Study of Allogeneic Bone Marrow Transplantation Using Matched, Related Donors in Patients With Nonmalignant Hematologic Disorders
Study of Allogeneic Bone Marrow Transplantation Using Matched, Related Donors in Patients With Nonmalignant Hematologic Disorders
OBJECTIVES: I. Determine the efficacy of bone marrow transplantation using matched related
 donors in patients with nonmalignant hematologic disorders.

 II. Determine the quality of life, absence of adverse effects (e.g., graft versus host
 disease and B cell lymphoproliferative disease), and completeness of recovery of their
 underlying condition in these patients with this treatment regimen.
PROTOCOL OUTLINE: Patients receive IV or oral busulfan every 6 hours on days -9 to -6;
 cyclophosphamide IV on days -5 to -2; anti-thymocyte globulin IV on days -4 to -2; and
 allogeneic bone marrow transplantation (BMT) on day 0.

 Patients with class 3 thalassemia (liver edge greater than 2 cm below costal margin, a
 history of inconsistent chelation, and portal fibrosis) receive a less intensive conditioning
 regimen consisting of oral busulfan every 6 hours on days -7 to -4; anti-thymocyte globulin
 IV on days -5 to -1 and days 1-5; cyclophosphamide IV on days -3 to -2; and allogeneic BMT on
 day 0.

 Patients are followed at day 28, and then at 3, 6, 12, and 24 months.
PROTOCOL ENTRY CRITERIA:

 --Disease Characteristics--

 Severe hemoglobinopathy including, but not limited to the following:

 Homozygous beta thalassemia Other beta chain mutation as demonstrated by hemoglobin
 electrophoresis Sickle cell anemia (age 16 to 50 years) Evidence of one or more the
 following prior complications: Stage I-II sickle cell lung disease Sickle cell nephropathy
 (moderate to severe proteinuria or glomerular filtration rate of 30-50% predicted normal
 for age) Acute chest syndrome requiring blood transfusions More than 3 debilitating pain
 episodes per year for 3 years lasting more than 4 hours each Any combination of episodes of
 acute chest syndrome and painful episodes adding up to 3 episodes per year for 3
 consecutive years Requirement for chronic transfusions with alloimmunization (more than 2
 antibodies) Sickle cell anemia (age under 16 years) Evidence of one or more the following
 prior complications: Prior stroke or hemorrhage Any neurologic event lasting more than 24
 hours Abnormal cerebral MRI and cerebral arteriogram MRI angiographic impaired
 neuropsychologic testing Stage I-II sickle cell lung disease Sickle cell nephropathy
 (moderate to severe proteinuria or glomerular filtration rate of 30-50% predicted normal
 for age) Significant visual impairment in at least one eye with bilateral proliferative
 retinopathy Acute chest syndrome with history of recurrent hospitalizations or exchange
 transfusions Osteonecrosis of multiple joints with destructive changes More than 3
 debilitating pain episodes per year or priapism Requirement for chronic transfusions with
 alloimmunization

 OR

 Bone marrow failure syndrome unresponsive to therapy, including but not limited to the
 following: Congenital pure red cell aplasia (Diamond Blackfan anemia) Confirmed by bone
 marrow aspirate More than 6 transfusions per year despite steroid therapy Kostmann's
 neutropenia Confirmed by bone marrow aspirate Unable to maintain absolute neutrophil count
 greater than 750/mm3 or recurrent life threatening infections or more than 4
 hospitalizations per year despite therapy with filgrastim (G-CSF) No myelodysplasia or
 aplastic anemia

 Must have a related donor with at least a 5 out of 6 HLA antigen match

 --Patient Characteristics--

 Age: Sickle cell anemia patients 0 to 50; All other patients under 18

 Performance status: Karnofsky 70-100%

 Hepatic: Bilirubin no greater than 3.0 mg/dL with a direct fraction no greater than 2.0
 mg/dL ALT no greater than 150 U/L No moderate or severe portal fibrosis No active hepatitis

 Renal: Glomerular filtration rate at least 30% predicted (except with sickle cell anemia)
 No renal dysfunction

 Cardiovascular: Left ejection fraction at least 50% No cardiac compromise

 Other: No severe, stable neurologic impairment HIV negative