Types of Lymphoma >
CNS (Central Nervous
History | Treatments
Blood-brain barrier - drugs that may cross it
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TOPIC SEARCH: PubMed: Diagnosis
System (CNS) Lymphoma
Lymphoma is a blood cell cancer - a condition where abnormal
lymphocytes (a type of white blood cell) expand in number forming tumors
often in lymph nodes but also in other regions, such as the bone marrow,
or, uncommonly, in the central nervous system.
See for details: Lymphoma Simplified
central nervous system lymphoma (PCNSL) is a
"high-grade non-Hodgkin B-cell neoplasm, usually large cell or
Secondary CNS: Lymphomas can sometimes migrate to the
central nervous system. This secondary form of CNS
lymphoma is not common, however.
In the News and What's New:
A Systematic Approach to the Diagnosis of Suspected
Central Nervous System #Lymphoma
Lymphomatous Meningitis in
Primary Central Nervous System Lymphoma
J Clin Onc 2013:
Rituximab, Methotrexate, Procarbazine, and Vincristine Followed
by Consolidation Reduced-Dose Whole-Brain Radiotherapy and
Cytarabine in Newly Diagnosed Primary CNS Lymphoma: Final
Results and Long-Term Outcome
Natural History - treated and untreated
The "natural history" of a lymphoma refers to the expected clinical
course of the disease if it is untreated. Along with the
availability of effective treatments, the natural history provides the
context that guides the most appropriate timing and approach to
treatment. For example, a lymphoma with a very short natural
history would require prompt and effective therapy - with curative
intent; while a less aggressive type of lymphoma might be observed and
treated (managed) as needed with less aggressive therapy.
"The clinical course of CNS lymphoma is ... coming
timing and choice of therapy
Which illustrates the complexity of treatment decisions and how they can interact;
and how each case and lymphoma can be unique, thus treatments may need
to be tailored accordingly - the reason professional
guidance is required.
Symptoms of primary CNS Lymphoma:
Medscape review article Eichler, Batchelor
"The presenting symptoms and signs in one large case series of 248
immunocompetent patients with PCNSL included the following:
(limited to a small area) neurological deficits in 70% of
neuropsychiatric symptoms in 43%;
headache/nausea/vomiting suggestive of increased intracranial
pressure in 33%;
symptoms in 4%.
Common focal deficits include
(Loss of ability to understand or express speech),
(weakness on one side of the body), and
of full control of bodily movements)
due to discrete intracerebral lesions as well as less common
cranial nerve palsies secondary to leptomeningeal deposits.
Neuropsychiatric (neurological and psychiatric)
changes such as
slowed thinking, and
confusion have been attributed to the infiltration of white
matter tracts by PCNSL lesions that involve the periventricular
regions or the corpus callosum.
The fact that seizures occur as the initial manifestation of
PCNSL in less than 15% of immunocompetent patients who have
these tumors may be partially explained by the fact that PCNSL
lesions less often involve excitable cerebral cortex than do
other types of brain tumors.
How is it diagnosed?
Previously a rare tumor accounting for less than 2% of cerebral
neoplasms, PCNSL is being seen with increasing frequency in
immunocompetent patients, patients with AIDS, and transplant
Age, performance status (PS),
LDH serum level, CSF protein concentration, and involvement of deep
structures of the brain were independent predictors of survival. A
prognostic score including these five parameters seems advisable in
distinguishing different risk groups in PCNSL patients. The proposed
score and its relevance in therapeutic decision deserve to be
validated in further studies."
Update on the Management of Primary CNS Lymphoma - full text
Syed Nasir, MD, and Lisa M. DeAngelis, MD Department of
Neurology, Memorial Sloan-Kettering Cancer Center, New York,
"Age and performance status
are important prognostic factors, regardless of specific
treatment. Methotrexate in high doses is the single most
effective chemotherapeutic agent for primary CNS lymphoma.
It substantially improves survival when combined with
radiation therapy and is better than radiotherapy alone as a
single agent. Multimodality treatment results in delayed
cognitive neurotoxicity, particularly in older patients. New
treatment protocols have focused on the use of chemotherapy
Central Nervous System Disease in Hematological
Malignancies: Historical Perspective and Practical
"In this article, we review
current and past practice of intrathecal therapy in ALL and
NHL and the risk-models that aim to identify predictors of
CNS relapse in NHL."
HIV-1 Associated Opportunistic Neoplasms: CNS Lymphoma emedicine
Central Nervous System Lymphoma asheducationbook.org
Andrew Lister, Lauren E. Abrey and John T. Sandlund
"Central nervous system involvement with malignant lymphoma whether primary or secondary is an uncommon but not rare complication observed in the management of patients with hematological malignancy.
