Non-Hodgkin Lymphomas Flashcards by Mario Luna

Non-Hodgkin Lymphomas

A family history of hematologic malignancy is a risk factor for developing lymphoma.

TRUE or FALSE?

True

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Non-Hodgkin Lymphomas

What are the 2 most common immunosuppression states associated with developing NHL?

HIV infection and solid transplant recipient status

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Non-Hodgkin Lymphomas

What are the 3 most common lymphomas in HIV-infected individuals that are considered AIDS-defining illnesses?

Burkitt lymphoma
DLBCL
PCNSL

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Non-Hodgkin Lymphomas

Autoimmune disorders such as AIHA, SLE, RA, are associated with the development of T-cell leukemia.

TRUE or FALSE?

False.

It’s DLBCL (because they are B-cell activating)

T-cell lymphoma is associated with T-cell activating autoimmune diseases such as celiac disease, psoriasis, bullous pemphigoid, and atopic dermatitis.

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Non-Hodgkin Lymphomas

What malaria species is implicated in the development of NHL?

Plasmodium falciparum

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Non-Hodgkin Lymphomas
DLBCL

Approximately 5% to 10% of patients with DLBCL have double-hit or triple-hit genetics, which carries a particularly poor prognosis

what are the genes rearranged in triple-hit genetics?
double-hit?

MYC, BCL2, and/or BCL6

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Non-Hodgkin Lymphomas
DLBCL

B symptoms are present in approximately one-third of patients and are the most important prognostic factors in DLBCL and NHL in general.

TRUE or FALSE?

False

B symptoms are present in approximately one-third of patients but are not prognostic.

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Non-Hodgkin Lymphomas

What are the variables of the International Prognostic Index?

When divided by age, which remained independently significant?

age
performance status*
stage*
number of extranodal sites
LDH*

*second question

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Non-Hodgkin Lymphomas
DLBCL

What are the values considered risk for this variable in the International Prognostic Index?

Age

> 60

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Non-Hodgkin Lymphomas
DLBCL

What are the values considered risk for this variable in the International Prognostic Index?

Performance status

≥2

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Non-Hodgkin Lymphomas
DLBCL

What are the values considered risk for this variable in the International Prognostic Index?

Stage

III-IV

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Non-Hodgkin Lymphomas
DLBCL

What is the value considered risk for this variable in the International Prognostic Index?

LDH

Elevated

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Non-Hodgkin Lymphomas
DLBCL

What are the values considered risk for this variable in the International Prognostic Index?

Extranodal site

> 1

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Non-Hodgkin Lymphomas
DLBCL

What is the score and 5-year survival for this number of factor/s in the International Prognostic Index?

Low

0–1

73%

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Non-Hodgkin Lymphomas
DLBCL

What is the score and 5-year survival for this number of factor/s in the International Prognostic Index?

Low Intermediate

51%

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Non-Hodgkin Lymphomas
DLBCL

What is the score and 5-year survival for this number of factor/s in the International Prognostic Index?

High Intermediate

43%

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Non-Hodgkin Lymphomas
DLBCL

What is the score and 5-year survival for this number of factor/s in the International Prognostic Index?

High

4–5

26%

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Non-Hodgkin Lymphomas
DLBCL

The GCB subtype has a more favorable prognosis
compared with the ABC subtype (defined using gene expression profiling) or
non–GCB-like subtype (defined using immunohistochemistry).

TRUE or FALSE?

True

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Non-Hodgkin Lymphomas

What medication/targeted agent is the most promising innovation in the last several decades in the treatment of B-cell HNLs?

This is a human chimeric anti-CD20 antibody that is quite well tolerated in humans.

This is also the first antibody of any type approved by FDA for treatment of any human malignancies.

Rituximab

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Non-Hodgkin Lymphomas
DLBCL

What is the most widely used chemotherapy combination in DLBCL?

CHOP

Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone

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Non-Hodgkin Lymphomas
DLBCL

What medication was added to CHOP and showed improved PFS (30% to 54%) and 5-year OS (45% to 58%) as observed by a GELA study in patients over 60.

In patients 18-60, 3-year PFS was 79% vs 59% and OS was 93% vs 84% (as observed by a European cooperative trial)

Rituximab

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Non-Hodgkin Lymphomas
DLBCL

What was the pattern of failure seen in patients with early stage DLBCL treated by RT alone (as this was the standard in the prechemotherapy era)?

distal failure

organ involvement or remote nodal failure

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Non-Hodgkin Lymphomas
DLBCL

The SWOG S8736 study compared brief CHOP chemotherapy (3 cycles) plus
RT (40 to 55 Gy) to a more extended CHOP regimen (8 cycles) without RT.

