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Oncology Exam 4
Frei Lymphoma F
| Question | Answer |
|---|---|
| What is Lymphoma? | Cancer that begins in the lymphocytes 2 main groups: (Hodgkin lymphoma – Reed Sternberg cells; Non-Hodgkin lymphoma – umbrella classification with at least 30 unique histopathologic diseases) |
| Lymphoma - Epidemiology? | -An estimated 66,120 people diagnosed in the United States in 2008 -Fifth most common cancer among men and women -Ninth most common cause of cancer death in men and seventh most common cause of cancer death among women -Non-Hodgkin lymphoma is a term that refers to many different types of lymphoma -Usually occurs in lymph nodes or other parts of the lymph system |
| Lymph System? | -Small vessels that transport lymph (common place of suprfollicular neck) -Four primary roles (Removal of interstitial fluid, Transporting fatty acids, Move lymphocytes between lymph nodes, Movement of APCs) -B-cells form antibodies (more often with B-cells) -T-cells have many properties and responsibilities |
| Lymphoma - Etiology can come from infectious agents such as? from what diseases? | -H. Pylori (MALT) -HIV (DLBCL, Burkitt lymphoma, Primary effusion lymphoma, PCNSL) -EBV (Burkitt lymphoma, Hodgkin) -HTLV-1/2 (T-cell lymphoma) -HHV8 (Primary effusion lymphoma) *HHV8 – human herpes virus 8; HTLV – human T lymphotrophic virus; EBV – Epstein Barr virus; MALT – mucosa associated lymphoid tissue; DLCBL – diffuse large B cell lymphoma; PCNSL – primary CNS lymphoma |
| Lymphoma - Etiology: Besides coming from infections, what other etiologies can a pt have an increased risk of lymphoma? | -Immunosuppression -Phenytoin -Chemotherapy/radiation |
| Symptoms of Lymphoma include? | -B-symptoms (such as night sweats) -Fatigue -Pain -Nausea/vomiting -Infection |
| Signs of Lymphoma include? | -Enlarged painless mass (swollen lymph node) -Myelosuppression -Increased LDH (lactate dehydrogenase) -Abnormalities due to tumor lysis |
| Diagnosis of Lymphoma includes? | -Presentation usually due to lymphadenopathy (lymph node enlarged) -Lymph node biopsy to confirm disease pathologically (Immunophenotype, Cytogenetics, Morphology) -Bone marrow biopsy -Other imaging is indicated for staging (CT scans, PET scans) -LDH (increased LDH is a sign of lymphoma) *PET scans are radio-labeled glucose (use of energy and cancer cells are usually hypermetabolic and helps to determine location) |
| Staging - Ann Arbor System: Stage I, nodal groups involved? *system uses diaphragm (upside down circle and use diaphragm to determine the stage, up or down limits involvements or both (makes it more advanced) | One nodal group (doesn't mean 1 lymph node, but chain) |
| Staging - Ann Arbor System: Stage II, nodal groups involved? | Two or more nodal groups on one side of the diaphragm |
| Staging - Ann Arbor System: Stage III, nodal groups involved? | Nodal groups above and below the diaphragm |
| Staging - Ann Arbor System: Stage IV, nodal groups involved? | Involvement of one or more organs rather than just the lymph node system alone |
| What is Hodgkin Disease? | -First described in 1832 by Thomas Hodgkin -The Reed-Sternberg cell is the “hallmark” of Hodgkin’s disease |
| Hodgkin Lymphoma amoeba sisters for visual learners: | *clonal B cell developed in lymphatic system (bi-nucleated (owl-eyes) 2 big circles in the cell and then see it spreads in orderly fashion from lymph node to lymph node. Swollen and have B symptoms (night sweats, unintentional weight loss, itching, splenomegaly) |
| Hodgkin Disease Information? | -Bimodal peak in incidence (in teenagers and older adults) -Good overall prognosis (Goal = cure) -Etiology – linked to EBV exposure (especially in older adults) |
| Hodgkin Disease Current Classification System is? | -Nodular sclerosis (75% of cases) -Mixed cellularity -Lymphocyte-rich -Lymphocyte-depleted |
