Myeloproliferative Disease Treatment & Management

Updated: Aug 31, 2022
  • Author: Haleem J Rasool, MD, FACP; Chief Editor: Emmanuel C Besa, MD  more...
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Approach Considerations

Treatment of myeloproliferative neoplasms varies by disease subtype. For full discussion, see the following Medscape articles:

In August 2022, the US Food and Drug Administration (FDA) approved the first targeted drug, pemigatinib, to treat relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with fibroblast growth factor receptor 1 (FGFR1) rearrangement. Approval was based on the phase 2 FIGHT-203 clinical trial. Study participants included patients with documented MLNs with an 8p11 translocation on conventional cytogenetics and/or an FGFR1 rearrangement on break-apart FISH testing.  

In patients with chronic phase in the marrow, with or without extramedullary disease (EMD) (N = 18), the complete response (CR) rate was 78%. The median time to CR was 104 days (range, 44 to 435 days). The median duration of CR was not reached. In patients with blast phase in the marrow, with or without EMD, 2 of the 4 patients achieved a CR. For all patients (N = 28, including 3 patients without evidence of morphologic disease) the complete cytogenetic response rate was 79% (95% confidence interval: 59-92%). [23]  


Treatment of Chronic Myelogenous Leukemia

Imatinib mesylate (Gleevec), a bcr-abl–specific tyrosine kinase inhibitor (TKI), is approved for use in Philadelphia chromosome–positive chronic myelogenous leukemia (CML) in chronic phase. In one study at 18 months, the complete response rate was 76.2% and the major cytogenetic response rate was 87.1%. Imatinib is also indicated for CML in blast crisis, accelerated phase, or in chronic phase after interferon alfa therapy failure. This is the treatment of choice for most patients. [1]

Interferon alfa, usually administered as a subcutaneous daily injection in a dose of 5 million U, produces hematologic and molecular remissions in some patients with CML. In these patients, evidence shows that it prolongs survival. Several patients who achieved molecular remissions have survived for more than 10 years. Addition of low-dose cytosine arabinoside to interferon alfa has been reported to achieve higher remission rates. Patients with CML who are intolerant of interferon alfa therapy can be treated with hydroxyurea.

Dasatinib (Sprycel) is a TKI indicated for the treatment of adults patients with CML in chronic, accelerated, or myeloid or lymphoid blast phase who are resistant or intolerant to prior therapy including imatinib. Nilotinib (Tasigna) is a TKI indicated for the treatment of chronic phase and accelerated phase Philadelphia chromosome-positive CML in adult patients resistant to or intolerant to prior therapy including imatinib.

Hematopoietic stem cell transplantation can be considered in young patients with CML in chronic phase, if a human leukocyte antigen (HLA)-matched donor is available.

When the disease progresses to the blast phase (see the image below), it is treated as acute leukemia, though the outcome is usually grave.

Peripheral smear of a patient with chronic myeloge Peripheral smear of a patient with chronic myelogenous leukemia (CML) in blastic phase shows several blasts.



Treatment of Polycythemia Vera

Treatment of polycythemia vera (PV) is palliative. Young (< 40 y), asymptomatic patients with PV can be considered for therapeutic phlebotomies alone to maintain hematocrit level below 45%.

High-risk patients—those with systemic symptoms, history of thrombosis or bleeding, high rate of phlebotomies, or age older than 69 years—are best treated with myelosuppressive therapy in the form of hydroxyurea. [24] An alternative therapy is the JAK1/JAK2 inhibitor ruxolitinib (Jakafi), which has FDA approval for the treatment of PV in patients who have an inadequate response to or intolerance of hydroxyurea. [25]

In older patients, radioactive phosphorus (32P) has been used for treatment of PV. However, this is unsuitable for younger patients because of the potential for causing secondary leukemia. In any event, production of this radionuclide has been discontinued and it is no longer available in the United States or elsewhere.


Treatment of Essential Thrombocythemia

Treatment of essential thrombocythemia (ET) is meant to relieve symptoms and to prevent complications because no curative modality is available at present. The aim of treatment is to maintain the platelet count within the reference range. This usually can be achieved with hydroxyurea or anagrelide.

There remains a question of the efficacy of ruxolitinib vs other conventional therapies. In ET patients resistant or intolerant to hydroxycarbamide therapy, ruxolitinib significantly improved some disease-related symptoms, but rates of thrombosis, hemorrhage, or transformation were no different when compared to best available therapy in the randomized phase 2 MAJIC trial. [26]


Treatment of Primary Myelofibrosis

Asymptomatic patients can be monitored clinically until symptoms develop. Treatment options for symptomatic MF include the following:

  • Anemia is treated with correction of reversible contributing factors, followed by erythropoiesis-stimulating agents, androgens, immunomodulating drugs, corticosteroids, and splenectomy; however, most patients eventually become transfusion dependent [27]
  • Hydroxyurea is useful to suppress the number of circulating cells
  • Patients with painful, massively enlarged spleens refractory to myelosuppressive therapy are occasionally treated with radiation therapy, but they may ultimately require splenectomy
  • Two case reports suggest that oral bisphosphonates may be beneficial in decreasing bone marrow fibrosis associated with this illness

In November 2011, the JAK1/JAK2 inhibitor, ruxolitinib (Jakafi), became the first US Food and Drug Administration (FDA)–approved drug for patients with intermediate- or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Approval was expedited in accordance with the US Orphan Drug Act and based on US and international data from the COMFORT-1 and COMFORT-2 trials. Results from the COMFORT-1 trial showed patients (n=309) who received ruxolitinib had a significant reduction in spleen volume (at least 35%) at 24 weeks when assessed by MRI or CT compared with placebo (41.9% vs 0.7%). [28]

Allogeneic hematopoietic stem cell transplantation (ASCT) is curative for primary myelofibrosis (PMF) and may be an alternative for selected patients whose disease is refractory to conventional therapies [27]  However, less than 10% of patients with MF are even referred for ASCT due to high transplant-related mortality (20%-40%). ASCT is limited to small proportion of MF patients, usually for those at younger age at transplant, without significant co-morbidities and at higher prognostic categories. [29]

Performing a pretransplantation splenectomy in patients with myelofibrosis (MF) is a matter of debate. While the procedure improves hematological recovery, it may lead to severe morbidities. Robin and colleagues retrospectively analyzed data from 85 consecutive patients who underwent transplantation for MF, including 39 patients who underwent splenectomy before their transplantation. The majority had PMF (78%), were considered high-risk patients (84% dynamic international prognostic scoring system intermediate-2 or higher), and had received transplants from HLA-matched sibling donors (56%) after a reduced-intensity conditioning regimen (82%). One-half of all splenectomized patients presented surgical or postsurgical morbidities, most frequently thrombosis and hemorrhage. However, retransplantation splenectomy was not associated with nonrelapse mortality or post-transplantation relapse but with an improved overall survival (OS) and event-free survival (EFS). [30]



Surgical consultation for permanent central venous access device placement may be required for patients in whom repeated blood draws, blood transfusions, and/or chemotherapy is anticipated.

A radiation oncologist may need to be involved in selected cases, when splenic radiation is considered appropriate.


Diet and Activity

Massive splenomegaly is usually associated with epigastric and left upper quadrant discomfort and early satiety. Patients with these symptoms are encouraged to eat frequent, small meals rather than 3 large meals.

Individuals with myeloproliferative diseases are not encouraged to restrict their daily activities, but they are encouraged to refrain from physical activities that might expose them to abdominal trauma because massively enlarged spleens are likely to rupture, sometimes in response to minimal trauma.