Griscelli Syndrome Medication

Updated: Jul 26, 2019
  • Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Dirk M Elston, MD  more...
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Medication

Medication Summary

To suppress the accelerated phase (lymphohistiocytic infiltration of multiple organs, in particular the brain and the meninges) of disease, immunosuppressive therapy is used.

Chemotherapy (VP16) or, more recently, antithymocyte globulins (ATG) (10 mg/kg for 5 d) and cyclosporin A have achieved remissions, and the use of intrathecal methotrexate injections transiently help treat the neurocerebral involvement. However, chemotherapy is sometimes ineffective for the treatment of the primary disease and frequently fails to control relapses. Recurrent infections have been minimized with antibacterial and antiviral agents.

Other regimens that have resulted in the induction of remission have been obtained with the combination of high-dose systemic methylprednisolone and etoposide and intrathecal methotrexate, cytosine arabinoside, and prednisone, and with a regimen of ATGs, steroids, and cyclosporine, but these therapies are palliative rather than curative.

In one case, before a bone marrow transplant was performed, a child was given a preparative regimen consisting of busulfan, thiotepa, and fludarabine with good effect. In another case, when a patient experienced HS (accelerated phase) characterized by hemophagocytosis, the patient was treated with prednisolone, rabbit ATGs, and intrathecal methotrexate. Remission was maintained with cyclosporin A until HLA-compatible peripheral blood stem cell transplantation from the patient's mother was performed.

Patients with Griscelli syndrome can be given antibiotics if they have HS. Seizures have not been reported to be controlled by anticonvulsants. Immunosuppressive medications are given in preparation for bone marrow transplants.

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Immunosuppressants

Class Summary

To suppress the accelerated phase (lymphohistiocytic infiltration of multiple organs, in particular the brain and the meninges) of disease, immunosuppressive therapy is used.

These agents include cyclic polypeptides that suppress some humoral immunity and, to a greater extent, cell-mediated immune reactions, such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft versus host disease, for a variety of organs. Prednisone is used to suppress T-cell and immune function.

Cyclosporine (Sandimmune, Neoral)

Cyclosporine is used with other immunosuppressive and chemotherapeutic agents to down-regulate the lymphohistiocytic infiltration that occurs in this disease.

Prednisone (Sterapred)

Prednisone is an immunosuppressant for the treatment of autoimmune disorders; it may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Prednisone stabilizes lysosomal membranes and suppresses lymphocyte and antibody production.

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Immunosuppressive Antibodies

Class Summary

This agent is used with other immunosuppressive and chemotherapeutic agents to down-regulate the lymphohistiocytic infiltration that occurs in this disease.

Antithymocyte globulin equine

ATG is usually used as an antirejection medication. The mechanisms of action of polyclonal ATGs are still poorly understood, and the selection of doses used in different clinical applications (eg, prevention or treatment of acute rejection in organ allografts, treatment of graft-vs-host disease, conditioning for allogeneic stem cell transplantation) remains empirical. Low T-cell counts are usually achieved in peripheral blood during ATG treatment, but the extent of T-cell depletion in lymphoid tissues is unknown. T-cell depletion is achieved rapidly and primarily in peripheral lymphoid tissues at high ATG dosage.

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Antineoplastics

Class Summary

Antineoplastics are used with other immunosuppressive and chemotherapeutic agents to down-regulate the lymphohistiocytic infiltration that occurs in this disease.

Etoposide (VePesid, Toposar)

Etoposide inhibits topoisomerase II and causes DNA strand breakage, resulting in cell proliferation to arrest in late S or early G2 portion of the cell cycle.

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Antimetabolites

Class Summary

Cytarabine is converted intracellularly to the active compound cytarabine-5'-triphosphate, which inhibits DNA polymerase. This inhibition, in turn, halts viral replication. Intrathecal methotrexate is an antimetabolite that inhibits dihydrofolate reductase, thereby hindering DNA synthesis and cell reproduction in malignant cells. Satisfactory response seen in 3-6 wk following administration. Adjust dose gradually to attain satisfactory response.

Cytarabine (Cytosar-U)

Cytarabine is used as part of an immunosuppressive regimen.

Intrathecal methotrexate (Folex PFS, Rheumatrex)

Intrathecal methotrexate is used with other immunosuppressive and chemotherapeutic agents to down-regulate the lymphohistiocytic infiltration that occurs in this disease. It is injected intrathecally to treat the neurologic complications. Patients are also given leucovorin to mitigate some effects of methotrexate.

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