Hematology pt 1 Flashcards
leukemia etiology
- unknown
- culmination of multiple processes resulting in genetic damage
things that can cause leukemia
- radiation
- carcinogens (benzene)
- chemotherapy
leukemia symptoms result from:
- bone marrow failure
- tissue infiltration
- circulating leukemia
labs that indicate bone marrow failure when low
WBC (leukopenia)
RBC (anemia)
platelets (thrombocytopenia)
technique to diagnose and stage leukemia
bone marrow aspiration and biopsy
AML
acute myelogenous leukemia
population AML is most common in
elderly
regular intense induction therapy for AML
7 + 3
- 3 days of an anthracycline
- 7 days of cytarabine
low intensity induction therapy for AML
azacitadine or decitabine
consolidation therapy for AML
- HiDAC (high dose cytarabine) for all cytogenetics
- AlloHSCT can be used for intermediate or high risk cytogenetics
salvage chemo for AML
- CLAG/CLAG-M (cladribine, cytarabine, GCSF +/- mitoxantrone)
- FLAG/FLAG-IDA (fludarabine + cytarabine + GCSF +/- idarubicin)
- MEC (mitoxantrone + etoposide + cytarabine)
APL
acute promyleocytic leukemia
APL etiology
fusion of chromosome 15 and 17 to form PML-RAR-alpha
effects of PML-RAR alpha in APL
- binds to DNA and blocks transcription
- prevents differentiation
- fusion to retinoic acid receptor (RAR)
APL induction treatment
-ATRA (all-trans retinoic acid) aka tretinoin given emergently -ATRA + ATO (arsenic trioxide) *curative*
APL has high risk of what complication and how does it work
hemorrhage
annexin II produced in APL cells bind plasminogen and tPA to increase plasmin activity
APL differentiation syndrome (retinoic acid syndrome) symptoms
- fever
- respiratory distress
- interstitial pulmonary infiltrates
- pleural or pericardial effusions
- weight gain
- hypotention
how does APL differentiation syndrome lead to death
pleural effusion -> pulmonary infiltration -> pulmonary hemorrhage
how to treat APL differentiation syndrome
dexamethasone
OR
prophylactic prednisone
arsenic trioxide MoA
- low concentrations = differentiation inducer
- high concentrations = direct apoptosis inducer
arsenic trioxide toxicities
- QT prolongation
- hepatotoxicity
ALL
acute lymphoblastic leukemia
where does ALL stem from
disorder of lymphoid progenitor cells
ALL is most common in which patients
children
ALL subtypes
B cell
T cell
ALL subtype with the better prognosis in adults
T cell
ALL prognosis in children
good, unless philadelphia chromosome is present
risk factors for ALL CNS relapse
- T cell ALL
- leukocytosis
- high risk cytogenetics
- presence of leukemic cells in CSF
Induction treatment for ALL
cortidosteroid vincristine anthracycline \+/- asparaginase \+/- BCR-ABL TKI
consolidation treatment for ALL
- continue chemo +/- TKI
- allogeneic stem cell transplant if age <65 and no comorbidities
L-asparaginase mechnism
catalyzes hydrolysis of asparagine to aspartic acid which depletes resources for RNA and DNA synthesis, leading to apotosis
L-asparaginase adverse effects
PE
pancreatitis
thrombosis
hepatotoxicity
drugs for relapsed/refractory ALL
blinatumomab
inotuzumab
blinatumomab MoA
bispecific T cell engager that binds both B and T cells at the same time
Inotuzumab MoA
binds to CD22 of B cells which allows for calicheamicin to induce double stranded breaks in the cell
CML
chronic myeloid leukemia
CML is most common in which patients
adult to elderly
CML is caused by what
bcr/abl philadelphia chromosome
phases of CML
chronic
accelerated
blast
chronic phase of CML features
- largely asymptomatic
- some splenomegaly and anemia
- lasts 3-5 years
- makes up 90% of new diagnoses
accelerated phase of CML features
- splenomegaly, anemia, bone/joint pain, fever
- lasts months
- cell maturation arrest
blast phase of CML features
- anemia, infections, bleeds
- duration is days to weeks
- presents as acute
