2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

CLASSIFICATION AND PROGNOSIS OF MPNs
Table 6. Score Values for the International Prognostic Scoring
System (IPSS) 14 and Dynamic International Prognostic
Scoring System (DIPSS) 13
outcome. 23 Patients who abrogated the JAK2 mutation 6
months after ASCT had a significantly lower relapse rate,
shedding light on the likely clinical benefit of reduced V617F
allele burden (p � 0.04).
Concerning less frequent mutations described so far in
MF, studies reported that mutations involving TET2 (approximately
15% to 30% of patients with MF) and MPL
(approximately 7% to 9% of patients with MF) genes seem
not to affect survival, while IDH1 (approximately 4% of
patients with MF) implies a worse survival and higher risk
of AML, as does EZH2 mutations (approximately 6% of
patients with MF). 24-27 Nullizygosity for the JAK2 46/1
haplotype was associated with shortened survival, raising
the possibility that non-46/1 haplotypes are associated with
a biologically more aggressive phenotype. 28
Chromosomal Abnormalities. An abnormal karyotype is
present in approximately 30% to 40% of MF and implies a
shorter survival. 14,29 A study of 433 patients with MF
provided a two-tiered cytogenetic-risk stratification with a
respective 5-year survival of 8% (high risk) and 51% (low
risk). 20 Cytogenetic profiles are discussed in Table 7.
Red Blood Cell Transfusion Dependency. Patients with
the JAK2 V617F mutation seem not as prone to anemia as
those carrying the MPL or TET2 mutations. 24,25 The prognostic
effect of red blood cell transfusion need was examined
in 254 consecutive patients. 30 Median survival was 35
months for patients receiving red blood cell transfusions and
117 months for patients who were nontransfused.
Prognostic Models at Diagnosis
The first prognostic model used to stratify PMF was the
Lille score, which included hemoglobin level less than10
g/dL and leukocyte count less than 4 � 10 9 /L or greater than
30 � 10 9 /L. 29 Patients were grouped into three categories
with median survivals of 93, 26, and 13 months.
More recently, the International Working Group on MPN
Research and Treatment (IWG-MRT) developed the IPSS to
predict survival in patients with PMF at diagnosis. 14 The
IPSS was developed using a dataset of 1,054 patients with
PMF from seven international centers. Currently, the IPSS
Author’s Disclosures of Potential Conflicts of Interest
Author
Francesco Passamonti*
*No relevant relationships to disclose.
Employment or
Leadership
Positions
Scores
Parameter
IPSS DIPSS
Age � 65 1 1
Hemoglobin � 10 g/dL 1 2
Leukocyte count � 25 � 109 /L 1 1
Blast cells � 1% 1 1
Constitutional symptoms 1 1
IPSS: score 0 for low risk, score 1 for intermediate-1 risk, score 2 for
intermediate-2 risk, score � 3 for high risk; DIPSS: score 0 for low risk, score 1-2
for intermediate-1 risk, score 3-4 for intermediate-2 risk, score 5-6 for high risk.
Consultant or
Advisory Role
Table 7. Score Values for the Dynamic International Prognostic
Scoring System-Plus (DIPSS-Plus)
is the prognostic scoring system used for diagnosis in clinical
practice. Table 6 illustrates risk factors and the score system.
According to the four risk categories, median survivals
were 135, 95, 48, and 27 months.
A composite prognostic model was developed by the University
of Texas M. D. Anderson Cancer Center involving
256 patients with PMF at diagnosis. 19 The risk factors were
unfavorable karyotype, hemoglobin level less than 10 g/dL,
platelet count less than 100 � 10 9 /L, and performance
status greater than 1. Overall survival ranged from 7 to 69
months.
Dynamic Prognostic Models
Dynamic prognostic models are based on the knowledge
that the acquisition of additional risk factors during the
disease course may substantially modify patients’ outcome.
The DIPSS Model. Among 1,054 patients evaluated to
develop the IPSS model, 525 had adequate follow-up data for
a time-dependent analysis aimed at the definition of the
DIPSS. 13 The DIPSS is based on the same factors as the
IPSS and the score system is illustrated in Table 6. Median
survival was not reached in patients at low risk; it was 14.2
years in intermediate-1, 4 years in intermediate-2, and 1.5
years in patients at high risk.
The DIPPS-Plus Model. The DIPSS-plus is a refinement
of the DIPSS, which includes additional variables as illustrated
in Table 7. DIPSS-plus includes four categories with
median survivals of 185, 78, 35, and 16 months, respectively.
18
Conclusion
MPN diagnosis must be done according to the 2008 WHO
criteria. Molecular analysis should include JAK2 and MPL
mutations. The risk stratification for patients with PV and
ET requires only two parameters: age older than 60 and
prior history of thrombosis. As for PMF, IPSS at diagnosis
and DIPSS anytime during disease course easily define
survival of these patients very adequately.
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Parameter Score value
DIPSS intermediate-1 1
DIPSS intermediate-2 2
DIPSS high risk 3
Unfavorable karyotype* 1
Red blood cell need 1
Platelet � 100 � 10 9 /L 1
* Unfavorable karyotype: complex karyotype or sole or two abnormalities that
include �8, �7/7q-, i(17q), �5/5q-, 12p-, inv(3), or 11q23 rearrangement;
favorable karyotype: normal and diploid karyotype, sole or two abnormalities not
included in the unfavorable karyotype category.
DIPSS-plus: score 0 for low risk, score 1 for intermediate-1 risk, score 2-3 for
intermediate-2 risk, score 4-6 for high risk.
Research
Funding
Expert
Testimony
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Remuneration
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