NHL Flashcards
What components make up the MIPI score?
WALE;
WBC, Age, LDH, ECOG Status
What components make up the FLIPI-1 score?
FLIPI-2?
5LASH;
5>= Nodal areas, LDH>ULN, Age>60, Stage III-IV, Hemoglobin <120
(5yr OS %)
Low risk = 0 (80%), Intermediate = 1-2 (51%), High = 3+ (19%)
6BASH;
Largest LN >6cm, B2M>ULN, Age>60, Stage IV(BM involvement), Hemoglobin <120
Low risk = 0 (76%), Intermediate = 1-2 (49%), High = 3+ (37%)
What components make up the IPI?
APLES;
Age >60, PS 2-4, LDH>ULN, Extranodal sites >1, Stage III-IV
What components make up the CLL-IPI?
B 65, SUM 53
B2M >3.5 (2) Age >65 (1) Stage (Rai 1-4) (1) Ig-UM (2) P53 Mut (4)
Low = 0-1, Intermediate = 2-3, High = 4-6, V. High = 7-10
What components make up the CNS-IPI
APLES + Adrenal/Kidney involvement
What are the translocations common to Burkitt Lymphoma, and what do they involve?
t(8;14), t(2;8), t(8;22)
They involve MYC on Chromosome 8, IGH gene on Chromosome 14, Kappa chain on Chromosome 2 and Lambda chain on Chromosome 22
What is the translocation common to Follicular Lymphoma, and what does it involve?
t(14;18), involves IGH on Chromosome 14, and BCL2 on chromosome 18
What it the translocation commonly seen in Mantle cell lymphoma?
t(11;14) CCND1 and IGH, CyCliN D1
What translocation is seen in Anaplastic Large Cell Lymphoma?
t(2;5); NPM1 and ALK
What translocation is seen in Extranodal Marginal Zone Lymphoma which predicts resistance to H. Pylori treatment?
t(11;18) -
What are the Rai stages?
What are the Binet stages?
Rai 0 - Lymphocytosis Rai 1 - Lymphadenopathy Rai 2 - Hepatosplenomegaly Rai 3 - Anemia Rai 4 - Thrombocytopenia
Binet A - Hb>100, Plt>100, and 2 or less clinical nodal areas involved
Binet B - Hb>100, Plt>100 and 3 or more clinical nodal areas involved
BinetC - Hb<100 or Plt <100
Common CLL Cytogenetic abnormalities, ranked by favorability to adverse risk
Del(13q) - favorable risk
Trisomy 12 - neutral risk
Del(11q) - poor prognosis
Del(17p) - worst prognosis
CLL Immunophenotype vs MCL Immunophenotype
CD5 +, CD10- for both
CLL commonly CD23+, CD200+, CD20dim and FMC7-neg
MCL commonly CD23-, CD200-, Cyclin D1 +ve
Hans Algorithm for subtyping DLBCL
CD10 + : GCB
CD10-, BCL6-: non-GCB
CD10-, BCL6+, MUM1+: non-GCB
CD10-, BCL6+, MUM1-: GCB
What is the difference between double/triple expressor vs double/triple hit lymphoma?
Double/Triple expressor has detectable MYC AND [BCL2 and/or BCL6] involvement on IHC
Double/Triple hit lymphoma has MYC AND [BCL2 and/or BCL6] involvement on FISH/Cytogenetics
Immunophenotype of HCL? What mutation is often seen in HCL?
CD11c+, CD25+, CD103+, CD123+
BRAF V600E
Front-line treatment of Hairy Cell Leukemia?
