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How are Leukemias classified?
- Disease acuity (acute vs chronic)
- cell of origin (lymphoid vs myeloid)
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What types of Leukemia mainly affect older adults?
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What type of leukemia is associated with Auer rods?
AML
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What type of leukemia is associated with hypertrophy of the gums?
AML (M4 and M5 especially)
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What type of leukemia is associated with infiltration of the gingivae, skin, soft tissues and meninges?
AML (M4 and M5 especially)
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What is the most important aspect of treatment to ensure best results?
start chemotherapy within 72h
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What is the induction tx for AML in pts < 60yo?
- 7 + 3:
- Cytarabine + Anthracycline (Daunorubicin or Idarubicin)
- HiDAC:
- High-dose Cytarabine + Anthracycline (2-3g)
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What is the induction tx for AML pts 60yo and older?
- 7 + 3:
- Cytarabine + Anthracycline (Daunorubicin, Idarubicin, or Mitoxantrone)
- Low-intensity:
- SC Cytarabine
- 5-Azacytidine
- Decitabine
- Intermediate-intensity:
- Clofarabine
- Best Supportive Care:
- Hydroxyurea
- Transfusions
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What are the SE of cytarabine?
- Myelosuppression
- N/V
- Mucositis
- Cerebellar toxicity (slurred speech, nystagmus, dysmetria) (HIGH DOSE)
- Conjunctivitis/keratitis (HIGH DOSE)
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What are the SE of Anthracyclines?
- Myelosuppression
- N/V
- Mucositis
- Cardiac toxicity
- Urine discoloration
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What is the appropriate supportive care for AML?
- Transfusion for Hb < 8g/dL or any sx of anemia
- Transfusion for PLT < 10,000/mm3 or any signs of bleeding
- CSF for leukopenia after induction and consolidation tx (esp in > 55yo)
- Rasburicase or Allopurinol with hydration for Tumor Lysis Syndrome
- Fluconazole, SMZ/TMP, or Acyclovir prophylaxis if 0 WBC
- Saline or steroid eye drops for conjunctivitis/keratitis
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What is the tx for CNS AML?
- Methotrexate +/- Cytarabine intrathecally +/- RT
- start concurrently with induction tx if CT/MRI or LP is positive at diagnosis
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What type of leukemia can affect any age?
APL
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What is the most diagnostic feature of APL?
presence of PML-RAR fusion protein
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What is the key sx of APL?
severe coagulopathy
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What is the induction tx for APL?
- ATRA (all-trans-retinoic acid; Tretinoin) +/- Cytarabine
- ATRA + As2O3
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What are the SE of ATRA (all-trans-retinoic acid; Tretinoin)?
- HA
- Skin and membrane rxns
- Bone pain
- Nausea
- APL differentiation syndrome (fever, rapidly rising WBC, SOB, hypoxemia, fluid retention, wt gain, pulmonary infiltrates, and pleural/pericardial effusions)
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What are the SE of As2O3?
- QT prolongation
- APL differentiation syndrome (fever, rapidly rising WBC, SOB, hypoxemia, fluid retention, wt gain, pulmonary infiltrates, and pleural/pericardial effusions)
- Peripheral neuropathy
- Fatigue
- Wt gain
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What is the supportive care for APL?
- Transfusion for PLT < 50,000/mm3Dexamethasone prophylaxis or treatment for APL differentiation syndrome
- NO CSF!!!!!!!
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What type of leukemia affects mainly children?
ALL
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What type of leukemia is associated with the Philadelphia Chromosome?
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Why is adult ALL not treated as intensively/aggressively as it is in kids?
adults are not able to tolerate tx as well
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What type of leukemia is associated with enlarged testicles?
ALL
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What is the induction tx for ALL?
- Corticosteroid (Dexamethasone, Prednisone, or Prednisolone)
- Vincristine
- Anthracycline
- Aspariginase
- Cytarabine
- Cyclophosphamide
- CNS prophylaxis always req'd (intrathecal Methotrexate and/or Cytarabine, or triple tx with hydrocortisone; or High-dose systemic Methotrexate or Cytarabine)
- Ph+ ALL: include TKI
- T-Cell ALL: include Nelarabine
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What is the supportive care for ALL?