| Stage strongly linked to prognosis: For Stage I and II disease – Early Stage Disease⭐️; Stage III and IV – Advanced Disease⭐️ . What are (-) Prognostic factors? | -B symptoms present -Male -Aged 45 years or older -Stage IV disease -Low blood albumin (protein) level (below 4 g/dL) -Low hemoglobin level (below 10.5 g/dl) -High white blood cell count (15,000/ml or higher) -Low lymphocyte count (below 600/ml or less than 8% of WBC # -High erythrocyte sedimentation rate (ESR) |
| Hodgkin Disease - Prognosis Factors: 0, 1,2, 3, 4, >/= 5: # of pts? 5-year progression free suvival %? what do we need to know? | *greater the number of those poor prognostic factors, the worse the 5-year survival is for the pt *progression free suvival--> alive and cancer hasn't come back |
| Early Stage HD with Favorable Prognostic Markers Therapy: Usually receive ______ & ________ x 2 cycles. Radiation--> to involved nodes (can cuase secondary cancer, esp breast cancer if thoracic radiation). | radiation & Chemotherapy |
| Early Stage HD with Favorable Prognostic Markers Therapy: Chemotherapy = current standard. What agents are 1st line chemo? remember ABVD | Adriamycin (doxyrubicin) Bleomycin Vinblastine Darcarbazine *ABVD x 2 cycles--> PET scan (reassess)--> ABVD x 1-2 cycles OR ABVD x 2 cycles + XRT OR ABVD x 4 cycles |
| ABVD: Be aware of Bleomycin Pulmonary toxicities such as? | Need to have Baseline and periodic pulmonary function tests More common in older adults More common when administering pulmonary irradiation Can be associated with use of growth factors (ie GCSF) Recommend smoking cessation *known for its pulmonary toxicitites |
| ABVD: Neutropenia is common with this treatment also seen with the Vinblastine- growth factor support not required bc the belomycin combo is not good. Decarbazine drug effects? | -Highly emetogenic (N/V) -Fertility issues (chemo and radiation to lower abdomen can cause fertility issues) *ovarian or testicular damage can occur and affect fertility BrECADD given with G-CSF since the regimen doesn't have bleomycin |
| ABVD: Vinblastine drug info and toxicities? | -From the Vinca alkaloid -Major dose limiting toxicity is neuropathy -Other toxicities – constipation and vesicant -Never give intrathecal – results in death (Test question) |
| ABVD: Doxorubicin cardiotoxicity? | -Baseline and periodic LVEF assessments -Late onset -Dose dependent -Irreversible -Max lifetime dose of doxorubicin is 550 mg/m2 -Dexrazoxane (Zinecard) is cardiotoxicity reversing agent ⭐️ *remember that Doxorubicin is a Vesicant (Dexarazoxane (Totect) is extravasation reversing agent) ⭐️ *DO NOT GIVE As Intrathecal |
| Bleomycin causes _____ and ____ toxicity | Lung & Skin (due to enzyme not present in large concentrations in these areas) |
| Early Stage HD with UNFavorable Prognostic Markers Therapy: usually receive ______ & _______ x 4-6 cycles. After these cycles--> Chemo + XRT--> | radiation & chemo ABVD x 2 cycles--> PET scan--> ABVD x 2 cycles OR ABVD x 2 cycles + XRT or ABVD x 4 cycles OR ⭐️BrECADD x 2 cycles + GCSF⭐️ (newest development) |
| What is in the BrECADD regimen? (first line in unfavorable) | -Brentuximab vedotin (BV) -Etoposide -Cyclophosphamide -Adriamycin (doxorubicin) -Dacabazine -Dexamethasone *Given with G-CSF |
| Brentuximab Vedotin drug information: | -MOA: anti-CD 30 conjugate antibody -Most HL cells express CD 30 -Black box warning for PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) -Contraindicated to be given at same time as bleomycin⭐️ due to pulmonary toxicity -Neuropathy is primarily sensory and is cumulative: Can be permanent -Pulmonary toxicity – uncommon but is serious and can be fatal |
| Advanced (Stage III – IV) HD Therapy-->(Age 18-60) Therapy? *more aggressive than just BrECADD | Initial Tx (Pick 1)--> Nivolumab-AVD OR BrECADD + G-CSF *radiation therapy is not an option (cant radiate wide areas without causing significant damage to the pt) *Be sure to be aware of SE of drug regimen options |
