Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation

This is an interventional treatment trial for Thalassemia focused on measuring bone marrow transplant, sickle cell disease, thalassemia, Glanzmann thrombasthenia, Wiskott-Aldrich syndrome, chronic-granulomatous disease, severe congenital neutropenia, leukocyte adhesion deficiency, Schwachman-Diamond syndrome, Diamond-Blackfan anemia, Fanconi anemia, dyskeratosis-congenita, Chediak-Higashi syndrome, severe aplastic anemia Read More

Inclusion Criteria:

1. Must be between the ages of 0-21 years at the time of admission for transplant
2. Must have been transfused with at least five platelet, erythrocyte or granulocyte units (partial or full)

3. Must have one of the following diseases:

   (a) hemoglobin SS or hemoglobin SB Sβ0 thalassemia and meet one of the criteria below for having severe sickle cell disease (i) Previous central nervous system event lasting longer than 24 hours, plus objective imaging evidence of CNS vasculopathy, with or without residual neurologic findings (ii) Frequent (≥ 3 per year for 2 years) painful vaso-occlusive episodes (defined as episode lasting ≥ 4 hours and requiring hospitalization or outpatient treatment with parenteral opioids/opiates). Must have also (iii) Recurrent (≥ 3 in lifetime) acute chest syndrome events which have necessitated exchange transfusion or chronic transfusion therapy. (iv) Any combination of ≥ 3 acute chest syndrome episodes and vasoocclusive pain episodes (defined as above) yearly for 3 years. (v) Stage I or II sickle lung disease (see appendix 1) (vi) Pulmonary hypertension, measured by tricuspid regurgitant jet velocity (TRV) of greater than 2.5m/s (vii) Osteonecrosis involving multiple joints. (viii) Sickle Cell nephropathy with moderately severe renal insufficiency estimated GFR ≥30 ml/min, but ≤60 ml/min/1.73 m2 (Requires evaluation by a nephrologist). (b) Thalassemia major (c) Glanzmann thrombasthenia (d) Wiskott-Aldrich syndrome (e) Chronic-granulomatous disease (f) Severe congenital neutropenia (g) Leukocyte adhesion deficiency (h) Shwachman-Diamond syndrome (i) Diamond-Blackfan anemia (j) Fanconi anemia (k) Dyskeratosis-congenita (l) Chediak-Higashi syndrome (m) Acquired (immune; non-inherited, non-congenital) severe aplastic anemia (only patients whose best graft source is a mismatched related donor, unrelated marrow donor or cord blood unit) (n) Other inherited or congenital marrow failure syndromes complicated by severe aplastic anemia (o) Other inherited or congenital red blood cell disorders requiring monthly chronic transfusion therapy. (p) Other inherited or congenital platelet disorders resulting in at least three inpatient hospitalizations in the past two years for bleeding. (q) Other inherited or congenital granulocyte disorders resulting in at least three inpatient hospitalizations in the past two years for infection.

4. Must have an available HLA identical sibling (HLA matched related), a non-HLA identical parent or sibling who is matched at least seven of eight loci (mismatch can be at an allele or antigen level), an unrelated adult donor who is matched at least seven of eight loci (mismatch can be at an allele or antigen level) or an unrelated cord blood unit that is matched at five of six loci (A (antigen level), B (antigen level), DRB1 (allele level)) and provides a minimum pre-cryopreservation TNC dose of 5.0 x 107 TNC/kg recipient weight.

Exclusion Criteria:

1. Hemophagocytic lymphohistiocytosis or other disorder characterized by NK cell dysfunction, since alefacept's effect is mediated by NK cells.
2. Biopsy proven cirrhosis (score IV).
3. SCD chronic lung disease ≥ stage III (see appendix 1)
4. Severe renal dysfunction defined as estimated GFR of <30 ml/min.
5. Severe cardiac dysfunction defined as shortening fraction < 25%.
6. Severe neurologic impairment other than hemiplegia alone, defined as full scale IQ ≤ 70, quadriplegia or paraplegia, inability to ambulate, inability to communicate without assistive device, or any impairment resulting in decline of Lansky performance score to <50%.
7. Karnofsky or Lansky functional performance score < 50%
8. Confirmed HIV seropositivity.
9. Patient with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate bone marrow transplantation.
10. Patient or patient's guardian(s) unable to understand the nature and risks inherent in the BMT process.
11. History of lack of compliance with medical care that would jeopardize transplant course.
12. Patient is pregnant or lactating
13. Donor who for psychological, physiologic, or medical reasons is unable to tolerate a bone marrow harvest or receive general anesthesia.
14. Donor is HIV infected.
15. Donor is pregnant
16. Hemoglobin SS, or hemoglobin Sβ0 thalassemia patient who is eligible for one of the two trials of myeloablative conditioning currently being conducted by the Aflac Center (SALT: Alternate-Donor Bone Marrow and Cord Blood Transplantation for Children with High-Risk Sickle Cell Disease Busulfan, fludarabine, ATG and Reduced-Dose Cyclophosphamide Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Severe Sickle Cell Disease: a pilot study
17. Patients with thalassemia major who are eligible for any multicenter study we are participating in.
18. Patients whose best graft source is a related or unrelated donor/cord blood unit that is mismatched and the patient's HLA antibody testing (see below) demonstrates an antibody directed against the disparate HLA molecule.