Pediatric Myelofibrosis

Updated: May 12, 2021
Author: Trisha Simone Natanya Tavares, MD; Chief Editor: Cameron K Tebbi, MD 


Practice Essentials

Myelofibrosis (bone marrow fibrosis) is characterized by the presence of excessive collagen and reticulin fibers in bone marrow. In most patients, it arises secondary to other disease processes. Pediatric myelofibrosis is uncommon; much of what is known about it is extrapolated from the adult literature or reported from isolated cases in children. See the image below.

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

Signs and symptoms of myelofibrosis

Patients with a condition predisposing to myelofibrosis present with a history of that disease. There may be a family history or a history of exposure to ionizing radiation. A detailed family history may identify an affected relative.

Clinical symptoms may be mild; some patients are asymptomatic at presentation. Manifestations of disease may include, but are not limited to, the following:

  • Pallor (anemia)

  • Bruising, petechiae, or bleeding (thrombocytopenia)

  • Fever

  • Weight loss

  • Night sweats

  • Bone pain

  • Left upper quadrant pain

  • Splenomegaly (frequent), hepatomegaly, or lymphadenopathy[1]

  • Stigmata of a predisposing condition

See Presentation for more detail.

Diagnosis of myelofibrosis

Laboratory testing may include the following:

  • Evaluation for peripheral blood abnormalities (eg, normocytic anemia, thrombocytopenia, or leukocytosis with left shift)

  • Endocrinologic testing (eg, hyper- or hypoparathyroidism)

  • Rheumatologic evaluation

  • Blood urea nitrogen (BUN) and creatinine testing (to rule out renal dysfunction)

  • Coombs (direct antiglobulin) test

  • Purified protein derivative (PPD) test

  • Chromosomal analysis in any child with onset before age 2 years

The following imaging studies may be helpful:

  • Abdominal ultrasonography

  • Abdominal computed tomography (CT)

  • Magnetic resonance imaging (MRI)

  • Positron emission tomography (PET)

Other studies include the following:

  • Bone marrow aspiration and biopsy

  • Cytogenetic analysis (to exclude myeloid neoplasms)

See Workup for more detail.

Management of myelofibrosis

When secondary childhood myelofibrosis is identified, treatment should be directed at the underlying process.

Supportive care of myelofibrosis typically includes the following:

  • Transfusions (red blood cells [RBCs] or platelets)

  • Prophylaxis against opportunistic infections in some patients with neutropenia

  • Aggressive treatment of fever and suspected infections

  • Intravenous immunoglobulin and bisphosphonates in selected cases

Medications that may be helpful include the following:

  • Corticosteroids

  • Interferon alfa

  • Hydroxyurea

  • Thalidomide and lenalidomide

  • Vitamin D

  • Decitabine

  • Janus kinase inhibitors (eg, ruxolitinib)

Other treatment measures that may be considered include the following:

  • Radiotherapy

  • Hematopoietic stem cell transplantation

  • Splenectomy

See Treatment and Medication for more detail.


Bone marrow fibrosis, known as myelofibrosis, was originally described in 1879 and is characterized by the presence of excessive collagen and reticulin fibers in bone marrow. This is an uncommon condition in children, and much of what is known is extrapolated from the adult literature or reported from isolated pediatric cases.

In most patients, the condition arises secondary to other disease processes.[2] In particular, myelofibrosis is frequently associated with malignancy (eg, acute megakaryoblastic leukemia [AMKL]). (See Clinical and Workup.)

Myelofibrosis may be observed prior to a clear diagnosis of acute leukemia[3] at the time of diagnosis of leukemia,[4] or as a late event in patients previously treated for leukemia. Numerous nonmalignant conditions have also been reported in association with myelofibrosis. (See Treatment.)

Importantly, primary or idiopathic myelofibrosis (IMF) is also described.[5, 6, 7]

Note the image below.

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


Patients can be expected to develop complications secondary to decreased production of functional white blood cells (infection), decreased numbers of red blood cells (anemia), and decreased numbers of platelets (bleeding).

Splenomegaly may lead to hypersplenism, thereby worsening cytopenias.

There is an increased risk of myelodysplasia and myeloid leukemia.

A single case report described subcutaneous lymphoma arising in a child with IMF.[8]

See Prognosis.

Patient education

Early onset myelofibrosis is occasionally inherited in a recessive pattern. Counsel parents about the possibility of a second affected child.


In normal marrow, the fine fibrous collagen network is faintly perceptible after conventional staining techniques with silver impregnation. Although not unique to this condition, increased staining is a hallmark of myelofibrosis.