| Advanced HD: Initial Therapy | Nivolumab-AVD (N-AVD) x 6 cycles OR BrECADD* + G-CSF x 4-6 cycles Radiation Therapy Not Useful in this stage *BrECADD--> ⭐️Use with caution with pts > 60 yo; Contraindicated in those with neuropathy⭐️ AVD – doxorubicin, vinblastine, dacarbazine BrECADD – Brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone |
| Clinical Trial: SWOG S1826 trial: N+ AVD superior to prior standard of care BV + AVD | N+AVD resulted in longer progression-free survival than BV+AVD in adolescents and adults with stage III or IV advanced-stage classic Hodgkin’s lymphoma and had a better side-effect profile. |
| HD 21 trial: 1st line tx for advanced stage HL. Treatment arms used were? Outcomes? | 4-6 cycles of BrECADD Compared to 4-6 cycles of eBEACOPP (more toxicities) -BrECADD guided by PET after two cycles is better tolerated and more effective than eBEACOPP in f irst-line treatment of adult patients with advanced-stage, classical Hodgkin lymphoma |
| Survivors of Hodgkin Lymphoma: Monitor for late effects of tx. Overall cancer rate in survivors is elevated compared to general populations. Most pts that are survivors must be monitored for secondary malignancies such as? | -Secondary malignancies can be elevated for 15 – 20 years -Induced by Radiation -Induced by Anthracyclines -Genetic susceptibilities -Shared etiologic exposures -Monitor for cardiac toxicity (delayed effect that can occur) |
| NON-Hodgkin Lymphoma (NHL) general info: | -5th most common cause of cancer -B-cell malignancy accounts for ~85% of lymphoma ⭐️ -More common in men than women⭐️ -More common in Caucasians⭐️ -Incidence has been rising about 3-4% each year |
| Non-Hodkin Lymphoma Types: | this shows the most commmo subtypes of lymphoma. know the top 2: -Diffuse large b-cell lymphoma ⭐️ (DLBCL abb. in literature) -Follicular lymphoma⭐️ (Follicular) |
| For Non-Hodkin lymphoas that are classified as "Indolent lympoma" (low grade) where survival is years⭐️ include which types of lymphomas? | -Follicular lymphoma ⭐️ -Marginal zone lymphoma -Mantle cell lymphoma -MALT *indolent--> slow growth and long survival for years, and diff. to cure ⭐️ |
| For Non-Hodkin lymphoas that are classified as "Aggressive lymphoma" where survival is months⭐️ include which types of lymphomas? | -Diffuse large b-cells (recognize this is aggressive and most common sybtype of NHL) ⭐️ *can extend survival with tx but pt would likely ahve death in months |
| For Non-Hodkin lymphoas that are classified as "Highly aggressive lymphoma" where survival is weeks⭐️ include which types of lymphomas? | -Burkitt lymphoma (3rd most common lymphoma and associated with pts with HIV) -Immunoblastic lymphoma |
| The IPI (International Prognostic Index) is used to estimate _____ where pts are stratified based on clinical features. Analysis determined based on anthracycline based chemotherapy. There are 2 types for the IPI. These are? | PFS; FL-IPI (original) and R-IPI (new data and trials with Rituximab for "R") |
| What goes into the FL-IPI analysis? | N - (# of nodes) (1-5) remember that 0-1 good PS; 4-> no chemo L (LDH) (high? poor prognostic) A (age) S (Stage) H (hemoglobin) |
| What goes into the R-IPI analysis? | A (age) P (performanse status) L (LDH) E (Extranodal disease) S (Stage) |
| R-IPI: Pt Risk: Poor: IPI score? % of pts? Disease free survival (4 year)? Overall survival (4 year)? | 3,4,5; 45; 54%; 55% *If you have a high IPI, you have worst survival |
| Treatment of lymphoma: Treatment depends on type of lymphoma and the stage of cancer. What are the options? (1 or more may be used) | Watch and wait Radiation therapy Chemotherapy Immunotherapy Stem cell transplantation |