Both PFS (77% vs. 64%) and OS (82% vs. 72%) at 5 years were improved in the
combined modality arm with less toxicity.

What was the outcome after long-term of follow-up (18 years)?

after median follow-up of
almost 18 years, no significant differences were apparent, because of late
systemic relapses in the arm with only 3 cycles of CHOP.

Interestingly, a
continual pattern of relapse was noted in both arms throughout the follow-up
period.

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Non-Hodgkin Lymphomas
DLBCL

Is there a role for consolidation RT in early stage DLBCL after extended chemotherapy (8 cycles of CHOP)?

Yes.

The Eastern Cooperative Oncology Group (ECOG) 1484 study evaluated
whether consolidation RT (30 Gy) would reduce the risk of relapse in the setting
of extended chemotherapy (8 cycles of CHOP in this case).59 The primary
outcome was PFS which was significantly improved with the addition of RT
(73% with consolidation RT vs. 56% with observation at 6 years) (P = .05).

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Non-Hodgkin Lymphomas DLBCL In early stage DLBCL, an aggressive chemotherapy regimen (induction ACVBP [doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone] followed by consolidation methotrexate, etoposide, ifosfamide, and cytarabine) was superior to CHOP plus RT. Why is this not generally used?

Toxicity profile

Non-Hodgkin Lymphomas DLBCL What study utilized PET CT in patients treated with rituximab which compared 4 to 6 cycles of R-CHOP with and without RT (40 Gy) in stage I to II nonbulky DLBCL who achieved a complete response by PET-CT.118 Event-free survival at 5 years was 87% with R-CHOP versus 91% with R-CHOP plus RT (P = .13). There were no local failures in the arm receiving RT, whereas approximately 50% of failures in the no-RT arm failed at original sites of disease involvement. Most patients in this study had low-risk disease by the IPI. To date, this study has only been presented in abstract form.

LYSA/GOELAMS

Non-Hodgkin Lymphomas DLBCL What is the mainstay of treatment for stages III to IV DLBCL?

chemoimmunotherapy (R-CHOP) with or without consolidation RT

Non-Hodgkin Lymphomas DLBCL What is the role of consolidative RT in stages III to IV DLBCL with bulky disease.

improved PFS and OS (RICOVER-noRTh trial) UNFOLDER (German) trial closed prematurely due to relapses in patients not receiving RT. (unpublished)

Non-Hodgkin Lymphomas DLBCL What is the standard treatment in relapsed and refractory DLBCL after salvage with dexamethasone, cisplatin, cytarabine.

HDC with ASCT | Parma trial

Non-Hodgkin Lymphomas DLBCL What are the doses for myeloablative and nonablative RT prior to ASCT as a conditioning regimen?

ablative 12 to 13.5 Gy | nonabltive 2 to 4 Gy

Non-Hodgkin Lymphomas DLBCL What is the dose of RT for bulky (≥5 cm) sites in relapsed/refractory patients being treated with DHAP or HDC with ASCT? (as was used in the Parma trial)

35Gy/1.75/20 in conventional chemo arm 26Gy/1.3/20 in the ASCT arm.

Non-Hodgkin Lymphomas DLBCL What is the only phase III trial ever done in relapsed DLBCL?

Parma trial

Non-Hodgkin Lymphomas DLBCL Name 2 salvage regimens usually employed in refractory diseases.

R-ICE, R-DHAP rituximab +ifosfamide +carboplatin +etoposide rituximab + DHAP

Non-Hodgkin Lymphomas DLBCL An shorter alternative to 24 to 30 Gy in the palliative setting which has a response rates of 50% to 80% with a median time to progression of about 1 year.

2 Gy x 2

Non-Hodgkin Lymphomas DLBCL For patients with stage I to II disease, the standard dose is __ Gy when a complete response (Deauxville 1 to 3) has been achieved by PET-CT after chemoimmunotherapy, typically R-CHOP.

Non-Hodgkin Lymphomas FL How is FL graded based on centrocytes (cleaved) and centroblasts (large)

predominance of cleaved (grade 1), predominance of large (grade 3), mixed (grade 2) WHO classification based on number of centroblasts 1 - 0-5 2 - 5-15 3 - >15 3A 3B - absence of centrocytes

Non-Hodgkin Lymphomas FL What is the significance of subdividing grade 3 to 3A and 3B?

