Leukemia Clinical Care 2 Flashcards
Study that was crucial in making Imatinib the standard treatment for CML, instead of IFN + Ara-C?
IRIS Study: showed significant improvement in treatment outcome
(progression-free survival at 18 mo.)
What are the 2 other tyrosine kinase inhibitors (2nd generation)?
- Nilotinib
- Dasatinib
wet purpura (blood blister)
Acute Myeloid leukemia
Acute Myeloid Leukemia
AML
(CD13 & CD33 positive distinguish myeloid cells from T cell or B cell)
Acute Myeloid Leukemia median age of onset
67 yo
(M:F = 1:1)
Predisposing factors to AML (5)
- radiation
- benzene
- myeloproliferative or myelodysplastic syndromes
- congenital DNA repair disorder
- smoking (2 fold increase)
How do you determine a good or poor prognosis in AML?
Cytogenetic analysis
How does the WHO classify AML?
- Recurrent genetic abnormalities
- Multilineage dysplasia
- Therapy-related
- ambiguous lineage (lymphoid + myeloid lineage)
Recurrent genetic abnormalities (AML) with a good prognosis (3)
- t(15;17) → PML/RARa
- inv 16 → CBFb/MYH11
- t(8:21) → AML/ETO
(11q23 → MLL is less common)
AML tx phases (2)
- remission induction phast : lower leukemia burden from 1012 → 109
- post-remission therapy: cure
AML tx
combo chemo: cytarabine + anthracycline (aka “7 + 3”)
(Complete remission (CR) depending on age - 80% if < 60 yo; ~45% if > 60 yo)
Acute Promyelocytic Leukemia (APL) -M3 translocation
(used to be called AML-M3)
t (15;17)
PML-RAR fusion
(blocks neutrophils from differentiation)
Auer rods (aka “faggot cells”)
APL - M3
Why do elderly patients have a poor AML prognosis (4)?
- emerge from antecedent hematologic disorder
- karyotype abnormalities
- express MDR genes
- co-morbidities
Evaluation of AML in the elderly
- ECOG PS
- ADLs
- Charleston comorbidity scores (to decide if chemo is approps)
Elderly patients may receive chemo tx for AML if they meet which criteria (3)?
- up to age 70 w/good PS
- independent ADLS
- low morbidity
Geriatric patient AML Tx
hypomethylating agents (low dose chemo)
Acute Lymphoblastic Leukemia prognosis: children vs. adults
- children ~ 80% cure
- adults ~ 30% cure
Acute lymphoblastic leukemia sx (5)
- cytopenia (bone marrow failure)
- CNS involvement
- bleeding
- organomegaly
- lymphadenopathy
(B symptoms: fever, sweats, weight loss)
Poor prognostic factors for ALL
- over 60 yo 10-15% survival
- B cell: > 30 x 109; T cell: >100 x 109
- Ph - ALL
AYA (adolescent & young adults - 15-39 y/o) do better
Favorable cytogenetic abnormalities with ALL
hyperdiploid; del9p
Cytogenetic abnormalities w/poor prognosis w/ALL
- Ph +ALL t(9;22)
- Ph - ALL:
- t(4;11) KMTZA translocation
- t(8;14) complex karyotype
- hypodiploid (30-39 chromosomes); near triploidy (60-78 chromosomes)
1st line therapy for B cell ALLs are based on ____ (2).
- phase (initiation, consolidation, maintenance, CNS prophylaxis)
- population-based (peds, AYA, Ph+ ALL)
T-cell ALL relapse tx
Nelarabine (purine nucleoside analogue)
(prodrug; not curative)
BiTE
Bispecific T-cell Engager: tethers T cell to cancer cell → engages & kills
Leukostasis
symptomatic hyperleukocytosis (>100,000/uL can be asymptomatic, if not → leukostasis)
(seen in AML & CLL)
CLL typically have a WBC count of
>400,000/uL
(low plts, low Igs)
Why is leukostasis bad?
increases viscosity → local hypoxemia → release of cytokines → coagulation cascade or bleeding
(HA, SOB)
Pulmonary leukostasis
(infiltration)
neurologic infarct
(result of leukostasis)
Why is this increased “buffy coat” bad?
it can cause an error in the reading of other blood components
Spurious Lab Tests
marked leukocytosis: hyperkalemia, hypoxemia , hypoglycemia
