Exam 2: Hematologic Malignancies Flashcards
What cells are affected in lymphoma?
- B and T lymphocytes
What are the two types of lymphomas?
- Hodgkin Lymphona
- Non-hodgkin lymphoma
What are the two subtypes of lymphomas?
- Hodgkin lymphoma
- Non-Hodgkin (NHL)
Hodgkin Pathology
- Reed-Sternberg Cells
Where does Hodgkin originate?
B-lymphocytes
HL Risk Factors
- impaired immune function
- EBV
HL Presentation
- painless, rubbery, enlarged lymph node
- B symptoms
- pruritius
B Symptoms
- fever greater 38º
- drenching sweats
- unintentional weight loss greater than 10% in ≤ 6 months
HL Diagnosis
Excisional biopsy
bone marrow biopsy in advanced stage
Early-stage favorable HL
stage I-II without unfavorable factors
Early-stage unfavorable HL
stage I-II with unfavorable factors
Advanced stage HL
stage III-IV
Unfavorable factors
- large mediastinal adenopathy
- multiple involve nodal regions
- B symptoms
- extranodal involvement
- ESR
International Prognostic Score (IPS) for HL
- higher the number of factors, the worse progression free survival
HL Treatment Treatment options
- Radiation
- Autologous stem cell transplant
Combo Chemo
- ABVD
- Stanford V
- BEACOPP
- AAVD
Stage IA, IIA Favorable Treatment
- ABVD + RT
Stage I-II Unfavorable
- ABVD + RT
Stage III/IV
- ABVD + RT
- AAVD
ABVD
- Doxorubicin (Adriamycin)
- Bleomycin
- Vinblastine
- Dacarbazine
Toxicities of ABVD
- cardio (doxorubicin)
- Pulmonary (bleomycin)
- Peripheral neuropathy (vinblastine)
- Dacarbazine (myelosupression)
- N/V
AAVD
- Doxorubicin
- Brentuximab vendotin
- vinblastine
- Dacarbazine
AAVD Toxicities
- Cardiotoxicity (doxirubicin)
- increased myelosuppression
- increased peripheral neuropathy
- N/V
ABVD Stage I or II HL
4 cycles
ABVD Stage III/IV HL
6 cycles
Relapsed HL Treatment
high dose chemo with autologous stem cell rescue ± maintenance brentuximab vendotin (if high risk disease post transplant)
NHL Patho
Malignant B or T lymphocytes and precursors (B cell more common)
NHL Risk Factors
- EBV (Burtkitt -> TLS, AIDS)
- Immunodeficiency
- environmental/physical agents
NHL Presentation
- B Cell: lymph nodes, spleen, bone marrow
- T cell: extrandal sites (skin and lungs)
- b symptoms in some patients
- primary CNS lymphoma
- NO ITCH
NHL Diagnosis
excisional biopsy
lumbar puncture in patients at high risk or symptoms as NHL can metastasize in the brain
Indolent B Cell lymphomas NHL
usually incurable
Aggressive B Cell lymphoma NHL
- rapid growth
- short survival
- usually curable
Highly aggressive B cell NHL
- doubling tine = 18 hours
- usully curable
what type of cancer is DLBCL
NHL
NHL Treatment Approaches
- RT
- multi-agent chemo (backbone)
- immuno
- high dose chem with stem cell rescue
- CAR-T
- T-cell engagers
What type of cancer is Follicular Lymphoma
NHL (2nd most common type)
What can follicular lymphoma transform into
- Richter’s transformation (aggressive nHL)
- treat like DLBCL with rituzimab
DLBCL Genetic abnormalities
- Double/triple hit (MYC+ BCL2 or BCL6 transformation or all three)
DLBCL Treatment Regimens
- R-CHOP
- DA-EPOCH + Rituximab
- Pola + R + CHP
R-CHOP
- rituximab
- cyclophos
- doxorubicin
- vincristine
- prednisone
DA-EPOCH + RituximB
- Etop
- Prednisone
- Vincristine
- Doxorubicin
- cyclophose
Pola + R + CHP
- polatuzumab vedotin
- rituximab
- cyclophose
- doxorubicin
- prednison
VERY Expensive
Stage I-II DLBCL treatment
3 cycles R-CHOP + RT
OR
6 cycles R-CHOP
Stage III-IV (+bulky stage 2)
- 6 cycles R-CHOP
- 6 cycles Pola + R + CHP
IPI ≥ 2
R-CHOP Toxicities
- neutropenia
NHL Rituximab and Hep B
- test for HBsAg and HBcAb prior to anti-CD20 directed therapy
- treat wit hentecavir 0.5 mg daily
Anti-CD20 late neutropenia DLBCL treatment
G-CSF
IVIG for refractory
Relapsed DLBCL/Aggressive NHL
- salvage chemo followed by autologous stem cell rescue
- better outcome if patient in complete remission going into transplant
- Bendamustine + rituximab + polatuzumab (palliative)
- BITE (epcoritamab, glofitamab)
What is the target antigen for CAR T-cells
CD19
BITE
- third line option after 2 lines of systemic therapy
- CD3 on t cell and CD20 on b cells
- activation of t cells =b cell lysis
CRS Treatment
- tocilizumab (anti-IL 6)
- steroids
- supportive care
ICANS (neurotoxicity syndrome)
- tremors, AMS, seizures, cerebral edema, neurological assessments (hand writing)
- steroids
MM Pathology
- plasma cells and MM cells produced from differentiated B cells
- secrete immunoglboulins (IgG, IgA)
Transformation to MM
- precedued by MGUS ans smoldering (asymptomatic MM)
MM CRAB
- Calcium > 11.5 mg/dL
