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1354 Part X: Malignant Myeloid Diseases Chapter 87: Myelodysplastic Syndromes 1355

TABLE 87–3. Diagnostic Criteria for Myelodysplastic TABLE 87–4. International Prognostic Scoring System for
Syndromes 577 Myelodysplastic Syndromes 579
Presence of one or more otherwise unexplained cytopenias* Score Value 0 0.5 1.0 1.5
Hemoglobin <11 g/dL Prognostic Variables
Absolute neutrophil count <1500/μL Marrow Blasts (%) <5 5–10 11–20
Platelet count <100,000/μL Karyotype Good Intermediate Poor
Presence of one or more myelodysplastic syndrome (MDS) Cytopenias 0, 1 2, 3
decisive criteria
>10% dysplastic cells in erythroid, myeloid, and/or megakaryocyte Risk groups: Low, 0; intermediate-1, 0.5–1.0; intermediate-2, 1.5–2.0;
lineages high, ≥2.5. Survival for each risk group is displayed in Table 87-5.
5 to 19% marrow blasts Karyotype: Good score, –Y, del(5q); poor score, complex abnormali-
Evidence of a cytogenetic abnormality typical for MDS : † ties and chromosome 7 abnormalities; intermediate score, all other
abnormalities. See “Marrow: Cytogenetics” in text above for further
–7 or del(7q) del(12p) or t(12p) t(1;3)(p36.3;q21.1) details.
–5 or del(5q) del(9q) t(2;11)(p21;q23) Cytopenias: anemia, hemoglobin <10 g/dL; neutropenia, absolute
neutrophil count <1.8 × 10 /L; thrombocytopenia, platelet count
9
i(17q) or t(17p) idic(X)(q13) inv(3)(q21q26.2) <100 × 10 /L.
9
–13 or del(13q) t(11;16)(q23;p13.3) t(6;9)(p23;q34)
del(11q) t(3;21)(q26.2;q22.1)
Exclusion of alternative diagnosis that explain blood and marrow with significant differences in overall survival and risk of clonal evolu-
findings tion to AML (Table 87–5). The IPSS was an extremely useful tool that
gained wide acceptance in clinical practice and is incorporated into
No AML-defining criteria (e.g., t[8;11], i[16], t[16;16], t[15:17], or
erythroleukemia) clinical practice guidelines published by the National Comprehensive
Cancer Network and European LeukemiaNet. 293,294 However, the IPSS
No other hematologic disorders (e.g., acute lymphocytic leukemia, has several limitations that include consideration of blast proportions
aplastic anemia, or various lymphomas) that were later redefined by the WHO classification system as AML and
Not explained by a propensity to underestimate risk in patients with severe cytopenias.
• HIV or other viral infection Several subsequent prognostic models that improve upon the IPSS
• Deficiencies of iron or copper have been published and validated, but have generally not been widely
• B , folate, or other vitamin deficiency adopted in routine clinical practice. 295–297
12 The IPSS-R, published in 2012, addresses most of the limitations
• Medications (e.g., methotrexate, azathioprine, or
chemotherapy) of the IPSS and provides improved prognostic accuracy over the IPSS
• Alcohol abuse (typically heavy and prolonged usage) and subsequent models. 298–300 The IPSS-R examined clinical data from
7012 MDS patients at the time of their diagnosis (Table 87–6). Like the
• Autoimmune conditions (e.g., immune thrombocytopenia IPSS, the IPSS-R excluded patients with proliferative CMML or ther-
purpura, immune hemolytic anemia, Evans syndrome, Felty
syndrome, or systemic lupus erythematosus) apy-related disease and censored patients if and when they received
• Congenital disorders (e.g., Fanconi anemia, Diamond-Blackfan disease-modifying therapy. The IPSS-R differs from the IPSS in that it
anemia, and Shwachman-Diamond syndrome, etc…) includes a much broader range of cytogenetic abnormalities which are
given greater weight in the overall risk calculation. The IPSS-R refines
*Present for 6 months or longer, if there is no typical cytogenetic the marrow blast percentages to exclude patients with 20 percent or
abnormality identified. greater blasts and considers each type of cytopenia as an independent
† The list of cytogenetic abnormalities shown in this Table was taken risk factor weighted by severity. Based on the total risk score, patients
from reference 578 and reiterated here. are assigned to one of five risk groups instead of the four used by the
IPSS. The risk score can be adjusted for age to take this variable into
account. Patients assigned to the “very low” and “low risk” groups are
CLINICAL PROGNOSTIC SCORING SYSTEMS considered to have lower-risk MDS whereas those in the “high” or “very
The estimation of prognosis is an integral element in the care for high” groups have higher-risk disease. Patients in the intermediate cat-
patients with MDS. It sets expectations for patients about their disease egory may be treated as lower or higher risk based on other prognostic
and helps physicians weigh the risks and benefits of specific treatments factors such as serum ferritin and serum lactate dehydrogenase (LDH)
versus observation alone. Historically, they have been used to describe which are not formally considered in the model.
participants with MDS in clinical trials, which has allowed for compari- The IPSS-R has been validated and shown to apply in contexts for
son among studies. The most prevalent prognostic model in clinical use which it was not originally defined. This includes risk stratification at
is the IPSS, first published in 1997. This model was created by exam- times other than diagnosis, use in patients who go on to receive disease-
ining 816 MDS patients at the time of their diagnosis. Patients with modifying treatment, and use in patients undergoing AHSCT. 299,301–303 It
therapy-related MDS, proliferative CMML, and those who received dis- is important to note that the median overall survival for patients strati-
ease-modifying therapy, such as AHSCT, were excluded. The IPSS con- fied by the IPSS and IPSS-R represent estimates based on patients who
sidered three major risk markers: the percentage of blasts in the marrow, did not receive disease-modifying therapy. Patients who respond to
the presence of specific cytogenetic abnormalities, and the number active treatments may, in fact, have a greater expected median survival
of cytopenias present in the blood. These elements were weighted as than predicted by these scoring systems. Currently, somatic mutations
shown in Table 87–4 to assign patients to one of four IPSS risk groups are not considered by any prognostic scoring system in widespread

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