Sections

Medication

Medication Summary

Treat any underlying disease (eg, rickets) as indicated for the specific disease. The medications listed here have shown some benefit in patients with idiopathic myelofibrosis (IMF). They include the following:

Calcitriol
Prednisone
Methylprednisolone
Interferon alfa 2a
IV immunoglobulin
Thalidomide
Lenalidomide
Decitabine

Class Summary

Myelofibrosis has been described in patients with severe vitamin D deficiency. In addition, some (adult) patients with myelofibrosis associated with essential thrombocythemia or myelomonocytic leukemia, as well as acute (idiopathic) myelofibrosis (IMF), have responded to vitamin D administration. A direct inhibitory effect on platelets has been proposed. However, other studies have not confirmed such a response in patients with IMF.

Calcitriol (Rocaltrol, Calcijex, Vectical)

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Calcitriol (ie, 1,25-dihydroxyvitamin D) is the primary active metabolite of vitamin D3. It increases calcium levels by promoting absorption of calcium in the intestines and retention in the kidneys. Doses for myelofibrosis are 5- to 10-fold higher than the physiologic dose.

Class Summary

These agents have immunosuppressive and cytotoxic effects. The mechanism of cytotoxicity is unknown (but apparently mediated through glucocorticoid receptors).

Prednisone

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Prednisone is an immunosuppressant for the treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear (PMN) cell activity. Prednisone stabilizes lysosomal membranes and also suppresses lymphocyte and antibody production. Its efficacy in some cases of myelofibrosis may reflect an underlying autoimmune defect and/or suppression of a proliferating clone.

Methylprednisolone (Solu-Medrol, Medrol, Depo-Medrol, A-Methapred)

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This agent decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability. Support for this higher-dose therapy in the literature is limited.

Class Summary

Proposed mechanisms of action for these agents are suppression of autoimmunity, enhanced immunoregulation of an abnormal clone, or both.

Interferon alfa-2a (Pegasys)

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Interferon alfa-2a is a protein product manufactured by recombinant DNA technology. It acts by modulation of the host's immune response. This treatment has shown long-term efficacy in 1 adolescent patient with an indolent form of myelofibrosis (essentially identical to adult agnogenic myeloid metaplasia with myelofibrosis [AMMM]). Transient responses have been observed in at least 2 adults with acute myelofibrosis.

IV immunoglobulin (Privigen, Hizentra, Octagam, Gammagard)

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Response to intravenous immunoglobulin was reported in 1 case of pediatric myelofibrosis, which was associated with autoimmune phenomena.

Thalidomide (Thalomid)

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Thalidomide is an immunomodulatory agent that may suppress excessive production of tumor necrosis factor-alpha (ie, TNF-α) and may down-regulate selected cell-surface adhesion molecules involved in leukocyte migration.

Because of concerns regarding teratogenicity, thalidomide can be prescribed only by physicians and dispensed only by pharmacists who are registered with the System for Thalidomide Education and Prescribing Safety (STEPS) program. Patients must participate in ongoing surveys to receive therapy, and only a 28-day supply can be prescribed at a time. Thalidomide is used to improve anemia and decrease blood/platelet transfusions associated with myelofibrosis.

Lenalidomide (Revlimid)

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Lenalidomide is indicated for the transfusion-dependent myelodysplastic syndrome (MDS) subtype of the deletion 5q cytogenetic abnormality. It is structurally similar to thalidomide and elicits immunomodulatory and antiangiogenic properties. Lenalidomide inhibits proinflammatory cytokine secretion and increases anti-inflammatory cytokines from peripheral mononuclear blood cells.

Class Summary

Antineoplastic agents inhibit cell growth and proliferation.

Decitabine (Dacogen)

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Decitabine is a hypomethylating agent believed to exert antineoplastic effects by incorporating into DNA and inhibiting methyltransferase, resulting in hypomethylation. Hypomethylation in neoplastic cells may restore normal function to genes critical for the cellular control of differentiation and proliferation.

Decitabine is indicated for the treatment of MDSs, including previously treated and untreated, de novo, and secondary MDSs of all French-American-British (FAB) subtypes (ie, refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia) and International Prognostic Scoring System (IPSS) groups intermediate-1 risk, intermediate-2 risk, and high risk.

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Media Gallery

Photomicrograph of a peripheral smear of a patient with agnogenic myeloid metaplasia (idiopathic myelofibrosis) shows findings of leukoerythroblastosis, giant platelets, and few teardrop cells.

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Author

Trisha Simone Natanya Tavares, MD Contract Clinical Hematologist and Oncologist, Department of Pediatric Hematology and Oncology, Presbyterian Healthcare; Volunteer Hematology/Oncology Physician, St Vincent de Paul Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

J Martin Johnston, MD Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Hematology/Oncology, The Children's Hospital at Memorial University Medical Center; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital

J Martin Johnston, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, International Society of Paediatric Oncology

Disclosure: Nothing to disclose.

Chief Editor

Cameron K Tebbi, MD Director, Children's Cancer Research Group Laboratories

Cameron K Tebbi, MD is a member of the following medical societies: International Society of Pediatric Oncology

Disclosure: Nothing to disclose.

Acknowledgements

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society

Disclosure: Nothing to disclose.

Sharada A Sarnaik, MBBS Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Attending Hematologist/Oncologist, Children's Hospital of Michigan

Sharada A Sarnaik, MBBS is a member of the following medical societies: American Association of Blood Banks, American Association of University Professors, American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Pediatric Myelofibrosis Medication

Medication Summary

Vitamin D Analogs

Class Summary

Calcitriol (Rocaltrol, Calcijex, Vectical)

Calcitriol (Rocaltrol, Calcijex, Vectical)

Corticosteroids

Class Summary

Prednisone

Prednisone

Methylprednisolone (Solu-Medrol, Medrol, Depo-Medrol, A-Methapred)

Methylprednisolone (Solu-Medrol, Medrol, Depo-Medrol, A-Methapred)

Immunomodulators

Class Summary

Interferon alfa-2a (Pegasys)

Interferon alfa-2a (Pegasys)

IV immunoglobulin (Privigen, Hizentra, Octagam, Gammagard)

IV immunoglobulin (Privigen, Hizentra, Octagam, Gammagard)

Thalidomide (Thalomid)

Thalidomide (Thalomid)

Lenalidomide (Revlimid)

Lenalidomide (Revlimid)

Antineoplastic Agents

Class Summary

Decitabine (Dacogen)

Decitabine (Dacogen)

Pediatric Myelofibrosis Medication

Medication Summary

Vitamin D Analogs

Class Summary

Calcitriol (Rocaltrol, Calcijex, Vectical)

Corticosteroids

Class Summary

Prednisone

Methylprednisolone (Solu-Medrol, Medrol, Depo-Medrol, A-Methapred)

Immunomodulators

Class Summary

Interferon alfa-2a (Pegasys)

IV immunoglobulin (Privigen, Hizentra, Octagam, Gammagard)

Thalidomide (Thalomid)

Lenalidomide (Revlimid)

Antineoplastic Agents

Class Summary

Decitabine (Dacogen)

References

Tables

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