Hematologic Disease Leukemias Flashcards
What is Chronic Myeloid Leukemia?
- Unregulated Myeloid proliferation of excess mature neutrophil [cell grow and dont die]
- Philadelphia chromosome = Bcr/Abl
What is the Phiadelphia Chromosome in Chronic Myeloid Leukemia?
- Break in chromosome 9 & 22 = Bcr/Abl
What are some of the risk factors in Chronic Myeloid Leukemia?
- No known risks
What is the presentation of Chronic Myeloid Leukemia?
- Find out by accident
- Fatigue, Sweating, Bone Pain, Weight Loss
- Full Faster
- Leukocytosis
What is Leukocytosis?
- MEDICAL EMERGENCY!!
- 1,000,000 cells/mm3
- Risk of Leukostasis = Thick Blood
What is the Diagnosis for Chronic Myeloid Leukemia?
- Bone Marrow Biopsy
- FISH or PCR
What is the difference between FISH and PCR in Chronic Myeloid Leukemia ?
- PCR = selected segment [more sensitive]
- FISH = detects a specific DNA sequence
What are the phases of Chronic Myeloid Leukemia?
- Chronic Phase: <10% blasts [immature cells]
- Accelerated Phase: 10-19% blasts
- Blast Crisis: >20% blasts; terminal stage
What is the treatment for Chronic Myeloid Leukemia?
- NO TREATMENT; FATAL IN 5 YEARS
- Goal: lower leukemic clone with Tyrosine Kinase Inhibitors
What is important to know about the Treatment Response Criteria for Chronic Myeloid Leukemia?
- Want the molecular response to be DEEP: BCR-ABL < 0.01%
What is the main TKI that is used in Chronic Myeloid Leukemia and what trial showed it effetiveness?
- Imatinib
- IRIS trial [everyone was either on or swtiched to it]
What is important to know about the Adverse effects from Imatinib within Chronic Myeloid Leukemia?
- Neutropenia, Thrombocytopenia, Anemia [all subside within 4 years]
What are the 2nd generation TKIs that are used in Chronic Myeloid Leukemia?
- Dasatinib, Nilotinib, Bosutinib
- Approved as 1st line
- Really only used when Imatinib cant be used
What is important to know about Imatinib?
- Daily
- 3A4
- NAUSEA
What is important to know about Dasatinib?
- Daily [avoid acid reducers]
- 3A4
- Fluid retention
What is important about Nilotinib?
- BID [Empty Stomach]
- 3A4
- QTc Prolongation, Metaboic Syndrome
What is important about Bosutinib?
- Daily
- 3A4
- DIARRHEA
What is important about Ponatinib?
- Daily
- 3A4
- ISCHEMIC REACTIONS, HYPERTENSION
- Works with T315I resistance
What is the most common resistance that is found in Chronic Myeloid Leukemia and how is it formed?
- T315I
- Overexpression; Mutated kinase domains; gene alterations`
What is the treatment summary of Chronic Myeloid Leukemia?
- Start: Imatinib
- Then: Dasatinib, Niloinib, Bosutinib
- T315I: Ponatinib, Asciminib [NEW]
- NO mutation: Stem Cell Transplant
Give a brief summary for Chronic Myeloid Leukemia?
- Caused by BCR-ABL [Philadelphia Chromosome; 9 & 22]
- Three Phases: Chronic, Accelerated, Blast Crisis
- TKIs!!!! based on patient and resistanceq
What is Chronic Lymphoid Leukemia?
- Monoclonal B lymphocytes transform, causing expansion [NO apoptosis], then Lymphocyte accumulation
- Possible Richter’s transformation
What are some of the risk factors for Chronic Lymphoid Leukemia?
- Family Hx: 1st Degree
- Male
- White
- Old
:(
What is the presentation for Chronic Lymphoid Leukemia?
- Accidentally finding it
- Maybe recurrent sinus infection
What are we looking for in cytogenetics within Chronic Lymphoid Leukemia?
- Del(11q) with organ failure [lymphadenopathy]
- Del(17p) is bad = TP53 lost [no checkpoint in apoptosis]
What is the Diagnosis of Chronic Lymphoid Leukemia?
- Monoclonal B lymphocytes > 5x10^9
- Look for CD19, CD20, CD5, CD23, CD10
What is the treatment overview for Chronic Lymphoid Leukemia?