The fibrous network observed in myelofibrosis is collagenous. Collagen types I, III, IV, and V are increased, with the most significant increased noted in type III. Fibrosis of the bone marrow presumably reflects overgrowth of the normal marrow matrix.[9] This can be observed in association with several diseases and has even been reported to have prognostic significance in childhood acute lymphoblastic leukemia.[10] Overgrowth has been shown to be related to the secretion of profibrotic cytokines and myeloproliferative growth factors.[11]

In cases of acute myelofibrosis of childhood (C-AMF), myelofibrosis may be secondary to the release of granules by abnormal megakaryocytes. In addition to platelet-derived growth factor (PDGF), these granules contain transforming growth factor-beta (TGF-b) and epidermal growth factor (EGF), both of which can stimulate proliferation of fibroblasts. TGF-b synthesis appears to be regulated by nuclear factor kappaB (NF-kB). Interestingly, the overexpression of an immunophilin, FK506-binding protein 51, has been observed in myelofibrosis megakaryocytes, and this protein appears, in turn, to activate NF-kB.[12]

Matrix homeostasis results from a balance between the deposition of the matrix and its removal. The former is regulated by various growth factors, most notably PDGF, whereas the latter presumably reflects the activity of collagenase-expressing monocytes, macrophages, and granulocytes. Thus, the diseases associated with myelofibrosis can be classified according to whether the basic defect is matrix overproduction, underresorption, or both.

Marrow blood flow and microvessel density are also increased in patients with myelofibrosis, most likely due to an increase in circulating endothelial cell progenitors.

Some investigators believe that the abnormal fibrotic marrow stroma directly enhances the circulation and dissemination of hematopoietic precursors.[13] This leads to extramedullary hematopoiesis in the liver, spleen, lymph nodes, or (occasionally) kidneys, causing myeloid metaplasia in these organs, which then become enlarged. Hypersplenism, if present, exacerbates cytopenias.

The gain-of-function V617F mutation in the Janus kinase 2 (JAK2) gene (on 9p) is seen in many adult patients with IMF.[14] Its presence correlates with a shift from thrombopoiesis toward increased erythropoiesis and may also predict progression to massive splenomegaly and leukemic transformation.[15, 16]

Among adults with IMF, conventional cytogenetic analysis of the marrow reveals an abnormal clone in approximately one third of patients. Using a comparative genomic hybridization technique, Al-Assar et al studied IMF marrow specimens and found chromosomal imbalances in 21 of 25 cases.[17] Gains of 9p, 13q, 2q, 3p, and 12q were among the most commonly seen abnormalities. Isolated del(20q) or del(13q) appears to confer a better prognosis. All other abnormalities confer an independent adverse effect on survival and are also associated with higher JAK2V617F mutational frequency.[18]

A study by Livun et al suggested that in primary myelofibrosis, several genes related to bone marrow homeostasis are aberrantly expressed, with the investigators finding upregulation of cyclo-oxygenase 2 (COX2) and down-regulation of chemokine (C-X-C motif) receptor 4 (CXCR4), paired box 5 (PAX5) C-terminus, and hypoxia inducible factor 1A (HIF1A).[19]

Predisposing conditions

Classification of myelofibrosis includes the following: primary (idiopathic) C-AMF, secondary (malignant) C-AMF, and secondary (nonmalignant) C-AMF.

Causes of secondary (malignant) C-AMF include:

  • Acute erythroblastic (M6) leukemia[20]

  • Acute megakaryoblastic (M7) leukemia (AMKL)

  • ALL[21]

  • Chronic myelogenous leukemia

  • Non-Hodgkin lymphoma

  • Essential thrombocythemia[22]

  • Hodgkin disease (reported cases in adults only)

Causes of secondary (nonmalignant) C-AMF include:

  • Langerhans cell histiocytosis

  • Hemophagocytic lymphohistiocytosis[23]

  • Sickle cell anemia (a single case report)[24]

  • Fanconi anemia

  • Vitamin D deficiency

  • Infectious conditions - Tuberculosis,[25] visceral leishmaniasis,[26] histoplasmosis (reported cases in adults only)[27]

  • Renal osteodystrophy

  • Systemic lupus erythematosus[28]

  • Juvenile rheumatoid arthritis

  • Gray platelet syndrome

  • Osteopetrosis

  • Hyperparathyroidism

  • Hypoparathyroidism (reported cases in adults only)

  • Pernicious anemia (reported cases in adults only)

  • Gaucher disease (reported cases in adults only)

  • Exposure to radiation, thorium dioxide, benzene (reported cases in adults only)


Occurrence in the United States

Approximately 100 cases of pediatric myelofibrosis have been reported worldwide. This is likely an underrepresentation, because cases associated with acute myeloid leukemia (AML) (the most common association) are not generally reportable.

