OVERVIEW OF KEY NHL SUBTYPES

FOLLICULAR LYMPHOMA (FL)

Definition and Natural History: Indolent B-cell NHL characterized by t(14;18)(q32;q21) leading to BCL2 overexpression. Median age ~60 years, chronic relapsing course, generally considered incurable. Approximately 15–30% present with limited (stage I/II) disease.

Treatment Indications: Symptomatic disease, B symptoms, end-organ threat, cytopenias, or bulky disease. Asymptomatic patients with low tumor burden → observation ("watch and wait"). Multiple studies including Ardeshna et al. show no survival benefit to early treatment in asymptomatic low-burden FL.

PROGNOSTIC INDICES

FLIPI — for Follicular Lymphoma

Five adverse prognostic factors:

• Age > 60 years
• Ann Arbor stage III or IV
• Hemoglobin < 12 g/dL
• Number of involved nodal areas > 4
• Serum LDH > upper limit of normal

Performance status and extranodal sites are NOT part of FLIPI. FL is nodal-predominant and hemoglobin is used instead because bone marrow involvement is common. FLIPI divides FL into three risk groups: Low (0–1 factors), Intermediate (2 factors), High (≥ 3 factors). 10-year OS with 0–1 factors = 71%.

Treatment by Stage and Situation

Maintenance Therapy after First-Line Chemoimmunotherapy: Rituximab 375 mg/m² every 8 weeks x 2 years is a Category 1 recommendation (PRIMA trial). Significantly prolongs PFS but not OS. No role for maintenance lenalidomide in FL. Maintenance obinutuzumab is reserved for patients who received obinutuzumab-based induction.

Key Rules:

• Single-agent obinutuzumab is NOT recommended as initial therapy for FL
• BR is preferred over R-CHOP in advanced FL (StiL NHL1 trial: PFS 69.5 vs. 31.2 months, fewer serious adverse effects)
• Radiotherapy is reserved for localized stage I/II disease only
• R/R options include PI3K inhibitors (e.g., copanlisib), tazemetostat, or CAR-T (axicabtagene ciloleucel, tisagenlecleucel)

Early Relapse Management (< 12 months): Prefer non-cross-resistant regimens; add rituximab if prior antibody therapy achieved > 6–12 months remission; auto-SCT prolongs both PFS and OS in relapsed FL.

DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)

Goal of therapy: CURE.

INTERNATIONAL PROGNOSTIC INDEX (IPI) — for aggressive NHL (DLBCL)

Five poor prognostic factors:

• Age > 60 years
• Serum LDH > upper limit of normal
• ECOG performance status ≥ 2
• Ann Arbor stage III or IV
• Number of extranodal sites > 1

Sex is NOT an IPI factor. Beta-2 microglobulin is NOT an IPI factor.

5-year OS by IPI score (without rituximab): score 0–1 = 73%, score 2 = 51%, score 3 = 43%, score 4–5 = 26%.

Treatment by Stage:

Key Rules:

• G-CHOP is NOT recommended: no PFS benefit over R-CHOP and more grade 3 toxicities
• R-CHOP alone (without RT) is acceptable for limited disease but combined modality is preferred
• Double-hit lymphoma (BCL2 + MYC or BCL6 + MYC rearrangements) requires more aggressive regimens
• No maintenance therapy recommended in DLBCL
• Repeating R-CHOP at relapse is not preferred due to prior anthracycline exposure and cumulative cardiotoxicity

DLBCL with Poor Cardiac Function (EF < 30% or underlying cardiac disease): Anthracyclines are NOT recommended. Acceptable alternatives (all given with rituximab): R-CEPP, R-CDOP (liposomal doxorubicin), R-CNOP (mitoxantrone), R-CEOP, dose-adjusted EPOCH-R. R-CVP is NOT recommended for DLBCL.

CNS Involvement by NHL: Median survival without treatment = 3–13 months. Risk is increased with bone marrow, testicular, paranasal sinus, or retroperitoneal node involvement, and with high-risk IPI. Treatment options: RT + intrathecal chemotherapy (cytarabine/methotrexate), high-dose IV cytarabine/MTX, or stem cell transplantation.