treatment goal of CML
complete cytogenetic response in 1 year
treatment of CML
TKIs
imatinib first line
most TKIs are inhibitors and substrates for what CYP
3A4
TKI with a BBW for vascular occlusion
ponatinib
discontinuation of TKI
its a trick
- guidelines recommend indefinite continuation in pts. with responsive disease
- this is to reduce relapse
treatment of CML accelerated phase
- imatinib
- dasatinib
- nilotinib
- omacetaxine
- allogeneic HSCT
CLL
chronic lymphocytic leukemia
CLL pathophysiology
clonal proliferation and accumulation of CD5 B cells in blood, bone marrow, lymph, and spleen
key genetic marker in CLL that indicates poor chemo response
Del 17p, most of which have P53 mutation
first line treatments for CLL with no del 17p present in pts <65
- fludarabine, cyclophosphamide, rituximab
- bendamustine, rituximab
first line treatments for CLL with no del 17p present in pts >65 or comorbidities
- obinutuzumab + chlorambucil
- ibrutinib
ibrutinib MoA
-covalently binds bruton tyrosine kinase to inhibit proliferation and survival of B cells
ibrutinib common side effects
n/d
fatigue
cough
ibrutinib and bleeding risk
- do not administer with warfarin
- hold for 3-7 days before and after surgery
preferred treatment of relapsed CLL without del 17p present
ibrutinib
OR
idelalisib + rituximab
idelalisib MoA
- PI3K delta inhibitor
- inhibits B cell and CSCR 4/5 signaling which prevents trafficking and homing of B cells to lymph and marrow
idelalisib adverse effects
hepatotoxicity
diarrhea/colitis
pneumonitis
infection
first line treatment for CLL with del 17p
-ibrutinib
-HDMP + R
others
treatment for relapsed/refractory CLL with del 17p
ibrutinib
venetoclax
idelalisib + R
others
venetoclax MoA
targets BCL-2 in order to help restore the process of apoptosis
venetoclax indication
CLL relapsed/refractory with del 17p present
two types of bone marrow transplant
allogeneic
autologous
type of BMT that has problems with graft vs. host
allogeneic
complications seen after stem cell transplant
infection
GVHD
pulmonary complications
autologous stem cell source
the patient
phases of SCT
- conditioning/ preparative from day-7 to day-3
- transplatation day 0
- post transplant
engraftment
when transplanted cells start to grow
acute GVHD features
- occurs before day +100
- affects skin, GI tract, liver
chronic GVHD features
- occurs after day +100
- affects all organ systems
GVHD prophylaxis is given to who
all allogeneic recipients
GVHD prophylaxis drugs
immunosuppressants
- cyclosporine/tacro + methotrexate
- cyclosporine/tacro + mycophenolate
- sirolimus + tacrolimus
vaccines that are contraindicated in pts with SCT
MMR
varicella
live ones
structures in the lymphatic system
- bone marrow
- lymph nodes
- spleen
- thymus
- tonsils
- MALT
bone marrow lymphocytes are primarily what type
b cells
role of b cells
- produce antibodies
- mature into memory b cells
types of t cells
cytotoxic CD8
helper CD4
role of cytotoxic CD8 cells
recognize infected cell membranes and destroy them
role of helper t CD4 cells
release cytokines that attract other WBCs
role of Natural killer cells
recognize foreign or infected cells via MHC 1
what is lymphoma
blood cancer that begins in the lymph node
pathophysiology of hodgkins lymphomas
malignant Reed-Sternberg cells recruit more cells
Reed-Sternberg cell features
large
bi-nucleated
express CD30 and CD15
risk factors for hodgkin lymphoma
- not well defined*
- same sex siblings as HL pt. have greater risk
- many tumors have Epstein-Barr virus
- previous solid organ transplant
- HIV
signs and symptoms of hodgkin lymphoma
- painless rubbery mass, most often in neck
- fever
- drenching night sweats
- often times asymptomatic
lymphoma age distribution for hodgkins lymphoma
bimodial
peak in 20-30s then again over 50
-death more common in older patients
diagnosis and work up of HL