- renal dysfunction SCr > 2 mg/dL or CrCL < 40 mL/min
- ANemia <10 or 2 g/dL below normal
- Bone: osteolytic lesions of patho fractures
MM Treatment Overview
- induction (chemo)
- consolidation (autologus stem cell transplant)
- maintenance
MM is the patient a transplant candidate
- No: 3 drug regimen
- Yes: 3 drug regimen x3-4 then stem cell transplant
MM Agents
- steroids
- thalidomide (-domide)
- proteasome inhibitors (-zomib)
- traditional chemo (cyclophos, doxorubicin)
- Mabs (daratumumab)
- Car T-cell therapy
- Selinexor
- BITE
VRD MM
lenalidomide
dexamethasone
bortezomib
(more neuropathy, longer progressive free survival)
CML Patho
- unregulated myeloid proliferation –> excess mature neutrophil production
- BCR-ABL
CML Presentation
- incidental finding durign routine exam
- Leukostasis (1,000,000 cells/ mm3)
CML Diagnosis
- bone marrow biopsy required
- FISH to assess philidelphia chromosome
- PCR to assess bCR-aBL transcript baseline
Chronic Phase CML
< 10% blasts
CML Accelerated Phase
- progressive
- 10-19% blasts
- increasing spleen size
- bone marrow evidence of progresssion
Blast Crisis CML
- terminal stage
- resembles acute leukemia
CML
- only cure is allogenic stem cell transplant
- TKI for disease control
CML Molecular response
Early: BCR-ABL ≤ 10% at 3 and 6 months
Major (MMR)≤0.1% or ≥ 3 log decrease
Deep: BCR-ABL ≤ 0.01%
CML TKI
- imatinib
- dasatnib, nilotinib, bosutinib
- all are approved in first line setting
What should you avoid with dasatinib
acid reducers
Which BRC-ABL TKI causes qtc prolongation and metabolic syndrome?
nilotinib
Posatinib side effects
- ischemic rxn
- vascular occlusion
- hypertension
Aciminib
- CML
- can be used in T315I resistent CML
2nd line treatment CML
- dose escalation of imatinib
- second generation TKI
- 3rd generation TKI (pon, asciminib, omacetazine)
- allogenic SCT
CML TKI Discontinuation
- no history of AP or BP
- on TKI for 3 years
- Deep molecular response
- stable deep response for ≥ 2 years, seen 4 times with test at least 3 months apart
Monitoring after TKI discontinuation
- PCR q 3 months
CLL Patho
monoclonal b lymphocyte transformation
CLL Cytogenetics
- Del (11q) associated with exgtensive lymphadenopathy, shorter median survival
- Del (17p) worst outcomes
Where does the CLL 17p deletion impact
G2 checkpont, causes the cell to keep dividing
Favorable CLL prognosis
Del (13q) only abnormality
wild type Tp53
CLL Treatment
- stage II or IV
- Clinical symptoms
- end organ dysfunction
- do not treat a number!
No Del17q/p53 mutation CLL treatment
- BTK inhibitor ± anti-CD20mAB
- venetoclax + obinutuzumab
- chemo immunotherappy
No Del17q/p53 mutation CLL treatment
BTK + obinutuzumab
or venetoclax + obinutuzumab
Ibrutinib vs Zanubrutinib vs Acalabrutinib
- CLL BTK inhbitior
- Zanubrutinib less toxicities, better response
- acalabrutinib decreases atrial fibrilation
-brutinib indication
indicated for relapse, disease refractory
Venetoclax Interactions
- PGP
- CYP 3A4
Lymphocytosis or Tumor flare in CLL
- BTK inhibitors
AML Patho
leukemic cells proliferate and crowd out normal cells
Which treatments cause secondary AML
- topo II
- alkylating agent
AML Presentation
- pancytopenia
- bone pain
- gum hypertrophy
AML Diagnosis
- bone marrow biopsy
- greater than >20% blast
Poor AML
FLT3 mutation
- midostaurin
- quizartinib
- gilteritinib (2nd line)
AML Treatment Overview
- bone marrow for diagnosis
- induction (remission
- bone marrow to confirm remisison
- consolidation (chemo or SCT)
Intensive induction eligible
Cytarabine (7 days) and idarubicin or daunorubicin (3 days)
Intensive induction inelegible (AML)
- venetoclax + hypo-methylating agent
AML consolidation
- 3-4 cycles of high dose cytarabine
- continue venetoclax + hypmethylating agent
- allogenic stem cell transplatn
AML APL
- t(15;17) = PML:RARA
- trans retinoic acid
- arsenic trioxide
ALL Patho
leukemic cell crowds out normal cells
Risk factors for ALL
genetic
EBV
HIV
radiaiton
ALL presentation
- pancytopenia
- bone pain
- gum hypertrophy
- lymphadenopathy
- abdominal masses
- painless testicular enlargement
ALL Diagnosis
bone marrow biopsy with ≥ 20% blasts
mostly b cell
ALL metastases
- brain and testis
- intrathecal chemo
FAcotr in ALL
BRC-aBL or 9;22 mutation
Ph Positive ALL
tKI + multiagent chemo
TKI + steroids
TKI + blinatumumab
maintenance: TKI+vincristine+ pred
PH negative
multiagent chemo
maintenance MTX+6mp+vincristine
ALL HyperCVAD
- hyperfractionated cyclophos
- vincristine
- docorubicin
-dexamethadose
for 21 days
+
mtx, cytarabine, vincristine intrathecal
for 21 days