| Indolent Lymphoma Therapy information? | -2nd most common of all NHL is Follicular Lymphoma ⭐️ -Follicular Lymphoma is the most common Indolent Lymphoma -Median age of diagnosis: 60 years old ⭐️ -Goal of therapy: palliation -Few patients will achieve cure since its slow growing "lymphoma" in multiple areas, cant radiate all the areas. -Many patients go years without needing treatment |
| Indolent Lymphoma Therapy: for Early stage what is the tx? | Radiation therapy only; no drug therapy |
| Indolent Lymphoma Therapy: For Advanced stage - most common stage for diagnosis (in multiple lymph node groups and involved in organs) --> | Not considered curable Watch and wait Immunotherapy +/- chemotherapy *CD20 therapy should be used in all regimens (obinituzumab or rituximab) |
| For the immunotherapy +/- chemotherapy for "Advanced Stage" Indolent lymphoma therapy consist of what options? *remember that CHOP is a common chemotherapy regimen *Rituximab and Obinutizumab are your immunotherapy agents | -CHOP + (obinutuzumab or rituximab) -Bendamustine + (obinutuzumab or rituximab) -CVP + (obinutuzumab or rituximab) -Lenalidomide + rituximab (R2) -Rituximab single agent (if low tumor burden or elderly or unfit) *CHOP = cyclophosphamide, doxorubicin (Hydroxydaunorubicin), vincristine, prednisone *CVP = cyclophosphamide, vincristine, prednisone |
| What is in CHOP chemotherapy regimen? | Cyclophosphamide Doxorubicin (Hydroxydaunorubicin) Vincristine (Oncovin) Prednisone |
| Chop contains Cyclophosphamide, Doxorubicin (Hydroxydaunorubicin), Vincristin (oncovin). Prednisone. What are the known major toxicities? | -Cyclophosphamide – hemorrhagic cystitis, nausea/vomiting, infertility -Doxorubicin – irreversible cardiomyopathy, nausea/vomiting, mouth sores -Vincristine – constipation, neuropathy, vesicant -Prednisone (100 mg on days 1 – 5): Long term toxicities – osteoporosis, adrenal suppression, infections, Short term toxicities – hyperglycemia, insomnia, weight gain |
| ADRs of Lenalidamide? BBW? | -Myelosuppression (common), rash, fatigue, fever BBW: Embryo-fetal toxicity, hematologic toxicity, VTE |
| ADRs of Bendamustine? BBW? | -Myelosuppression (common), infections, nausea/vomiting, fatigue -BBW: NONE |
| BBW of Rituximab and Obinutuzumab? | -Fatal infusion reactions (R) -Severe mucocutaneous reactions (R) -Hepatitis B virus reactivation -Progressive multifocal leukoencephalopathy (PML) |
| Using Rituximab and Obinutuzumab, we recommend screening in all pts at baseline for hepatitis for? | Hepatitis B surface antigen (HBsAg) Hepatitis B core antibody (HGcAb) |
| Immunotherapy: Most lymphomas are B cell lymphomas and rituximab can be combined with CHOP for treatment (regimen called R-CHOP). In Indolent lymphomas, ________ can be added to CHOP in the place of rituximab for tx phase. This regimen is called G-CHOP bc brand name of obinutuzumab is _______ | obinutuzumab, Gazyza. |
| Immunotherapy: T cell lymphomas receive CHOP and ___ ___ ____ Rituximab and Obinutuzumab | Do Not Receive *not effective and all your doing is increasing toxicities. bc t-cell don't have the target that obi and ritux are targeting |
| Comparison of Rituximab to Obinutuzumab: Rituximab information? | Better tolerated⭐️ MORE infusion related reactions⭐️ Less neutropenia Less thrombocytopenia Similar efficacy in Aggressive lymphoma⭐️ Biosimilars available: Rituximab-abbs, Rituximab-pvvr, Rituximab SQ formulation (benefit to less infusion rxn): Rituxan Hycela – only given after tolerated one IV dose |
| Comparison of Rituximab to Obinutuzumab: Obinutuzumab information? | -Increased toxicities⭐️ -Increased secondary malignancies⭐️ -Better response in Indolent lymphoma⭐️ |
| Indolent Lymphoma Maintenance: After initial therapy, indolent lymphoma pts will receive ______ therapy.Preferred consolidation or extended dosing? | -maintenance Rituximab maintenance q 8 – 12 weeks for 2 years Obinutuzumab maintenance q 8 weeks for 12 doses *stop chemo and go with immuno therapy and continue the one they are on. Woudnt switch from G-CHOP to R-CHOP for example. Timeframe depends on the pt's response *for about 2 years ⭐️ don't worry about the frequency |