MANTLE CELL LYMPHOMA (MCL)

• Diagnostic Hallmark: Cyclin D1 overexpression + t(11;14)(q13;q32). The translocation juxtaposes CCND1 (chromosome 11) with IGH (chromosome 14), causing dysregulated Cyclin D1 expression and uncontrolled B-cell proliferation. Confirmed by FISH or IHC.
• Immunophenotype: CD20+, CD5+, Cyclin D1+, SOX11+.
• Clinical Features: Median age 60–70 years, male predominance, typically advanced stage at diagnosis with frequent extranodal involvement (GI tract, bone marrow, spleen). Indolent onset but aggressive relapsing course.

Treatment by Patient Fitness

• TRIANGLE Regimen: R-CHOP + ibrutinib (Category 2A) or acalabrutinib/zanubrutinib (Category 2B) alternating with R-DHA + platinum, followed by ASCT + 2 years BTKi maintenance.
• NORDIC Regimen: R-maxi-CHOP alternating with rituximab + high-dose cytarabine (Ara-C), followed by ASCT. High-dose cytarabine is specifically shown to improve outcomes in younger MCL patients.
• R-DHAP vs. R-DHAX: Both use rituximab + dexamethasone + high-dose cytarabine. R-DHAP uses cisplatin; R-DHAX uses oxaliplatin (preferred to reduce nephrotoxicity). Also used as salvage in relapsed/refractory DLBCL.

BTK Inhibitor Comparison

Brexucabtagene autoleucel (CAR-T): Only recommended AFTER receipt of both chemoimmunotherapy AND a BTK inhibitor.

Pharmacist Considerations: Screen for hepatitis B before CD20 antibody use. Monitor for tumor lysis syndrome in bulky/aggressive disease. Monitor BTK inhibitor toxicities (bleeding, AFib, diarrhea). Monitor cytopenias, infections, and neuropathy with vincristine-containing regimens.

BURKITT LYMPHOMA (BL)

Definition: Highly aggressive B-cell NHL; hematologic emergency due to rapid proliferation and high TLS risk.

Molecular Hallmark: MYC gene translocation, most commonly t(8;14)(q24;q32). Ki-67 proliferation index ~100%.

Three Clinical Variants

• Treatment: CHOP and R-CHOP are INADEQUATE. Intensive short-course chemotherapy is required: CODOX-M/IVAC (cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate / ifosfamide, etoposide, cytarabine) or DA-EPOCH-R (dose-adjusted, includes rituximab) or R-HyperCVAD. CNS prophylaxis with intrathecal methotrexate or cytarabine is mandatory.
• TLS Prophylaxis: Mandatory due to near-100% proliferative rate. Use allopurinol or rasburicase with aggressive hydration and electrolyte monitoring.
• Pharmacist Considerations: Methotrexate requires leucovorin rescue with careful timing; avoid nephrotoxic drugs. Monitor for myelosuppression, mucositis, cardiotoxicity (doxorubicin), and neurotoxicity (vincristine). G-CSF and antiemetics as indicated. Screen for hepatitis B before rituximab.

T-CELL LYMPHOMAS

• PERIPHERAL T-CELL LYMPHOMA NOS (PTCL-NOS): Standard first-line therapy is CHOP. If CD30-positive, use brentuximab vedotin + CHP. Rituximab is NOT used because PTCL-NOS is CD20 negative. Other first-line options (performance-status dependent): clinical trial, CHOEP-21, or DA-EPOCH. Belinostat is reserved for the relapsed/refractory setting only.
• CUTANEOUS T-CELL LYMPHOMA (CTCL): Most common supportive care issue is pruritus, which is frequent and debilitating especially in widespread or refractory disease. Bleomycin is not routinely used in CTCL. Anti-CD20 agents are not used (tumor is T-cell origin), so hepatitis B reactivation from rituximab is not a concern. Mucositis is not a universal feature.
• NODULAR LYMPHOCYTE-PREDOMINANT HODGKIN LYMPHOMA (NLPHL): Distinct from classical HL. Characterized by CD20-positive "popcorn" LP cells expressing B-cell markers (CD20, BCL6). For advanced-stage NLPHL with B symptoms, the preferred regimen is ABVD + rituximab. Brentuximab vedotin + AVD is used for classical HL, NOT NLPHL (tumor is CD20+, not CD30+).

