MYELODYSPLASTIC SYNDROMEMYELODYSPLASTIC SYNDROME

Masatoshi Kida, M.D.Dept. of Pathology

University of Vermont

Myelodysplastic SyndromeMyelodysplastic Syndrome

• heterogeneous group of hematologic disorders• maturation defects resulting in ineffective hematopoiesis

pancytopenia in peripheral blood• “preleukemia” many progress to overt acute leukemia

classification (FAB classification) (based on % blasts and ringed sideroblasts)

1. refractory anemia (RA)2. refractory anemia with ringed sideroblasts (RARS)3. refractory anemia with excess blasts (RAEB)4. refractory anemia with excess blasts in transformation (RAEB-T)5. CMML (chronic myelomonocytic leukemia)

Myelodysplastic SyndromeMyelodysplastic Syndrome2001 WHO classification2001 WHO classification

refractory anemia (RA)

refractory anemia with ringed sideroblasts (RARS)

refractory cytopenia with multilineage dysplasia (RCMD)

RCMD with ringed sideroblasts (RCMD-RS)refractory anemia with excess blasts-1 (RAEB-1) <5% blasts

refractory anemia with excess blasts-2 (RAEB-2) 5-19% blasts

myelodysplastic syndrome, unclassified (MDS-U)MDS with isolated del(5q) <5% blasts

myelodysplastic syndromemyelodysplastic syndromeclassificationclassification

RA <5% <1% --

RARS <5% <1% +

RAEB 5-20% <5%

RAEB-T 20-30% >5%

CMML dysplastic monocytosis

blasts ringed sideroblasts

BM peripheral

myelodysplastic syndromemyelodysplastic syndrome

Etiology:• vast majority of cases are sporadic

“risk factors”• chemical solvent (benzene)• pesticides• chemotherapy / radiation therapy

“therapy-related MDS/AML”

myelodysplastic syndromemyelodysplastic syndrome

Incidence:

de novo MDS 1 per 100,000 per year

(>60 y/o --- 25 to 50 per 100,000 per year)

t-MDS/AML 4 to 18% in autologous BMT

myelodysplastic syndromemyelodysplastic syndromegenetic abnormalitiesgenetic abnormalities

“loss of genetic material”• 5q- 15% of de novo MDS

50% of t-MDS• monosomy 7• trisomy 8• 21q-• 17q-• 20q-• t(11;16)(q23;p13) -- exclusively with t-MDS/AML• t(3;21)(q22;q22) -- with some of t-MDS/AML• t(5;12)(q33;p13) -- CMML

myelodysplastic syndromemyelodysplastic syndromeclinical featuresclinical features

peripheral cytopenia

neutropenia 24 to 39% of patients

anemia 45 to 93%

thrombocytopenia 28 to 45%

both quantitative and qualitative defect

highly susceptible to bacterial infection

normal T- and B-cell numbers and functions

no opportunistic infection

Myelodysplastic SyndromeMyelodysplastic Syndrome

•anemia•macrocytosis•large plts without granules•PMNs

•hypogranulated•pseudo Pelger-Huët cells•abnormally segmented nuclei•Döhl bodies

•circulating myeloblasts

myelodysplastic syndromemyelodysplastic syndromeclinical featuresclinical features

de novo MDS -- occurs in elderly population

30% die of unrelated underlying disease(s)

40% die of complication(s) of marrow failure

30% die of transformation to acute leukemia

myelodysplastic syndromemyelodysplastic syndrometreatmenttreatment

1. supportive care (blood transfusion, etc.)

2. allogeneic bone marrow transplant

42% disease-free survival at 4 years