Chronic Lymphocytic Leukemia

- highest incidence of all leukemias - high prevalence/slow progression TYPES OF CLL: B-cell and T-cell

- Family Hx - Age - Sex - Exposed to agent orange - Monoclonal B-cell lymphocytosis

- established by flow cytometry of blood ( monoclonal B lymphocytes) - Clonality of B cell to be confirmed by flow cytometry - Adequate immunophenotyping to establish dx

- fatigue, fever, swollen LN, night sweats, unexplained weight loss, pain or sense of fullness under ribs

- can develop into lymphoma - increased risk of skin, lung or colon cancer - Anemia - Thrombocytopenia - Frequent Infections

- Relief of symptoms - Correct cytopenias - Response

fever > 100.4F, drenching night sweats, weight loss (>10% in 6 mos)

H&P, Peripheral blood smear, performance status, Assess B symptoms, Perform flow cytometry

CLL Cytogenetics Analysis

Deletion 11q & Del 17P/TP53 11q MAY respond well to fludarabine + alkylator, 17P has poor response to chemoimmunotherapy

watchful waiting, radiation therapy, chemotherapy, surgery, targeted therapy, transplant (if refractory)

CLL 1st line treatment

- venetoclax + obinutuzumab - venetoclax + acalabrutinib +/- obinutuzumab - Zanubrutinib - Acalabrutinib +/- Obinutuzumab

* Acalabrutinib = avoid CYP3A4 strong inh or inducers, antacids and H2 blockers and grapefruit *Zanubrutinib = Avoid CYP3A4 inhib or inducer and avoid GF * Obinutuzumab = NONEEE * Venetoclax = CYP3A4 inducers and inhibitors and PgP inhibitors

Philadelphia Chromosome

- leads to production of BCR-ABL protein - constitutively active tyrosine kinase

CML clinical presentation

- leukocytosis, thrombocytosis, anemia, basophilia + eosinophilia, splenomegaly, no increases infection risk

Factors considered during risk calculation: patient age, spleen size, plt count, % blast in peripheral blood. Risk Category: LOW: 1.2

* Low risk: imatinib, dasatinib, nilotinib, bosutinib, asciminib * Intermediate OR HIGH risk: Bosutanib, Asciminib, Nilotinib, Dasatinib * T315I mutation: Ponatinib (preferred), Asciminib

MOA: BCR-ABL tyrosine kinase inhibitor, especially targets CML cell with T315I mutation

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CHRONIC LEUKEMIA

CHRONIC LUNG CANCER

Question	Answer
Chronic Lymphocytic Leukemia	- highest incidence of all leukemias - high prevalence/slow progression TYPES OF CLL: B-cell and T-cell
RF of CLL	- Family Hx - Age - Sex - Exposed to agent orange - Monoclonal B-cell lymphocytosis
Dx of CLL	- established by flow cytometry of blood ( monoclonal B lymphocytes) - Clonality of B cell to be confirmed by flow cytometry - Adequate immunophenotyping to establish dx
Symptoms of CLL	- fatigue, fever, swollen LN, night sweats, unexplained weight loss, pain or sense of fullness under ribs
Complications of CLL	- can develop into lymphoma - increased risk of skin, lung or colon cancer - Anemia - Thrombocytopenia - Frequent Infections
Goals in CLL	- Relief of symptoms - Correct cytopenias - Response
B symptoms	fever > 100.4F, drenching night sweats, weight loss (>10% in 6 mos)
Work up for CLL	H&P, Peripheral blood smear, performance status, Assess B symptoms, Perform flow cytometry
CLL Cytogenetics Analysis	Deletion 11q & Del 17P/TP53 11q MAY respond well to fludarabine + alkylator, 17P has poor response to chemoimmunotherapy
CLL treatments	watchful waiting, radiation therapy, chemotherapy, surgery, targeted therapy, transplant (if refractory)
CLL 1st line treatment	- venetoclax + obinutuzumab - venetoclax + acalabrutinib +/- obinutuzumab - Zanubrutinib - Acalabrutinib +/- Obinutuzumab
ADRs of CLL regimens	* Acalabrutinib = avoid CYP3A4 strong inh or inducers, antacids and H2 blockers and grapefruit Zanubrutinib = Avoid CYP3A4 inhib or inducer and avoid GF Obinutuzumab = NONEEE * Venetoclax = CYP3A4 inducers and inhibitors and PgP inhibitors
Philadelphia Chromosome	- leads to production of BCR-ABL protein - constitutively active tyrosine kinase
CML clinical presentation	- leukocytosis, thrombocytosis, anemia, basophilia + eosinophilia, splenomegaly, no increases infection risk
Sokal Risk Score	Factors considered during risk calculation: patient age, spleen size, plt count, % blast in peripheral blood. Risk Category: LOW: <0.8 Intermediate: 0.8 to 1.2 HIGH: >1.2
CML 1st line therapy	* Low risk: imatinib, dasatinib, nilotinib, bosutinib, asciminib * Intermediate OR HIGH risk: Bosutanib, Asciminib, Nilotinib, Dasatinib * T315I mutation: Ponatinib (preferred), Asciminib
Asciminib (Scemblix)	MOA: BCR-ABL tyrosine kinase inhibitor, especially targets CML cell with T315I mutation

Created by: texantaco

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