RITUXIMAB AND HEPATITIS B — KEY RULES

Mandatory pre-treatment screening: HBsAg and HBcAb (hepatitis B core antibody).

Preferred antiviral: Entecavir or tenofovir (higher barrier to resistance, better viral suppression). Lamivudine is NOT preferred due to resistance concerns. CMV testing, ESR, and ANA are NOT routine pre-rituximab screening tests.

TREATMENT MANAGEMENT PEARLS

• Rituximab: First-dose infusion reactions are common — premedicate with acetaminophen and antihistamine. Subcutaneous formulation (Rituxan Hycela) is available after the first IV dose.
• Bendamustine: Monitor for infusion reactions, rash, and prolonged lymphopenia. NOT interchangeable with other alkylating agents.
• CAR-T Therapy: Requires specialized center. Key toxicities are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
• TLS Risk: Highest in aggressive lymphomas (Burkitt, DLBCL) and with venetoclax-containing regimens. Always ensure allopurinol or rasburicase prophylaxis and close monitoring.

OG is a 67-year-old male with Stage III, grade 2 follicular lymphoma. He has B symptoms (fever, night sweats, weight loss) and symptomatic bloating. Bone marrow biopsy is negative. He has no significant comorbidities. Which is the most appropriate treatment?

A. Radiotherapy
B. BR x 6 cycles
C. Obinutuzumab x 12 cycles
D. CHOP x 8 cycles

[expand] Answer: B. BR x 6 cycles

Explanation: OG has advanced-stage (Stage III), symptomatic follicular lymphoma with B symptoms, which are clear indications for systemic therapy. BR (bendamustine + rituximab) is the preferred first-line chemoimmunotherapy for advanced FL. The StiL NHL1 trial demonstrated significantly longer PFS (69.5 vs. 31.2 months) and fewer serious adverse effects compared to R-CHOP. Radiotherapy is only appropriate for localized stage I or non-bulky stage II disease. Single-agent obinutuzumab is not recommended as initial therapy for FL. CHOP without rituximab is not the standard of care for B-cell malignancies, and 8 cycles is not the standard duration for BR.

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OG completed 6 cycles of BR and achieved a complete response. He asks whether maintenance therapy is appropriate. Which is the most appropriate response?

A. Yes, rituximab every 2 months x 2 years
B. Yes, lenalidomide daily x 3 years
C. Yes, obinutuzumab monthly x 1 year
D. No, maintenance therapy is not indicated in FL

[expand] Answer: A. Yes, rituximab every 2 months x 2 years

Explanation: Rituximab maintenance is a Category 1 recommendation for FL patients who respond to first-line chemoimmunotherapy. The landmark PRIMA trial randomized FL patients with partial or complete response to observation versus rituximab 375 mg/m² every 8 weeks for 2 years and demonstrated significantly prolonged PFS. There is no established role for maintenance lenalidomide in FL. Maintenance obinutuzumab is reserved for patients who received obinutuzumab-based induction, not rituximab-based regimens like BR. Maintenance therapy is definitively indicated and should not be withheld from responding patients.

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OG completed 6 cycles of BR and achieved a complete response. Which is the most appropriate next option?

A. Ofatumumab monthly x 1 year
B. Lenalidomide daily
C. Rituximab monthly x 1 year
D. Rituximab every 2 months x 2 years

[expand] Answer: D. Rituximab every 2 months x 2 years

Explanation: Per the PRIMA trial, the correct maintenance schedule for FL after chemoimmunotherapy response is rituximab every 2 months (every 8 weeks) for 2 years, not monthly. Ofatumumab is not a standard maintenance option in FL. Lenalidomide has no established maintenance role in FL. Monthly rituximab does not reflect the evidence-based schedule from the PRIMA trial.