Classically Cladribine or Pentostatin
Some groups consider adding Rituximab up-front
Treatment options for R/R Hairy Cell Leukemia:
If refractory:
Try alternative purine analogue, or Vemurafenib + Rituximab
If relapsed:
>24 months: Re-treat with purine analogue previously used + Rituximab
<24 months: Vemurafenib + Rituximab (or Dabrafenib) Moxetumomab Pasudotox (anti CD-22 antibody) Alternative purine analogue Monoagent rituximab
1L Treatment for Advanced stage Follicular Lymphoma
BR > R2 / RCHOP > RCVP
Treatment for R/R FL:
- If relapsed within 24 months, or 12 months from monoagent Rituximab, then considered v. high risk. Should be offered salvage chemotherapy into autoHSCT
- If relapsed >24 months can consider:
R2, RCHOP, BR (Ideally substitute Rituximab for Obinutuzumab based off GADOLIN and GALLIUM studies) - Multiply relapsed:
Copanlisib + Rituximab, R2, Tazemetostat, CAR-T, Clinical Trial
What is the role of maintenance Rituximab in FL? How is it dosed?
It improves PFS, but makes no impact to OS
It is dosed q2-3months x 2 years (8-12 doses)
What is the role of maintenance Rituximab in Mantle-Cell Lymphoma?
How is it dosed?
Maintenance Rituximab has roles in both post-autoHSCT and post-induction therapy. Post-HSCT it improves OS and PFS. Post-induction (trial was with R-CHOP) it showed OS advantage.
It is dosed after autoHSCT q2months x 3 years
It is dosed after induction therapy q2months until progression (Controversial for BR; MAINTAIN study-branch of the StIL trial demonstrated no PFS/OS advantage)
What is the 1L treatment for transplant-eligible MCL?
What is the 1L treatment options for transplant-ineligible MCL?
Transplant eligible:
A cytarabine containing regimen x4-6 cycles into cytarabine-based transplant would be optimal. Maintenance rituximab after.
Options are R-CHOP/RHiDAC, R-CHOP/R-DHAPx6, BR, VR-CAP
Transplant ineligible:
BR, R-CHOP, VR-CAP
What treatment-options are available to R/R MCL
- Ibrutinib/Acalabrutinib/Zanubrutinib (BTKi)
- Lenalidomide
- Bortezomib
- BR (If not used front-line)
- Intensive chemotherapy into alloHSCT (R-DHAP, R-ICE, R-GDP)
- CAR-T (Brexu-cel)
What is the 1L treatment for Splenic Marginal Zone Lymphoma?
3 options:
Splenectomy, Monoagent Rituximab, BR
What are the treatment options for R/R Splenic MZL
BR (if not used up-front) Re-treatment with mono-agent Rituximab Ibrutinib (BTKi family) Lenalidomide / R2 PI3Ki (Idelalisib)
What are the treatment options for Gastric EMZL?
What are the strategies for failure after this?
If H Pylori positive: Trial treamtent of H. Pylori. Re-assess q6monthly with endoscopy, so long as no progression can wait up to 2 years before calling failure
If H Pylori negative, or t(11;18) then:
A) If all disease sites can be contained in one radiation field can consider IFRT
B) If above not true consider Monoagent rituximab, BR, R-CHOP, R-CVP
For R/R:
C) Consider targeted agents such as BTKi, PI3Ki, or Lenalidomide +/- Rituximab
Name the purported etiologic agent with these types of Extra-nodal marginal zone lymphoma:
Ocular: Salivary Gland: Thyroid: Lung: Stomach: Small Intestine: Skin: Splenic:
Ocular: Chylamydophyla Psittica Salivary Gland: Sjogrens Syndrome Thyroid: Hashimoto's thyroiditis Lung: Sjogrens Syndrome / LIP Stomach: Helicobacter Pylori Small Intestine: Campylobacter Jejuni Skin: Borrelia Burgforderi Splenic: Hepatitis C
What non-classical (Not in CLL-IPI) risk factors influence risk?
CD38 and ZAP70 expression are both deleterious and increase risk. They are surrogates for IGHV-UM status. IGHV-UM does not change with disease evolution, so only needs to be done once.
What are the criteria to treat CLL?
Lymphocyte doubling rate >6 months, or >50% increase over 2 months (BUT ABSOLUTE LYMPHOCYTOSIS MUST BE >30)
Splenomegaly with spleen >6cm Below Costal Margin
Lymphadenopathy >10cm
Cytopenias from CLL marrow involvement
Autoimmune phenomena from CLL not-responsive to steroids
Constitutional symptoms from CLL
What are the 1L treatment options for CLL, and who should receive what?