| Aggressive Lymphoma: Most common aggressive lymphoma and most common NHL is? Goal of Tx? *tx duration depedent on stage and size | Diffuse large B cell lymphoma (DLBCL); CURE *no maintenance rituximab ⭐️ *Obinutuzumab is NOT recommended⭐️ in the aggressive setting (not recommended for aggressive form bc clinical data shows no advantage with G-CHOP over R-CHOP but G-CHOP has more ADRs). R-CHOP is preferred *Chemoimmunotherapy of choice is R-CHOP ⭐️ |
| Aggressive Lymphoma: Workup includes? | -Physical exam -CBC, Comprehensive metabolic panel, LDH, uric acid, -Scans – PET/CT Scan -Calculate IPI -Hep B testing -ECHO or MUGA if receiving anthracycline (i.e doxorubicin) to determine decreased Ejection Fraction -Pregnancy testing |
| Aggressive Lymphoma: Early stage tx? *one nodal or localized on same side of diaphragm | -Chemoimmunotherapy -R-CHOP x 3 – 4 cycles or Pola-R-CHP -AND radiation therapy⭐️ *localized and in same area; radiate a small group of lymph nodes and are close together on same side of diaphragm |
| Aggressive Lymphoma: Advanced Stage tx? | -Chemoimmunotherapy alone -R-CHOP x 3 – 4 cycles or Pola-R-CHP x 6 cycles *radiation not offered in advanced setting (in organs and both sides of the diaphragm) |
| Treatment – CHOP no different than other more toxic regimens: landmark trial in 1993 | *showed that the CHOP was non-infererior to other regimens and CHOP was better tolerated ⭐️ |
| Treatment: R-CHOP shows improved responses: 2005 trial was studied and did R-CHOP vs CHOP | R-CHOP was sig. better in free survival and overall survival. *shows improved responses over CHOP. |
| Polarix Trial studied in 2022 and Polatuzumab was introduced to be superior to R-CHOP | -First-line treatment with the pola-R-CHP combination evaluated in the current trial showed a progression-free survival benefit over the R-CHOP regimen at 2 years and had a similar safety profile *statistically superior for progression free and got Pola-R-CHP, Both are still recommended in guidelines |
| Chemotherapy: What is in the Pola-R-CHP regimen? | -Polatuzumab vedotin-piiq -Rituximab -Cyclophosphamide -Doxorubicin (Hydroxydaunorubicin) -Prednisone |
| Chemotherapy: What are the known major toxicities of Pola-R-CHP? | -Polatuzumab vedotin-piiq – peripheral neuropathy, neutropenia, infusion reaction, fatigue, diarrhea *POLA with R-Chop--> too much neuropathy which is why Vincristine is removed from the regimen |
| Which of the following disease states would it not be appropriate to use rituximab? A. Peripheral T-Cell Lymphoma B. Mantle Cell Lymphoma C. Diffuse Large B-Cell Lymphoma D. Follicular Lymphoma | A. Peripheral T-Cell Lymphoma *b/c rituximab and obinatuzumab will not target your T-cells |
| Conclusions: Lymphomas: | -Hodgkin lymphoma: Most patients treated with combination chemotherapy -Non-Hodgkin lymphoma: Consider B symptoms and bulky disease. Most express CD 20; -Indolent Lymphomas: R-CHOP or G-CHOP standard of care. Obinutuzumab can be used instead of rituximab with indolent lymphomas -Aggressive lymphomas: Early Stage - R-CHOP or Pola-R-CHP; Advanced Stage - R-CHOP or Pola-R-CHP *do not pick Obi in the aggressive lymphomas |
| Summary of Hodgkin Lymphomas: | -B cell -Usually only single group of affected LN -Treatment involves ABVD or N+AVD or BrECADD -Reed Sternberg Cells *looks like an owl (binucleated) and hallmark of hodgkin's lymphoma *Common Features: Painless lymphadenopathy; B Symptoms; Pruritus |
| Summary of non-Hodgkin Lymphomas: | -90% of all lymphomas -B or T cell -Affects multiple groups of nodes (usually) *Common Features: Painless lymphadenopathy; B Symptoms; Pruritus |
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Xander635
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