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DM is a 63-year-old male with Stage IVB DLBCL, IPI score 3, ECOG PS 0, no BCL2/BCL6/MYC rearrangements. What is the goal of therapy?

A. Disease cure
B. Improve disease-free survival
C. Symptom palliation
D. Decrease disease burden prior to autologous SCT

[expand] Answer: A. Disease cure

Explanation: Unlike follicular lymphoma where the goal is palliation, the goal of treatment in DLBCL is always disease cure, even in advanced-stage disease. Even Stage IVB DLBCL is potentially curable with appropriate chemoimmunotherapy. Options B, C, and D do not reflect the curative intent that defines DLBCL management.

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DM has Stage IVB DLBCL with IPI score 3 and ECOG PS 0. Which is the most appropriate first-line treatment regimen?

A. R-CHOP x 3 cycles + RT
B. R-ICE x 3 cycles
C. Pola-R-CHP x 6 cycles
D. G-CHOP x 6 cycles

[expand] Answer: C. Pola-R-CHP x 6 cycles

Explanation: With an IPI score of 3 (≥ 2), DM is a candidate for Pola-R-CHP. R-CHOP x 6 cycles is also acceptable for advanced disease and would be the answer if IPI were not specified as ≥ 2. R-CHOP x 3 + RT is the limited-stage approach and is inappropriate for Stage IVB disease. R-ICE is a second-line salvage regimen, not first-line. G-CHOP showed no PFS advantage over R-CHOP but had significantly more grade 3 toxicities and is therefore not recommended. The absence of double-hit rearrangements means more aggressive regimens are not required.

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For the same patient DM, if IPI is not the deciding factor, which is the most appropriate treatment for advanced-stage DLBCL without double-hit rearrangements?

A. R-CHOP x 3 cycles + RT
B. R-ICE x 3 cycles
C. R-CHOP x 6 cycles ± RT
D. G-CHOP x 6 cycles ± RT

[expand] Answer: C. R-CHOP x 6 cycles ± RT

Explanation: For advanced-stage DLBCL without double-hit rearrangements, R-CHOP x 6 cycles with or without local radiation therapy is the standard of care based on long-term survival data. R-CHOP x 3 + RT is reserved for limited (stage I/II) disease. R-ICE is second-line salvage therapy. G-CHOP is not recommended due to greater toxicity without PFS benefit compared to R-CHOP.

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DM achieved complete response after first-line therapy. Eighteen months later he relapsed with Stage IVB DLBCL. ECOG PS remains 0. Which is the most appropriate treatment?

A. R-CHOP x 6 cycles
B. R-ICE followed by maintenance rituximab
C. R-DHAP followed by maintenance lenalidomide
D. R-GDP or R-ESHAP followed by autologous SCT

[expand] Answer: D. R-GDP or R-ESHAP followed by autologous SCT

Explanation: DM relapsed more than 12 months after completing first-line therapy with a good performance status, making him eligible for salvage chemotherapy followed by autologous SCT. Acceptable salvage regimens include R-ICE, R-GDP, R-ESHAP, and R-DHAP. Repeating R-CHOP is not appropriate due to prior anthracycline exposure and cumulative cardiotoxicity risk. There are no current recommendations for maintenance therapy (rituximab or lenalidomide) in DLBCL, making options B and C incorrect.

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Before starting rituximab, DM's hepatitis B panel shows HBsAb positive, HBsAg negative, HBcAb negative. LFTs are normal. What is the most appropriate action?

A. Initiate rituximab as scheduled
B. Reschedule and give the hepatitis B vaccine series
C. Eliminate rituximab and start entecavir
D. Start lamivudine and proceed with rituximab

[expand] Answer: A. Initiate rituximab as scheduled

Explanation: HBsAb positivity alone indicates protective immunity from prior vaccination or resolved infection. Prophylactic antiviral therapy is only required in patients who are HBsAg-positive or HBcAb-positive. DM is negative for both, so rituximab can be initiated as planned. If antiviral therapy were indicated, entecavir would be preferred over lamivudine due to a higher barrier to resistance.

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Which screening test should be performed before initiating rituximab therapy?