- biopsy
- chest Xray
- CT
- PET scan most important
staging of HL
- stage 1 = single node region or structure
- stage 2 = two or more nodes regions on same side of diaphragm
- stage 3 = lymph nodes regions on both sides of diaphragm
- stage 4 = diffuse or disseminated involvement
factors used in the International Prognostic Score for advanced stage HL
- albumin < 4
- hemoglobin <10.5
- male
- stage 4
- age >45
- WBC >15000
- lymphopenia <600
treatment modalities for HL
radiation
chemo
surgery
autologous SCT
HL cure rate
81%
chemo regimens for acute HL
MOPP
ABVD
MOPP regimen drugs
mechlorethamine vincristine (oncovin) procarbazine prednisone -28 day cycle
problem with MOPP
lots of secondary leukemias occur
ABVD regimen drugs
doxorubicin (adriamycin) bleomycin vinblastine dacarbazine -28 day cycle
acute toxicities of ABVD and MOPP
N/V
myelosuppression
anemia
mucositis/stomatitis
long term toxicities of ABVD and MOPP
- secondary malignancies (MOPP)
- pulmonary fibrosis - bleo
- CHF - doxorubicin
- gonadal dysfunction/sterility (MOPP)
treatment for favorable early stage HL
ABVD for 2-4 cycles + involved field RT
treatment for unfavorable early stage HL
ABVD for 4-6 cycles +/- RT
indicators of unfavorable early stage HL
b symptoms
bulky disease
extra nodal or >3 sites
treatment for advanced stage HL
ABVD for 6 cycles
escalated BEACOPP for unfavorable
escalated BEACOPP regimen
bleomycin etoposide doxorubicin (adriamycin) cyclophosphamide vincristine (oncovin) procarbazine prednisone *21 day*
brentuximab vedotin MoA
- targets CD30
- carries MMAE which potentially disrupts microtubule polymerization
brentuximab side effects
peripheral neuropathy
neutropenia
risk factors for non hodgkins lymphoma
- older people
- Hx of lymphoma
- exposure to radiation, pesticides
- immuno-suppressants
- lupus, RA
- HIV
- epstein-barr
- hep C
clinical presentation of non hodgkins lymphoma
- lymphadenopathy
- B symptoms (fever, night sweats)
NHL diagnosis
- biopsy
- molecular tests
- cell surface markers
- cytogenetics (C. 14)
NHL staging
same as HL, but does not work as well because spread is not contiguous
prognostic index for NHL
- age >60
- serum LDH >normal
- performance status 2-4
- stage 3 or 4
- extranodal involvement
main indolent NHL example
follicular lymphoma
aggressive NHL type
diffuse large b-cell lymphoma
highly aggressive NHL type
burkitt lymphoma
indolent NHL definition
- survival of untreated disease is measured in years
- waxing and waning of lymph nodes is commonly seen
aggressive NHL definition
survival of untreated disease is measured in months
highly aggressive NHL definition
survival of untreated disease is measure din weeks
treatment for indolent NHL
-watch and wait b/c its slow growing
-single-agent chemo
o chlorambucil
o cyclophosphamide
o fludarabine
-immunotherapy - rituximab
-chemo-immuno combo - R-CHOP
-targeted - ibrutinib
treatment for aggressive NHL
R-CHOP
DA-R-EPOCH
-CODOX-M
R-CHOP drugs
Rituximab Cyclophosphamide Hydroxydaunorubicin (doxorubicin) Oncovin (vincristine) Prednisone
rituximab adverse reactions
fever
chills
rigors
*push through these because they really only show in the first cycle or two
rituximab requires what pre-medication
tylenol
diphenhydramine
ranitidine
rituximab MoA
causes apoptosis by:
- recruiting NK cells
- activating compliment cytotoxicity
- apoptosis via calcium influx
cyclophosphamide adverse effects
SIADH
- hemorrhagic cystitis
- pulmonary tox
- alopecia
cyclophosphamide MoA
alkylator
forms covalent bonds at N7 of quanine
doxorubicin MoA
topo II inhibitor
vincristine MoA
microtubule stabilization
NHL type with best chance for cure
aggressive
treatments for NHL relapse after autologous BMT
ICE
DHAP
GemOx
Yescarta
treatment for highly aggressive NHL
R-CODOX-M/IVAC
DA-R-EPOCH
R-CHOP is not adequate
which lymphoma is harder to cure
NHL