Primary CNS lymphoma of T-cell origin: a descriptive
analysis from the international primary CNS lymphoma
J Clin Oncol. 2005 Apr 1;23(10):2233-9. PMID:
15800313 | Related
Imaging of central nervous system lymphomas with
iodine-123 labeled rituximab. Eur J Haematol. 2005
Gene expression and angiotropism in
primary CNS lymphoma
Questions for your doctor - Patients
General, Treatment & Side Effects, and Tests
For help with locating
Experts - See Doctors
"Due to the
unsatisfactory results of whole-brain irradiation alone and to the
neurologic toxic effects of chemotherapy and radiation therapy,
there is now a major focus on trials with chemotherapy alone.
There are now several single-institution reports in which
systemic chemotherapy has been employed alone or with osmotic
blood-brain barrier disruption. Currently, most
regimens are employing high-dose Methotrexate and require
hospitalization. For patients who do not respond to
chemotherapy alone or with radiation therapy, but are still
responsive to salvage chemotherapy with cytarabine and etoposide,
intensive chemotherapy with autologous peripheral stem cell
transplantation is under evaluation."  - cancerweb.ncl.ac.uk
Cytarabine (ARA-C) Plus Methotrexate Superior for Patients With Primary
CNS Lymphoma http://bit.ly/3am1t8
Primary non-Hodgkin's lymphoma of the CNS treated with CHOD/BVAM or BVAM chemotherapy before radiotherapy: long-term survival and prognostic factors.
Int J Radiat Oncol Biol Phys. 2004 Jun 1;59(2):501-8. PMID: 15145169
Patients with primary CNS non-Hodgkin's lymphoma aged <60
years treated with CHOD/BVAM or BVAM followed by radiotherapy have
a similar long-term survival to that of patients with large B cell
non-Hodgkin's lymphoma at other extranodal sites.
Intensive Chemotherapy Followed by Hematopoietic Stem-Cell Rescue for Refractory and Recurrent Primary CNS and Intraocular Lymphoma:
Societe Francaise de Greffe de
Moelle Osseuse-Therapie Cellulaire. J Clin Oncol. 2008 Apr 14;
The respective median progression-free survival (PFS) times
after IC + HCR were 11.6 and 41.1 months. The 2-year overall
survival probability was 45% in the whole population and 69% among
the 27 patients who received IC + HCR. The 2-year PFS probability
was 43% among all the patients and 58% in the IC + HCR
subpopulation. CONCLUSION: IC + HCR is an effective treatment for
refractory and recurrent PCNSL.
Combined immunochemotherapy with reduced
whole-brain radiotherapy for newly diagnosed primary CNS lymphoma.
J Clin Oncol. 2007 Oct 20;25(30):4730-5. PMID: 17947720
The addition of Rituximab to MPV increased the risk of
significant neutropenia requiring routine growth factor support.
Additional cycles of R-MPV nearly doubled the CR rate.
Reduced-dose WBRT was not associated with neurocognitive decline,
and disease control to date is excellent.
Primary CNS lymphoma treated with combined
intra-arterial ACNU and radiotherapy - http://www.springerlink.com
The intra-arterial administration of ACNU combined with
radiation therapy yielded a high response rate at acceptable
toxicity levels in younger patients with PCNSL. However, late
neurotoxicity was a serious complication in patients above 60
years of age.
Management of central nervous system lymphomas
using monoclonal antibodies: challenges and opportunities.
Clin Cancer Res. 2005 Oct 1;11(19 Pt 2):7151s-7157s. Review. PMID:
Case report of a patient with primary central
nervous system lymphoma treated with radioimmunotherapy. Clin
Lymphoma Myeloma. 2006 Nov;7(3):236-8.
Salvage therapy for primary central nervous
system lymphoma with (90)Y-Ibritumomab and Temozolomide.
J Neurooncol. 2007 Jul;83(3):291-3. Epub 2007 Jan 24. PMID:
Aggressive initial treatment of Primary Central Nervous System
Lymphoma (PCNSL) has achieved prolonged survival and occasional
cures. However, some patients do not respond to initial therapy
and others relapse after an initial remission. The optimal salvage
regimen is not known and many different strategies have been
proposed. In this report we describe the efficacy of a combination
of (90)Y-Ibritumomab Tiuxetan (Zevalin) and Temozolamide as a
maintenance therapy for recurrent PCNS Lymphoma in two patients
that are both alive and in complete remission after 9 and 10
months respectively. This combination merits further study and
provides a reasonable therapeutic alternative for older patients
with progressive PCNSL.