3A is similar to grade 1-3, and has similar biologic behavior and response to therapy 3B is treated to DLBCL because of an almost similar clinical course

Non-Hodgkin Lymphomas FL What translocation in combination with BCL-2 rearrangement is characteristic of FL (except 3B)

t(14;18)

Non-Hodgkin Lymphomas FL A PET-CT scan documentation of bone marrow involvement still warrants a biopsy confirmation. TRUE or FALSE?

True. This is in contrast to DLBCL.

Non-Hodgkin Lymphomas FL Scenarios which raises the clinical suspicion of large-cell transformation to DLBCL?

- development of B symptoms - extranodal sites become involved - disproportionate growth occurs - rising LDH - SUV max (>10)

Non-Hodgkin Lymphomas FL What is the standard treatment for early-stage localized FL?

Non-Hodgkin Lymphomas FL NCCN guidelines consider observation the “standard practice for patients with advanced stage low tumor burden FL.” Define "high" tumor burden based on the GELF criteria.

any of the following signifies a high tumor burden: (1) three distinct nodal sites each ≥ 3 cm, (2) a single nodal site ≥ 7 cm, (3) symptomatic splenomegaly, (4) organ compression or compromise, (5) pleural effusions or ascites, (6) B symptoms, and (7) elevated LDH or beta-2 microglobulin.

Non-Hodgkin Lymphomas FL advanced stage Give the general treatment choices for the following general disease condition: asymptomatic, low burden

observation or single-agent rituximab

Non-Hodgkin Lymphomas FL advanced stage Give the general treatment choices for the following general disease condition: asymptomatic, high burden

observation or chemotherapy along with rituximab

Non-Hodgkin Lymphomas FL advanced stage Give the general treatment choices for the following general disease condition: symptomatic, low burden

single-agent rituximab or in combination with chemotherapy

Non-Hodgkin Lymphomas FL advanced stage Give the general treatment choices for the following general disease condition: symptomatic, high burden

rituximab-containing chemotherapy with maintenance rituximab

Non-Hodgkin Lymphomas FL advanced stage What alkylating agent has been used in combination with rituximab that showed prolongation of PFS (no OS difference) when compared to R-CHOP, as well as less toxicity profile that led to its adaption as first-line systemic therapy in the US?

Bendamustine | SCIL phase III trial (BRIGHT study)

Non-Hodgkin Lymphomas FL advanced stage In this trial, patients with previously untreated FL who had responded to chemoimmunotherapy were randomly assigned 2 years of maintenance with rituximab or placebo. With short follow-up, the 2-year PFS in the rituximab maintenance arm was 75% compared with 58% in the observation arm.

PRIMA

Non-Hodgkin Lymphomas MZL What is the most frequent MZL encountered in clinical practice?

MALT

Non-Hodgkin Lymphomas MZL Involvement of paired organs simultaneously, or less commonly two distinct extranodal sites is occasionally encountered. With such scenarios, it is best to stage each site separately as opposed to making a stage IV designation. Such patients may be treated with local RT to both paired sites with long-term disease control. TRUE or FALSE?

TRUE

Non-Hodgkin Lymphomas MZL What is the most common site of MALT?

stomach

Non-Hodgkin Lymphomas MZL What infection/s is associated with the development of MALT in gastrointestinal sites?

H. pylori infection (detected in 92% of patients). Campylobacter jejuni has also been described to be associated with small intestine MALT. Lymphoid tissue is not normally present in the stomach, but in response to an antigenic stimulus brought about by H. pylori, normally, present T cells in the gastric mucosa attract a B-cell population, giving rise to lymphoid follicles and, after prolonged antigenic stimulation, lymphomas.

Non-Hodgkin Lymphomas MZL What infection is associated with the development of MALT in the orbit?

Chlamydia psittaci

Non-Hodgkin Lymphomas MZL What infection is associated with the development of MALT in the skin?

Borrelia burgorferi

Non-Hodgkin Lymphomas MZL In gastric MALT, what are the predictive factors associated with a lower chance of achieving and maintaining a complete response after antibiotic therapy?

deep gastric wall invasion, nodal involvement, translocation t(11;18).

Non-Hodgkin Lymphomas MZL What is the first-line treatment for H. pylori positive gastric MALT?

antibiotic therapy (omeprazole + clarithromycinn + metronidazole) A complete response is achieved in approximately 80% of patients, though this may take up to 2 years or longer to achieve. As long as the lymphoma is regressing on serial endoscopy, a watch and wait policy is appropriate.

