickle/variant resulting in chronic hemolytic anemia with hemoglobin (hgb) ≤10 mg/dl * age ≤30 * matched sibling donor and asymptomatic, or 8/8 human leukocyte antigen (hla) matched unrelated adult donor patient must have adequate organ function as below: * adequate renal function defined as serum creatinine ≤1.5 x normal, or creatinine clearance or radioisotope glomerular filtration rate (gfr) \>100 ml/min/1.73 m2 or \>70ml/min/1.73m2 for patients \>16 years old * adequate liver function defined as serum glutamic oxaloacetic transaminase (sgot) (aspartate aminotransferase (ast)) or serum glutamic-pyruvic transaminase (sgpt) (alanine aminotransferase (alt)) \< 5.0 x normal * adequate cardiac function defined as shortening fraction of ≥28% by echocardiogram, or ejection fraction of ≥48% by radionuclide angiogram or echocardiogram * adequate pulmonary function defined as corrected diffusing capacity of the lungs for carbon monoxide (dlco) ≥40% by pulmonary function test, or for children who are unable to perform dlco maneuver ≥85% o2 saturation, no evidence of dyspnea at rest exclusion criteria: general * karnofsky/lansky performance score \<60% * demonstrated lack of compliance with medical care * pregnant or nursing * evidence of uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms) within 1 month prior to starting the conditioning regimen. patients with fever or suspected minor infection should await resolution of symptoms before starting the conditioning regimen. histologic exam of liver (liver biopsy) with bridging fibrosis or cirrhosis.

Keywords: stem cell transplant sickle cell disease thalassemia moderately ablative cord blood transplant matched family donor