1. Myeloproliferative/Myeloproliferative/
MyelodysplasticMyelodysplastic
Dr. Rafi Ahmed GhoriDr. Rafi Ahmed Ghori
Professor MedicineProfessor Medicine
Liaquat University of Medical &Liaquat University of Medical &
Health Sciences, JamshoroHealth Sciences, Jamshoro

2. BIKHABIKHA
Myeloproliferative DisordersMyeloproliferative Disorders
Chronic Myelocytic LeukemiaChronic Myelocytic Leukemia
Acute Non-Lymphoblastic LeukemiaAcute Non-Lymphoblastic Leukemia
Polycythemia VeraPolycythemia Vera
Essential ThrombocythemiaEssential Thrombocythemia
MyelofibrosisMyelofibrosis
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3. BIKHABIKHARafi

4. BIKHABIKHA
Essential ThrombocythemiaEssential Thrombocythemia
clonal myeloproliferative disorderclonal myeloproliferative disorder
involving increased megakaryopoiesisinvolving increased megakaryopoiesis
Diagnostic criteriaDiagnostic criteria
– platelet count over 600,000platelet count over 600,000
– hemoglobin less than 13.0 g/dL or a normalhemoglobin less than 13.0 g/dL or a normal
redcell massredcell mass
– stainable iron or failure of iron therapystainable iron or failure of iron therapy
– No Ph’ chromosome, no marrow fibrosis,No Ph’ chromosome, no marrow fibrosis,
splenomegaly, leukoerythroblastic reaction orsplenomegaly, leukoerythroblastic reaction or
cause for reactive thrombocytosiscause for reactive thrombocytosis
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5. BIKHABIKHA
Essential ThrombocythemiaEssential Thrombocythemia
Peripheral bloodPeripheral blood
• thrombocytosis - variation in size andthrombocytosis - variation in size and
shapeshape
• increased segmented neutrophils withoutincreased segmented neutrophils without
basophiliabasophilia
• RBC normocytic/normochromic unlessRBC normocytic/normochromic unless
complicated by iron deficiencycomplicated by iron deficiency
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6. BIKHABIKHA
Essential ThrombocythemiaEssential Thrombocythemia
Bone marrowBone marrow
• Hypercellularity with increasedHypercellularity with increased
megakaryocytic elements showingmegakaryocytic elements showing
clustering and increased sizeclustering and increased size
Therapy and prognosisTherapy and prognosis
• relative long survivalrelative long survival
• thromboemboic or hemorrhagicthromboemboic or hemorrhagic
complicationscomplications
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7. BIKHABIKHA
Agnogenic Myeloid MetaplasiaAgnogenic Myeloid Metaplasia
(Myelofibrosis)(Myelofibrosis)
Clonal ineffective hematopoiesisClonal ineffective hematopoiesis
manifesting marrow hypercellularity andmanifesting marrow hypercellularity and
fibrosis with myeloerythroblastosis infibrosis with myeloerythroblastosis in
the peripheral blood - Causes pg 378the peripheral blood - Causes pg 378
Fibrosis is secondary to increasedFibrosis is secondary to increased
release of fibroblastic growth factorsrelease of fibroblastic growth factors
Production of extramedullaryProduction of extramedullary
hematopoiesishematopoiesis
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8. BIKHABIKHA
Agnogenic Myeloid MetaplasiaAgnogenic Myeloid Metaplasia
(Myelofibrosis)(Myelofibrosis)
Age 50 - 70Age 50 - 70
Clinical featuresClinical features
• splenomegaly - hepatomegalysplenomegaly - hepatomegaly
• anemiaanemia
• bleedingbleeding
• bone painbone pain
• night sweatsnight sweats
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9. BIKHABIKHA
Agnogenic Myeloid MetaplasiaAgnogenic Myeloid Metaplasia
(Myelofibrosis)(Myelofibrosis)
Peripheral bloodPeripheral blood
• leukoerythroblastic blood pictureleukoerythroblastic blood picture
• may have abnormal neutrophil functionsmay have abnormal neutrophil functions
• RBC poikilocytosis with tear dropsRBC poikilocytosis with tear drops
• platelets decreased, normal or increasedplatelets decreased, normal or increased
and may have abnormal functionand may have abnormal function
Bone marrowBone marrow
• hypercellularhypercellular
• dyspoiesisdyspoiesis
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10. BIKHABIKHA
Agnogenic Myeloid MetaplasiaAgnogenic Myeloid Metaplasia
(Myelofibrosis)(Myelofibrosis)
Radiologic osteosclerosisRadiologic osteosclerosis
Immunological abnormalitiesImmunological abnormalities
PrognosisPrognosis
• mean survival is 5 yearsmean survival is 5 years
• mortality associated with infection,mortality associated with infection,
