Myeloproliferative Disease Treatment & Management

• Treatment of chronic myelogenous leukemia (CML):

  • Hematopoietic stem cell transplantation can be considered in young patients with chronic myelogenous leukemia in chronic phase if a human leukocyte antigen (HLA)-matched donor is available.
  • Imatinib mesylate (Gleevec), a bcr-abl –specific tyrosine kinase inhibitor, is approved for use in Philadelphia chromosome–positive chronic myelogenous leukemia patients 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 chronic myelogenous leukemia in blast crisis, accelerated phase, or in chronic phase after interferon alfa therapy failure. This is the treatment of choice for most patients.^[9]
  • 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 chronic myelogenous leukemia. 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 chronic myelogenous leukemia who are intolerant of interferon alfa therapy can be treated with hydroxyurea.
  • Dasatinib (Sprycel) is indicated for the treatment of adults patients with chronic myeloid leukemia in chronic, accelerated, or myeloid or lymphoid blast phase who are resistant or intolerant to prior therapy including imatinib.
  • Nilotinib (Tasigna) is a kinase inhibitor indicated for the treatment of chronic phase and accelerated phase Philadelphia chromosome-positive chronic myelogenous leukemia in adult patients resistant to or intolerant to prior therapy including imatinib.
  • 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 myelogenous leukemia (CML) in blastic phase shows several blasts.
• Treatment of polycythemia vera (PV): Treatment is palliative. Young (< 40 y), asymptomatic patients with polycythemia vera can be considered for therapeutic phlebotomies alone to maintain hematocrit level at less than 45%.

  • High-risk patients with systemic symptoms, history of thrombosis or bleeding, or high rate of phlebotomies or patients older than 69 years are best treated with myelosuppressive therapy in the form of hydroxyurea.^[10]
  • An alternative therapy in older patients is radioactive phosphorous (32P), but this is unsuitable for younger patients because of the potential for causing secondary leukemia.
• Treatment of essential thrombocythemia (ET): Treatment of essential thrombocythemia 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 by hydroxyurea or anagrelide.
• Treatment of myelofibrosis (MF): No curative treatment is available at the present time.

  • Asymptomatic patients can be monitored clinically until symptomatic. 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.
  • A few recent reports have shown that allogeneic bone marrow transplantation may be effective in some cases.
  • 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%).

Splenectomy is occasionally required in myelofibrosis for symptomatic relief of pain associated with the massive splenomegaly refractory to medical management.

• 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.

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.