Non-Hodgkin Lymphomas MZL What is the treatment for patients with H. pylori gastric MALT who relapsed and was diagnosed subclinically for biopsy during UGI endoscopy?

Watch and wait. Of patients achieving a complete response to antibiotics, approximately 30% will relapse. Many such relapses are subclinical and only apparent on histologic examination of random biopsies performed during upper endoscopy. Continued observation and monitoring is preferred for these patients as many will subsequently revert to a histologic complete response

Non-Hodgkin Lymphomas MZL What is the standard of care treatment for ocular adnexal lymphomas, and refractory/clinically relapsed gastric MALT?

Non-Hodgkin Lymphomas MZL RT total dose for gastric MALT?

30 Gy

Non-Hodgkin Lymphomas MZL RT total dose for orbital/ocular adnexal lymphoma?

24 to 30 Gy (24 Gy preferred)

Non-Hodgkin Lymphomas MZL In the unusual circumstance of disseminated MALT lymphoma, treatment generally follows the guidelines for advanced FL. TRUE or FALSE?

True

Non-Hodgkin Lymphomas MZL 2 x 2 RT is often superior to systemic RT in palliative setting TRUE or FALSE?

True

Non-Hodgkin Lymphomas MCL What is the characteristic translocation that involves the BCL-1 gene resulting in the overexpression of cyclin D1?

t(11;14)

Non-Hodgkin Lymphomas MCL IHC staining of MCLs

CD5 and 20 (+) | CD23 and CD10 (-)

Non-Hodgkin Lymphomas MCL What are the four parameters of the MIPI, which the scores allow discrimination into three prognostic subgroups: median survival was not reached in the low-risk group with a 5-year OS of 60%, but was 51 and 29 months in the intermediate- and high-risk groups, respectively?

age PS LDH WBC count

Non-Hodgkin Lymphomas PCNSL What are the most important prognostic factors in PCNSL according to MSKCC, stratifying the patients into three classes?

Age and PS Class 1 includes patients < 50 years with a median survival of 8.5 years. Class 2 patients are ≥50 years with good performance status (KPS ≥ 70) with median survival of 3.2 years. Class 3 includes patients ≥ 50 years with poor performance status (KPS < 70) with median survival of 1 year.

Non-Hodgkin Lymphomas PCNSL What is the contemporary treatment for PCNSL?

Reduced dose WBRT (23.4 Gy) following complete response to rituximab and MTX-based chemotherapy.

Non-Hodgkin Lymphomas PTCL Approximately 60% of cases overexpress the ALK protein; such cases have a worse prognosis than ALK-negative cases TRUE or FALSE?

False

Non-Hodgkin Lymphomas PTCL What type of ALCL is more common in young adults and is more common in males?

ALK-positive ALCL

Non-Hodgkin Lymphomas PTCL What type of ALK-negative ALCL carries an excellent prognosis?

Cutaneous type

Non-Hodgkin Lymphomas PTCL What are the factors comprising the PIT? (Prognostic Index for PTCL-U)

age (≥ 60 years), elevated LDH, and ECOG performance ≥ 2.

Non-Hodgkin Lymphomas PTCL Total RT dose for NK/T-cell lymphomas when using RT alone?

50 to 56 Gy

Non-Hodgkin Lymphomas PTCL Total RT dose for NK/T-cell lymphomas when using RT with concurrent or sequential chemotherapy?

45 to 56 Gy

Non-Hodgkin Lymphomas PTCL What is the most commonly used chemotherapy regimen for PTCL?

CHOP CHOEP (etoposide) can be considered for younge patients

Non-Hodgkin Lymphomas PMBCL What is the treatment for PMBCL?

Almost similar to DLBCL RCHOP + 30 Gy RT (20 Gy if a CR was seen in PET-CT) or more intensive chemo with no RT (DA-EPOCH-R) although data are still lacking.

Non-Hodgkin Lymphomas CLL/SLL What is the difference in diagnosing CLL and SLL?

A diagnosis of CLL requires the presence of > 5.0 × 10^9/L monoclonal CLL cells in the peripheral blood with or without lymph node/splenic involvement, whereas a diagnosis of SLL includes CLL involvement of the lymph nodes and/or spleen in the absence of a lymphocytosis >5.0 × 10^9/L.

Non-Hodgkin Lymphomas PTLPD What virus is implicated in cases of post transplant lymphoproliferative disorders?

EBV