International occurrence

Cases of pediatric myelofibrosis have been described in association with tuberculosis (in Pakistan) and visceral leishmaniasis (in Sudan). Thus, myelofibrosis is presumably more common in areas of endemicity for these diseases. Detailed epidemiologic data are not available. Autosomal recessive familial myelofibrosis appears to be more common among children from Saudi Arabia.[29, 30, 31]

Sex- and age-related demographics

In published cases of pediatric myelofibrosis, females outnumber males by a ratio of approximately 2:1.

In infants, the presentation may be atypical and lack some of the classic clinical features.

A large percentage of published cases of pediatric myelofibrosis occurs in children younger than 3 years. These younger patients are more likely to have Down syndrome, rickets, or a familial (possibly autosomal recessive) form of myelofibrosis. Among older patients, AML, systemic lupus erythematosus, and tuberculosis are the most common associations.


The prognosis of childhood myelofibrosis varies depending on the clinical context in which it occurs. With appropriate treatment for rickets, tuberculosis, systemic lupus erythematosus, and other conditions, the myelofibrosis may completely resolve.

Idiopathic acute myelofibrosis of childhood may be a fulminant disease. Without effective therapy, life expectancy is typically less than 1 year. Potentially effective and/or curative treatments include chemotherapy and allogeneic bone marrow transplantation (BMT). Treatment with medications may also result in a temporary amelioration of the disease. Occasionally, pediatric patients have a more indolent course than what is observed in adults. With supportive care alone, they may survive for many years.

In adult patients with myelofibrosis, several alternative prognostic scoring systems (PSSs) are available.[32, 33] Neither the patient's symptoms nor the percentage of circulating blasts is taken into account in the Mayo Clinic PSS (in contrast to other PSSs). A retrospective review of 334 patients with myelofibrosis showed the Mayo Clinic PSS to be more effective than other PSSs in terms of (1) identifying long-lived patients and (2) delineating an intermediate-risk disease category.[33] The Mayo PSS assigns a score of 1-4 by allotting 1 point for each of the following:

  • Hemoglobin level more than 10 g/dL

  • White blood cell (WBC) count less than 4 or more than 30 X 109/L

  • Platelet count less than 100 X 109/L

  • Absolute monocyte count at or above 1 X 109/L

A new prognostic scoring system for primary myelofibrosis has been determined based on data collected during a study conducted by the International Working Group for Myelofibrosis Research and Treatment.[34]

Multivariate analysis identified the following risk factors:

  • Age older than 65 years

  • Constitutional symptoms

  • Hemoglobin less than 10 g/dL

  • Circulating blast cells 1% or greater

Pediatric patients were included in this study but not in sufficient numbers to analyze as a separate group.

Morbidity and mortality

Myelofibrosis causes, or accompanies conditions that cause, disruption of normal hematopoiesis. Patients may experience anemia, neutropenia, and/or thrombocytopenia. Patients may also experience pain secondary to hepatosplenomegaly. Neutropenia may lead to opportunistic infections. Thrombocytopenia may lead to hemorrhage.

In a study of 15 cases of pediatric idiopathic myelofibrosis, Mishra et al reported that 14 of the patients (93%) presented with transfusion-dependent anemia. In addition, findings included myeloid hyperplasia (13 patients, 87%); megakaryocytic hyperplasia (10 patients, 67%); dysmegakaryopoiesis (8 patients, 53%); small, loose megakaryocytic clustering (3 patients, 20%); and leukoerythroblastosis with dacryocytes (1 patient, 7%).[35]




Patients with a predisposing condition presents with a history of that disease. There may be a family history or a history of exposure to ionizing radiation.

Clinical symptoms may be mild and can include insidious onset of signs related to marrow dysfunction and resulting cytopenias. Patients may present with pallor and fatigue due to anemia, with bruising or bleeding due to thrombocytopenia. In some patients, fever, weight loss, night sweats, bone pain, and left upper quadrant pain are reported.

Some patients are asymptomatic at the time of presentation, and the condition is identified as an incidental finding during an evaluation of another condition.

A detailed family history may identify an affected relative. Parental consanguinity may be present in autosomal recessive cases.

Physical Examination

Physical findings reflect the cytokine release, marrow malfunction, and extramedullary hematopoiesis. Symptoms may include, but are not limited to, the following:

  • Pallor (anemia)

  • Bruising, petechiae, or bleeding (thrombocytopenia)

  • Splenomegaly (frequent), hepatomegaly, or lymphadenopathy

  • Stigmata of a predisposing condition

Multiple hemangiomas have been described in 1 affected pair of siblings with idiopathic myelofibrosis (IMF).