hemorrhage, and transformation to acutehemorrhage, and transformation to acute
leukemialeukemia
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11. BIKHABIKHA
PolycythemiaPolycythemia
Increase in absolute red cell massIncrease in absolute red cell mass
measure with Crmeasure with Cr5151
Relative polycythemiaRelative polycythemia
• decreased plasma volumedecreased plasma volume
• spurious, stress, Gaisbocks diseasespurious, stress, Gaisbocks disease
Primary polycythemiaPrimary polycythemia
Secondary polycythemiaSecondary polycythemia
• physiologically appropriatephysiologically appropriate
• physiologically inappropriatephysiologically inappropriate Rafi

12. BIKHABIKHA
PolycythemiaPolycythemia
Importance of erythropoietinImportance of erythropoietin
• produced in kidney in response to tissueproduced in kidney in response to tissue
hypoxiahypoxia
erythropoietin
BM
RBCTissue
hypoxia
kidney
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13. BIKHABIKHA
PolycythemiaPolycythemia
Polycythemia
erythropoietin
(P. vera)
erythropoietin
(Secondary
polycythemia)
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14. BIKHABIKHA
Polycythemia veraPolycythemia vera
One of the group of myeloproliferativeOne of the group of myeloproliferative
diseases - group of diseases of bonediseases - group of diseases of bone
marrow proliferationmarrow proliferation
Myeloproliferative DisordersMyeloproliferative Disorders
• RBC - P. vera - DiGuglielmo’sRBC - P. vera - DiGuglielmo’s
• fibrotic - myelofibrosis ( agnogenic myeloidfibrotic - myelofibrosis ( agnogenic myeloid
metaplasiametaplasia
• WBC - chronic myelocytic - acuteWBC - chronic myelocytic - acute
myeloblasticmyeloblastic
• Platelets - Primary thrombocythemiaPlatelets - Primary thrombocythemia Rafi

15. BIKHABIKHA
Polycythemia veraPolycythemia vera
Diagnosis of P. veraDiagnosis of P. vera
• generally over age 50 - ruddy complextiongenerally over age 50 - ruddy complextion
• All 3 A criteria or A1 and A2 plus 2 BAll 3 A criteria or A1 and A2 plus 2 B
criteriacriteria
– A1. Increased red cell massA1. Increased red cell mass
– A2. OA2. O22 saturation normalsaturation normal
– A3. SpenomegalyA3. Spenomegaly
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16. BIKHABIKHA
Polycythemia veraPolycythemia vera
Diagnosis of P. veraDiagnosis of P. vera
• B1. Leukocytosis - left shift - increasedB1. Leukocytosis - left shift - increased
basophilsbasophils
• B2. Thrombocytosis (abnormal)B2. Thrombocytosis (abnormal)
• B3. Increased LAPB3. Increased LAP
• B4. Increased vit BB4. Increased vit B1212 or unbond Bor unbond B1212 bindingbinding
capacitycapacity
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17. BIKHABIKHA
Polycythemia veraPolycythemia vera
Diagnosis of P. veraDiagnosis of P. vera
• May have enlarged liverMay have enlarged liver
• 75% have enlarged spleen75% have enlarged spleen
• May have itching (basophils)May have itching (basophils)
• may have increased uric acid (gout)may have increased uric acid (gout)
• 30-40% have bleeding or thrombosis30-40% have bleeding or thrombosis
• 15% progress to AML15% progress to AML
• life span 11 - 13 years after diagnosislife span 11 - 13 years after diagnosis
• treatment - phlebotomy - thentreatment - phlebotomy - then
chemotherapy - radiation for high platelets.chemotherapy - radiation for high platelets. Rafi

18. BIKHABIKHA
Secondary PolycythemiaSecondary Polycythemia
Physiologically appropriatePhysiologically appropriate
• decreased Odecreased O22 saturationsaturation
• high altitude, chronic obstructivehigh altitude, chronic obstructive
pulmonary disease, heart shunt disorders,pulmonary disease, heart shunt disorders,
hemoglobinopathies, smokers,hemoglobinopathies, smokers,
emphasema, carboxyhemoglobinemphasema, carboxyhemoglobin
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19. BIKHABIKHA
Secondary PolycythemiaSecondary Polycythemia
Physiologically inappropriatePhysiologically inappropriate
• normal or increased Onormal or increased O22 saturationsaturation
• tumors producing erythropoietin (renal,tumors producing erythropoietin (renal,
liver, adrenal, uterine fibroid) renal causesliver, adrenal, uterine fibroid) renal causes
(cysts, hydronephrosis, transplantation,(cysts, hydronephrosis, transplantation,
nephrotic syndrome pheochromocytoma)nephrotic syndrome pheochromocytoma)
familialfamilial
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20. BIKHABIKHA
Myelodysplastic syndromesMyelodysplastic syndromes
