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:
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:
- 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)
- DNA methylation
3) Upregulated expression of MYC
What do you send for in CSF testing?
Protein and glucose concentration
Kappa- or lambda-restricted evidence
What does the IELSG (International Extranodal lymphoma study group) described as poor prognosticators?
ECOG > 1
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?
What are some of the CNS-penetrant agents that you know of?
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.
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
5# IV MTX 2.5g/m2/Vincristine/Procarbazine/IntraVetricular MTX 12mg
High-dose Cytarabine after RT
36% with >50% PR
Med PFS 24m
- 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#