Inborn errors of metabolism:
Indications for: SKYSONA
To slow the progression of neurologic dysfunction in boys 4–17 years of age with early, active cerebral adrenoleukodystrophy (CALD).
Limitations of Use:
Skysona does not treat or prevent adrenal insufficiency. An immune response to Skysona may cause rapid loss of efficacy of Skysona in patients with full deletions of the human adenosine triphosphate binding cassette, sub family D, member 1 (ABCD1) gene. Skysona has not been studied in CALD secondary to head trauma. Given the hematologic malignancy risk with Skysona, and unclear long-term durability of Skysona and human adrenoleukodystrophy protein (ALDP) expression, careful consideration should be given to the timing of treatment for each boy and treatment of boys with isolated pyramidal tract disease as clinical manifestations do not usually occur until adulthood.
≥18yrs: not established.
<4yrs: not established. For autologous and IV use only. Confirm that hematopoietic stem cell (HSC) transplantation is appropriate prior to mobilization, apheresis, and conditioning. Full myeloablative and lymphodepleting conditioning must be administered prior to treatment. Do not use an in-line blood filter or an infusion pump. Must undergo HSC mobilization followed by apheresis to obtain CD34+ cells for product manufacturing; the target number of CD34+ cells to be collected is 12x106 CD34+ cells/kg. 4–17yrs: Infuse a minimum dose of 5.0x106 CD34+ cells/kg over <60mins. A back-up collection is required for rescue treatment: CD34+ cells of ≥1.5x106 CD34+ cells/kg (if collected by apheresis) or ≥1.0x108 TNC/kg (Total Nucleated Cells, if collected by bone marrow harvest). Mobilization, apheresis, myeloablative conditioning, preparation and administration for infusion: see full labeling.
Risk for hematologic malignancy (including myelodysplastic syndrome). Prior to initiation, consider other alternative therapies or consult with hematology experts. Monitor lifelong for hematologic malignancies with CBCs (with differential) at least every 6 months, via integration site analysis or other testing for evidence of clonal expansion and predominance at least twice in the first year, and then annually thereafter for at least the first 15 years; consider bone marrow evaluations as clinically indicated; contact bluebird if malignancy occurs. Risk for severe infections (eg, bacterial, viral, opportunistic, or unspecified). Monitor for infection; give prophylactic antimicrobials according to guidelines. Avoid in those with active infections. Risk for prolonged cytopenias. Monitor blood counts until normalization; assess for bleeding and/or infection before and after treatment. Risk for delayed platelet engraftment, increased bleeding. Monitor for thrombocytopenia and bleeding accordingly. Obtain platelet counts frequently until platelet engraftment and recovery are achieved. Perform blood cell count determination and other appropriate testing whenever bleeding symptoms occur. Risk for neutrophil engraftment failure. Monitor neutrophil counts until engraftment is achieved. Administer rescue treatment with back-up collection of CD34+ cells if neutrophil engraftment failure occurs. Patients with a full ABCD1 deletion may lead to disease progression. Patients seropositive for HIV. Renal or hepatic impairment: not studied; assess for impairment to ensure HSC transplantation is appropriate. Advise males and females of reproductive potential to use effective contraception from the start of mobilization through at least 6 months after infusion. Pregnancy, nursing mothers: no available data.
Autologous hematopoietic stem cell-based gene therapy.
Concomitant vaccines: not studied. Vaccination during the 6 weeks preceding the start of myeloablative conditioning and until hematological recovery after treatment: not recommended. If feasible, give childhood vaccinations prior to myeloablative conditioning. Avoid prophylactic antiretroviral drugs for at least 1 month prior to mobilization, or the expected duration for elimination of the drugs, and until all apheresis cycles are completed; if needed, confirm negative HIV test prior to mobilization and apheresis. Avoid screening for HIV infection using a PCR-based assay; may result in a false (+) test.
Mucositis, nausea, vomiting, febrile neutropenia, alopecia, decreased appetite, abdominal pain, constipation, pyrexia, diarrhea, headache, rash, lab abnormalities (leukopenia, lymphopenia, thrombocytopenia, neutropenia, anemia, hypokalemia); hypersensitivity reactions (eg, anaphylaxis).
Generic Drug Availability:
Infusion bag (20mL)—1 or 2 (overwrap, each in a metal cassette)