Primary Myelofibrosis Guidelines

Updated: Feb 02, 2021
  • Author: Asheesh Lal, MBBS, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Guidelines

Guidelines Summary

The following organizations have published guidelines for the diagnosis and treatment of primary myelofibrosis:

  • National Comprehensive Cancer Network (NCCN)
  • European Society for Medical Oncology (ESMO)

Diagnosis 

In addition to the history and physical examination, NCCN guidelines recommend the following workup for patients with suspected myeloproliferative neoplasms [25] :

  • Complete blood cell count (CBC) with differential
  • Comprehensive metabolic panel with uric acid, lactate dehydrogenase (LDH), and liver function tests (LFTs)
  • Multiplex real time polymerase chain reaction (RT-PCR) (preferred) or fluorescence in situ hybridization (FISH) (if RT-PCR is not available) for  BCR-ABL1to exclude the diagnosis of chronic myeloid leukemia
  • Examination of blood smear
  • Bone marrow aspirate and biopsy with trichrome and reticulin stain
  • Bone marrow cytogenetics (blood, if bone marrow is inaspirable) (karyotype ± FISH)
  • Molecular testing of blood for  JAK2 V617F mutation; if negative, test for  CALR and  MPL mutations; or molecular testing using multigene next-generation sequencing (NGS) panel that includes  JAK2, CALR, and  MPL
  • Assessment of symptom burden using MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS; MPN-10; MPN-E 2 of 2)
  • Human leukocyte antigen (HLA) testing, if allogeneic hematopoietic cell transplant (HCT) is being considered
  • Serum erythropoietin (EPO) level
  • Serum iron studies
  • Coagulation tests to evaluate for acquired von Willebrand disease (VWD) and/or other coagulopathies in selected patients

Both guidelines recommend use of the World Health Organization (WHO) diagnostic criteria for the most accurate diagnosis and grading of primary myelofibrosis. [25, 51]

Risk Stratification

The NCCN prefers use of the Mutation-Enhanced International Prognostic Scoring System (MIPSS) for the initial stratification of risk at diagnosis. The Dynamic International Prognostic Scoring System (DIPSS)-Plus is recommended if molecular testing is unavailable. The DIPSS is used if karyotyping is not available. The DIPSS-Plus is preferred for assessing risk during treatment. [25]  The ESMO guidelines are in concurrence with NCCN. [51]

Treatment

All patients should be evaluated for allogeneic hematopoietic cell transplantation  (HCT). Enrollment in clinical trials is also recommended for all patients with primary myelofibrosis. [25, 51]

The NCCN guidelines recommend administering the MPN-SAF Total Symptom Score (MPN-10) to assess symptom burden at baseline and during the course of treatment. Changes in symptom status can be an indication of disease progression and should trigger evaluation of current treatment efficacy and/or disease risk stratification. [25]

Lower-risk myelofibrosis

NCCN guidelines recommend monitoring asymptomatic patients for signs and symptoms of disease progression every 3-6 months. For symptomatic patients, NCCN recommends the following treatments in selected patients [25] :

  • Ruxolitinib
  • Peginterferon alfa-2A
  • Hydroxyurea, if cytoreduction would be beneficial

Higher-risk myelofibrosis

The NCCN and ESMO recommend allogeneic HCT. [25, 51] In patients who are not candidates, NCCN-recommended treatments include the following [25] :

  • Ruxolitinib
  • Fedratinib
  • Enrollment in clinical trials

Advanced myelofibrosis/acute myeloid leukemia

NCCN treatment recommendations include clinical trial enrollment or, for transplant candidates, inducement of remission with azacitidine or decitabine or intensive induction chemotherapy followed by HCT; for non-candidates for HCT, azacitidine or decitabine or low-intensity induction chemotherapy. [25]

Supportive Care

NCCN recommendations for supportive care include the following [25] :

  • Red blood cell (RBC) transfusions for symptomatic anemia
  • Platelet transfusions for thrombocytopenic bleeding or a platelet count < 10,000 m 3
  • Antifibrinolytic agents for bleeding that is refractory to transfusions
  • Iron chelation can be considered in patients receiving more than 20 transfusions, but NCCN cautions that the role of iron chelation is unclear [25]
  • Erythropoietin-stimulating agents (ESAs) for myelofibrosis-associated anemia [25, 51]
  • Granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) for recurrent infections in patients with neutropenia; however, these agents are associated with splenic rupture and should be used with caution in patients with enlarged spleens [25]
  • Antibiotic prophylaxis for recurrent infections
  • Vaccinations
  • Hydroxyurea should be considered for treatment of thrombocytosis or leukocytosis
  • Tumor lysis syndrome (TLS) prophylaxis should be considered for patients undergoing induction therapy
  • Ruxolitinib may stabilize bone/muscle pain and improve pruritus