Approach Considerations

Laboratory testing

Varying degrees of peripheral blood abnormalities may be present at diagnosis, and deviations from the normal ranges may be moderate or severe. Patients likely have one or more of the following changes: normocytic anemia, thrombocytopenia, or leukocytosis (with left shift).

Review of the peripheral blood smear is key and likely reveals several abnormalities. Dacryocytes (teardrop-shaped red blood cells) are common. Nucleated red blood cells and aniso-poikilocytosis are also frequently seen. Myelocytes and promyelocytes are present in small proportions in most patients; blasts may also be seen. Platelets may be large or unusually shaped. In rare cases, the platelet count may be elevated.[11, 36]

Endocrinological testing may be indicated. Hyperparathyroidism (primary or secondary to vitamin D deficiency) has been described. In addition, hypoparathyroidism is sometimes observed. Bony abnormalities, including osteosclerosis, are reported.

In the appropriate clinical setting, a rheumatological evaluation is needed. Perform antinuclear antibody (ANA) testing because myelofibrosis occasionally complicates systemic lupus erythematosus. A low neutrophil alkaline phosphatase (LAP) score suggests chronic myeloid leukemia; a high level suggests chronic inflammation, as might be expected with systemic lupus erythematosus.

Megakaryocytes are present in the systemic venous blood. A characteristic finding is increased CD34+ cells in circulating blood.

Blood urea nitrogen (BUN)/creatinine testing should be performed to rule out renal dysfunction, which may suggest renal osteodystrophy as an underlying diagnosis.

A Coombs (direct antiglobulin) test can be ordered because myelofibrosis has been observed in association with autoimmune hematologic phenomena.

A purified protein derivative (PPD) test should also be performed because myelofibrosis has been described as a complication of tuberculosis.

Consider chromosomal analysis in any child with onset before age 2 years as trisomy 21, which is associated with marrow fibrosis, may be undiagnosed.

Imaging studies

Abdominal ultrasonography or computed tomography (CT) scanning often reveals hepatosplenomegaly, with or without adenopathy. Nephromegaly has also been described (secondary to myeloid metaplasia).[37, 38]

Magnetic resonance imaging (MRI) scanning, if performed because of particular symptoms (eg, headache), often shows diagnostic changes in marrow signal. Osteosclerosis is a common finding. Also seen is marked radiodensity of superior and inferior margins of the vertebral body; this finding is known as “sandwich vertebrae.” Periosteal reactions are also seen.

Positron emission tomography (PET) scanning can identify osteosclerosis.

Other diagnostic considerations

The workup of children with myelofibrosis frequently leads to a diagnosis of acute myeloid (specifically, megakaryoblastic) leukemia or, less commonly, myelodysplastic syndrome.

Conditions to consider in the differential diagnosis include, along with those listed previously, osteopetrosis, gray platelet syndrome, and rickets.

Bone Marrow Aspirate and Biopsy

The biopsy demonstrates increased silver (reticulin) staining. Moreover, the aspirate is frequently hypocellular or shows insufficient cellularity ("dry"). An increased number of megakaryocytes that may be morphologically abnormal supports a diagnosis of primary myelofibrosis. Increased blasts are often observed, but the presence of more than 25% blasts is, by definition, more consistent with acute myelofibrosis.

Cytogenetic studies in myelofibrosis ensure diagnostic exclusion of myeloid neoplasms that are sometimes associated with bone marrow fibrosis (eg, BCR-ABL1).[18]

Abnormalities may support a diagnosis of myelodysplasia (eg, monosomy 7) or acute megakaryoblastic leukemia (eg, t[1;21][p13;q13]).

Marrow biopsies typically exhibit marked fibrosis with pockets of cellularity that have fibroblasts and atypical megakaryoblasts. Less commonly, hyperplasia with predominance of megakaryocytic and erythroid precursors is observed, with only a slight increase in reticulin staining. The latter pattern is more typical of (adult) agnogenic myeloid metaplasia with myelofibrosis (AMMM) and may be observed in an older pediatric patient.



Approach Considerations

Treatment should be directed at the underlying process when secondary childhood myelofibrosis is identified.

Supportive Care and Monitoring

Supportive care of myelofibrosis with transfusions (red blood cells [RBCs], platelets) is crucial to short-term management. Blood products should be leukodepleted (to decrease the likelihood of human leukocyte antigen [HLA] sensitization) and, ideally, cytomegalovirus (CMV) negative.

Prophylaxis against opportunistic infections (eg, fluconazole) may be indicated for some patients with neutropenia. Aggressive treatment of fever and suspected infections is also important.