Ibrutinib:
Should be given to patients with IGHV-UM or TP53 +ve
Venetoclax - Obinuzutumab (12 months):
Can be given to patients not needing BTKi
Fludarabine Cyclophosphamide Rituximab:
Consider in young (<65) patients with IGHV-Mutated. Can be curative in some patients, or at-least v. prolonged disease control
Chlorambucil (+/- Rituximab):
Essentially no role anymore except v. frail. Consider adding Rituximab if you think can tolerate
BR:
Can be used in older (>65) patients with IGHV-Mutated disease. VO was better than BR in
What are the options for R/R CLL?
- BTKi (Acalabrutinib, Ibrutinib, Zanubrutinib)
- Venetoclax + Rituximab (2 years)
- Idelalisib + Rituximab or Duvelalisib + Ritux
- AlloHSCT
- Chemoimmunotherapy (select patients only)
Name 3 chemotherapies that cause MAHA
- Gemcitabine
- Oxaliplatin
- Proteosome inhibitors
- Pentostatin
- Mitomycin
- Bevacizumab
- Sunitinib and Ponatinib
What is PTLD, how is it diagnosed?
PTLD occurs typically from EBV reactivation in the setting of suppressed cytotoxic T-cell function post transplant.
It is diagnosed on histology. In a patient post-transplant 2/3 diagnostic criteria are needed to call PTLD:
Distorted nodal architecture from lymphoproliferative disease
Mono/Oligoclonal B-cells
EBV +ve
Any 2/3 makes the diagnosis.
The subclasses of PTLD are division between Early Lesions (non-malignant) vs Malignant (late lesions).
Early: Benign Polyclonal Lymphoproliferation, and Florid Follicular Hyperplasia
Malignant: Monomorphic PTLD (DLBCL, BL, PCN, PTCL-NOS), Polymorphic PTLD (Architecture distortion, poly/monoclonal B-cells, usually EBER+ve, does not meet criteria for a WHO B/T/NK cell neoplasm)
NOTE: Small lymphocytic disorders (FL, SLL, MZL) are NOT PTLD.
How do we treat PTLD?
Division between Early Lesion and Monomorphic/Polymorphic.
In general the steps are:
- Reduce immunosuppression
- Rituximab (if CD20+ve)
- Rituximab +/- Chemotherapy
In patients with monomorphic/polymorphic disease patients may require advancement to 2 or 3 pending on how they are doing. They are expected to respond less to just reduction of IS, and if PS is poor from malignancy, or anticipated to worsen to point they won’t tolerate chemotherapy soon, you may choose to treat more immediately more aggressively. NB: PTLD can present like cHL. Treat like cHL if this occurs.
1L Treatment options for WM/LPL
- BR (Omit Ritux first cycle if IgM >40g/L) (mPFS in StIL was 70 months vs 28 in RCHOP)
- Bortezomib, Rituximab, Dexamethasone (mPFS in one study 43months)
- Cyclophosphamide, Rituximab, Dexamethasone (mPFS 34 months)
- Ibrutinib, Acalabrutinib, Zanubrutinib (I: estimated PFS at 5 yrs 54%, A:estimated PFS at 2 yrs 90%, Z: too early)
(May use Rituximab with Ibrutinib if desired)
All are acceptable up-front agents. For frail patients consider BTKi monotherapy.
Rituximab maintenance numerically improved PFS in StiL-MAINTAIN, but was not statistically significant. Can discuss with patient re: addition or not. May have benefit in patients >60yo in subgroup analysis of StiL-MAINTAIN
Treatment of R/R WM
- Patients relapsing >3yrs from frontline treatment can consider re-treatment with the same agents
- BTKi
- Cyclo/Dex/Ritux
- Bortez/Dex/Ritux, CyBorD-R, PI+Ritux
- Purine analogues (FR, Cladribine-Ritux, FCR) - only for multiply relapsed patients with good PS
- AutoHSCT - Only for young fit patients who have multiply relapsed disease. DO NOT PERFORM ALLO.
