EXam 2 lecture 7 Flashcards
What are the diseases of myeloid cell lines?
Myelodysplastic syndrome (MDS)
chronic myeloid leukemia (CML)
acute myeloid leukemia (AML)
What are lymohoid cell line diseases
Hodgkin lymphoma (HD)
non-hodgkin lymphoma (NHL)
chronic lymphocytic leukemia (CLL)
acute lymphocytic leukemia (ALL)
multiple myeloma (MM)
What are the 2 major types of lymphomas? what is the backbone of tx?
hodgkin lymphoma (HL)
non-hodgkin lymphoma
Chemo is backbone of therapy
risk factors for HL
Epstein-barr virus (EBV)
impaired immune function
symptoms of HL
Painless rubery enlarged lymph node.
B symptoms (25%-50%)
-fever
drenching sweats
unintentional weightloss
How is HL diagnosed
Excisional biopsy is gold standard
staging of HL
stage I-II without unfavorable factors
STage I-II with unfavorable factors
stage III-IV
How to treat IA, IIA favorable HL
ABVD + RT
Stanford V + RT
ABVD
ABVD + escelated BEACOPP
How to treat I-II unfavorable HL
ABVD + RT
STanford + RT
Escalated BEACOPP x 2 + ABVD x 2 + RT
stage III/IV HL treatment
ABVD +/- RT
AAVD
Stanford + RT
Escelated BEACOPP +/- RT (IPS>or=3)
What does ABVD stand for? toxicities?
Doxorubicin (adriamycin)
Bleomycin
Vinblastine
Dacarbazine
toxicities
- cardiotoxicity (from doxorubicin)
- pulmonary toxicity (from bleomycin)
What does AAVD stand for
Doxorubicin
Brentuximab vendotin
Vinblastine
Dacarbazine
How to treat relapsed HL? When is early relapses time frame?
Early relapse is less than 1 year after tx
AUTOLOGOUS stem cell transplant and high dose chemo used with brentuximab as maintenance therapy following transplant
Which one occurs earlier, HL or NHL? which one occurs more?
HL
NHL occurs more
What happens in NHL
malignant cells proliferate and replace normal cells in lymph nodes and/or bone marrow
What cells do NHL primarily affect
85% B cell and 15% t cell
risk factors for NHL
EBV, infections and other viruses, immunodeficiency states (autoimmune)
How does NHL present
presentation depends on tumor location,
B cell: Lymph nodes, spleen, bone marrow (40% of patients)
T cell: Extra nodal sites (skin and lung) 10-35% of patients)
DO we give chemo even if the patient is neutropenic in HL
yes
What are the B symptoms associated with NHL presentation?
Fever
drenching sweats
unintentional weight loss
Diagnosis of NHL
Excisional biopsy
What are the different types of B cell lymphomas?
Indolent (25=40%)
Aggressive (60-75%)
Highly aggressive
among indolent, aggressive and highly aggressive, which ones are curable? Which ones arent? Why?
Indolent is usualy incurable due to how slow it grows.
aggressive and highly aggressive are usually curable
In general, what are the different treatment approaches to NHL
Radiation therapy
multi agenttherapy
immunotherapy
high dose chemo with stem cell rescue
CAR-T
T cell engagers
What is the name of the 2nd most common NHL? HOw to treat it?
follicular lymphoma
treated if symptomatic or patient preference with chemotherapy
What is richters transformation? How to treat? What can we expect after tx?
FOllicular lymphoma can transform into an aggressive NHL
Chemo yields 40% Complete remission, but still have underlying follicular lymphoma (Treat like DLBCL)
What is DLBCL? genetic abnormalities to identify? How does it present?
DLBCL is 30% of NHL cases. 30-40% present with extranodal disease (head/neck, GI tract, skin, bone)
genetic abnormalities to identify- double hit/ triple hit (BCL translocation)
What are the multi agent chemotherapies we can use in NHL
R-CHOP- rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone
DA-EPOCH- Etoposide, prednisone, vincristine, doxorubicin, cyclophosphamide
POLA+R+CHP- Polatuzumab, rituximab, cyclophosphamide, doxorubicin, prednisone
How to treat the dufferent stages of DLBCL
Stage I-II- 3 cycles RCHOP + Rituximab or 6 cycles R-CHOP
Stage III-IV (+bulky stage II)- 6 cycles R-CHOP or 6 cycles pola + R + CHP (IPI> or = 2)
R-CHOP toxicities
neutropenia
thrombocytopenia
infection
anemia
What is seen with rituximab use? How to avoid this?
Hepatitis B reactivation seen.
Treatment with pre emptive therapy- entecavir
late neutropenia also seen. Treat with growth stimulating factors. (IVIG if GSF do not work)
How to treat relapsed DLBCL/ aggressive NHL
two rounds of salvage chemo followed by autologous stem cell rescue if they respond well to chemo
another option can be CART therapy
Another option can be Palliative chemo (bendamusine, rituximab+polatuzumab)
another option cane be BITEs (epcoritamab, glofitamab)
MOA of CART cell
take CART cell out of body
modify them so that they recognize the cancer
then we give back the t cells back into body
this poses a lot of risk for side effects (CD-19 is a target)
What are the names of the different CART cells used in NHL? What diseases do they specifically treat? MOA of CAR T
Tisagenlecucel- treats ALL, follicular lymphoma, NHL
Axicaptagine- treats follicular lymphoma, NHL
Lisocaptagine treats NHL
rememeber that T cell therapy targets CD 19. They activate T cell immune response to cause T cell destruction of the lymphome by genetically modifying patients T cells
What do we treat patients that did not reposnd to CAR T or stem Cell transplants (i.e 3rd line NHL)
BITE
1. epocritamab
2. glofitamab
MOA of BITE
They take patient T cell and and takes it to CD 19 lymphoma. and forces T cell to turn on to start destructing
BITE and CART unique toxicities
Cytokine release syndrome (CRS)
Immune effector cell associated neurotoxicity syndrome (ICANS)
how to handle CRS caused by BITE or CART
tocilizumab (anti IL-6 antibody) is used for CART cells- decreases cytokine storm (for grade 2)
corticosteroids for grade 3 or higher
How to handle ICANS associated with CART and BITE
treatment must be with corticosteroids (IL6 does not cross BBB)
Higher risk for ICANS with CART therapy compared to BITEs
What are the tests we do before starting RCHOP
hepatitis B surface antigen and hepatitis core antibody
what cells do MM affect?
Plasma cells (they produce antibodies)
What goes wrong in MM
Abnormal clone plasma cells in bone marrow (they usually should not be in marrow)
plasma cells and MM cells are produced from differentiated B cells after antigen stimulation. Normal plasma cells die after a few days, MM plasma cells are long luved and they slowly proliferate.
They secrete 60% igG, 20% igA and are secreted in urine
what are the preceding cells before MM
MGUS and smoldering
MGUS-> MM rate 1% per year
smoldering MM-> MM rate 10% per years for 1st five years
When do we know when to treat MM
CRAB
What does CRAB stand for? What is its use?
Calcium >11.5
Renal dysfunction Scr > 2 mg/dr or CrCL <40
Anemia <10 g/dl or 2 g/dl below normal
bone frcature or osteolytic lesions
USed to see whether or not to treat MM
MM treatment overview
It is incurable
but we wanna control disease
Induction followed by consolidation followed by maintenance therapy
Induction therapy in MM
If transplant candidate do high dose chemotherapy followed by stem cell rescue.
If they are not a transplant candidate- 3 drug regimen
