Pediatric Myelofibrosis Medication

  • Author: Trisha Simone Tavares, MD; Chief Editor: Robert J Arceci, MD, PhD   more...
 
Updated: May 14, 2012
 

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
Next

Vitamin D Analogs

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.

View full drug information

Calcitriol (Rocaltrol, Calcijex, Vectical)

 

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.

Previous
Next

Corticosteroids

Class Summary

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

View full drug information

Prednisone

 

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.

View full drug information

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

 

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.

Previous
Next

Immunomodulators

Class Summary

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

View full drug information

Interferon alfa-2a (Pegasys)

 

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.

View full drug information

IV immunoglobulin (Privigen, Hizentra, Octagam, Gammagard)

 

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

View full drug information

Thalidomide (Thalomid)

 

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.

View full drug information

Lenalidomide (Revlimid)

 

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.

Previous
Next

Antineoplastic Agents

Class Summary

Antineoplastic agents inhibit cell growth and proliferation.

View full drug information

Decitabine (Dacogen)

 

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.

Previous
 
Contributor Information and Disclosures
Author

Trisha Simone Tavares, MD  Assistant Professor of Pediatrics, Attending Physician, Department of Pediatrics, Section of Hematology and Oncology, Center for Children's Cancer and Blood Disorders, Golisano Children's Hospital, State University of New York Upstate Medical University; Attending Physician, Department of Pediatrics, Crouse Hospital

Trisha Simone Tavares, MD is a member of the following medical societies: Children's Oncology Group and Medical Society of the State of New York

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 and American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD  King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine

Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Additional Contributors

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.

References

  1. Naithani R, Tyagi S, Choudhry VP. Secondary myelofibrosis in children. J Pediatr Hematol Oncol. 2008;30(3):196-8. [Medline].

  2. Inoue S, Limsuwan A, McQueen R. Spontaneous resolution of myelofibrosis and pancytopenia followed by the development of acute myeloid leukemia with an extramedullary mass. J Pediatr Hematol Oncol. May-Jun 1998;20(3):268-70. [Medline].

  3. Maj JS, Roslan K, Fic-Sikorska B. Acute myelofibrosis in children: report on two cases. Acta Haematol Pol. 1996;27(1):79-84. [Medline].

  4. Boxer LA, Camitta BM, Berenberg W. Myelofibrosis-myeloid metaplasia in childhood. Pediatrics. Jun 1975;55(6):861-5. [Medline].

  5. Sekhar M, Prentice HG, Popat U. Idiopathic myelofibrosis in children. Br J Haematol. May 1996;93(2):394-7. [Medline].

  6. Reilly JT. Idiopathic myelofibrosis: pathogenesis, natural history and management. Blood Rev. Dec 1997;11(4):233-42. [Medline].

  7. Hung IJ, Kuo TT, Sun CF. Subcutaneous panniculitic T-cell lymphoma developing in a child with idiopathic myelofibrosis. J Pediatr Hematol Oncol. Jan-Feb 1999;21(1):38-41. [Medline].

  8. McCarthy DM. Annotation. Fibrosis of the bone marrow: content and causes. Br J Haematol. Jan 1985;59(1):1-7. [Medline].

  9. Noren-Nystrom U, Roos G, Bergh A, et al. Bone marrow fibrosis in childhood acute lymphoblastic leukemia correlates to biological factors, treatment response and outcome. Leukemia. 2008;22(3):504-10. [Medline].

  10. Lichtman MA, Tefferi A. Primary Myelofibrosis. In: Williams Hematology. 8th ed. New York, NY: McGraw-Hill Professional; 2010:1381.

  11. Komura E, Tonetti C, Penard-Lacronique V. Role for the nuclear factor kappaB pathway in transforming growth factor-beta1 production in idiopathic myelofibrosis: possible relationship with FK506 binding protein 51 overexpression. Cancer Res. Apr 15 2005;65(8):3281-9. [Medline].

  12. Wolf BC, Neiman RS. Myelofibrosis with myeloid metaplasia: pathophysiologic implications of the correlation between bone marrow changes and progression of splenomegaly. Blood. Apr 1985;65(4):803-9. [Medline].

  13. Barosi G, Bergamaschi G, Marchetti M, et al. JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis. Blood. Dec 1 2007;110(12):4030-6. [Medline].

