Lymphoma Flashcards
What are lymphomas?
malignancies that develop from lymphocytes. The site of the maturation defines the type of lymphoma present
Clinically, what can lymphomas do to people?
- mass presence (LAD, ureteral obstruction, cord compression)
- replacement (pancytopenia)
- reduction (hypogammaglobinemia)
- tumor products (uric acid, calcium lysis)
- paraneoplastic (AHA, ITP, neuropathy)
- toxicity of therapy (infected, numb and short of breath)
-psychosocial/economic: broke and alone
What things does a physician need to know if order to treat a lymphoma patient?
- tumor histology
- tumor stage
- condition of patent
- available therapies
How is lymphoma histology divided clinically?
indolent
aggressive
highly aggressive
B or T cell
What are indolent (low grade) lymphomas?
slowly progressive, tend to be higher stage (more widespread), and tend to respond to simple therapies
tend to be incurable (except stage I-II)
T or F. Survival of indolent lymphoma is independent of early treatment
T. Treatment is more based on symptomatic presentation
What are some examples of indolent lymphomas?
- follicular (most common indolent)
- small lymphocytic/CLL
- MALT lymphomas
- Mycosis fungoides
not curable mostly
What do aggressive lymphomas look like?
often lower stage, rapidly progressive, requires complex therapies
tend to be curable
T or F. Survival of aggressive lymphoma is independent of early treatment
F. Early therapy required
What are some examples of aggressive lymphomas?
- diffuse large B cell
- mantle cell
- peripheral T cell lymphoma (NOS, anaplastic, angioimmunoblastic)
What are some examples of highly aggressive lymphomas?
- Burkitt/ Burkitt like
- T cell lymphoblastic lymphoma
What is a “stage 1” lymphoma?
single node or lymphoid structure
What is a “stage 2” lymphoma?
two+ lymph regions on one side of the diaphragm
What is a “stage 3” lymphoma?
lymph nodes on both sides of diaphragm
What is a “stage 4” lymphoma?
disease is extranodal beyond E
What is stage I/II E?
lymphoma originated in an extra nodal area and spread to adjacent lymph nodes
What are some tests used in staging lymphoma patients?
- H&P
- chest, abdomen, and pelvis CAT
- PET scan
- bone marrow aspirate and biopsy (CD20)
- CBC, LDH, check CSF
What does a PET scan allow?
irradiates nuclei so that you can see functional changes in lymph nodes in lymphoma whereas normal lymph nodes would not show up on the PET scan
What is the most common lymphoma?
diffuse large B cell (then follicular)
What is the International Prognosis Index?
Age>60 1 Stage III-IV 1 LDH elevated 1 P status >1 1 Extranodal sites > 1 1
APLES
Low risk: 0-1
Low intermediate risk: 2
High intermediate risk: 3
High risk: 4
5 yr. Survival 0-1 73% 2 51% 3 43% 4-5 26%
What is the Follicular lymphoma IPI?
Age > 60 Nodal sites > 4 LDH increased Stage III-IV Hemoglobin
0-1 = 90% 5 yr sv 2 = 77% 5 yr sv 3-5 = 52% 5 yr sv
What are some therapy options for indolent lymphomas?
remember, don’t treat unless symptomatic
- local irradiation
- Alkylators and prednison
- Anthracyclines
- Fludarabine
- CD20 antibodies
- Combo chemo
What are some therapy options for aggressive lymphomas?
- combo chemo-CHOP; HyperCVAD
- antibody therapy plus CHOP (rituximab)
- radio-immunotherapy
- autologous BM transplant for relapse (survival advantage)
What is CHOP?
cyclophosphamide, hydroxydaunorubicin,
oncovin (vincristine),
prednisone
What is the antibody drug against CD20?
Rituximab- activates complement or phagocytosis
T or F. Adding rituximab to CHOp therapy for diffuse B cell lymphoma helps a lot
T. Almost always use R-CHOP therapy
What is the current therapy for stage I/II (IE/IIE) intermediate grade NHL?
CHOP-3 plus RT (stage 1-83% 5 yr survival; stage II-74%)
What is the current therapy for stage bulky II/IIE, III, and IV intermediate grade NHL?
