Final Flashcards
What is Hodgkin Lymphoma (HL) characterized by? How do HL symptoms present? What is the best way to diagnose?
Reed-Sternberg cells
B symptoms:
- Fever (38º C)
- Drenching sweats (esp. at night)
- Unintentional weight loss of greater than 10% in less than 6 months
Diagnosis:
- Excisional biopsy (take the whole lymph node out
How do you treat early stage, advanced stage, relapsed disease, and mainthenance therapy for Hodgkin Lymphoma?
Goal: CURE
Early stage:
- Radiation
- ABVD (Doxorubicin, Bleomycin, Vinblastine, Dacarbazine)
SEs: pulmonary toxicity
Advanced stage:
- ABVD (Doxorubicin, Bleomycin, Vinblastine, Dacarbazine)
- or AAVD (Doxorubicin, Brentuximab vendotin, Vinblastine, Dacarbazine)
SEs: peripheral neuropathy
Relapsed:
- High dose chemo, then autologous stem cell transplant
Maintenance:
- Brentuximab vedotin after stem cell transplant if high risk
How do patients with Non-Hodgkin Lymphoma (NHL) present? How should you diagnose NHL?
Presentation depends on tumor location:
- B-cell: lymph nodes, spleen, bone marrow
- T-cell: extra nodal sites (skin and lungs)
- Lymphadenopathy (can lead to organ dysfunction)
- B symptoms
- Extranodal involvement
- Primary CNS lymphoma
Diagnosis: Excisional biopsy
What are the differences between HL and NHL based on # of nodes, spread, Mesenteric nodes/Waldeyer ring, and extranodal presentation?
Hodgkin:
- single group of nodes
- orderly spread
- mesenteric nodes and Wadeyer ring are rarely involved
- extranodal presentation is rare
Non-Hodgkin Lymphoma:
- multiple peripheral nodes
- noncontinuous spread
- mesenteric nodes and Waldeyer ring are commonly involved
- extranodal presentation is common
How do we treat Diffuse Large B-Cell Lymphoma (DLBCL)? What do we test in NHL patients due to viral reactivation?
R-CHOP (Rituximab (anti-CD20), Cyclophosphamide, Doxorubicin, Vincristine, Prednisone)
SEs: neutropenia
Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb).
- Treat with entecavir 0.5mg daily
What are the 4 aspects of Multiple Myeloma presentation?
C: Calcium (hypercalcemia)
R: Renal dysfunction
A: Anemia
B: Bone lesions or fractures
What is the pathophysiology behind Chromic Myeloid Leukemia (CML)? How do these patients present? How should we diagnose?
Unregulated myeloid proliferation leads to excess mature neutrophil production. The philadelphia chromosome (BCR-Abl) is involved, which causes a constitutively active tyrosine kinase, which increases proliferation of the CML clone.
Presentation:
- Incidental finding during routine exam or CBC
- Leukocytosis (sticky blood)
Diagnosis:
- Bone marrow biopsy
What is our goal of treatment for CML and how do we treat it? What is the molecular response we are looking for?
Goal: Eradicate leukemic clone with minimal toxicity. The only way to cure is an allogenic hematopoietic stem cell transplant (HSCT)
Treatment: Tyrosine Kinase Inhibitors (TKIs)
- Imatinib (nausea)
- Dasatinib (fluid retention/pleural effusion)
- Nilotinib (QTc interval prolongation and metabolic syndrome)
- Bosutinib (Diarrhea) - Last line
- Ponatinib (ischemic reactions, vascular occlusion, hypertension)
for all of these, watch for CYP3A4 reactions (antifungals need dose reduction
Response:
- Gold standard is ≤ 0.01% BCR-ACL
What is the pathophysiology behind Chronic Lymphoid Leukemia (CLL)? How do you diagnose CLL?
Monoclonal B lymphocyte transformation undergoes clonal expansion, which leads to lymphocyte accumulation.
Diagnosis:
- Bone marrow biopsy
When do we treat CLL? How we treat CLL? What is important to know about venetoclax?
We treat when there are symptoms. We do NOT treat a number.
Treatment:
1. BTK inhibitors: acalabrutinib +/- obinutuzumab (anti-CD20), venetoclax + obinutuzumab, zanubrutinib
*watch out for transient lymphocytosis. It does NOT signify disease progression & resolves by week 12.
Venetroclax: SO MANY DRUG INTERACTIONS!! CYP3A4 and p-GP. Also SEVERE toxicities (tumor lysis syndrome)
What is the pathophysiology behind Acute Myeloid Leukemia (AML)? How do these patients present? How do we diagnose?
A single leukemic cell expands & mutates, then proliferates, which results in monoclonal population of leukemic cells. This throws off the balance between proliferation and differentiation.
Presentation:
- Signs of pancytopenia: anemia, neutropenia, thrombocytopenia
- Bone pain from hyperactive bone marrow
- Gum hypertrophy
Diagnosis:
- Bone marrow biopsy showing greater than 20% basts
How do we treat AML?
NO CURE
Induction (goal is remission)
- Intensive: cytarabine + idarubicin OR daunorubicin (7+3)
Consolidation (goal is to prevent relapse)
- Favorable: high dose cytarabine (watch out for neurotoxicities and chemical conjunctivitis)
- Unfavorable: stem cell transplant
What is the pathophysiology of Acute Lymphoblastic Leukemia? How do these patients present? How do you diagnose?
Like AML, a single leukemic cell expands & mutates, then proliferates, which results in monoclonal population of leukemic cells. This throws off the balance between proliferation and differentiation. Occasionally, philadephia chromosome can be associated (worse outcomes). In this case, add a TKI to the multi-agent chemotherapy.
These patients present similarly to AML.
- Signs of pancytopenia: anemia, neutropenia, thrombocytopenia
*One important difference is that ALL can hide in the brain.
Diagnosis: Bone marrow biopsy
How do you treat ALL?
Induction (goal -> remission)
Consolidation (goal -> eradicate residual disease)
- Hyper CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone)
all pts need CNS phophylaxis/treatment (intrathecal chemo)
Maintenance (goal -> prevent relapse): for 2-3 years
- 6-MP, methotrexate, prednisone, vincristine
What happens in these phases of the cell cycle: G1, S, G2, Mitosis
What phase is the CDK4/6 checkpoint and the R point?
G1 - gathering building blocks for DNA replication
- CDK4/6 check point (check if we have the building blocks, if there’s DNA damage, and if there’s a signal to proceed through the cell cycle)
- Restriction point (point of no return)
S - synthesis. DNA is replicated here
G2 - assembling machinery for mitosis
Mitosis - chromosomes are segregated and split into two cells
