Miscellaneous hematological agents:
Indications for: ZYNTEGLO
Treatment of patients with β-thalassemia who require regular red blood cell (RBC) transfusions.
Adults and Children:
<4yrs: not established. For autologous and one-time single-dose IV use only. Confirm that hematopoietic stem cell (HSC) transplantation is appropriate prior to mobilization, apheresis, and myeloablative conditioning. Full myeloablative conditioning must be administered prior to treatment. Prior to myeloablative conditioning: stop iron chelation at least 7 days; prophylaxis for hepatic veno-occlusive disease is recommended; and consider prophylaxis for seizures. 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. ≥4yrs: Infuse a minimum dose of 5.0x106 CD34+ cells/kg over ≤30mins. If the minimum dose is not met, may undergo additional cycles of mobilization and apheresis, separated by 14 days to obtain more cells. 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 of delayed platelet engraftment, increased bleeding. Monitor for thrombocytopenia and bleeding accordingly. Obtain platelet counts frequently until platelet engraftment and platelet recovery are achieved. Perform blood cell count determination and other appropriate testing whenever bleeding symptoms occur. Risk of 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. Risk of insertional oncogenesis. Monitor lifelong for hematologic malignancies with CBCs (with differential) at Months 6 and 12, then at least annually for at least 15 years, and integration site analysis at Months 6, 12, and as warranted; report to bluebird bio if malignancy occurs. Renal or hepatic impairment: not studied; assess for impairment to ensure HSC transplantation is appropriate. Elderly (>65yrs). Patients seropositive for HIV. Advise males and females of reproductive potential to use effective contraception from the start of mobilization through at least 6 months after infusion. Exclude pregnancy status prior to mobilization, conditioning procedures, and before infusion. Pregnancy, nursing mothers: not recommended.
Autologous hematopoietic stem cell-based gene therapy.
Concomitant live vaccines: not studied. Granulocyte-colony stimulating factor (G-CSF): not recommended for 21 days after infusion. Discontinue iron chelators at least 7 days prior to myeloablative conditioning. Avoid iron chelators for 6 months after Zynteglo infusion, if needed, consider nonmyelosuppressive iron chelators or phlebotomy may be used. Avoid prophylactic antiretroviral drugs or hydroxyurea for at least 1 month prior to mobilization, or for 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, febrile neutropenia, vomiting, pyrexia, alopecia, epistaxis, abdominal pain, musculoskeletal pain, cough, headache, diarrhea, rash, constipation, nausea, decreased appetite, pigmentation disorder, pruritus, lab abnormalities (neutropenia, thrombocytopenia, leukopenia, anemia, lymphopenia); hypersensitivity reactions.
Generic Drug Availability:
Infusion bag (20mL)—up to 4 (overwrap, each in a metal cassette)