MYELOPROLIFERATIVE DISORDERS

MPD

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

* 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

*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

*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

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

Also increased granulocytes & Platelets

Polycythemia Rubra Vera (PRV)

*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

*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

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

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

Physical Signs

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

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

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

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

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

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

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

Complications

Survival after phlebotomy alone 13.9 y

Phosphorus treated pt 11.8 y

Thrombosis most common cause of death

Next is acute leukemia

Prognosis

MPD

MYELOPROLIFERATIVE DISORDERS