Myelofibrosis Clinical Considerations

Risk

In myelofibrosis (MF), the presence of any of the following risk factors* indicates that a patient is already at intermediate risk1,2:

  • Hemoglobin level <10 g/dL
  • Leukocyte count >25 × 109/L
  • Age >65 years
  • Red cell transfusion dependency
  • Circulating blast cells ≥1%
  • Platelet count <100 × 109/L
  • Constitutional symptoms
  • Unfavorable karyotype

New or increasing splenomegaly is considered to be a marker of disease progression in MF.3

IWG-MRT and ELN response criteria state that appearance of a new splenomegaly that is palpable at least 5 cm below the left costal margin constitutes progressive disease.3†

Splenomegaly can cause/exacerbate cytopenias due to splenic sequestration.4

Splenomegaly may cause pain, early satiety, abdominal discomfort, and other symptoms.4,5

In a study of 428 patients with primary MF, 90% were considered to be intermediate or high risk within one year of diagnosis.2
ELN, European LeukemiaNet; IWG-MRT, International Working Group-Myeloproliferative Neoplasms Research and Treatment.
*As included in the Dynamic International Prognostic Scoring System Plus tool. Progressive disease assignment for splenomegaly requires confirmation by computed tomography (CT) or magnetic resonance imaging (MRI) showing a ≥25% increase in spleen volume from baseline. Baseline values for both physical examination and imaging studies refer to pretreatment baseline and not to posttreatment measurements.3

Most Patients With MF Present With Splenomegaly at Diagnosis

Approximately 90% of patients with MF present with splenomegaly at the time of diagnosis.1 Symptoms related to splenomegaly include abdominal fullness, early satiety, and pain under the left ribs.6

image shows an enlarged spleen on patient torso
Marked splenomegaly in myelofibrosis.
In a study of 1054 patients with primary MF, approximately 90% of patients had palpable splenomegaly at diagnosis.1

Clinical Presentation of MF

Disease-associated symptoms and clinical findings of myelofibrosis are listed below.6,7

Most common6:

  • Fatigue
  • Fever
  • Weight loss
  • Anemia
  • Leukoerythroblastosis
  • Pruritus7
  • Night sweats
  • Splenomegaly
  • Increased or decreased WBC levels
  • Bone marrow fibrosis

Other possible6:

  • Hepatomegaly
  • Lymphadenopathy
  • Pleural effusion
  • Osteosclerosis
  • Periostitis
  • Portal hypertension
  • Ascites
  • Nerve or spinal cord compression
  • Hypertrophic osteoarthropathy
  • Megakaryocytic dysplasia

Investigators created the Myeloproliferative Neoplasm-Symptom Assessment Form Total Symptom Score (MPN-SAF TSS), a 10-item instrument designed to assess the most representative and clinically relevant symptoms among patients with MPNs. The tool records the patient's assessment of the incidence and severity of these disease-related symptoms.8 It can be used to track symptoms over time and guide subsequent management decisions.8

WBC, white blood cell.

Self-Reported Symptoms of MF8
image of graph that shows the percentage of self-reported myelofibrosis symptoms broken out by symptoms
Symptom assessment of 293 patients with myelofibrosis. Incidence is a score of >0 on the MPN-SAF TSS. Symptom severity was rated on a 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be) scale.8 The MPN-SAF TSS has a possible range of 0 to 100, with 100 representing the highest level of symptom severity. Fatigue was independently measured by coadministration of the Brief Fatigue Inventory.8

Analysis of Myeloproliferative Neoplasm (MPN) Symptom Burden

The MPN Landmark survey was a large-scale analysis of 813 patients with MPNs (myelofibrosis, n=207) and assessed perceptions of overall disease burden, quality of life (QOL), activities of daily living, and work productivity. In this survey, the 5 most common symptoms reported over the prior 12 months among patients with MF were9‡§:

image showing symptom burden of myelofibrosis – 80% Fatigue, 53% Abdominal discomfort, 51% Night sweats, 40% Bone pain, 40% Itching
Survey sponsored by Incyte Corporation. §Symptoms represent only those included in the MPN-SAF TSS and are not inclusive of all symptoms that were assessed in the MPN Landmark survey.

Effects on Quality of Life (QOL), Activities of Daily Living, and Work/Productivity

In the MPN Landmark survey9:

  • 81% of patients reported reduced QOL related to their condition
    • This was true even for patients with low prognostic risk scores and with lowest symptom severity
  • 53% (110/207) of patients reported interference with daily activities at some point||
    • 21% (43/207) reported a great deal of interference
  • 79% (163/207) indicated that myelofibrosis interfered with family or social life||
  • 59% (70/119) reported reduced work hours at some point
||A score of >1 on a scale of 1 (not at all) to 5 (a great deal) A score of 5 on a scale of 1 (not at all) to 5 (a great deal)
References

1. Cervantes F, Dupriez B, Pereira A, et al. Blood. 2009;113(13):2895-2901. 2. Gangat N, Caramazza D, Vaidya R, et al. J Clin Oncol. 2011;29(4):392-397. 3. Tefferi A, Cervantes F, Mesa R, et al. Blood. 2013;122(8):1395-1398. 4. Mesa RA. Blood. 2009;113(22):5394-5400. 5. Scherber RM, Geyer HL, Mesa RA. Curr Hematol Malig Rep. 2014;9(4):324-330. 6. Abdel-Wahab OI, Levine RL. Annu Rev Med. 2009;60:233-245. 7. Barosi G. J Clin Oncol. 1999;17(9):2954-2970. 8. Emanuel RM, Dueck AC, Geyer HL, et al. J Clin Oncol. 2012;30(33):4098-4103. 9. Mesa R, Miller CB, Thyne M, et al. BMC Cancer. 2016;16:167. doi: 10.1186/s12885-016-2208-2.

 
Resources
By: World Health Organization (WHO)
A diagnostic worksheet from the WHO for primary MF, PV, and ET.
By: International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
Diagnostic criteria from the IWG-MRT.