History
The development of myelodysplastic syndrome (MDS) may be preceded by a few years by an unexplained macrocytic anemia with no evidence of megaloblastic anemia and a mild thrombocytopenia or neutropenia. Clinical symptoms that should prompt a workup for MDS are due to low peripheral blood counts, usually from the anemia but also from the thrombocytopenia or neutropenia.
Symptoms such as fatigue and malaise result from anemia. Signs and symptoms of chronic heart failure may develop in patients with underlying cardiac problems, depending on the degree of anemia.
Petechiae, ecchymoses, and nose and gum bleeding are common manifestations of a low platelet count. If underlying dysplastic changes were missed initially, thrombocytopenia as the presenting symptom may be mistaken for immune thrombocytopenia.
Fever, cough, dysuria, or shock may be manifestations of serious bacterial or fungal infections in patients with neutropenia.
Physical Examination
On physical examination, patients with myelodysplastic syndrome (MDS) may have evidence of thrombocytopenia, anemia, and/or neutropenia. Thrombocytopenia typically manifests as petechiae or ecchymoses; epistaxis and gum bleeding suggest severe thrombocytopenia. Hemoptysis, hematuria, and blood in stools may occur.
Pallor of the skin and mucosal membranes or evidence of fatigue, tachycardia, or congestive heart failure may be manifestations of severe anemia.
An enlarged spleen may be found in persons with chronic myelomonocytic leukemia (CMML), often indicating an overlap syndrome with MDS. CMML must be differentiated from chronic myelogenous leukemia (CML). Patients with an enlarged spleen may have complications related to spontaneous rupture and intra-abdominal exsanguination.
The presence of fever and infections, such as pneumonias and urinary tract infections, may be due to the neutropenia associated with MDS.
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Blood film (1000× magnification) demonstrating a vacuolated blast in a refractory anemia with excess of blasts in transformation. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
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This bone marrow film (400× magnification) demonstrates an almost complete replacement of normal hematopoiesis by blasts in a refractory anemia with an excess of blasts in transformation. Note the signs of abnormal maturation such as vacuolation, double nucleus, and macrocytosis. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
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Bone marrow film (1000× magnification) demonstrating ring sideroblasts in Prussian blue staining in a refractory anemia with excess of blasts in transformation. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
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Bone marrow film (1000× magnification) demonstrating granular and clotlike positive reaction in periodic acid-Schiff staining in a refractory anemia with excess of blasts in transformation. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
Tables
- Table 1. Revised International Prognostic Scoring System risk groups and prognosis [19]
- Table 2 Cytogenetic abnormalities assigned an IPSS-R value for scoring
- Table 3.Calculation of IPSS-R score
- Table 4. IPSS-R prognostic risk scores and categories
- Table 5. Clinical outcome by IPSS-R risk category
- Table 6. Categories of FAB classification versus WHO classification for myelodysplastic syndrome (MDS)
- Table. 2008 and 2016 World Health Organization (WHO) classifications of myelodysplastic syndromes
Risk Group |
Time to Development of AML (y) |
Median Survival (y) |
Very low |
NR |
8.8 |
Low |
10.8 |
5.3 |
Intermediate |
3.2 |
3.0 |
High |
1.4 |
1.6 |
Very High |
0.7 |
0.8 |
AML – Acute myelogenous leukemia |
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Cytogenetic prognostic subgroups |
Cytogenetic abnormalities |
Very good |
-Y, del(11q) |
Good |
Normal, del(5q), del(12p), del(20q), double including del(5q) |
Intermediate |
Del(7q), +8, +19, t(17q), any other single or double independent clones |
Poor |
-7, inv(3)/t(3q)/del(3q), double including -7,/del(7q), complex: 3 abnormalities |
Very poor |
Complex: >3 abnormalities |
Points Assigned |
||||||||
0 |
0.5 |
1 |
1.5 |
2 |
3 |
4 |
||
Variable |
Cytogenetic subgroup |
Very Good |
Good |
Intermediate |
Poor |
Very Poor |
||
Bone marrow blasts (%) |
≤2 |
>2- < 5 |
5-10 |
>10 |
||||
Hemoglobin (g/dL) |
≥10 |
8-9.9 |
< 8 |
|||||
Platelet count (x 109/L) |
≥100 |
50-99.9 |
< 50 |
|||||
Absolute neutrophil count (x 109/L) |
≥0.8 |
< 0.8 |
||||||
Risk Score |
Risk Category |
≤1.5 |
Very Low |
>1.5-3 |
Low |
>3-4.5 |
Intermediate |
>4.5-6 |
High |
>6 |
Very High |
IPSS-R Risk Category |
||||||
Very Low |
Low |
Intermediate |
High |
Very High |
||
Clinical Outcome |
Median survival (years) |
8.8 |
5.3 |
3.0 |
1.6 |
0.8 |
Median time to 25% acute myelogenous leukemia evolution (years) |
NR |
10.8 |
3.2 |
1.4 |
0.7 |
|
FAB Classification |
WHO–2004 Classification |
WHO–2008 Classification |
RA |
RA RCMD 5q- |
RCUD RCMD 5q- |
RARS |
RARS RCMD-RS |
RARS RCMD-RS RARS-T |
RAEB |
RAEB-1 RAEB-2 |
RAEB-1 RAEB-2 |
CMML |
CMML-1 CMML-2 |
CMML-1 CMML-2 |
RAEB-T |
AML |
AML |
| 2008 WHO Classification [17] | 2016 WHO Classification [51] |
| Refractory cytopenia with unilineage dysplasia (RCUD) encompassing refractory anemia (RA), refractory neutropenia (RN), and refractory thrombocytopenia (RT) | MDS with single-lineage dysplasia (MDS-SLD) |
| Refractory cytopenia with multilineage dysplasia (RCMD) | MDS with multilineage dysplasia (MDS-MLD) |
| Refractory anemia with ringed sideroblasts (RARS) | MDS with ring sideroblasts (MDS-RS) MDS-RS with single lineage dysplasia (MDS-RS-SLD) MDS-RS with multilineage dysplasia (MDS-RS-MLD) |
| Myelodysplastic syndrome associated with isolated del(5q) | MDS with isolated del(5q) |
| MDS with excess blasts (MDS-EB) | |
| Refractory anemia with excess blasts–1 (RAEB-1) | MDS-EB-1 |
| Refractory anemia with excess blasts–2 (RAEB-2) | MDS-EB-2 |
| Myelodysplastic syndrome, unclassified (MDS-U) | MDS, unclassifiable (MDS-U) with 1% blood blasts with single lineage dysplasia and pancytopenia based on defining cytogenetic abnormality |
| Refractory cytopenia of childhood | Refractory cytopenia of childhood |