CHOP-8
stage II bulky -49% 5 yr survival; stage III/IV-46%
What is the current therapy for first relapse for all stages of intermediate grade NHL?
autotransplant (53% 5 yr survival)
DHAP (32% 5 yr survival)
What drug targets CD52 (B and T cells)?
alemtuzumab
What drug targets CD30 (common on Hodgkin lymphoma)?
brentuximab vedotin
What drug targets BTK?
ibrutinib
What drug targets CD22?
inotuzumab ozogamicin
Describe the B cell receptor pathway
Antigen binding induces the aggregation of the BCR with its coreceptors CD79A and B, which become phosphorylated by the tyrosine kinases LYN and SYK. SYK activates phosphoinositide 3–kinase (PI3Kδ), which in turn converts phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-triphosphate PIP3. PIP3 serves as a docking site for the cytoplasmic kinases Bruton’s tyrosine kinase (BTK) and AKT. BTK phosphorylates and thereby activates phospholipase C gamma 2 (PLCγ2), which in turn generates a set of second messengers to activate protein kinase C beta (PKCβ). PKCβ phosphorylates IκB kinase (IKK) to activate nuclear factor κB (NF-κB) transcription factors that regulate gene expression of several survival factors. The kinases inhibited by small molecules with promising clinical activity are indicated.
What drug inhibits SYK?
Fostamatinib
What drug blocks PI3Kδ?
Idelalazib (GS-1101)
What infections are associated with lymphoma?
HIV (primary CNS lymhpoma)
HHV8, (primary plueral effusion lymphoma)
HTLV-1, (T cell lymphomas-ATLL)
EBV, (Burkitt)
H. pylori (MALT type lymphomas of GI tract)
What organ does mycosis fungicides (MF) target primarily?
skin (when blood is involved- Sezary)
How is early stage MF treated?
Soralin (sp?) and UV light only
when disease becomes systemic, need radiation
What are some T cell lymphomas?
- Angioimmunoblastic T cell (AITL)
- Anaplastic large cell
- Adult T-cell leukemia/lymphoma (ATLL)
T or F. ALK+ is favorable in anaplastic large cell lymphoma patients
T. Mediastinal presentation in young adults
What is AITL associated with?
- hypergammaglobinemia
- AHA
What are the types of Hodgkin’s disease?
1) lymphocyte predominant (in between indolent and aggressive B cell lymphoma)
2) Classical Hodgkin’s
- lymphocyte rich
- nodular sclerosis
- mixed cellularity
- lymphocyte depleted (more aggressive)
What is the most common type of classical hodgkin’s in children?
nodular sclerosis. As you get older, mixed cellularity and lymphocyte depleted become more common
How is Hodgkin’s Disease different than NHL?
-Hodgkin is CD30+
progress differently (goes from one lymph node to the next)
same staging and tests
How is early stage Hodgkin treated?
Treat with short course chemotherapy and focal radiation to area of disease or radiation alone or chemo alone
How is late stage Hodgkin treated?
chemotherapy
-ABVD: adriomycin, bleomycin vinblastine, DTIC
-good prognosis
The problem with Hodgkin disease is that they live a long time and may develop complications (via chemo) like:
- Acute leukemia and myelodysplasia
- Solid tumors-breast, lung, stomach, bone, soft tissues
- Coronary artery disease
- Radiation and chemotherapy pneumonitis
- Infertility
- Hypothyroidism
What is chronic lymphocytic leukemia (CLL)?
-indolent B cell malignancy
patient population for CLL?
50+ y/o
Symptoms of CLL?
Often asymptomatic (may never need treatment)
Lymphocytosis Lymphadenopathy Splenomegaly Anemia (from AHA) Autoimmune cytopenias Hypogammaglobulinemia
What is RAI staging for CLL?
0 = lymphocytosis 1 = enlarged lymph nodes 2= hepatosplenomegaly 3 = Hgb less than 10 (non-immune) 4 = Platelets less than 100,000 (non-immune)
What is Binet staging for CLL?
based on lymph node involvement:
A=0-2 areas
B=> 2 areas
C= Hgb less than 10 or platelets less than 100K
What are some negative prognostic indicators for CLL?
High Stage
Increased rate of lymphocyte doubling time (double in less than 6 months is bad)
Beta 2 microglobulin elevated (poor)
Deletion 17p, TP53 mutations, 11q deletion (very bad)
Unmutated VH genes, ZAP-70, CD 38
How is CLL treated?
Alkylator: Chlorambucil, cyclophosphamide, bendamustine
Purine analogues: Fludarabine
Chemotherapy combinations: FCR
Immunotherapy: rituximab (CD 20), alemtuzumab (CD 52), ibrutinib (if p53 mutation is present)
Radiation
Corticosteroids
What is Hairy cell lymphoma (HCL)?
indolent B cell lymph proliferative disorder
Are men or women more likely to be affected by HCL?
male (4:1)
Symptoms of HCL?
- splenomegaly
- pancytopenia
- decreased cell mediated immunity
Immunophenotype of HCL?
11c,19,20,22,25,103
What are the treatment indications for HCL?
Treatment Indications:
Cytopenias
ANC
Treatment for HCL?
Very high and enduring response rates to 2- chlorodeoxyadenosine and deoxycoformycin
