Page 1257 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 68 The Polycythemias 1103

exhibited enhanced proliferative signals, relative resistance to cell Liver transplantation is a potential option for treatment of PV
death upon growth factor deprivation, and a growth advantage over BCS patients with continued hepatic decompensation. The indica-
control cells under suboptimal growth conditions. A JAK inhibitor tions for liver transplantation are cirrhosis, fulminant hepatic failure,
was shown to reduce mast cell numbers and alleviate pruritis in and failure of a portosystemic shunt. The overall actuarial survival at
JAK2V617F transgenic mice. Some uncontrolled studies have attrib- 1 year was 76% and was 68% at 10 years. Because PV is a slowly
uted pruritus to hyperhistaminemia or severe iron deficiency, with progressive disease, transplantation should not be withheld from
relief associated with the use of histamine antagonists or ferrous these patients. Pretransplant predictors of mortality based on a
sulfate. Iron replacement is frequently not possible because it can lead multivariable analysis were impaired renal function and a history of
to dangerous elevations of the RBC mass. In a number of instances, a shunt. The hematologic consequences of polycythemia must be
however, iron replacement has been possible with disease control with aggressively treated in the posttransplantation setting; hepatic vein
IFN-α. The association between pruritus and tissue infiltration by occlusion may reoccur in the transplanted liver.
mast cells would appear to explain the response of occasional patients Therapy of CVT and sinuses includes anticoagulation with
to photochemotherapy with psoralens and ultraviolet irradiation. In heparin to arrest the thrombotic process and to prevent pulmonary
addition, 80% of patients with pruritus have been reported to embolism. LMWH should be started as soon as the diagnosis is
respond to the selective serotonin uptake inhibitors paroxetine or confirmed even in the presence of hemorrhagic infarcts. After the
fluoxetine. Other effective options include anticonvulsant drugs such acute phase, life-long oral anticoagulant therapy is recommended.
as pregabalin. Ruxolitinib and other JAK inhibitors both in PV and There is currently no available evidence from randomized clinical
PMF have a remarkable effect on reducing the severity of intractable trials regarding the efficacy or safety of thrombolytic therapy.
pruritus that not infrequently affects PV patients. These drugs appear The performance of any surgical procedures on patients with PV
to be much more effective in treating this particular symptom of PV is, as previously discussed, accompanied by excessively high morbidity
compared with both hydroxyurea and IFN, but in occasional patients and mortality. Elective surgery should not be contemplated unless
this effect, unfortunately, is not sustained. the patient’s hematologic values have been normalized for several
BCS is a catastrophic illness that can lead to significant morbidity months. The longer the hematologic control has been in effect, the
and mortality in patients with PV. Patients with MPN are at a high lower the incidence of postoperative complications. If emergency
risk of developing this syndrome. Independently, the use of oral surgery is required, the patient should be phlebotomized rapidly until
contraceptive pills and congenital and acquired thrombophilic factors a normal hematocrit is reached, and platelets should be available in
are involved in its development. A number of cases of hepatic vein case excessive perioperative or postoperative bleeding occurs. After
thrombosis have been reported in nonpolycythemic women taking emergency or elective surgery, the patient should be mobilized as soon
oral contraceptives. Although no data are available, one must be as possible, and strong consideration should be given to anticoagula-
concerned about the use of oral contraceptives in women with PV. tion with LMWH unless the patient has some contraindication.
The optimal approach to the problem of BCS is obviously preven- Dental extractions can also result in excessive hemorrhage and should
tive and involves maintenance of normal blood values in the patient not be performed unless the patient is under strict hematologic
with PV. When BCS develops, the prognosis without treatment is control.
dismal. The goals of therapy are to prevent further propagation of Perhaps the most difficult and frustrating period encountered
thrombus, relieve the intense hepatic congestion, and manage the during the clinical course of a patient with PV is the development of
severe ascites that often plague these patients. If untreated, these post-PV MF. The origins, manifestations, and management options
patients often have a slowly progressive course, with deterioration and are discussed in detail in Chapter 70.
death occurring within 3.5 years. Spontaneous resolution of the Limited information is available concerning the treatment of
hepatic vein occlusion rarely occurs. There are no prospective ran- patients who develop acute leukemia after PV. The overwhelming
domized trials of anticoagulation in BCS, but retrospective studies majority of such cases involve myeloid leukemias. The leukemia is
suggest a survival benefit. Anticoagulation should be continued frequently preceded by post-PV MF but not always. Patients with
indefinitely unless there is a contraindication. Typically, low- post-PV MF and acute leukemia frequently have greater than 20%
molecular–weight heparin (LMWH) is used as the initial treatment blasts in the peripheral blood but far fewer blast cells in the BM,
with subsequent switch to warfarin. New oral anticoagulants that act which has led to a hypothesis that the leukemia originates from an
by direct thrombin or factor Xa inhibition are being increasingly used extramedullary site, particularly the spleen. These cases tend to have
for various prophylactic and therapeutic indications, but their use for a more indolent course, but patients with a greater degree of BM
these patients should be avoided until more reversal agents become infiltration have a more highly proliferative form of leukemia that is
available and the experience of using them becomes more widespread. associated with an even more aggressive course. The optimal treat-
The use of thrombolytic therapy directly in the thrombosed vein is ment of such patients is unknown. In elderly adults with significant
infrequent due to the lack of data and potentially high risk of bleeding comorbidities, the choice not to institute chemotherapy is a reason-
Angioplasty with or without the use of stents attempts to restore able option. These patients are frequently elderly, and poor results
hepatic blood flow and is often used if anticoagulation is not success- with standard regimens have been reported. Patients rarely achieve a
ful, and should be considered if liver function is deteriorating despite complete remission but rather return to a clinical condition that
therapeutic anticoagulation. The overall success rate is about 95%, resembles their original MPN for limited periods of time. In a retro-
with a low periprocedural complications rate. The clinical deteriora- spective analysis on 23 patients with leukemic transformation of PV,
tion of patients with BCS results from damage to the hepatocytes the median patient age was 68 years, and leukemia developed a
from necrosis associated with marked elevation in sinusoidal pressure median of 12.8 years from the diagnosis of PV. Twelve of the 14
coupled with ischemia from reduced hepatic arteriole perfusion. The patients in whom cytogenetic analyses were performed had complex
only rational therapeutic intervention, therefore, involves some sort cytogenetic abnormalities associated with high-risk leukemias. Fifteen
of portal vein decompression to achieve an effective reduction of patients were treated with palliative measures and had a median
sinusoidal pressure. Portosystemic shunting such as transjugular survival of 2.5 months. Of the eight patients treated with standard
intrahepatic portosystemic shunt (TIPS) has been used extensively to induction therapy, one obtained a complete remission, and seven died
treat refractory portal hypertension. Recent data show good long- without obtaining a response. The median survival time of these
term outcomes when using TIPS, and it is now considered standard chemotherapy-treated patients was 5.6 months. The median survival
management if anticoagulation or angioplasty are not successful, or time of the entire cohort of 23 patients was 2.9 months. This poor
if patients have high-risk disease. It has been shown that about a third outcome is likely the result of clinical and biologic features of the
of patients with BCS require TIPS placement. One-year survival in acute leukemia, advanced patient age, unfavorable cytogenetics, and
a recent large UK single-center study was 97% and 5-year survival patient comorbidities associated with advanced age. Selected patients
72%. Procedure-related complications are frequent but mortality are likely to tolerate and have a favorable outcome with allogeneic
rates are low. stem cell transplantation and reduced-intensity conditioning. In fact,