Page 1258 - Hematology_ Basic Principles and Practice ( PDFDrive )

1104 Part VII Hematologic Malignancies

the only long-term survival with post-PV leukemia has been observed K. Rapid mobilization of the mother after delivery is of great
in patients receiving allogeneic stem cell transplantation. Whether the importance.
patients should receive some form of induction chemotherapy before Because PV is ultimately a stem cell disorder, it should be possible
receiving conditioning therapy for preparation of the transplant or to achieve a cure with stem cell transplantation. Thus far, the majority
proceed directly to transplant is a decision that varies from patient to of patients undergoing allogeneic stem cell transplantation have been
patient and from center to center. Most patients with PV-related relatively young and have been transplanted after evolution to MF,
acute leukemia should be considered candidates for experimental MDS, or acute leukemia. Transplantation during the polycythemia
therapeutic strategies. Recently, promising results with the use of phase of the disease is rarely appropriate.
DNA hypomethylating agents such as decitabine or azacitidine alone
or in combination with ruxolitinib have been reported, with 50–60%
of patients achieving clinically significant responses persisting for FUTURE DIRECTIONS
6–24 months in the majority of cases. These chemotherapeutic regi-
mens can frequently be administered as an outpatient but require The discovery of JAK2V617F mutations has led to a more com-
treatment for at least six monthly cycles before clinical responses can prehensive understanding of the pathophysiology of the MPNs,
be evaluated. Although many of these patients do not achieve true including PV. There is no question that the diagnostic tests for
complete remissions, their prolonged survival and quality of life, at JAK2V617F and exon 12 mutations of JAK2, as well as mutations
least based upon single-institutional studies, appears to be superior in VHL, HIF-1, HIF-2, the EPOR, and PHD have revolutionized
to that achieved with standard induction chemotherapy. The use of the diagnostic approach to patients with erythrocytosis. PV is a
hypomethylating agents, JAK2 inhibitors, or both is now being stem cell disease that will ultimately require curative therapies at
explored as bridging therapies before patients receive allogeneic a minimum to deplete or eliminate malignant stem cells if cura-
transplants. tive small-molecule therapies are to become a reality. Before the
PV occurs frequently during childbearing years. A discussion of JAK2V617F allele burden is used as a biomarker for outcomes of
contraception options is imperative because the use of oral contracep- novel therapeutic approaches to treat patients with PV, studies
tive pills may be associated with an increased risk of deep venous are needed to determine the extent of reduction of allele burden
thrombosis as well as splanchnic vein thrombosis. It seems prudent that would be predictive of altering the natural history of PV and
to entertain alternative forms of contraception with such individuals. eliminating complications from thrombotic episodes or evolution
Discontinuation of hydroxyurea in both men and women desiring to MF or acute leukemia. The use of drugs affecting only JAK2 are
to have a child is recommended. Hydroxyurea is capable of inducing unlikely to be curative because multiple genetic and epigenetic events
azoospermia in men, frequently limiting their ability to father a child. likely contribute to the origins and progression of PV. Randomized
Pregnancy is itself a prothrombotic condition. PV in a pregnant clinical trials of combinations of drugs, rather than single drugs, and
individual has been reported to lead to an increased incidence of comparing these outcomes with the standard of care are more likely
fetal wastage, with 30% of pregnancies in PV patients terminating to lead to significant advances in improving the natural history of
in spontaneous abortions. In addition, preeclampsia occurs more PV patients.
frequently in these women. A team approach requiring close com-
munication between an obstetrician skilled in providing care for
high-risk pregnancies and the responsible hematologist provides the
optimal integration of care to the mother and the child. Pregnancy REFERENCES
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