A. Erythrocyte sedimentation rate
B. Hepatitis B surface antigen
C. Cytomegalovirus viral load
D. Antinuclear antibody level

[expand] Answer: B. Hepatitis B surface antigen

Explanation: Mandatory pre-rituximab screening includes HBsAg and HBcAb because rituximab carries a risk of HBV reactivation, which can be fatal if undetected. Antiviral prophylaxis is required if either test is positive. CMV testing is only performed for symptomatic patients or specific therapy indications, not routinely. ANA levels and ESR are not routinely monitored before rituximab. Hepatitis C has no formal screening recommendations before rituximab.

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A 69-year-old male with DLBCL is HBsAg-negative but HBcAb-positive with undetectable HBV PCR. He is starting rituximab. What is recommended?

A. Lamivudine during rituximab only
B. Lamivudine during rituximab + 12 months post-therapy
C. Entecavir during rituximab only
D. Entecavir during rituximab + 12 months post-therapy

[expand] Answer: D. Entecavir during rituximab + 12 months post-therapy

Explanation: HBcAb positivity indicates prior HBV exposure and places this patient at moderate-to-high risk for HBV reactivation with rituximab, even with undetectable HBV DNA. Prophylactic antiviral therapy must be started before rituximab and continued for at least 12 months after completing immunochemotherapy. Entecavir or tenofovir is preferred over lamivudine due to a higher barrier to resistance and superior long-term viral suppression.

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TR is a 72-year-old male with relapsed mantle cell lymphoma who has residual peripheral neuropathy from prior VR-CAP therapy. Which is the most appropriate treatment?

A. Acalabrutinib + obinutuzumab
B. Bortezomib + rituximab
C. Brexucabtagene autoleucel
D. Zanubrutinib

[expand] Answer: D. Zanubrutinib

Explanation: TR has residual peripheral neuropathy from prior VR-CAP, so bortezomib must be avoided since it is a known cause of peripheral neuropathy. Zanubrutinib is a selective oral BTK inhibitor recommended for relapsed MCL without significant neuropathy risk. Acalabrutinib is also appropriate for relapsed MCL, but there is no evidence supporting the combination of acalabrutinib + obinutuzumab in this setting. Brexucabtagene autoleucel is only recommended after receipt of both chemoimmunotherapy AND a BTK inhibitor, which has not yet occurred in TR's treatment course.

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PG is a 67-year-old female with refractory cutaneous T-cell lymphoma. Which supportive care issue is a frequent consideration in CTCL patients?

A. Bleomycin-induced pulmonary toxicity
B. Hepatitis B reactivation
C. Pruritus
D. Mucositis

[expand] Answer: C. Pruritus

Explanation: Pruritus is a frequent and debilitating symptom in patients with CTCL, especially those with widespread or refractory disease, and requires ongoing supportive management. Bleomycin is not routinely used in CTCL treatment. Anti-CD20 agents are not used in CTCL because the tumor is of T-cell origin and does not express CD20, so hepatitis B reactivation from rituximab is not a concern. Mucositis may occur with certain systemic treatments but is not a universal or defining feature of CTCL management.

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BH is a 61-year-old male with Stage IV PTCL-NOS. Flow cytometry shows CD20 negative, CD30 negative, ALK-1 negative. What is the most appropriate first-line treatment?

A. Brentuximab vedotin + CHP
B. R-CHOP
C. CHOP
D. Belinostat

[expand] Answer: C. CHOP

Explanation: The standard of care for CD30-negative PTCL-NOS is CHOP. Rituximab is not used because the tumor is CD20 negative, making R-CHOP incorrect. Brentuximab vedotin targets CD30 and is only appropriate if the tumor is CD30 positive. Belinostat is a histone deacetylase inhibitor reserved exclusively for relapsed or refractory PTCL, not first-line therapy. Other first-line options depending on performance status include CHOEP-21, DA-EPOCH, or clinical trial enrollment.

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Which of the following is NOT an IPI prognostic factor for NHL?