- Transfusion for Hb < 8 g/dL or any sx of anemia
- Transfusion for PLT < 10,000/mm3CSF after induction for leukopenia
- Allopurinol or Rasburicase and hydration for Tumor Lysis Syndrome
- Acyclovir or SMZ/TMP for infection prophylaxis if 0 WBC
- Leucovorin + NaCl urine alkalinzationfor Methotrexate rescue
- MESNA to prevent hemorrhagic cystitis from Cyclophosphamide
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What type of leukemia transitions from <10% blasts to >30% blasts in the bone marrow?
CML
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What is the normal level of blasts in the bone marrow?
< 5%
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What type of leukemia is associated with thrombocytosis (increased platelet count)?
CML
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What type of leukemia is associated with blood hyperviscosity?
CML d/t thrombocytosis
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What does the Philly chromosome cause?
mutant tyrosine kinase which leads to uncontrolled cell proliferation
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What is the tx for CML?
- Chronic Phase:
- Imatinib
- Dasatinib
- Nilotinib
- Accelerated Phase:
- Dasatinib
- Nilotinib
- Blast Phase:
- Cytarabine + Anthracycline +TKI
- Corticosteroid + Vincristine + Anthracycline + TKI
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What should be done if Imatinib resistance develops?
- Primary resistance (lack of efficacy at start): switch to Nilotinib or Desatinib
- Secondary resistance (loss of efficacy over time): increase Imatinib dose
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What is the supportive tx for CML?
- Neutropenia: hold drug until ANC at least 1000-1500/mm3 then resume or reduce dose; CSF
- Thrombocytopenia: hold drug until PLT at least 50,000 - 75,000/mm3 then resume or reduce dose
- Anemia (grade 3-4): RBC transfusions
- Diarrhea: supportive care
- GI upset: take with meal and large glass of water, divide dose
- Rash: topical/systemic steroids, dose reduction, interruption, or d/c
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What type of lymphoma is associated with Reed-Sternberg cells?
Hodgkin's lymphoma
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What are the sx of Hodgkin's Lymphoma?
- Lymphadenopathy (usually painless)
- Systemc B sx (fever, night sweats, wt loss)
- Chronic pruritis
- Extranodal involvement (spleen, lungs, liver, and bone marrow)
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What is the tx for classical Hodgkin's Lymphoma?
- Early stage: RT + chemo
- Advanced state: chemo
- Chemotherapy:
- ABVD (Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine)
- Stanford V (Doxorubicin, Vinblastine, Mechlorethamine, Etoposide, Vincristine, Bleomycin, Prednisone)
- BEACOPP (Bleomycin, Etoposide, Doxorubicin, Cyclophosphomide, Vincristine, Procarbazine, Prednisone) - reserved for high-risk disease d/t greater long-term toxicity
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When does Hodgkin's Lymphoma primarily strike?
15-30 and >55 yo (BIMODAL)
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When does Non-Hodgkin's Lymphoma strike?
any age
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What is the tx for asymptomatic early-stage CLL (non-Hodgkin's Lymphoma)?
observation and supportive care
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What is the tx for symptomatic or high-risk CLL (non-Hodgkin's Lymphoma)?
- Chlorambucil
- Cyclophosphamide
- Bendamustine
- Fludarabine
- Cladribine
- Pentostatin
- Rituximab
- Alemtuzumab
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What type of lymphoma is associated with Autoimmune disease?
CLL (non-Hodgkin's)
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What type of lymphoma is associated with secondary malignancy?
CLL (non-Hodgkin's)
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What type of lymphoma is associated with Richter transformation?
CLL (non-Hodgkin's)
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What is the supportive tx for CLL (non-Hodgkin's Lymphoma)?
- Blood product support
- Rasburicase or Allopurinol with hydration for Tumor Lysis Syndrome
- Corticosteroids, Rituximab, IVIG, Cyclosporine, Splenectomy, Eltrombopag, or Romiplostim for Autoimmune cytopenias
- SMZ/TMP, Acyclovir, or Gancyclovir prophylaxis for infections
- Vaccinations (annual influenza, pneumococcal q 5yrs) (Avoid live vaccines)
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