eMedicine Specialties > Pediatrics: General Medicine > Hematology

Myelofibrosis: Treatment & Medication

Author: J Martin Johnston, MD, Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Pediatric Hematology/Oncology, Backus Children's Hospital; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital
Contributor Information and Disclosures

Updated: Oct 2, 2009

Treatment

Medical Care

As noted, the workup of children with myelofibrosis (MF) frequently leads to a diagnosis of acute nonlymphoblastic (specifically, megakaryoblastic) leukemia or, less commonly, myelodysplastic syndrome. The treatment of these patients is not discussed here.

The identification of another treatable underlying diagnosis (eg, rickets, tuberculosis) should prompt treatment of that disorder.

Treatment should be directed at the underlying process when childhood myelofibrosis is identified. Other therapeutic options include transfusion support, corticosteroids, intravenous (IV) immunoglobulin, alfa interferon, vitamin D, conventional antileukemic chemotherapy (eg, hydroxyurea), and allogeneic bone marrow transplantation (BMT). In addition, splenectomy may be palliative in selected patients. 

Treatment with imatinib mesylate (Gleevec) is occasionally effective. Patients who do respond to imatinib sometimes exhibit increased platelet or WBC counts, which, in turn, require treatment with hydroxyurea or interferon.

Other promising new agents in adult myelofibrosis include thalidomide (alone or in combination with prednisone), lenalidomide, and decitabine.35

  • Vitamin D: Myelofibrosis is observed in some patients with severe vitamin D deficiency. In addition, cases of myelofibrosis associated with essential thrombocythemia or myelomonocytic leukemia, as well as acute (idiopathic) myelofibrosis, have responded to vitamin D administration.36,37
  • Corticosteroids: Corticosteroids have been used to treat many cases of pediatric myelofibrosis, with occasional apparent successes.38 However, one concern is that the literature does not always allow for a clear distinction between primary and secondary cases of myelofibrosis. Patients with systemic lupus erythematosus or even acute nonlymphoid leukemia (ANLL) might show a response to steroid therapy, although this would be only a temporary effect with the latter diagnosis.31 In particular, treatment with high-dose methylprednisolone has been touted as an effective therapy; however, this recommendation is based on a published series of only 5 older pediatric patients (aged 9-14 y), at least one of whom had a positive purified protein derivative (PPD) finding and was also treated with isoniazid.39
  • Thalidomide: For palliation of anemia and thrombocytopenia in adult patients with agnogenic myeloid metaplasia with myelofibrosis (AMMM), the combination of prednisone and thalidomide appears to be reasonably effective.40 Among 36 patients with symptomatic AMMM who enrolled in either a trial of single-agent thalidomide (n = 15) or a trial of low-dose thalidomide (50 mg/d) combined with prednisone (n = 21), 20 (56%) showed some improvement.41 Responses included improvements in anemia (15 of 36 [42%]), thrombocytopenia (10 of 13 [77%]) and splenomegaly (5 of 30 [17%]). The combination of low-dose thalidomide and prednisone was better tolerated and more efficacious than thalidomide alone. After a median follow-up of 25 months, 10 of 36 patients (28%) showed a persistent response, including 8 patients whose protocol treatment had been discontinued for a median of 21 months.
  • Lenalidomide: Another inhibitor of angiogenesis, this agent has also shown efficacy in adults with myelofibrosis or AMMM.42 Protocol treatment consisted of oral lenalidomide 10 mg daily for 3-24 months, depending on response. Among 68 patients, overall response rates were 22% for anemia, 33% for splenomegaly, and 50% for thrombocytopenia. Response in anemia was deemed "impressive" in 8 patients. Additional observed effects included resolution of leukoerythroblastosis (4 patients), a decrease in medullary fibrosis and angiogenesis (2 patients), and del(5)(q13q33) cytogenetic remission accompanied by a reduction in JAK2(V617F) mutation burden (1 patient). A follow-up report suggests that responses are more likely in patients exhibiting del(5q).43
  • Intravenous (IV) immunoglobulin: An 8-month-old girl with myelofibrosis and dysgranulopoiesis responded to IV immunoglobulin (added to previous corticosteroid therapy).44 Her disease was unusual and was characterized by a positive Coombs test result and antineutrophil antibodies, suggesting an autoimmune etiology.
  • Alfa interferon: Alfa interferon has been used to treat at least 2 adults with acute MF and one 14-year-old boy with indolent myelofibrosis. The adolescent patient showed resolution of fibrosis and restoration of blood counts after 6 months of therapy with alfa interferon 3 million IU, 3 times a week.45 He continued to do well for at least 2 years on a maintenance dose of 2 million IU twice a week. Two adult males (aged 63 and 71 y) with acute myelofibrosis (and excess blasts) were treated with subcutaneous interferon alfa-2a at doses of 1-6 million IU daily. Both showed resolution of fibrosis. The first patient was maintained on interferon for 12 weeks, but his disease progressed shortly after it was discontinued. After 4 weeks of interferon, the second patient stayed in an unmaintained remission for 4 months before dysplastic hematopoiesis recurred.
  • Chemotherapy: Conventional chemotherapy, as would otherwise be used to treat acute myeloid/megakaryocytic leukemia, has been used to treat patients with acute myelofibrosis of childhood (C-AMF), under the assumption that C-AMF is a preleukemic condition. The details of such therapy are beyond the scope of this article and are discussed in Acute Myelocytic Leukemia. Decitabine, an S-phase specific inhibitor of DNA methyltransferase, has shown promise in adult patients with myelofibrosis.46 Pediatric dosing for this drug has not been established, and no literature regarding its use in children with myelofibrosis has been published.
  • BMT: Similarly, allogeneic BMT has been used successfully to treat patients with MF.47 Thirteen adult patients with myelofibrosis (8 primary and 5 associated with either polycythemia vera or essential thrombocytosis) received allogeneic BMTs at the Fred Hutchinson Cancer Research Center.48 Preparative regimens and donors varied. Four patients died of transplant-related complications. Nine patients are apparent long-term survivors, 2 of whom experienced a relapse and are in a chronic myeloproliferative state. Published experience from Sweden and Germany demonstrates that reduced-intensity preparative regimens are often effective for treating myelofibrosis and clearly have less treatment-related mortality than do myeloablative regimens.49,50 In a recent report, 2 children with infantile myelofibrosis were successfully treated with unrelated hematopoietic stem cell transplantation.51
  • Imatinib: In one published report, 11 adult patients with idiopathic myelofibrosis (IMF) or postpolycythemic myelofibrosis (PPMF) were treated with imatinib at a dose of 400 mg/d.52 Nine patients were in an advanced disease phase. At the time of publication, the patients had been followed for a median of 2 months. A beneficial effect of imatinib was documented in 3 patients. Leukocytosis and thrombocytosis were seen in most patients with myelofibrosis during treatment with imatinib. Other reports have been less encouraging.53 Combination therapy with hydroxyurea or interferon seems safe and well tolerated and is followed by a decrease in disease activity.

