Exam 2 - Leukemia Flashcards
List characteristics of acute leukemias?
rapid onset, symptomatic, rapid fatality, immature cells (“blasts”), usually leukopenia
List characteristics of chronic leukemias?
slowly progressive, mostly asymptomatic, higher survival, immature and mature cells
Myeloid cancers usually involve? (3) Lymphoid usually involve?
basophils, neutrophils, and eosinophils; B and T cells
How is AML diagnosed?
bone marrow aspirate and biopsy demonstrating 20% isolated blasts
List risk factors for AML?
increasing age, prior chemotherapy (therapy-related), cigarette smoke, radiation/benzene/pesticide/petrochemical exposures
List signs and symptoms of AML?
hyperleukocytosis, anemia (fatigue, SOB), thrombocytopenia (higher bleeding), neutropenia (infections), spontaneous tumor lysis syndrome, CNS involvement is rare
What is the treatment for hyperleukocytosis?
hydroxyurea
What is the MOA of hydroxyurea?
ribonucleotide reductase inhibitor
What are AEs of hydroxyurea?
GI, tumor lysis, toxicities (cutaneous vasculitic ulcerations, mucositis, alopecia, hyperpigmentation)
What are prognostic markers for AML?
cytogenetics, age, primary vs secondary AML, performance status, donor availability, WBC count at diagnosis, extramedullary disease
List the FMS-like-tyrosine kinase (FLT3) mutations? (2)
those involving internal tandem duplication, tyrosine kinase domain
List the other common AML mutations? (5)
those to isocitrate dehydrogenase, DNA methyltransferase 3A, RUNX1, TET2, spliceosomal
What is days 1-7 for induction chemotherapy? Adverse effects during this time?
chemotherapy administration; N/V, GI
What is days 8-24 for induction chemotherapy? Adverse effects and what occurs during this time?
cell count nadir and recovery; fatigue, fever/infection, high red blood cell and platelet transfusion requirement
What is days 25+ for induction chemotherapy? What occurs during this time?
complete cell count recovery; discharge from hospital once ANC >500 and no longer platelet transfusion dependent
What is treatment for induction chemotherapy in AML? (2)
cytarabine 100 mg/m^2 IV x7 days plus daunorubicin 60 mg/m^2/d x3 days OR idarubicin 12 mg/m^2/d x3 days
What is treatment for FLT3-ITD+ AML?
quizartinib (Vanflyta)
What is treatment for FLT3-ITD+/TKD+ AML?
midostaurin (Rydapt)
What is treatment for favorable/intermediate cytogenetics in AML?
gemtuzumab ozogamicin (Mylotarg)
What is treatment for secondary or therapy-related AML?
liposomal daunorubicin with cytarabine (Vyxeos)
List goal treatment response criteria in AML? (3)
“leukemia-free state” by day 14, complete remission/complete response by day 28, complete remission with incomplete count recovery
What is treatment for AML post-remission therapy in those receiving intensive chemo? (2)
high dose cytarabine (HiDAC) or liposomal daunorubicin with cytarabine (Vyxeos)
What is treatment for intermediate and poor risk diseased AML patients?
allogeneic stem cell transplant
What is used in “low-intensity chemo” for AML? (4)
hypomethylating agents (decitabine (Dacogen) or azacitidine (Vidaza)) plus venetoclax, low-dose cytarabine (LDAC) plus venetoclax, ivosidenib plus venetoclax, LDAC plus glasdeglib
What are AEs of quizartinib (Vanflyta)?
needs dose adjustments for DDIs
List the IDH inhibitors? (2)
ivosidenib (Tibsovo), enasidenib (IDHIFA)
What does supportive care entail in AML? (2)
transfusions (pRBCs, platelets), infection prophylaxis
What are AEs of anthracyclines (daunorubicin, idarubicin, mitoxantrone)? (3)
reddish or blueish urine/sclerae, myelosuppression, cardiac toxicity
What are AEs of cytarabine?
neurotoxicity (cerebellar syndrome), conjunctivitis
What are AEs of gemtuzumab ozogamicin (Mylotarg)? (2)
infusion-related reactions (premedicate with APAP, diphenhydramine, and methylprednisone), hepatotoxicity (including veno-occlusive disease)
What are AEs of low-intensity chemo?
constipation (give standing bowel medications), low-moderate emetogenicity (premedicate with ondansetron), myelosuppression (venetoclax)
What is treatment for bone pain as an AE from myeloid growth factors? (2)
loratadine, hydroxyzine
Explain the Philadelphia chromosome?
fusion chromosome of 9 and 22 via a translocation that involves the upregulation of bcr by abl which leads to a constitutively active expression
List signs and symptoms for CML?
asymptomatic (up to 50%), leukocytosis (WBC > 25x10^9/L), Philadelphia chromosome, anorexia, bone pain, weight loss, fatigue
What is the first generation tyrosine kinase inhibitor (TKI)? Second? Third?
1st = imatinib (Gleevec), 2nd = dasatinib (Sprycel) and nilotinib (Tasigna), 3rd = bosutinib (Bosulif) and ponatinib (Iclusig)
What is the MOA of imatinib (Gleevec)?
inhibits BCR-ABL tyrosine kinase (1st gen), inhibits c-KIT and platelet-derived growth factor receptor (PDGFR)
What are AEs of imatinib (Gleevec)? (4)
edema, myalgias, hypophosphatemia, GI
List mechanisms of resistance to TKIs? (3)
organic cation transporter 1, P-gp, point mutations in ABL kinase domain
What are AEs of dasatinib (Sprycel)? (3)
pleural/pericardial effusions, bleeding risk, pulmonary arterial hypertension
What are AEs of nilotinib (Tasigna)?
elevated pancreatic enzymes, hyperbilirubinemia, QTc prolongation, CV events
What are AEs of bosutinib (Bosulif)?
GI, HA, rash
If there are no contraindicated mutations, which treatments are recommended? (5)
asciminib (Scemblix), ponatinib (Iclusig), omacetaxine mepesuccinate (Synribo), allogeneic stem cell transplant, clinical trial
What are AEs of ponatinib (Iclusig)? (3)
vascular occlusion (hypertension, heart failure, ischemic reactions), skin toxicity, hepatotoxicity
What is the MOA of asciminib (Scemblix)?
STAMP inhibitor, targets myristoyl pocket
What is the MOA of omacetaxine mepesuccinate (Synribo)?
reversible inhibitor of protein synthesis
What are AEs of omacetaxine mepesuccinate (Synribo)?
myelosuppression, nausea, diarrhea, fever
What is the most important factor contributing to relapse and TKI failure?
poor medication adherence
