MYELOPROLIFERATIVE DISORDERS
description
Transcript of MYELOPROLIFERATIVE DISORDERS
![Page 1: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/1.jpg)
MYELOPROLIFERATIVE DISORDERS
MPD
![Page 2: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/2.jpg)
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
![Page 3: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/3.jpg)
* 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
![Page 4: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/4.jpg)
*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
![Page 5: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/5.jpg)
*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
![Page 6: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/6.jpg)
Definition: Clonal neoplastic myeloproliferative disorder involving erythroid series (erythrocytosis)
Also increased granulocytes & Platelets
Polycythemia Rubra Vera (PRV)
![Page 7: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/7.jpg)
*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
![Page 8: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/8.jpg)
*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
![Page 9: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/9.jpg)
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
![Page 10: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/10.jpg)
Plethora secondary to polycythemia (dusky color)Petechiae and/or ecchymosisPalpable spleen and/or liver
Physical Signs
![Page 11: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/11.jpg)
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
![Page 12: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/12.jpg)
Serum uric acid level increasedSerum lysozyme increased Serum Histamine increasedSerum B12 increasedSerum EPO – low
![Page 13: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/13.jpg)
BM aspirate & biopsy with cytogenetic study – hypercellular , megakaryocytes increased and arranged in clumps or sheets
![Page 14: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/14.jpg)
![Page 15: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/15.jpg)
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
![Page 16: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/16.jpg)
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
![Page 17: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/17.jpg)
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
![Page 18: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/18.jpg)
1- Thrombosis2- Bleeding (esp UGI) 3- PU4- Gout5- Iron deficiency6- Myelofibrosis (Spent phase)7- Acute leukemia (AML)
Complications
![Page 19: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/19.jpg)
Survival after phlebotomy alone 13.9 y
Phosphorus treated pt 11.8 y
Thrombosis most common cause of death
Next is acute leukemia
Prognosis
![Page 20: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/20.jpg)
![Page 21: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/21.jpg)
![Page 22: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/22.jpg)
![Page 23: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/23.jpg)
![Page 24: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/24.jpg)
![Page 25: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/25.jpg)
![Page 26: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/26.jpg)
![Page 27: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/27.jpg)
![Page 28: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/28.jpg)
![Page 29: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/29.jpg)
![Page 30: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/30.jpg)
![Page 31: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/31.jpg)
![Page 32: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/32.jpg)
![Page 33: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/33.jpg)
![Page 34: MYELOPROLIFERATIVE DISORDERS](https://reader033.fdocuments.us/reader033/viewer/2022050909/56815265550346895dc09a00/html5/thumbnails/34.jpg)
MPD
MYELOPROLIFERATIVE DISORDERS