  14. Rudzki Z, Sacha T, Stoj A. The gain-of-function JAK2 V617F mutation shifts the phenotype of essential thrombocythemia and chronic idiopathic myelofibrosis to more "erythremic" and less "thrombocythemic": a molecular, histologic, and clinical study. Int J Hematol. Aug 2007;86(2):130-6. [Medline].

  15. Al-Assar O, Ul-Hassan A, Brown R. Gains on 9p are common genomic aberrations in idiopathic myelofibrosis: a comparative genomic hybridization study. Br J Haematol. Apr 2005;129(1):66-71. [Medline].

  16. Hussein K, Van Dyke DL, Tefferi A. Conventional cytogenetics in myelofibrosis: literature review and discussion. Eur J Haematol. 2009;82(5):329-38. [Medline].

  17. Fadilah SA, Raja-Zahratul-Azma RS, Leong CF. Extensive myelofibrosis responsive to treatment for acute erythroblastic leukaemia. Malays J Pathol. 2006;28(1):55-8. [Medline].

  18. Abla O, Ye CC. Acute lymphoblastic leukemia with massive myelofibrosis. J Pediatr Hematol Oncol. Sep 2006;28(9):633-4. [Medline].

  19. Alvarez-Larran A, Cervantes F, Bellosillo B, et al. Essential thrombocythemia in young individuals: frequency and risk factors for vascular events and evolution to myelofibrosis in 126 patients. Leukemia. 2007;21(6):1218-23. [Medline].

  20. Uysal Z, Ileri T, Gozdasoglu S. Reversible myelofibrosis associated with hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. Jul 2007;49(1):108-9. [Medline].

  21. Rao SP, Miller ST, Thelmo W. Myelofibrosis in a child with sickle cell anemia. Am J Pediatr Hematol Oncol. Winter 1991;13(4):487-9. [Medline].

  22. Hashim MS, Kordofani AY, el Dabi MA. Tuberculosis and myelofibrosis in children: a report. Ann Trop Paediatr. Mar 1997;17(1):61-5. [Medline].

  23. Saleem M, Anwar M, Khan AH. Myelofibrosis in visceral leishmaniasis. Br J Haematol. Aug 1991;78(4):573-4. [Medline].

  24. Paquette RL, Meshkinpour A, Rosen PJ. Autoimmune myelofibrosis. A steroid-responsive cause of bone marrow fibrosis associated with systemic lupus erythematosus. Medicine (Baltimore). May 1994;73(3):145-52. [Medline].

  25. Rossbach HC. Familial infantile myelofibrosis as an autosomal recessive disorder: preponderance among children from Saudi Arabia. Pediatr Hematol Oncol. Jul 2006;23(5):453-4. [Medline].

  26. Sheikha A. Fatal familial infantile myelofibrosis. J Pediatr Hematol Oncol. 2004;26(3):164-8. [Medline].

  27. Mallouh AA, Sa'di AR. Agnogenic myeloid metaplasia in children. Am J Dis Child. 1992;146(8):965-7. [Medline].

  28. Ivanyi JL, Mahunka M, Papp A. Prognostic significance of bone marrow reticulin fibres in idiopathic myelofibrosis: evaluation of clinicopathological parameters in a scoring system. Haematologia (Budap). 1994;26(2):75-86. [Medline].

  29. Tefferi A, Huang J, Schwager S. Validation and comparison of contemporary prognostic models in primary myelofibrosis: analysis based on 334 patients from a single institution. Cancer. May 2007;109(10):2083-8. [Medline].

  30. Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. Mar 26 2009;113(13):2895-901. [Medline].

  31. El-Moneim AA, Kratz CP, Böll S, Rister M, Pahl HL, Niemeyer CM. Essential versus reactive thrombocythemia in children: retrospective analyses of 12 cases. Pediatr Blood Cancer. 2007;49(1):52-5. [Medline].

  32. Cohn SL, Cohn RA, Chou P. Infantile myelofibrosis with nephromegaly secondary to myeloid metaplasia. Clin Pediatr (Phila). Jan 1991;30(1):59-61. [Medline].

  33. Fernbach SK, Feinstein KA. Extramedullary hematopoiesis in the kidneys in infant siblings with myelofibrosis. Pediatr Radiol. 1992;22(3):211-2. [Medline].

  34. Pilorget H, Bangui A, Adam M. [Myelofibrosis regressing under corticotherapy and intravenous immunoglobulins in an infant(in French)]. Arch Pediatr. Jan 1996;3(1):40-3. [Medline].