A. Age > 60
B. Sex
C. Nodal sites
D. Extranodal sites > 1

[expand] Answer: B. Sex

Explanation: The five validated IPI factors for aggressive NHL are age > 60, serum LDH above normal, ECOG performance status ≥ 2, Ann Arbor stage III or IV, and number of extranodal sites > 1. Sex is not included. Notably, nodal sites are also not a separate IPI factor — extranodal involvement is what matters. 5-year OS without rituximab: IPI 0–1 = 73%, IPI 2 = 51%, IPI 3 = 43%, IPI 4–5 = 26%.

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Which of the following is NOT included in the FLIPI for follicular lymphoma?

A. Hemoglobin < 12 g/dL
B. Performance status
C. Nodal areas > 4
D. Age > 60
E. All except B and D

[expand] Answer: E. All except B and D (meaning performance status AND extranodal sites are both excluded)

Explanation: The five FLIPI factors are age > 60, Ann Arbor stage III/IV, hemoglobin < 12 g/dL, nodal areas > 4, and LDH > ULN. Performance status and extranodal sites are excluded because FL is predominantly nodal in distribution, and hemoglobin is used since bone marrow involvement is common in FL and hemoglobin better reflects disease extent. FLIPI divides patients into Low (0–1), Intermediate (2), and High (≥ 3) risk groups. 10-year OS with 0–1 factors = 71%.

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What is the preferred treatment for stage IA DLBCL?

A. R-CHOP x 3 cycles followed by PET-CT and RT if PET negative
B. R-CHOP x 2 cycles followed by PET-CT and 2 more cycles if PET negative
C. Radiotherapy alone
D. R-CHOP x 6 cycles followed by PET-CT and 2 more cycles if PET negative

[expand] Answer: A. R-CHOP x 3 cycles followed by PET-CT and RT if PET negative

Explanation: Limited-stage (Stage I or II) DLBCL is defined as disease containable within one radiation field and accounts for less than 30% of DLBCL cases. The preferred treatment is combined modality therapy: 3 cycles of R-CHOP followed by involved-field radiation therapy. Studies show this approach has equivalent or improved survival compared to 8 cycles of chemotherapy alone in non-bulky limited-stage disease over 10 years of follow-up, with less toxicity. Full-course chemotherapy alone (6–8 cycles) without radiation is a less desirable alternative. Radiotherapy alone is insufficient for DLBCL.

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Which of the following is NOT an appropriate treatment for DLBCL in a patient with poor left ventricular function?

A. R-CVP
B. R-CEPP
C. R-CNOP
D. Dose-adjusted EPOCH-R

[expand] Answer: A. R-CVP

Explanation: Anthracyclines (as in standard R-CHOP) are not recommended for patients with baseline ejection fraction below 30% or significant underlying cardiac disease. Cardiotoxicity occurs in 4% of patients at doxorubicin doses of 500–550 mg/m² and in 36% at doses ≥ 600 mg/m². For patients unable to receive anthracyclines, NCCN-recommended alternatives (all combined with rituximab) include R-CEPP, R-CDOP (liposomal doxorubicin), R-CNOP (mitoxantrone), R-CEOP, and dose-adjusted EPOCH-R. R-CVP is not mentioned in NCCN guidelines for DLBCL treatment and is therefore the incorrect option. Poor ECOG performance status alone is not a contraindication to anthracyclines if cardiac function is preserved.

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Which of the following is true regarding secondary CNS involvement by NHL?

A. Median survival without treatment is 3–13 months
B. Risk is increased with bone marrow involvement
C. More common with high-grade lymphomas
D. All of the above

[expand] Answer: D. All of the above

Explanation: All three statements are accurate. Median survival after CNS involvement by NHL without treatment ranges from 3 to 13 months. Risk is increased with lymphomatous involvement of bone marrow, testes, paranasal sinuses, and retroperitoneal lymph nodes. CNS involvement is more common in high-grade lymphomas and in patients with advanced IPI risk. Treatment options include radiation therapy with intrathecal chemotherapy (cytarabine or methotrexate), high-dose IV cytarabine or methotrexate, and stem cell transplantation, which may prolong survival.

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What is the preferred treatment for stage I follicular lymphoma?