Defect in “colony forming unit” whichDefect in “colony forming unit” which
results in abnormal production andresults in abnormal production and
maturation of all three marrow cell linesmaturation of all three marrow cell lines
Morphologically falls short of acuteMorphologically falls short of acute
nonlymphoblastic leukemianonlymphoblastic leukemia
5 subgroups5 subgroups
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21. BIKHABIKHA
Myelodysplastic syndromesMyelodysplastic syndromes
5 subgroups5 subgroups
• Refractory anemiaRefractory anemia
• Refractory anemia with “ringed”Refractory anemia with “ringed”
sideroblastssideroblasts
• Refractory anemia with excessive “blasts”Refractory anemia with excessive “blasts”
• Refractory anemia with excessive “blasts”Refractory anemia with excessive “blasts”
in transitionin transition
• Chronic Myelomonocytic LeukemiaChronic Myelomonocytic Leukemia
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22. BIKHABIKHA
Myelodysplastic syndromesMyelodysplastic syndromes
Clinical FeaturesClinical Features
• RA and RAEB are the most commonRA and RAEB are the most common
• Age 50 - 60Age 50 - 60
• Males > femalesMales > females
• insidious onset of fatigue and weakness,insidious onset of fatigue and weakness,
bleeding or infections related tobleeding or infections related to
pancytopeniapancytopenia
• CMMoL - 50% have mild splenomegalyCMMoL - 50% have mild splenomegaly
and/or cervical adenopathyand/or cervical adenopathy
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23. BIKHABIKHA
Myelodysplastic syndromesMyelodysplastic syndromes
Hematologic features Peripheral smearHematologic features Peripheral smear
• typically cytopenias of 2 or all 3 cell linestypically cytopenias of 2 or all 3 cell lines
except in RA and RA-S which commonlyexcept in RA and RA-S which commonly
present as isolated refractory anemiapresent as isolated refractory anemia
• RBC - macrocytosis - some aniso -RBC - macrocytosis - some aniso -
poikilocytosis with microangiopathicpoikilocytosis with microangiopathic
changes - few teardrops - poly and coarsechanges - few teardrops - poly and coarse
basophilic stippling - dimorphism in RA-S -basophilic stippling - dimorphism in RA-S -
Pappenheimer bodies in splenectomized -Pappenheimer bodies in splenectomized -
NRBC’s in over 50-70%NRBC’s in over 50-70%
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24. BIKHABIKHA
Myelodysplastic syndromesMyelodysplastic syndromes
Peripheral smearPeripheral smear
• Platelets - increased numbers of giantPlatelets - increased numbers of giant
and/or bizarre forms - variation in size -and/or bizarre forms - variation in size -
poor or clumped granulation -poor or clumped granulation -
thrombocytosis in 10-30% of RA-S and allthrombocytosis in 10-30% of RA-S and all
cases with chromosome abnormalitiescases with chromosome abnormalities
• Granulocytes - few type I and II blasts -Granulocytes - few type I and II blasts -
Pelgeroid cells - hypermature chromatinPelgeroid cells - hypermature chromatin
clumping and hypogranulation - may haveclumping and hypogranulation - may have
fine vacuolization and Dohle bodiesfine vacuolization and Dohle bodies
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25. BIKHABIKHA
Myelodysplastic syndromesMyelodysplastic syndromes
Peripheral smearPeripheral smear
• In CMMoL the monocytes may beIn CMMoL the monocytes may be
morphologically normal or atypical andmorphologically normal or atypical and
difficult to distinguish from myelocytes anddifficult to distinguish from myelocytes and
metas - abnormal monocytes may havemetas - abnormal monocytes may have
hypersegmented and/or horseshoe shapedhypersegmented and/or horseshoe shaped
nuclei - recognized as monocytes bynuclei - recognized as monocytes by
nuclear characteristics, abundantnuclear characteristics, abundant
cytoplasm and vacuolescytoplasm and vacuoles
• Hypersegmented neutrophils NOT seenHypersegmented neutrophils NOT seen
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26. BIKHABIKHA
Myelodysplastic syndromesMyelodysplastic syndromes
Bone MarrowBone Marrow
• At least normocellular and usuallyAt least normocellular and usually
hypercellularhypercellular
• Erythroid series - megaloblastoidErythroid series - megaloblastoid
maturation with early nuclear chromatinmaturation with early nuclear chromatin
clumping - nuclear budding andclumping - nuclear budding and
