Hematology | Chronic 438 teamwork Leukemia
Color index: Red: Important Gray: notes Blue: extra Editing file | Chronic leukaemia ➔ Heterogeneous group of hematopoietic neoplasms. ➔ It is uncontrolled proliferation and decreased apoptotic activity with variable degrees of differentiation. ➔ Composed of relatively mature cells. ➔ Indolent. (If untreated, the course is in months or years). ➔ Occurs mainly in adults ➔ Types : MPN , MDS , MPN/MDS. Main types of leukemia
Acute Chronic
Lymphoid ALL LPN(CLL)
MPN/MD AML Myeloid S (CML)
Mixed Acute Biphenotypic
Non Acute | Myeloid proliferative neoplasms (MPN)
➔ Malignant proliferation of myeloid cells (maturing cells) which are mainly granulocytes, in blood and bone marrow. ➔ Slow onset and long course. ➔ Occurs mainly in adults.
|Features:
Organomegaly ➔ Pathoma Hypercellular Bone Chronic myeloid leukemia can transform to (mainly AML (⅔ of cases) or ALL (⅓ of cases) since marrow splenomegaly) mutation is in a pluripotent stem cell.
01 02 03 04 05
Cytosis High uric acid Progression to acute (increasing WBCs) leukaemia (Mainly AML) | Chronic myeloid leukemia (CML) Acute ➔ Stem cell MPN. ➔ Predominant proliferation of granulocytic cells. ➔ Consistently associated with the BCR-ABL1 fusion gene, located in the Philadelphia (Ph)
chromosome which results from t(9;22). Chronic ➔ If the mutation happened at (myeloblast) it is AL, otherwise it will be CL especially neutrophils.
|Pathogenesis:
04 03 02 Uncontrolled 02 proliferation 01 Activation of signal Increase Tyrosine transduction pathways BCR-ABL1 Kinase t(9;22) happened Neutrophil Alkaline Phosphatase (NAP)score: | Clinical presentation of CML Cytochemical stain that estimate the amount of alkaline phosphatase enzyme in neutrophils .
01 02 Asymptomatic Abdominal discomfort presentation(20-40%) due to splenomegaly 03 04 Routine CBC : marked leukocytosis (increase in Splenomegaly (Massive ) | Treatment of CML WBCs )
05 If no response Targeted therapy Common symptoms : Stem cell Tyrosine kinase Fatigue ,weight loss or transplantation inhibitors night sweating Imatinib , Gleevec
Excellent response (5 years overall survival ≥ 90%) | CML phases
Chronic phase: 01 ● Leukocytosis (12-1000×10⁹/L) ● Mainly neutrophils & myelocytes ● Blasts ≤10% ,Basophils≤ 20% ● Stable course (years)
Accelerated phase: 02 ● Increasing counts ● 10-19% blasts (basophils ≥20%) ● Unstable course (months)
Blastic phase: 03 ● ≥20% blasts = Acute Leukemia ● 80% AML & 20% ALL ● (coarse: Weeks) | Myelodysplastic Syndromes (MDS) Group of myeloid neoplasms characterized by: death happens within the BM ie; ➔ Peripheral cytopenia ( Low HB ± Low WBC & Low PLT ). premature death of RBC, ➔ 01 thrombocytes, granulocytes And Dysplasia (abnormal morphology). monocytes. ➔ Ineffective hematopoiesis (hypercellular marrow). just like CML Blood: Pancytopenia ➔ Progression to AML (preleukaemic disease). with dysplasia. ➔ Enhanced apoptosis.
Subtypes Treatment according to: Supportive ± Blast count, degree of BM: Hypercellular chemotherapy. with dysplasia. dysplasia and genetics.
01 02 03
Genetic Abnormalities
Mainly in -5 and -7 ↑ Proliferation + ↑ Apoptosis = Ineffective Hematopoiesis | Differential Diagnosis
CML Leukemoid Cytosis Cytopenia Age Adult Any age
WBC count High High but < 100,000
Mainly myelocytes & Differential Mainly bands segmented
Morphology Hypogranular Toxic MPN MPN/MDS MDS
Splenomegaly + ±
NAP score Low High
BCR/ABL +ve -ve 1- Chronic myelomonocytic leukemia: (monocytosis ,BCR-ABL –ve) . N.B chronic myeloid leukemia was mainly granulocytes “neutrophils” 2-Leukemoid reaction: Leukocytosis due to physiological response Onset Chronic Acute to stress or infection | Chronic Myelomonocytic Leukemia (CMML) Clonal hematopoietic malignancy characterized by:
● Proliferation of monocytes. ● Proliferation of neutrophils. ● Negative for Philadelphia Chromosome. Course ● Blast must be less than 20%. Treatment Aggressive course (survival rate around Chemotherapy ± Stem 2.5 years). MDS Features Cell Transplant (SCT) Dysplasia & enhanced apoptosis.
MDS/MPN The reason why it’s called by these two diseases:
MPN Features Marked proliferation. Key answers: | Quiz 1-A 2-B 3-B 4- D
1-22 years old male come to ER with splenomegaly; 3- The most important characteristic for CMML examination show increasing in WBCs and high Uric acid. Microscopic results show hypercellular bone A. Basophil proliferation marrow. What’s your diagnosis? B. Monocyte proliferation C. B lymphocyte proliferation A. MPN D. Eosinophil proliferation B. CML C. MDS 4- The most important characteristic for MDS (from D. CMML dr.notes)
2- CML associated with A. HyperCellular bone marrow B. HypoCellular bone marrow A. BCR-ABL2 fusion gene in Ph chromosome C. Peripheral blood cyropenia which result from t(9;22) D. A & C B. BCR-ABL1 fusion gene in Ph chromosome which result from t(9;22) C. BCR-ABL1 fusion gene in Ph chromosome which result from t(8;14) D. BCR-ABL1 fusion gene in Ph chromosome which result from t(9;21) THANKS | TEAM MEMBERS
● Amirah Alzahrani ● Abdullah Alghamdi ● Deema Almaziad ● Hashem Bassam | TEAM LEADERS ● Jude Alotaibi ● Mashal Abaalkhail ● Njoud Almutairi ● Moath Aljehani ● | Abdulaziz Alghamdi ● Nouf Albraikan Mohammed Alasmari ● Mohammed H.Alshehri ● Noura Almazrou ● Mohammed Alkhamees | Elaf Almusahel ● Razan Alzohaifi ● Mohammed Alshalan ● Rema Almutawa ● Naif Alsolais ● Renad Alhaqbani ● Raed Alojayri ● Renad Almutawa ● Saud Bin Queid = Done by ● Taif Alotaibi ﺿﻠﻌﻲ Editor = ● Wejdan Alnufaie = Note taker
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