A. Radiotherapy
B. Chemotherapy
C. Combined chemoradiotherapy
D. Rituximab only
E. Watch and wait

[expand] Answer: A. Radiotherapy

Explanation: For stage I or II follicular lymphoma (15–30% of FL cases), involved-site radiation therapy (ISRT) at 30–36 Gy is the preferred treatment. This is associated with a 10-year OS of 60–80% and a median survival of approximately 19 years, and may be curative in some patients. Chemotherapy alone is rarely used because of the excellent response to radiation. Observation is acceptable only when radiotherapy is contraindicated. Watch and wait is reserved for asymptomatic advanced-stage disease, not localized stage I disease.

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What is the appropriate treatment for asymptomatic stage IV relapsed follicular lymphoma?

A. Watch and wait
B. Radiotherapy
C. R-CHOP
D. R-CHOP followed by radiotherapy

[expand] Answer: A. Watch and wait

Explanation: Asymptomatic relapse of follicular lymphoma does not require immediate treatment. Expectant management (observation) is the appropriate approach, consistent with the indolent nature of the disease. Multiple studies support that asymptomatic patients with no end-organ threat, cytopenias, or bulky disease do not benefit from immediate therapy. Treatment is initiated when symptoms develop, cytopenias worsen, or bulky disease appears.

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What is the appropriate treatment for symptomatic stage IV relapsed follicular lymphoma?

A. Watch and wait
B. Radiotherapy
C. R-CHOP
D. Clinical trials

[expand] Answer: D. Clinical trials

Explanation: For symptomatic relapsed FL, particularly early relapse (less than 12 months from prior therapy), clinical trial enrollment is the preferred recommendation. Non-cross-resistant regimens are preferred (e.g., bendamustine after CHOP or CHOP after bendamustine). Rituximab should be re-added if prior antibody therapy achieved more than 6–12 months of remission. High-dose chemotherapy with autologous SCT prolongs both PFS and OS in relapsed FL, especially after short remissions from R-containing regimens. For early or refractory relapse, fludarabine-containing regimens with consideration of auto or allogeneic transplantation are options. Radio-immunotherapy is considered when intensive chemotherapy or stem cell harvest is not feasible.

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Which of the following is NOT a poor prognostic factor in DLBCL?

A. Age > 60 years
B. High beta-2 microglobulin
C. LDH > upper limit of normal
D. Stage IV disease

[expand] Answer: B. High beta-2 microglobulin

Explanation: The five validated IPI poor prognostic factors in DLBCL are age > 60, elevated LDH, Stage III or IV disease, ECOG PS ≥ 2, and more than 1 extranodal site. Beta-2 microglobulin is not part of the IPI and is not a standard poor prognostic factor in DLBCL risk stratification, although it may correlate with tumor burden in certain other lymphomas such as CLL or myeloma.

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Which finding is diagnostic for mantle cell lymphoma?

A. Cyclin D1 overexpression and t(14;18)(q32;q21)
B. MYC mutation and t(11;14)(q13;q32)
C. Cyclin D1 overexpression and t(11;14)(q13;q32)
D. MYC mutation and t(14;18)(q32;q21)

[expand] Answer: C. Cyclin D1 overexpression and t(11;14)(q13;q32)

Explanation: MCL is defined by t(11;14)(q13;q32), which places the CCND1 (Cyclin D1) gene on chromosome 11 adjacent to the IGH gene on chromosome 14, causing dysregulated Cyclin D1 overexpression and uncontrolled B-cell proliferation. t(14;18) with BCL2 overexpression is the hallmark of follicular lymphoma. MYC translocations, particularly t(8;14), are characteristic of Burkitt lymphoma. MYC rearrangements combined with BCL2 or BCL6 are seen in double-hit DLBCL, not MCL.

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A 45-year-old asymptomatic female has grade 2 follicular lymphoma with ECOG PS 0, normal CBC, PET-positive nodes less than 3 cm, and no bone marrow involvement. What is the most appropriate initial management?

