Complications
The leukemogenicity of busulfan is unclear as studies have reported conflicting results.[14][97][120][141][142][143]
Long-term follow-up of a randomized controlled trial suggests that sequential use of busulfan and hydroxyurea may significantly increase the risk of secondary malignancies.[143]
The National Comprehensive Cancer Network (NCCN) guidelines do not recommend the use of busulfan for polycythemia vera.[71]
The 10-year and 15-year risks of post-PV myelofibrosis (also known as spent-phase polycythemia vera [PV]) have been estimated at 4.9% to 6%, and 6% to 14%, respectively.[173] A hallmark of this switch is the development of anemia or a sustained reduction in the need for phlebotomy or cytoreductive therapy to control the hematocrit. Patients develop increased marrow fibrosis, and usually the spleen becomes much larger.[69] Post-PV myelofibrosis presumably occurs because of clonal evolution of the disease.
Formal criteria for a diagnosis of post-PV myelofibrosis have been published.[100] A higher allele burden of mutant JAK2 at diagnosis of PV and the presence of bone marrow fibrosis at baseline are directly correlated with the risk of developing post-PV myelofibrosis.[8][58]
White blood cells and platelet counts may increase or may fall to subnormal levels.
Management by a hematologist is required. Treatment is generally palliative, although allogeneic stem cell transplant can be curative in patients fit enough to undergo the procedure. There is no evidence that any of the treatments for PV effectively lower the risk of progression to post-PV myelofibrosis.
Acute leukemia may be a feature of the natural history of the disease. The 10-year and 15-year risks of this complication have been estimated at 2.3% to 14.4%, and 5.5% to 18.7%, respectively.[173] The prognosis is poor.
There is no evidence that any of the treatments for polycythemia vera (PV) effectively lower the risk of progression to acute leukemia.
While it is appropriate to consider therapy for leukemia consistent with the patient's age and performance status, post-PV acute leukemia is generally quite resistant to therapy and the likelihood of prolonged remission is low.[174]
Once complete remission is achieved, allogeneic stem cell transplant could be considered for the rare patient fit enough to undergo the procedure.[175]
The potential leukemogenicity of hydroxyurea is debated.[122]
It is unclear why thrombosis occurs. It may be related to hyperviscosity and/or leukocytosis, although data on the association with leukocytosis are conflicting.[51][54][59][144]
The most common thrombotic events are myocardial infarction, stroke, and deep vein thrombosis. Arterial clots are more common than venous clots. Clots can also occur in unusual locations (e.g., splanchnic vein thrombosis).
Any thrombosis that arises in the setting of polycythemia vera should be treated according to standard guidelines, plus appropriate cytoreduction, preferably under the guidance of an experienced hematologist.
Aspirin should not be used because it increases the risk of bleeding due to acquired von Willebrand disease.[106][169]
The most common serious reaction to hydroxyurea.
With appropriate monitoring of blood count, the risk is decreased. However, there is evidence that the development of cytopenias while on hydroxyurea significantly increases the risk of developing post-polycythemia vera myelofibrosis and acute leukemia.[176]
Toxicity with peginterferon alfa-2a is common and can be severe. Adverse events and discontinuation rates in studies were high; 22% of patients discontinued therapy due to toxicity in one open-label, phase 2 trial.[127][129]
Common adverse effects of peginterferon therapy include gastrointestinal upset, fever or flu-like symptoms. Patients may also develop weakness, weight loss, severe depression, cardiovascular symptoms, and autoimmune disease. Patients should be screened for depression and other psychiatric illnesses prior to starting peginterferon. Monitoring of toxicity (including regular thyroid function testing) is required during treatment.
Management can be difficult, although sometimes antihistamine medications and other treatments (e.g., selective serotonin-reuptake inhibitors) are successful. Pegylated interferon or ruxolitinib may be effective.[90][91]
A retrospective case series suggests that omalizumab, an anti-IgE monoclonal antibody, may have potential in treating polycythemia vera-associated pruritus; however, further research is needed.[177]
Bleeding complications can be severe, including gastrointestinal and cerebral bleeding. At initial presentation, it is reported that 1.7% to 20% of patients have major bleeding.[2]
It is unclear why hemorrhage occurs.
In some cases, hemorrhage may be related to marked thrombocytosis (platelet count ≥1000 × 10³/microliter [≥1000 × 10⁹/L]).
Antiplatelet (including low-dose aspirin) and anticoagulant therapy should be stopped.[47][97]
Acquired von Willebrand syndrome can also occur at near-normal platelet counts; thus, assessment of ristocetin cofactor activity should be performed in the presence of abnormal bleeding, regardless of platelet count.[97][170] Aspirin should be stopped if ristocetin cofactor activity is less than 20% to 30%; consult local guidance.[97]
Cytoreductive therapy should be considered if platelet count is extremely high (≥1000 × 10³/microliter [≥1000 × 10⁹/L]) as this may be associated with an increased risk of bleeding due to acquired von Willebrand disease.
Hematologist consultation is required.
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