Alemtuzumab; What are the toxicities? What monitoring is needed? What prophylaxis is needed
Highly potent immunosuppressive antibody against CD52.
Toxicities: Infusion reaction, Cytopenias, Immunosuppressive +++, May provoke autoimmune disease ANYWHERE, vigilent monitoring. May increase risk of 2dry malignancies. PML possible. Stroke possible.
Monitoring: Weekly CMV + treatment if starts to spike
Prophylaxis: PJP + VZV prophylaxis. If HepB CAb positive needs prophylaxis against reactivation.
HIV-related lymphomas/LPD
cHL DLBCL BL Primary effusion lymphoma Plasmablastic lymphoma Primary CNS lymphoma
EBV-related lymphomas
cHL PTLD Primary CNS Lymphoma DLBCL Extranodal NK/T cell lymphoma Burkitt Lymphoma Plasmablastic Lymphoma + Primary Effusion Lymphoma
HHV-8 Related Diseases
HHV +ve multicentric Castleman’s Disease
Kaposi’s Sarcoma
Primary Effusion Lymphoma
Primary CNS Lymphoma - HIV Related;
Treatment options
1L. High-dose Methotrexate + ART
1L-alt. Temozolomide and Rituximab if not fit for HD-MTX
2L: WBRT, Focal irradiation + Lenalidomide,
Primary CNS Lymphoma: Staging
IELSG (International Extranodal Lymphoma Study Group)
- MRI Brain
- LP with cytology
- Slit-lamp/Ophthalmology exam (15-25% involvement of eyes)
5 criteria: CLAPD CSF Protein - Elevated LDH - Elevated Age - >60 PS - >2 Deep brain structures involved (cerebellum, brainstem, corpus callosum, basal ganglia)
There is also a MSKCC scoring system:
Good risk Age <50
Int risk Age >50 but KPS >70
High risk Age >50, KPS <70
Primary CNS Lymphoma Treatment - Immunocompetent patients
HD-MTX is backbone. Rituximab should be considered for all patients as well. Based off results of RCT MATRix (Methotrexate, AraC, Thiotepa, Rituximab) is an excellent 1L choice. Consolidation with AutoHSCT, using Thiotepa based conditioning (not BEAM/Carmustine based)
Induction:
- MATRix (HD-MTX, Ara-C, Thiotepa, Rituximab)
- R-MT (Rituximab, HD-MTX, Temozolomide)
- R-MVP (Rituximab, HD-MTX, vincristine, and procarbazine)
- R-MVBP (Rituximab, HD-MTX, teniposide, carmustine (BCNU), and prednisone)
Consolidation with Thiotepa/Busulfan/Cyclophos based AutoHSCT if fit.
10-15% are primary refractory and 50% of patients responding will relapse R/R: 1. Rechallenge with HD-MTX 2. WBRT 3. BTKi (Ibrutinib) 4. Lenalidomide + Rituximab
Secondary CNS Lymphoma: Treatment options
Typically a high-grade lymphoma like DLBCL/BL
- R-CHOPM (R-CHOP with HD-MTX) + Thiotepa-based autologous HSCT
- HyperCVAD / MA
- R-CODOX-M/IVAC
- MATRix/R-ICE
Consider autologous HSCT in those fit enough to receive
R/R Therapies:
- Ibrutinib - particularly ABC-subtypes
- Lenalidomide + Ritux
- PD-L1/PD-1 inhibitors
Palliative:
- Steroids
- WBRT
CNS-IPI
APLES + Adrenal/Renal involvement
Differences between HCL and HCL-v
Compared to HCL, HCL variant has:
- Higher WBC
- Less/no monocytopenia
- Less likely to get dry tap (less reticulin fibrosis)
- CD 25, CD 123, annexin A1 negative
- BRAF V600E mutation is not present
- Less responsive to cladrabine