Surgical Care

  • Some adult patients with AMMM are candidates for splenectomy, but patient selection for this procedure is controversial.54 Transfusion-dependent anemia, portal hypertension, and/or symptoms of hypercatabolism are potential indications for splenectomy, but the surgery-related mortality rate may be as high as 9%.55 Similar statistics are not available for pediatric patients.
  • In adults with symptomatic splenomegaly, irradiation of the spleen is sometimes performed as an alternative to splenectomy.
  • Placement of a central venous access device may facilitate care in patients requiring complex therapies or frequent transfusions.

Medication

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).

Antirachitics

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, 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 idiopathic myelofibrosis (IMF).


Calcitriol (Rocaltrol)

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 MF are 5- to 10-fold higher than the physiologic dose.

Adult

2.5 mcg/d PO

Pediatric

0.1 mcg/kg/d PO

Cholestyramine and colestipol decrease absorption of calcitriol; magnesium-containing antacids and thiazide diuretics can increase calcitriol effects

Documented hypersensitivity; hypercalcemia; malabsorption syndrome

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Adequate response to calcitriol depends on adequate dietary calcium intake; maintain adequate fluid intake

Corticosteroids

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


Prednisone (Deltasone, Orasone)

Immunosuppressant for treatment of autoimmune disorders. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocyte and antibody production. Efficacy in some cases of MF may reflect an underlying autoimmune defect and/or suppression of a proliferating clone.

Adult

5-60 mg/d PO qd or divided bid/qid

Pediatric

2 mg/kg/d PO

Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI bleeding or ulceration

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use


Methylprednisolone (Solu-Medrol, Medrol)

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

Adult

Pediatric

30 mg/kg PO/IV every am for 3 d, then 20 mg/kg PO/IV every am for 4 d, then 10 mg/kg PO/IV every am for 7 d, then 5 mg/kg PO/IV every am for 7 d, then 1 mg/kg every am maintenance until blood counts are adequate, then gradually wean as tolerated

Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels of methylprednisolone; phenobarbital, phenytoin, and rifampin may decrease levels of methylprednisolone (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics

Documented hypersensitivity; viral, fungal, or tubercular skin infections

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use

Immunomodulators

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


Interferon alfa-2a (Roferon-A)

Protein product manufactured by recombinant DNA technology. Acts by modulation of host immune response. This treatment has shown long-term efficacy in one adolescent patient with an indolent form of MF (essentially identical to adult AMMM). Transient responses have been observed in at least 2 adults with acute MF.