A. Rituximab + bendamustine
B. R-CHOP
C. Observation
D. Rituximab monotherapy x 4 doses

[expand] Answer: C. Observation

Explanation: This patient has asymptomatic, low tumor burden follicular lymphoma with no B symptoms, normal labs, small nodes under 3 cm, and no bone marrow involvement. Observation (watch and wait) is the standard of care. Multiple studies including Ardeshna et al. demonstrated no survival benefit to early treatment versus observation in asymptomatic low-burden FL, while avoiding treatment-related toxicity. BR and R-CHOP are reserved for symptomatic or high tumor burden disease. Rituximab monotherapy can be considered for patients who prefer treatment but observation remains the standard.

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A 68-year-old female with relapsed low-grade FL (prior R-CHOP then R-lenalidomide) prefers oral-only therapy. She has uncontrolled T2DM, history of small bowel perforation, and HTN. Which treatment is most appropriate?

A. Acalabrutinib
B. Copanlisib
C. Ibrutinib
D. Venetoclax

[expand] Answer: A. Acalabrutinib

Explanation: Acalabrutinib is a selective oral BTK inhibitor with fewer off-target effects than ibrutinib and is the most appropriate choice given this patient's need for oral therapy and her comorbidity profile. Copanlisib is a PI3K inhibitor administered intravenously (patient prefers oral) and significantly worsens hyperglycemia, making it contraindicated in uncontrolled diabetes; it is also associated with hypertension and GI toxicity. Ibrutinib carries higher risks of cardiac arrhythmia (AFib), hypertension, and bleeding compared to acalabrutinib, making it less suitable given her HTN. Venetoclax is a BCL-2 inhibitor approved for CLL/SLL and AML but is not standard therapy in FL, carries a high TLS risk, and is not appropriate in this setting.

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43. BL is a 63-year-old male who recently received a diagnosis of Burkitt’s lymphoma. He comes to your clinic to be evaluated for chemotherapy initiation. His pertinent blood work reveals sodium 148 mEq/L, potassium 4.5 mEq/L, serum creatinine 1.8 mg/dL, blood glucose 130 mg/dL, and LDH 1500 IU/L. Which of the following are risk factors for tumor lysis syndrome (TLS)?

• A. High sodium, high lactate dehydrogenase, Burkitt’s lymphoma (10%)
• B. High lactate dehydrogenase, high blood glucose, existing renal insufficiency (9%)
• C. Existing renal insufficiency, high sodium, Burkitt’s lymphoma (10%)
• D. Burkitt’s lymphoma, high lactate dehydrogenase, existing renal insufficiency (72%)

[expand] Answer (D)

• The last answer is correct because cancers with a high proliferative rate and tumor burden put patients at an increased risk for TLS. In addition, cancers sensitive to chemotherapy treatment will go under rapid tumor lysis, which further increases the risk of TLS. Burkitt’s lymphoma has a high proliferative rate and is responsive to chemotherapy. In addition, elevated LDH is an indirect indicator of high tumor burden.
• Patients with impaired renal function are at an increased risk for TLS and its complications due to the inability to handle excess concentration of uric acid, phosphate, and potassium.
• All other answers are incorrect because high sodium and high blood glucose do not increase the risk of TLS.
• Cancers with a high proliferative rate and tumor burden elevated LDH and existing renal insufficiency are all risk factors for TLS.
• Rapid tumor lysis leads to increased levels of phosphate, potassium, uric acid, and cytokines which lead to the development of TLS.
• Allopurinol inhibits xanthine oxidase, which prevents uric acid production but does not remove existing uric acid. whereas rasburicase removes uric acid by enzymatically degrading it into allantoin.

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78. What does the acronym CHOP represent?

• A Cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone (34%)
• B Cyclophosphamide, hydroxydoxorobicin, Oncovin, prednisone (27%)
• C Cyclophosphamide, hydroxydaunorubicin, oxaliplatin, prednisone (27%)
• D Cyclophosphamide, hydroxydoxorobicin, oxaliplatin, prednisone (11%)

[expand] Answer (A)

• CHOP - Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone
• Hydroxydaunorubicin is another name for doxorubicin.
• Oncovin is the brand name of vincristine.

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