  35. Ozsoylu S, Ruacan S. High-dose intravenous corticosteroid treatment in childhood idiopathic myelofibrosis. Acta Haematol. 1986;75(1):49-51. [Medline].

  36. Schwartz CL, Cohen H. Myeloproliferative and myelodysplastic syndromes. In: Pizzo PA, Poplack DG, eds. Principles and Practice of Pediatric Oncology. 3rd ed. Philadelphia, PA: JB Lippincott Company; 1997:512-4.

  37. Domingues MA, Haepers AT, Massaut IH, Vassallo J, Lorand-Metze I. Reversal of bone marrow fibrosis in idiopathic myelofibrosis after treatment with alpha-interferon. Haematologica. Dec 1998;83(12):1124-5. [Medline].

  38. Rambaldi A, Barbui T, Barosi G. From palliation to epigenetic therapy in myelofibrosis. USA: American Society of Hematology; 2008. Hematology. [Medline]. [Full Text].

  39. Tefferi A. Treatment approaches in myelofibrosis with myeloid metaplasia: the old and the new. Semin Hematol. Jan 2003;40(1 Suppl 1):18-21. [Medline].

  40. Tefferi A, Cortes J, Verstovsek S, et al. Lenalidomide therapy in myelofibrosis with myeloid metaplasia. Blood. 2006;108(4):1158-64. [Medline].

  41. Arlet P, Nicodeme R, Adoue D. Clinical evidence for 1,25-dihydroxycholecalciferol action in myelofibrosis. Lancet. May 5 1984;1(8384):1013-4. [Medline].

  42. Richard C, Mazorra F, Iriondo A. The usefulness of 1,25-dihydroxy-vitamin D3(1,25(OH)2vitD3) in the treatment of idiopathic myelofibrosis. Br J Haematol. Feb 1986;62(2):399-400. [Medline].

  43. Danilov AV, Relias V, Feeney DM, Miller KB. Decitabine is an effective treatment of idiopathic myelofibrosis. Br J Haematol. 2009;145(1):131-2. [Medline].

  44. Ostojic A, Vrhovac R, Verstovsek S. Ruxolitinib for the treatment of myelofibrosis: its clinical potential. Ther Clin Risk Manag. 2012;8:95-103. [Medline]. [Full Text].

  45. Domm J, Calder C, Manes B, Crossno C, Correa H, Frangoul H. Unrelated stem cell transplant for infantile idiopathic myelofibrosis. Pediatr Blood Cancer. 2009;52(7):893-5. [Medline].

  46. Soll E, Massumoto C, Clift RA. Relevance of marrow fibrosis in bone marrow transplantation: a retrospective analysis of engraftment. Blood. Dec 15 1995;86(12):4667-73. [Medline].

  47. Kerbauy DM, Gooley TA, Sale GE. Hematopoietic cell transplantation as curative therapy for idiopathic myelofibrosis, advanced polycythemia vera, and essential thrombocythemia. Biol Blood Marrow Transplant. Mar 2007;13(3):355-65. [Medline].

  48. Anderson JE, Sale G, Appelbaum FR. Allogeneic marrow transplantation for primary myelofibrosis and myelofibrosis secondary to polycythaemia vera or essential thrombocytosis. Br J Haematol. Sep 1997;98(4):1010-6. [Medline].

  49. Merup M, Lazarevic V, Nahi H. Different outcomes of allogeneic transplantation in myelofibrosis using conventional or reduced-intensity conditioning regimens. Br J Haematol. Nov 2006;135(3):367-73. [Medline].

  50. Platzbecker U, Ehninger G, Schmitz N, Bornhauser M. Reduced-intensity conditioning followed by allogeneic hematopoietic cell transplantation in myeloid diseases. Ann Hematol. 2003;82(8):463-8. [Medline].

  51. Mesa RA, Nagorney DS, Schwager S. Palliative goals, patient selection, and perioperative platelet management: outcomes and lessons from 3 decades of splenectomy for myelofibrosis with myeloid metaplasia at the Mayo Clinic. Cancer. Jul 2006;107(2):361-70. [Medline].

  52. Tefferi A, Mesa RA, Nagorney DM. Splenectomy in myelofibrosis with myeloid metaplasia: a single-institution experience with 223 patients. Blood. Apr 1 2000;95(7):2226-33. [Medline].

 
Previous
Next
 
Photomicrograph of a peripheral smear of a patient with agnogenic myeloid metaplasia (idiopathic myelofibrosis) shows findings of leukoerythroblastosis, giant platelets, and few teardrop cells.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.