cytoplasmic vacuoles (PAS positive) - incytoplasmic vacuoles (PAS positive) - in
RA-S greater than 15% ringed sideroblastsRA-S greater than 15% ringed sideroblasts
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27. BIKHABIKHA
Myelodysplastic syndromesMyelodysplastic syndromes
Bone MarrowBone Marrow
• Myeloid - less than 20% myeloblasts (I/II)Myeloid - less than 20% myeloblasts (I/II)
except in RAEB-T (20-30%) - may haveexcept in RAEB-T (20-30%) - may have
Auer rods - minimal abnormalities in RAAuer rods - minimal abnormalities in RA
and RA-S - RAEB and CMMoL haveand RA-S - RAEB and CMMoL have
myeloid hyperplasia with bulge atmyeloid hyperplasia with bulge at
myelocyte stage - myelocytes appearmyelocyte stage - myelocytes appear
immature with poor cytoplasmicimmature with poor cytoplasmic
granulation - often show monocytoidgranulation - often show monocytoid
featuresfeatures
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28. BIKHABIKHA
Myelodysplastic syndromesMyelodysplastic syndromes
Bone MarrowBone Marrow
• Megakarycytes - often occur in clusters -Megakarycytes - often occur in clusters -
many are small and uninucleatedmany are small and uninucleated
(micromegakarycytes)(micromegakarycytes)
Other features - usually haveOther features - usually have
significantly increased amounts ofsignificantly increased amounts of
reticuloendothelial storage iron -reticuloendothelial storage iron -
mild/moderate reactive plasmocytosismild/moderate reactive plasmocytosis
without significant myelofibrosiswithout significant myelofibrosis
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29. BIKHABIKHA
Myelodysplastic syndromesMyelodysplastic syndromes
Laboratory FindingsLaboratory Findings
• LAP often lowLAP often low
• PNH-like alteration with positive sucrosePNH-like alteration with positive sucrose
and Ham’s hemolysis testand Ham’s hemolysis test
• Increased serum iron, decreased TIBC,Increased serum iron, decreased TIBC,
increased saturation, increased ferritinincreased saturation, increased ferritin
• May have increased HbF (30% in CMMoL)May have increased HbF (30% in CMMoL)
• Increased serum and/or urine lysozymeIncreased serum and/or urine lysozyme
levels in CMMoLlevels in CMMoL
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30. BIKHABIKHA
Myelodysplastic syndromesMyelodysplastic syndromes
Laboratory FindingsLaboratory Findings
• May have acquired thrombopathy evenMay have acquired thrombopathy even
with normal platelet numberswith normal platelet numbers
• Moderate increased LDH is commonModerate increased LDH is common
PrognosisPrognosis
• Survival relates to % blastsSurvival relates to % blasts
• RA/RA-S --- RAEB/CMMoL -- RAEB-TRA/RA-S --- RAEB/CMMoL -- RAEB-T
• Decreased with thrombocytopenia and/orDecreased with thrombocytopenia and/or
anemia and/or chromosomal abnormalitiesanemia and/or chromosomal abnormalities
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31. BIKHABIKHA
Myelodysplastic syndromesMyelodysplastic syndromes
Differential DiagnosisDifferential Diagnosis
• Aplastic anemia - lacks morphologicAplastic anemia - lacks morphologic
atypias characteristic of MDS - boneatypias characteristic of MDS - bone
marrow hypocellularmarrow hypocellular
• PNH - laboratory evidence of intravascularPNH - laboratory evidence of intravascular
hemolysis - decreased or absent marrowhemolysis - decreased or absent marrow
iron storesiron stores
• Megaloblastic anemia - hypersegmentationMegaloblastic anemia - hypersegmentation
of PMN - marrow megaloblastic -of PMN - marrow megaloblastic -
decreased Bdecreased B1212 or folateor folate
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32. BIKHABIKHA
Myelodysplastic syndromesMyelodysplastic syndromes
Differential DiagnosisDifferential Diagnosis
• CML - peripheral count usually muchCML - peripheral count usually much
higher with eosinophilia and basophilia -higher with eosinophilia and basophilia -
splenomegaly - presence of Ph’ - bonesplenomegaly - presence of Ph’ - bone
marrow in CMMoL may closely resemblemarrow in CMMoL may closely resemble
CMLCML
• Agnogenic myeloid metaplasia - teardropsAgnogenic myeloid metaplasia - teardrops
and poik - more prominent NRB’s andand poik - more prominent NRB’s and
splenomegaly - bone marrow myelofibrosissplenomegaly - bone marrow myelofibrosis
• ANLL - marrow contains over 30% blastsANLL - marrow contains over 30% blasts
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