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Flashcards in CNS Lymphoma Deck (19):

How can CNS be involved in NHL?

1) Primary CNS Lymphoma (PCNSL)
- limited to brain parenchyma, intraocular compartment, CN, leptomeninges, and rarely, spinal cord

2) Secondary CNS Lymphoma (SCNSL)
- Concomitant systemic, and CNS localization of lymphoma, often within the leptomeningeal compartment


What is the frequency of PCNSL?

3% of all newly diagnosed brain tumors
2-3% of NHL
Incidence increases >65yo, esp >75


What are the risk factors for PCNSL

Acquired or congenital immunodeficiency states

Following have 4% lifetime risk for developing PCNSL:
Wiskott-Aldrich syndrome
Severe-combined or common-variable immunodeficiency

Lifetime risk for development of CNS post-transplant lymphoproliferative disorder (PTLD) =
- 1-2% for renal transplant
- 2-7% for cardiac/lung/liver transplant

PCNSL is also an AIDS-defining illness
A/w EBV infection in immunocompromised patients, AIDS-related PCNSL share a near 100% association with EBV
* if immunocompetent, EBV infection is rarely detected.


What histological can PCNSL come from?

95% are CD20+, DLBCL
2% are T-Cell PCNSL
The rest include:
- Burkitt
- Lymphoblastic
- Intraparenchymal MZL


Tell me about Intraocular involvement by PCNSL

~20% of PCNSL present with intraocular involvement, with cellular infiltrates in the vitreous and retina, and with lymphoid hyperplasia of the uveal tract.

Sometimes, thickened choroid invested with lymphoma may extend into the orbit.

Intraocular lymphoma progresses to clinically evident CNSL in at least 80%


Tell me the expected immunophenotyping of PCNSL

1) Somatic hypermutation of genes
- eg. BCL6, MYC, PIM1, PAX5
2) CD10 + in 10-20%
3) Near-uniform activated B-cell-like immunophenotype. 95% + for MUM-1


What are the genetic aberrations of PCNSL that you know of?

1) Chromosome 6
- Focal losses of chromosome 6p21 (containing HLA locus)
- Deletions on 6q21-6q25
- several candidate tumor suppressor genes are linked to deleted loci on chromosome 6q (eg. PRDM1, PTPRK, A20)
- Deletion
- DNA methylation
3) Upregulated expression of MYC


What do you send for in CSF testing?

Cell count
Protein and glucose concentration
Kappa- or lambda-restricted evidence


What does the IELSG (International Extranodal lymphoma study group) described as poor prognosticators?

Age >60
ECOG > 1
LDH >normal
High CSF protein
Deep location of tumor (periventricular, basal ganglia, brain stem, cerebellum)


How does the IELSG prognosticators correlate with OS?

(Age>60, ECOG>1, LDH>Normal, Deep location of tumor, High CSF Protein concentration)

Correlates with OS.
2y OS with 0-1 factors: 80%
2y OS with 2-3 factors: 50%
2y OS with 4-5 factors: 15%


Any evidence for resection of CNS lymphoma?

Yes, retrospective analysis of German PCNSL Study Group-1 GPSG-1) Trial

In this trial, when controlled for the number of lesions, aggressive resection correlated with improved PFS.


What are the benefits of tumor debulking?

1) May provide immediate relief of mass effect
2) Facilitate rapid tapering of glucocorticoids
3) Eliminate cell populations with drug resistance potential


Why is the utility of WBRT limited in the tx of PCNSL?

1) Insufficient control of lymphoma
2) Dissemination of lymphoma cells within the CSF circulation, outside of RT field
3) Detrimental effects of RT on brain function


How does long-term neurotoxicity of WBRT manifest as?

Gait disturbances
Memory disturbances


What are some of the CNS-penetrant agents that you know of?

High-dose Cytarabine


How did combined modality therapy for PCNSL came about?

1) DeAngelis JCO 1992

B/g: Conventional Tx consisted of WBRT and steroids. But median OS 15-18m and 3-4% 5y OS.
Chemo found to be useful in recurrent PCNSL
Hence combined modality came about.

2 groups:
A) Pre-RT IV MTX via Ommaya --> 6# IT MTX--> Cranial RT --> 2# Ara-C
- IV MTX at 1g/m2
- IT MTX at 12mg per dose
- RT 4000 cGy WBRT + 1440 cGy boost
- Ara-C 3G/m2 Q24H x2 per cycle.
B) RT alone

Prolonged time to recurrence 41m vs 10m
Trend to increased survival 43 vs 22m.
RT patients received systemic chemo for recurrent PCNSL, which improved survival.


What was the De Angelis Protocol?

RTOG 93-10 JCO 2002

Immunocompetent patients

5# IV MTX 2.5g/m2/Vincristine/Procarbazine/IntraVetricular MTX 12mg
High-dose Cytarabine after RT

60% CR
36% with >50% PR
Med PFS 24m
OS 37m
- 60yo, med OS 22m
15% experienced severe delay neurological toxicity ,8/12 patients died


What about immunochemotherapy in PCNSL?

Yes, accordance to Shah Protocol JCO 2007

Aim of study: evaluate safety of adding Rituximab to MTX-based chemotherapy for PCNSL as well as efficacy of regimen in a/w decreased WBRT after CR

F/u 3 y
2y OS 70% 2yPFS 60%
40% with CR after 5 or fewer cycles, and 80% CR after 7#
ORR 93%


Is WBRT necessary in the management f PCNSL?

Thiel et al Lancet Oncol 2010 G-PCNSL-SG-1

Aim: To investigate if HDMTX = HDMTX--> WBRT
- in terms of OS


- HD MTX 4g/m2 D1
- HD MTX + Ifosfamide 1.5g/m2 D3-5
Q14 days, 6#

Med OS 32m (WBRT) vs 37m - not significant
Med PFS 18m (WBRT) vs 12m - not significant