- Treatment reserved for Stage III or IV; Organ Failure; clinical symptoms
- DONT treatment a Number?
What are some of the treatment options for Chronic Lymphoid Leukemia?
- Acalabrutinib +/- Obinutuzumab
- Venetoclax + Obinutuzumab
- Zanubrutinib
What are the BTK inhibitors that are use in Chronic Lymphoid Leukemia?
- Ibrutinib, Zanubrutinib, Acalabrutinib
- Stops phophorylation in B-Cells
What did the trials for the BTK inhibitors show for Chronic Lympoid Leukemia?
- That Ibrutinib had toxicities
- ALPINE showed Zanubrutinib was better
What is Venetoclax within Chronic Lymphoid Leukemia?>
- Inhibits BCL-2 resulting in release of BIM and PUMA –> releases proapoptotic proteins
What is important to know about Ventoclax in Chronic Lymphoid Leukemia?
- PGP interactions: inhibits or induces
- 3A4 interactions
Give a brief summary of Chronic Lympoid Leukemia?-
- Early Stage ONLY observe
- Treatment is based on age, comorbidites, cytogenetics [Del(17p) is bad]
- Lymphocytosis = BTK inihibitors and Idelalisb
What is AML?
- Arise from single leukemia cells that expand & acquire additional mutation causing proliferations resulting in monoclonal population of leukemic cells [single clone that expands]
What are some of the risk factors for AML?
- Unknown
- from other diseases?
- Genetics or Environmental?
What is the presentation of AML?-
- Pancytopenia: Anemia [fatigue, pallor, palpitations], Neutropenia [infections], Thrombocytopenia [bleeding]
- Bone Pain
What is the risk stratification/cytogenetics within AML?
- Favorable [NPM1 & CEBPA]
- Intermediate [NPM1+FLT3-ITD]
- Unfavorable [FLT3-ITD (bad)]
What is important to know about the FLT3 Mutation in AML?
- Newly Diagnosed AML
- Worse overall prognosis [more aggressive, lower remission]
- TKIs: Midostaurin, Gilteritinib, Quiartinib
What is the treatment goal for AML?
- Induction of remission to cause consolidation [preventing relapse]
- Consolidation: Favorable - Chemo; Unfavorable - transplant
What is the treatment for AML?
- Intensive: Cytarabine + Anthracycline 7+3
- Low to Moderate: Venetoclax + Hypo-methylating agent
- Low-Intensity: Hypo-methylating agents; low does chemo
- Supportive Care: Blood products
What is Instensive Chemotherapy 7+3 in AML?
- INDUCTION
- Cytarabine x7d
- Idarubicin or Daunorubicin x3d
What is used for Consolidation in AML?
- Cytarabine [HiDAC] - Dose depends on age
- Cerebellar side effects & Conjunctivitis
What do you use in FLT3+ Positive Disease in AML?
- Midostaurin [QTc Prolongation & Nausea]
- Gilterinib
What is a brief summary of AML?
- BONE MARROW BIOPSY
- Treatment is induction and consolidation [induce remission then eradicate disease]
What is ALL?
- Arise from single leukemia cells that expand & acquire additional mutation causing proliferations resulting in monoclonal population of leukemic cells [single clone that expands]
What are the risk factors for ALL?
- Genetic, Radiation, EBV/HIV [because of lymphoid]
What is the presentation of ALL?
- Pancytopenia: Anemia [fatigue, pallor, palpitations], Neutropenia [infections], Thrombocytopenia [bleeding]
- Bone Pain
- Can go into brain
What is the diagonsis of ALL?
- BONE MARROW biopsy
What is one thing we look for in ALL?
- Philadelphia Chromosome [BCR-ABL] - both in myeloid & lymphoid
- TKI added to Chemo
What is the adult treatment overview for ALL?
- Induction to cause remission then consolidate with eradicating the disease follwoed by maintenace to prevent relapse
- CAN HIDE IN BRAIN AND TESTES [intrathecal chemo]
What is main treatment for ALL?
- HyperCVAD
What is in HyperCVAD?
- Hyper-Fractionated Cyclophosphamide
- Vincristine
- Doxorubicin
- Dexamethasone
- THEN: Methotrexate & Cytarabine
