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H40 Hematology
Myeloproliferative Neoplasms Toronto Notes 2019
• bonemarrowaspirateandbiopsywithcytogeneticanalysisrequiredfordefinitivediagnosis
■ bone marrow: dysplastic and often normocellular/hypercellular
■ cytogenetics: high risk (partial or total loss of chromosome 7) and complex (>3 abnormalities)
Treatment
• lowriskoftransformationtoacuteleukemia(IPSS-RVeryLoworLow)
■ erythropoietin stimulating agents weekly is first line in reducing transfusion requirements (EPO
level must be <500)
■ hypomethylating agents: decitabine and azacitidine
■ if 5q deletion based on cytogenetics: lenalidomide PO
■ supportive care: RBC and platelet transfusion (consider iron chelation if frequent RBC transfusions)
• highriskoftransformationtoacuteleukemia(IPSS-Rintermediate,highorveryhigh)
■ supportive care
■ consider stem cell transplantation according to patient factors (age, frailty, overall health)
■ epigenetic therapy: DNA methyltransferase inhibitors (e.g. 5-azacytidine), histone deacetylase
inhibitors
Prognosis
• RevisedInternationalPrognosticScoringSystem(IPSS-R)uses5factorstoestimatemeansurvival:
■ cytology, % bone marrow blasts, hemoglobin, platelets, and absolute neutrophil count
■ based on the calculated score, a patient’s MDS prognostic risk is “Very Low”, “Low”, “Intermediate”,
“High”, or “Very High” with a mean survival of 8.7, 5.3, 3.0, 1.6, and 0.8 yr, respectively
Myeloproliferative Neoplasms
Definition
• clonalmyeloidstemcellabnormalitiesleadingtooverproductionofoneormorecelllines(leadingto abnormalities in erythrocytes, platelets, and other cells of myeloid lineage)
Use of Epoetin and Darbepoetin in Patients with Cancer
Blood 2008;111:25-41
Clinical practice guideline update by American Societies of Hematology and Clinical Oncology (2007).
Initial Recommendations
1. Initiateanerythropoiesis-stimulatingagent(ESA) when hemoglobin (Hb) is 100 g/L
(10 g/dL) in patients with palliative chemotherapy-associated anemia to decrease the need for transfusions.
2. DiscontinueESAswhenpatientnotresponding to treatment beyond 6-8 wk.
3. Monitorironstoresandsupplementironintake for ESA-treated patients when necessary.
4. UseESAscautiouslywithchemotherapyor in patients with an elevated risk for thrombo- embolic complications.
5. It is not recommended that ESA be used
for therapy in patients with cancer who are not receiving chemotherapy, as it increases thromboembolic risks and lowers survival rate. Patients with low-risk myelodysplasia are an exception.
Myelodysplastic Syndromes
ineffective maturation
Myeloproliferative Neoplasms
overproduction of mature cells
Epidemiology
• mainly middle-aged and older patients (peak 60-80 yr)
Prognosis
• maydevelopmarrowfibrosiswithtime • alldisordersmayprogresstoAML
Table 31. Chronic Myeloproliferative Disorders
Hct
WBC
Plt
Marrow Fibrosis Splenomegaly Hepatomegaly Genetic Association
CML
i/N
hh
h/i
±
+++
+
bcr-abl mut. (95+%)
PV
hh
h
h
±
+
+
JAK2 mut. (96%)
IMF
i
h/i
h/i
+++
+++
++
JAK2 mut. (~50%) CALR mut (~30%)
ET
N
N
hhh
±
+
–
JAK2 mut. (~50%) CALR mut (~30%)
Basophilia is uncommon in other medical conditions
CML = chronic myeloid leukemia; ET = essential thrombocythemia; IMF = idiopathic myelofibrosis; PV = polycythemia vera CALR = Calreticulin
Chronic Myeloid Leukemia
Definition
• myeloproliferativedisordercharacterizedbyincreasedproliferationofthegranulocyticcelllinewithout the loss of their capacity to differentiate
Epidemiology
• occursinanyagegroup(mostlymiddleagetoelderly)withamedianageof65yr
Pathophysiology
• Philadelphiachromosome(Ph)
■ translocation between chromosomes 9 and 22
■ the c-Abl proto-oncogene is translocated from chromosome 9 to “breakpoint cluster region” (BCR)
of chromosome 22 to produce BCR-Abl fusion gene, and an active tyrosine kinase
Clinical Features
• 3clinicalphases
■ chronic phase: 85% diagnosed here
◆ few blasts (<10%) in peripheral film
◆ ± slightly elevated eosinophils and basophils ◆ no significant symptoms