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MYELOPROLIFERATIVE DISORDERS MPD

MYELOPROLIFERATIVE DISORDERS

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MYELOPROLIFERATIVE DISORDERS. MPD. Definition. Myeloproliferative neoplasms (MPN) constitute one of five categories of myeloid malignancies, according to the World Health Organization (WHO) classification system for hematopoietic tumors - PowerPoint PPT Presentation

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Page 1: MYELOPROLIFERATIVE DISORDERS

MYELOPROLIFERATIVE DISORDERS

MPD

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Myeloproliferative neoplasms (MPN) constitute one of five categories of myeloid malignancies, according to the World Health Organization (WHO) classification system for hematopoietic tumors

*Chronic myelogenous leukemia, BCR-ABL1 positive (CML)

*Polycythemia vera (PV)*Primary myelofibrosis (PMF)*Essential thrombocythemia (ET)

Definition

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* Acute myeloid leukemia (AML) and related precursor neoplasms

* Myeloproliferative neoplasms (MPN) - Classic MPN Chronic myelogenous leukemia, BCR-ABL positive (CML)Polycythemia vera (PV)Primary myelofibrosis (PMF)Essential thrombocythemia (ET) - Nonclassic MPN Chronic neutrophilic leukemia (CNL)Chronic eosinophilic leukemia, not otherwise specified

(CEL-NOS)MastocytosisMyeloproliferative neoplasm, unclassifiable (MPN-U)

WHO classification of Myeloid neoplasms

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*Myelodysplastic syndromes (MDS) Refractory cytopenia with unilineage dysplasia (RCUD)Refractory anemia (ring sideroblasts <15% of erythroid

precursors)Refractory neutropeniaRefractory thrombocytopeniaRefractory anemia with ring sideroblasts (RARS; dysplasia

limited to erythroid lineage and ring sideroblasts 15% of bone marrow erythroid precursors)

Refractory cytopenia with multi-lineage dysplasia (RCMD; ring sideroblast count

does not matter)Refractory anemia with excess blasts (RAEB)RAEB-1 (2–4% circulating or 5–9% marrow blasts)RAEB-2 (5–19% circulating or 10–19% marrow blasts or

Auer rods present)MDS associated with isolated del(5q)MDS, unclassifiable

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*MDS/MPNChronic myelomonocytic leukemia (CMML)Atypical chronic myeloid leukemia, BCR-ABL1

negativeJuvenile myelomonocytic leukemia (JMML)MDS/MPN, unclassifiableProvisional entity: Refractory anemia with ring

sideroblasts associated withmarked thrombocytosis (RARS-T)*Myeloid and lymphoid neoplasms with eosinophilia

and abnormalities of PDGFRA,c PDGFRB,c or FGFR1cMyeloid and lymphoid neoplasms with PDGFRA

rearrangementMyeloid neoplasms with PDGFRB rearrangementMyeloid and lymphoid neoplasms with FGFR1

abnormalities

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Definition: Clonal neoplastic myeloproliferative disorder involving erythroid series (erythrocytosis)

Also increased granulocytes & Platelets

Polycythemia Rubra Vera (PRV)

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*The incidence of polycythemia vera in the United States is approximately 5-17 cases per 1 million population per year

*The incidence of polycythemia vera is 0.2-28 per 1 mlillion per year; Japan has the lowest incidence.

*More in Jews *Female>male 1.4:1*Age 40-60 years (uncommon below 40)

Epidemiology

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*The exact cause still unknown ?*Genetic factors are playing a pathogenetic

roleJAK2 gene mutationTransformation of single HSC into a cell with

selective growth advantage that becomes the predominant myeloid progenitor.

It can grow independent of erythropoietin

Etiology

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In many patients, abnormal blood counts are noted on a blood test performed for other reasons. HeadacheAnorexia, weight loss, weakness Abdominal discomfort and early satiety secondary to splenomegaly Easy bruising, bleeding, and/or symptoms of thrombosisSwollen, painful joint(s) secondary to gouty arthritis secondary to

hyperuricemiaThrombosis (arterial>venous) - Priapism, Budd-Chiari syndrome, stroke,

TIA or stupor, DVT & Pulm embBleeding – less common – Cutaneous, GIT (PU) Left upper quadrant and left shoulder pain as a consequence of splenic

infarction and perisplenitisPruritis especially after hot bath Vasomotor symptoms – tinnitus, dizziness, digital pain (erythromelalgia),

sweating

Clinical Manifestations

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Plethora secondary to polycythemia (dusky color)Petechiae and/or ecchymosisPalpable spleen and/or liver

Physical Signs

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CBC counts and differential counts with microscopic examination of the peripheral smear

Hb ↑, PCV↑, neutrophilia, eosinophilia, basophilia, thrombocytosis

Leukocyte alkaline phosphatase (LAP) score normal or increased (to differentiate chronic myelogenous leukemia from other types)

Polymerase chain reaction (PCR) or fluorescent in-situ hybridization (FISH) run on peripheral blood can detect

JAK2 gene; bcr-abl gene rearrangement (-ve unlike CML). This helps differentiate chronic myelogenous leukemia from other myeloproliferative diseases.

Red blood cell mass study (true vs spurious polycythemia)

Lab Invx

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Serum uric acid level increasedSerum lysozyme increased Serum Histamine increasedSerum B12 increasedSerum EPO – low

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BM aspirate & biopsy with cytogenetic study – hypercellular , megakaryocytes increased and arranged in clumps or sheets

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1- Familial & congenital polycythemia2- Secondary Polycythemia Geographical location, hypernephroma, PCKD,

uterine leiomyoma, atrial myxoma, liver hamartoma &liver focal hyperplasia, cerebellar hemangiomas

Pulmonary & cardiac disease, obst sleep apnea, smoking, high affinity hemoglobins,

Post-renal transplant polycythemia3- Relative polycythemia (spurious) 4- Other MPD

DD

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Phlebotomy – periodic control RBC mass & blood viscosity

Myelosuppressive agents 1- Hydroxyurea – effective, short acting, safe,

no risk of increased malignancy2- Busulfan – Severe myelosupp, risk of leuk

& malig (no more used)3- Radioactive Phosphorus 32 – elderly pt

Treatment

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4- Interferon α(IFN) – ameliorate disease & pruritis . Drug of choice in pregnant.

Symptomatic treatment –Aspirin – low dose judicious use control digital

pain & ThAllopurinolPhotochemotherapy PUVA – pruritusHydration – prevent Th

Ttt-cont

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1- Thrombosis2- Bleeding (esp UGI) 3- PU4- Gout5- Iron deficiency6- Myelofibrosis (Spent phase)7- Acute leukemia (AML)

Complications

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Survival after phlebotomy alone 13.9 y

Phosphorus treated pt 11.8 y

Thrombosis most common cause of death

Next is acute leukemia

Prognosis

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MPD

MYELOPROLIFERATIVE DISORDERS