Adult

1-6 million U/d SC

Pediatric

2-3 million U SC 2-3 times/wk

Theophylline, zidovudine, or vinblastine may increase toxicity; cimetidine may increase antitumor effects

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Flulike symptoms are common (fatigue, myalgias and/or arthralgia, chills); headache, depression, occasional dizziness, nausea and/or vomiting, diarrhea, local reactions, partial alopecia, and rare hyperglycemia


Immune globulin intravenous (Gamimune, Gammagard)

Response to IVIG was reported in one case of pediatric MF, which was associated with autoimmune phenomena.

Adult

Pediatric

0.5-1 g/kg IV infused over 2-4 h; 2-3 infusions may be administered over consecutive days; repeat treatments q1-3wk

Globulin preparation may interfere with immune response to live virus vaccine (MMR) and reduce efficacy (do not administer within 3 mo of vaccine)

Documented hypersensitivity; IgA deficiency

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Check serum IgA before IVIG (use an IgA-depleted product, eg, Gammagard S/D); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 d postinfusion); increases risk of renal tubular necrosis in elderly patients and in patients with diabetes mellitus, volume depletion, and preexisting kidney disease; laboratory result changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia


Thalidomide (Thalomid)

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 Thalomid Education and Prescribing Safety (STEPS) program. Patients must participate in ongoing surveys to receive therapy, and only a 28-d supply can be prescribed at a time.
Used to improve anemia and decrease blood/platelet transfusions associated with myelofibrosis.

Adult

200 mg/d PO, then titrate dose to target dose of 800 mg/d PO
In combination with prednisone, doses of 50 mg/d PO have been used

Pediatric

Not established

May increase sedation of alcohol, barbiturates, chlorpromazine, and reserpine

Documented hypersensitivity; sexually active males not using latex condom (risk to fetus from semen of patients taking thalidomide unknown), women of childbearing potential not using 2 forms of contraception

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Perform pregnancy test within 24-h period prior to initiating therapy (weekly during the first month, followed by monthly tests in women with regular menstrual cycles or q2wk with irregular menstrual cycles); bradycardia may occur; use protective measures (eg, sunscreens, protective clothing) against exposure to sunlight or UV light (eg, tanning beds); prescribing physician must register with the STEPS program established by manufacturer


Lenalidomide (Revlimid)

Indicated for transfusion-dependent MDS subtype of deletion 5q cytogenetic abnormality. Structurally similar to thalidomide. Elicits immunomodulatory and antiangiogenic properties. Inhibits proinflammatory cytokine secretion and increases anti-inflammatory cytokines from peripheral blood mononuclear cells.

Adult

10 mg PO qd initially; dose adjustment required if renal impairment, thrombocytopenia, or neutropenia occurs

Pediatric

<18 years: Not established
>18 years: Administer as in adults

Documented hypersensitivity; pregnancy

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Available only through RevAssist, a risk management plan to prevent fetal exposure; only pharmacists and prescribers registered with the program may prescribe and dispense (program requires mandatory pregnancy testing and limits prescription to 1-mo supply via mail); male patients, including those with vasectomy, must use latex condom during sexual contact with female of childbearing potential; women must not become pregnant 4 wk before starting lenalidomide and 4 wk after discontinuing lenalidomide; may cause anemia, DVT, pulmonary embolism, thrombocytopenia, neutropenia, diarrhea, pruritus, rash, and fatigue; renal excretion substantial, caution in elderly patients or those with renal impairment (may need to decrease dose); not break, chew, or open cap


Decitabine (Dacogen)

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 cellular control of differentiation and proliferation. Indicated for treatment of myelodysplastic syndromes (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.

