MYELODYSPLASTIC SYNDROMES

Myelodysplastic syndromes are a group of heterogeneousdisorders characterized by the presence of dysplastic changesin at least two of three hematopoietic cell lines.3,13 Patientswith MDS usually present with anemia and other cytopenias14and are classified as having one of five subtypes ofdisease: refractory anemia (RA), RA with ringed sideroblasts(RARS), RA with excess of blasts (RAEB), RAEBin transformation (RAEB-T), and chronic myelomonocyticleukemia. The proportion of individuals whose MDSevolves to acute myeloid leukemia (AML) ranges from5% to 15% in the low-risk RA/RARS group and from40% to 50% in the RAEB/RAEB-T group.13

The International Prognostic Scoring System (IPSS)stratifies patients with MDS into four distinct risk groupsin terms of survival and evolution of AML based on threemajor variables: marrow blast percentage, cytogeneticsubgroup, and number of cytopenias. The four risk groupsand percentage of the population are: low (33%), intermediate-1 (Int-1–38%), intermediate-2 (Int-2–22%), and high(7%). Median survival in the absence of therapy rangesfrom 5.7 years for those in the low risk category to 0.4 yearsin the high risk category.13 Males experience poorer survivalthan females.15


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MDS is primarily a disease of the elderly. Among individuals>70 years of age, incidence is 22 to 45 individualsper 100,000 people, which increases further with age.Morbidities caused by cytopenias and the potential of MDSto evolve into AML are the major clinical problems observedin patients with MDS.16

SCREENING PATIENTS FOR TRANSFUSIONINDUCEDIRON OVERLOAD

Blood transfusions are increasingly prevalent in the treatmentof individuals with beta-thalassemia, SCD, and MDS,1primarily because these patients have a better prognosis.16,17This is due to an improved understanding of the disordersand to newly available treatments. Therefore, regularscreening for iron overload is more important than ever.One unit of packed RBCs contains approximately200 mg to 250 mg of iron. Patients who are chronicallytransfused will have an iron excess of approximately0.4 mg/kg/day to 0.5 mg/kg/day (1 g/month).18 Withrepeated transfusions, iron accumulation and signs ofiron overload may be apparent after 10 to 20 transfusions(Table 1).

Accurate assessment of iron burden in the body—bymonitoring serum ferritin levels, liver iron concentration(LIC), and cardiac iron—is necessary not only to diagnoseiron overload but also to manage therapy effectively.19

Serum ferritin, the most commonly used test for estimatediron burden, is inexpensive and noninvasive. The normalrange for males is 12 mcg/L to 300 mcg/L; for females, itis 12 mcg/L to 150 mcg/L.20 Consistently high levels ofserum ferritin indicate high iron burden21; ≥1000 mcg/Lis the clinical benchmark for transfusion-induced ironoverload.5,21 Measuring serum ferritin levels has disadvantages.It is an indirect measurement of iron burden; itcan be inf luenced by complications (eg, infection,inflammation, ascorbate deficiency); and it requires serialmeasurements and/or interpretation with other indicatorsof iron overload.1

LIC, the most valid surrogate marker for total body ironburden, can be measured by liver biopsy, superconducting

TABLE 1. Clinical Signs and Symptoms of Transfusion-Induced Iron Overload

SYSTEM SIGNS AND SYMPTOMS
 General
  • Weight Loss
  • Fatigue
  • Bronze/Gray Skin
 Hermatologic
  • Underlying anemia
  • Transfusion dependence
  • Duration of transfusion dependence
  • Number of transfusions each year
  • Chelation history and compliance
Cardiac – Heart Failure  
  • Dyspnea
  • Orthopnea
  • Paroxysmal nocturnal dyspnea
  • Swelling of lower extremities
Gastrointestinal –
Cirrhosis
  • Abdominal distention
  • Abdominal pain
  • Hematemesis
  • Melena
  • Encephalopathy
 Endocrine
  • Stunted growth
  • Delayed puberty
  • Decreased libido
  • Delayed menarche
  • Diabetes mellitus

-Polyuria
-Polydipsia
-Polyphagia

 Musculoskeletal
  • Arthralgias

Source: Mir.22

quantum interference device, and magnetic resonanceimaging (MRI)19 (Table 2). Normal LIC values are<1.2 mg Fe/g dry weight; values for mild, moderate, andsevere iron load are 3 mg Fe/g to 7 mg Fe/g dry weight,8 mg Fe/g to 15 mg Fe/g dry weight, and >15 mg Fe/gdry weight, respectively.1