hematologic malignancies- acute leukemias

diagnosis of acute leukemia and how to get to diagnosis

bone marrow biopsy, when blast cells in bone marrow are greater than 20%

arise from single leukemic cell, expands and acquires additional mutations, proliferation resulting in monoclonal population of leukemic cells

acute myeloid leukemia

what happens in AML when leukemic cells crowd out normal cells

spill out of the bone marrow and into the peripheral blood

how do patients get secondary AML

from other diseases or from previous chemotherapy treatments

primary AML risk factors

genetic predisposition or environmental carcinogens

AML presentation

pancytopenia

bone pain

gum hypertrophy

what makes up pancytopenia

anemia, neutropenia, thrombocytopenia

gene mutation that leads to intermediate or poor prognosis with AML

FLT3-ITD

two treatment phases for AML and goal for each phase

induction: remission

consolidation: prevent relapse

how to confirm remission of AML

bone marrow biopsy after induction treatment and after blood counts recovered

what is considered remission of AML

less than 5% blasts on bone marrow biopsy and normal hematopoiesis

consolidation treatment for favorable vs unfavorable risk

favorable: chemotherapy

unfavorable: stem cell transplant

intensive induction eligible AML treatment options

continuous infusion cytarabine + anthracycline OR

venetoclax + hypomethylating agent

intensive induction ineligible AML treatment options

venetoclax + hypomethylating agent

hypomethylating agents + lower dose chemotherapy

AML treatment option that does not prolong life but just manages symptoms

supportive care with blood products/ anti-infectives

intensive chemotherapy regimen for AML

cytarabine infusion for days 1-7

anthracycline (idarubicin or daunorubicin) for days 1-3

cytarabine toxicity

myelosuppression

consolidation treatment options for AML

high dose cytarabine

venetoclax + hypomethylating agent

allogenic stem cell transplant

side effects of high dose cytarabine

cerebellar side effects

chemical conjuctivitis

arise from a single leukemic cell, expands and acquires additional mutations, proliferation resulting in monoclonal population of leukemic cells

acute lymphoblastic leukemia

most common demographic of ALL patients

children less than 20 years old

presentation of ALL that is different than AML

lymphadenopathy, abdominal masses, hepatomegaly, splenomegaly, painless testicular enlargement

diagnosis of ALL

bone marrow biopsy with greater than or equal to 20% blasts

standard cytogenetic characteristics for ALL

hyperdiploidy (51-65 chromosomes)

BCR: ABL without underlying CML

high risk cytogenetic characteristics for ALL

hypodiploidy (<44 chromosomes)

BCR: ABL with CML precursor

TP53 mutations

what is added to multi agent chemo for the treatment of philadelphia positive ALL and how does this affect their prognosis

TKIs, worse prognosis

ALL treatment phases and goals for each phase

induction: remission

consolidation: eradicate residual disease

maintenance: prevent relapse

prophylaxis treatment for ALL and why is this required

CNS prophylaxis, ALL can hide in sanctuary sites (brain and testes)

ALL remission requirements

less than 5% blasts on bone marrow biopsy AND normal hematopoiesis

consolidation ALL treatment options

multiagent therapy (continue chemo)

blinatumomab

allogeneic stem cell transplant

ALL chemo treatment regimen (part A and B)

HyperCVAD for part A (21 days)

methotrexate and cytarabine for part B (21 days)

what chemo makes up HyperCVAD

hyper-fractionated cyclophosphamide

vincristine

doxorubicin

dexamethasone

how many total cycles of part A and B should be completed before a patient is checked for remission

4 cycles of A and 4 cycles of B

what is given with each cycle of ALL treatment

intrathecal cytarabine and intrathecal methotrexate

how long is maintenance ALL treatment given

2 years

enzyme that breaks down asparagine and is utilized in many multiagent chemo regimens for ALL

asparaginase

unique toxicities of asparaginase

hypersensitivity

anaphylaxis

pancreatitis

what characterizes refractory ALL

do not achieve a complete response after 2 cycles of HyperCVAD

what characterizes relapsed ALL

achieved remission and then seen blast count rise

treatment options for ALL refractory or relapsed disease

blinatumomab

CART

allogenic stem cell transplant

drug class of blinatumomab and MOA

bispecific T cell engager, fragment of antibody that binds CD19 and CD3

toxicities of blinatumomab

cytokine release syndrome

what can be used with blinatumomab to lower WBC count

steroids or chemotherapy