Adult

15 mg/m2 IV q8h for 3 d; infuse over 3 h; repeat q6wk for at least 4 cycles and as long as continued benefit observed

Pediatric

Not established

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Common adverse effects include neutropenia (90%), thrombocytopenia (89%), anemia (82%), pyrexia (53%), fatigue (48%), nausea (42%), cough (40%), petechiae (39%), constipation (35%), and diarrhea (34%); males must avoid fathering children while receiving decitabine and for 2 mo following discontinuation; decrease or delay dose if hematologic recovery requires >6 wk

More on Myelofibrosis

Overview: Myelofibrosis
Differential Diagnoses & Workup: Myelofibrosis
Treatment & Medication: Myelofibrosis
Follow-up: Myelofibrosis
Multimedia: Myelofibrosis
References
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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. Manoharan A. Idiopathic myelofibrosis: a clinical review. Int J Hematol. Dec 1998;68(4):355-62. [Medline].

  8. Brovall C, Mitchell H, Saral R. Acute myelofibrosis in a child. J Pediatr. Jul 1983;103(1):91-3. [Medline].

  9. Evans DI. Acute myelofibrosis in children with Down's syndrome. Arch Dis Child. Jun 1975;50(6):458-62. [Medline].

  10. Lewis DS. Association between megakaryoblastic leukaemia and Down syndrome. Lancet. Sep 26 1981;2(8248):695. [Medline].

  11. 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].

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

  13. Stephan JL, Galambrun C, Dutour A. Myelofibrosis: an unusual presentation of vitamin D-deficient rickets. Eur J Pediatr. Oct 1999;158(10):828-9. [Medline].

  14. Walka MM, Daumling S, Hadorn HB. Vitamin D dependent rickets type II with myelofibrosis and immune dysfunction. Eur J Pediatr. Jul 1991;150(9):665-8. [Medline].

  15. 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].

  16. 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].

  17. 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].

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

  19. 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].

  20. 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].

  21. 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].

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

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

  24. 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].

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

  26. 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].

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

  28. 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].

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

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

  31. 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].

  32. 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].

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

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

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

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

  37. 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].

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

  39. 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.

  40. 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].

  41. Mesa RA, Elliott MA, Schroeder G. Durable responses to thalidomide-based drug therapy for myelofibrosis with myeloid metaplasia. Mayo Clin Proc. Jul 2004;79(7):883-9. [Medline].

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

  43. Tefferi A, Lasho TL, Mesa RA, Pardanani A, Ketterling RP, Hanson CA. Lenalidomide therapy in del(5)(q31)-associated myelofibrosis: cytogenetic and JAK2V617F molecular remissions. Leukemia. 2007;21(8):1827-8. [Medline].

  44. 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].

  45. 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].

  46. 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].

  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. 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].

  52. Hasselbalch HC, Bjerrum OW, Jensen BA, et al. Imatinib mesylate in idiopathic and postpolycythemic myelofibrosis. Am J Hematol. Dec 2003;74(4):238-42. [Medline].

  53. Tefferi A, Mesa RA, Gray LA. Phase 2 trial of imatinib mesylate in myelofibrosis with myeloid metaplasia. Blood. May 15 2002;99(10):3854-6. [Medline].

  54. 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].

  55. 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].

  56. [Guideline] Mesa RA, Schwager S, Radia D, et al. The Myelofibrosis Symptom Assessment Form (MFSAF): an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis. Leuk Res. Sep 2009;33(9):1199-203. [Medline].

  57. 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].

  58. 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].

  59. 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].

  60. 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].

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Further Reading

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Keywords

myelofibrosis, MF, bone marrow fibrosis, myelosclerosis, osteomyelofibrotic syndrome, agnogenic myeloid metaplasia with myelofibrosis, AMMM, acute myelofibrosis of childhood, C-AMF, primary MF, idiopathic MF, IMF, fibrosis of the bone marrow, acute megakaryoblastic leukemia, AMKL, chronic myeloproliferative disorders, clonal hematopoiesis, splenomegaly, erythroblastic peripheral blood smear, myeloid metaplasia, thrombopoiesis, tuberculosis, visceral leishmaniasis, anemia, neutropenia, thrombocytopenia, hepatosplenomegaly, bacterial sepsis, rickets, systemic lupus erythematosus, histiocytosis, acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, non-Hodgkin lymphoma, Hodgkin disease, Langerhans cell histiocytosis, sickle cell disease, Fanconi anemia, vitamin D deficiency, osteodystrophy, juvenile rheumatoid arthritis, osteopetrosis, hyperparathyroidism, hypoparathyroidism, pernicious anemia, Gaucher disease, treatment, diagnosis

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Contributor Information and Disclosures

Author

J Martin Johnston, MD, Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Pediatric Hematology/Oncology, Backus Children's Hospital; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital
J Martin Johnston, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

Medical Editor

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.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

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; 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.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
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.

 
 
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