Intravenous immunoglobulin and bisphosphonates may be useful in selected cases. An 8-month-old girl with myelofibrosis and dysgranulopoiesis responded to intravenous immunoglobulin (added to previous corticosteroid therapy).[39] Her disease was unusual and was characterized by a positive Coombs test result and antineutrophil antibodies, suggesting an autoimmune etiology.



In pediatric patients, high-dose glucocorticoid therapy may ameliorate marrow fibrosis and improve hematopoieses.[11, 28, 40, 41]


Interferon-alfa has been useful for treatment of splenic enlargement, bone pain, and thrombocytosis, including in pediatric patients. Interferon-alfa and interferon-gamma act together to inhibit myeloproliferation.[11, 42]


Hydroxyurea is one of the most commonly used agents in the management of this condition. It has been shown to decrease spleen size and reduce constitutional symptoms. Improvement in peripheral blood cell counts and bone marrow fibrosis are also seen.

Thalidomide and lenalidomide

These antiangiogenic agents are used to reduce transfusion requirements and decrease spleen size. These medications are believed to down-regulate the proinflammatory response. They may be used in combination with glucocorticoids.[43, 44, 45]

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 (IMF), have responded to vitamin D administration.[46, 47]


Decitabine, an S-phase–specific inhibitor of deoxyribonucleic acid (DNA) methyltransferase, has shown promise in adult patients with myelofibrosis.[48] Pediatric dosing for this drug has not been established, and no literature regarding its use in children with myelofibrosis has been published.

Janus kinase inhibitors

Ruxolitinib is an orally bioavailable, selective JAK1 and JAK2 inhibitor approved for the treatment of myelofibrosis. Other JAK inhibitors with similar clinical profiles are in clinical development but have yet to be approved for therapeutic use.[49]  

In June 2013, the US Food and Drug Administration (FDA) updated the prescribing information for ruxolitinib to include new recommended dosing for patients with low platelet counts and a warning about a possible treatment-related risk for progressive multifocal leukoencephalopathy (PML).[50]  For patients with baseline platelet counts of 50-100 × 10⁹/L (50,000-100,000/µL), the updated prescribing information recommended a starting dosage of 5 mg twice daily and the flexibility for subsequent dosage modifications based on safety and efficacy.[50] Additionally, healthcare professionals were advised to educate patients regarding early signs and symptoms of PML.

Results from a phase 3 trial indicated that pacritinib, which inhibits JAK2 and FMS-like tyrosine kinase-3 (FLT3), is not only effective against myelofibrosis but is safer than ruxolitinib for use in patients with a low platelet count. The trial involved 327 patients.[51, 52]


Radiotherapy has been offered to patients with painful massive splenomegaly who are not surgical candidates. This treatment should be used sparingly, however, as it may worsen cytopenias. Radiation therapy has also been used for palliation of bony lesions, ascites, and other mass lesions.

Hematopoietic Stem Cell Transplantation

Bone marrow transplantation is the only potential cure to primary myelofibrosis. Patients with a matched sibling donor with a poor prognosis should be evaluated for transplantation.

A retrospective analysis of 203 adult patients with myelofibrosis suggested, in contrast to earlier reports, that myelofibrosis has little adverse effect on engraftment following allogeneic hematopoietic cell transplant.[53]

Allogeneic bone marrow transplantation has been used successfully to treat patients with myelofibrosis.[54, 55] Preparative regimens and donors varied. Nonmyeloablative conditioning is appropriate in certain patients.

Published experience from Sweden and Germany demonstrated that reduced-intensity preparative regimens are often effective for treating myelofibrosis and clearly have less treatment-related mortality than do myeloablative regimens.[56, 57]

Donor lymphocyte infusion in posttransplanted patients can be used to cause regression of fibrosis in patients with evidence of relapse.

A study by McLornan et al of allogeneic hematopoietic cell transplantation for myelofibrosis performed in Europe between 1995 and 2018 found that overall survival rates improved over time and relapse risk fell, with the rate of nonrelapse mortality remaining stable. These data were determined despite the fact that the number of older, less fit patients undergoing the procedure had increased, as had the use of unrelated donors.[58]


Patient selection for spleen removal is controversial.[59] Transfusion-dependent anemia, portal hypertension, and/or symptoms of hypercatabolism are potential indications for splenectomy, but the surgery-related mortality rate may be significant.[60]



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

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.

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.


Class Summary

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


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)

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)

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)

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

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.

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.

Antineoplastic Agents

Class Summary

Antineoplastic agents inhibit cell growth and proliferation.

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.