Page 1276 - Hematology_ Basic Principles and Practice ( PDFDrive )

1122 Part VII Hematologic Malignancies

with ET who are already at an increased risk of developing throm- TABLE
bosis. Gangat et al retrospectively reviewed the consequences of such 69.9 Response Criteria for Essential Thrombocythemia
hormonal interventions in 305 women. Oral contraceptive therapy
was associated with a high incidence of venous thrombosis occurring Criteria
within the abdominal cavity, but estrogen-replacement hormone Complete Remission
therapy in menopausal women did not appear to be associated with A Durable resolution of disease-related signs
a
an increased incidence of thrombosis. This observation is surprising including palpable hepatosplenomegaly, large
and might be a consequence of the limited numbers of patients symptoms improvement, AND
b
included within this study. a
If a patient with ET develops a thrombotic episode, anticoagula- B Durable peripheral blood count remission,
9
tion with low-molecular–weight heparin and then transition to an defined as: platelet count ≤400 ×10 /L, WBC
9
oral anticoagulant is recommended. The thrombotic episode places count <10 × 10 /L, absence of
a patient into a high-risk group in which myelosuppressive therapy is leukoerythroblastosis, AND
clearly indicated. Whether patients should have life-long anticoagula- C Without signs of progressive disease, and
tion or should receive only 6–12 months of anticoagulation after they absence of any hemorrhagic or thrombotic
are in a complete hematologic remission has not been investigated in events, AND
a systematic fashion. Because the data necessary to make this decision D Bone marrow histological remission defined as
are not available, this decision can only be made at the discretion of disappearance of megakaryocyte hyperplasia
the treating physician. Antiplatelet therapy has been shown to reduce and absence of >grade 1 reticulin fibrosis.
the risks of deep venous thrombosis and pulmonary embolism in a Partial Remission
variety of high-risk groups. In patients who have a new thrombosis A Durable resolution of disease-related signs
a
while they are in complete hematologic remission and are optimally including palpable hepatosplenomegaly, and
anticoagulated, some consideration should be given to adding low- large symptoms improvement, AND
dose aspirin if the risk of hemorrhage is not excessive.
a
Lastly, consensus response criteria have been updated recently to B Durable peripheral blood count remission,
9
allow for more uniform reporting of therapeutic response within defined as: platelet count ≤400 × 10 /L, WBC
9
clinical trials (Table 69.9). Standardized response categories were count <10 × 10 /L, absence of
created by a working group formed by the ELN and IWG-MRT in leukoerythroblastosis, AND
2013 in an attempt to incorporate symptom response with clinical, C Without signs of progressive disease, and
hematologic, and histologic response criteria in order to ultimately absence of any hemorrhagic or thrombotic
3
enhance the evaluation of novel therapies tested in clinical trials. It events, AND
is important to note that these response criteria have not been vali- D Without bone marrow histological remission,
dated in a prospective fashion and their utility in the management defined as the persistence of megakaryocyte
of an individual patient with ET in the clinic is uncertain. hyperplasia
No response Any response that does not satisfy partial
FUTURE DIRECTIONS remission
Progressive disease Transformation into PV, post-ET myelofibrosis,
ET is a hematologic malignancy with its own distinct clinical mani- myelodysplastic syndrome or acute leukemia c
festations and associated complications. Better means of identifying Molecular response is not required for assignment as complete response or
patients at risk for developing fatal thrombotic or hemorrhagic partial response. Molecular response evaluation requires analysis in peripheral
complications are necessary to provide the basis with which to develop blood granulocytes. Complete response is defined as eradication of a
the optimal care of such patients. The ability to reduce the incidence preexisting abnormality. Partial response applies only to patients with at least
20% mutant allele burden at baseline. Partial response is defined as ≥50%
of thrombohemorrhagic episodes with cytoreductive therapy in high- decrease in allele burden.
risk patients is well established. a Lasting at least 12 weeks.
Multiinstitutional studies comparing the efficacy of such promis- b Large symptom improvement (≥10-point decrease) in MPN-SAF TSS. 10
For the diagnosis of PV see World Health Organization criteria (WHO) ; for the
13
ing agents as IFN-α or pegylated IFN for the treatment of high-risk c diagnosis of post-ET myelofibrosis, see the IWG-MRT criteria ; for the diagnosis
12
patients compared with hydroxyurea are currently being pursued and of myelodysplastic syndrome and acute leukemia, see WHO criteria. 13
initial results are anticipated in 2017. The use of low-dose aspirin ET, Essential thrombocythemia; PV, polycythemia vera; WBC, white blood cell.
therapy to reduce the number of episodes of erythromelalgia and From Barosi G, Mesa R, Finazzi G, et al: Response criteria for polycythemia
transient ischemic attacks is widely practiced, but whether aspirin vera and essential thrombocythemia: an ELN and IWG-MRT consensus project.
Blood 121:4778, 2013.
therapy should be indiscriminately used remains a subject of dispute
that will only be resolved with the completion of appropriately
powered clinical trials. Another pressing question that requires resolu-
tion is the degree of reduction of platelet or leukocyte numbers
required for optimal management of ET patients. treatment of ET is yet to be determined and currently MF is the focus
The report of 18 patients with high-risk, treatment-refractory ET of ongoing clinical investigation.
treated with imetelstat, a 13-mer oligonucleotide competitive inhibi- Finally, the discovery of the JAK2V617F, MPL, and CALR muta-
tor of telomerase, was recently published indicating a novel MPN tions have already had a major impact on disease classification during
therapeutic approach. The rationale for this prospective clinical trial routine clinical practice. Diagnostic strategies have now incorporated
was based on laboratory findings of selective inhibition of malignant screening for these driver mutations. This new understanding of the
megakaryopoiesis compared with megakaryocytes isolated from molecular pathogenesis of MPN has led to the development of novel
normal controls after in vitro exposure to imetelstat. In this open targeted therapies. The use of specific JAK2 inhibitors for ET patients
label, phase II study, the complete hematologic remission was 89% should be carefully studied in well-controlled clinical trials in which
and reductions in driver mutation allele burden (JAK2, MPL, CALR) significant endpoints such as incidence of thrombosis, hemorrhage,
were observed (median reduction of JAK2V617F of 59% at 12 and transformation to MF and acute leukemia are incorporated. This
months and reductions in CALR and MPL allele burden of 15–60%. is critical because the degree of reduction of platelet numbers has
Grade 3 neutropenia was seen in 22% of treated patients, and low- not served as a suitable biomarker for the development of these
grade reversible transaminitis was seen in the majority of patients. complications (see box on Personal Approach to Therapy of Essential
The role of this infusional agent administered every 3 weeks in the Thrombocythemia).