Phase II Trial of the Bonn
Polychemotherapy Protocol with Deferred Radiotherapy in Patients
with Primary Central Nervous System Lymphoma. - ASH
Conclusions: Primary chemotherapy based on high-dose MTX and
ara-C is highly efficient in PCNSL. A substantial fraction of
patients < 60 years can obviously be cured with this regimen.
High-Dose Chemotherapy With Autologous Stem-Cell
Transplantation and Hyperfractionated Radiotherapy As First-Line
Treatment of Primary CNS Lymphoma.
J Clin Oncol. 2006 Jul 24; PMID:
With a median follow-up of 63 months (range, 4 months to 84
months), 5-year overall survival probability is 69% for all
patients and 87% for the 23 patients receiving HDT plus ASCT. The
5-year probability of relapse-related death is 21% for all
patients (n = 30) and 8.7% for patients treated with HDT plus ASCT
(n = 23). CONCLUSION: Sequential systemic methotrexate and AraC
and thiotepa followed by HDT plus ASCT and hyperfractionated WBRT
is very effective with little toxicity as initial therapy for
application of rituximab as a treatment option in patients with
CNS lymphoma and leptomeningeal disease. ASCO
Phase I Study of Intraventricular
Administration of Rituximab in Patients With Recurrent CNS and
Intraocular Lymphoma - http://jco.ascopubs.org
The maximum tolerated dose was determined to be 25 mg and
rapid craniospinal axis distribution was demonstrated. Cytologic
responses were detected in six patients; four patients exhibited
Two patients experienced improvement in intraocular NHL and one
exhibited resolution of parenchymal NHL. High RNA levels of Pim-2
and FoxP1 in meningeal lymphoma cells were associated with disease
refractory to rituximab monotherapy.
Conclusion: These results suggest that intrathecal rituximab (10
to 25 mg) is feasible and effective in NHL involving the CNS.
and efficacy of a multicenter study using intraarterial
chemotherapy in conjunction with osmotic opening of the
blood-brain barrier for the treatment of patients with malignant
brain tumors. Cancer. 2000 Feb 1;88(3):637-47. PMID:
10649259 | Related
Enhanced chemotherapy delivery by intraarterial
infusion and blood-brain barrier disruption in malignant brain
tumors: the Sherbrooke experience. Cancer. 2005 Jun
15880378 | Related
Due to the difficulties in treating PCNSL (as of
2004), we think it reasonable
specifically ask your treating physician about
See Studies for CNS in
Contact investigators listed
Arrange to have the
investigator talk with your treating physician.
Salvage chemotherapy with temozolomide in primary
CNS lymphomas: preliminary results of a phase II trial. Eur J
Cancer. 2004 Jul;40(11):1682-8. PMID:
Primary cerebral lymphoma: a retrospective study
in 22 immunocompetent patients.
Tumori. 2004 May-Jun;90(3):294-8 PMID: 15315308
of Primary CNS Lymphoma With Methotrexate and Deferred
Radiotherapy: A Report of NABTT 96-07. J Clin Oncol. 2003 Mar
15;21(6):1044-9. PMID: 12637469 PubMed
New in Primary Central Nervous System Lymphoma, An interview with
Virginia Stark-Vance, M.D. dfw-neuronetwork.com
Treatment of Primary CNS Lymphoma With Methotrexate and Deferred Radiotherapy: A Report of NABTT 96-07
Tracy Batchelor, Kathryn Carson, Alison O’Neill, Stuart A. Grossman, Jane Alavi, Pamela New, Fred Hochberg, Regina Priet
"These results indicate that high-dose methotrexate is associated with modest toxicity and a radiographic response proportion (74%) comparable to more toxic regimens. "
Prophylactic intrathecal methotrexate and hydrocortisone
reduces central nervous system recurrence and improves survival in
aggressive non-Hodgkin lymphoma cat.inist.fr/
Active Lymphoma Drugs
that May Cross Blood-Brain Barrier?
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keywords: antineoplastic small molecule drugs blood brain barrier
Articles and Tools:
Bridging the Blood-Brain Barrier: New Methods Improve the
Odds of Getting Drugs to the Brain Cells That Need Them
Drugs that appear to cross blood brain barrier
(some of these are investigational)
ClinicalTrials.gov searches by:
Resources & Research News
Ocular presentation of primary central nervous system
lymphoma: diagnosis and treatment. Br J Haematol. 2004
Methotrexate Induction Therapy Followed by High-Dose Chemotherapy ...
Doctor's Guide ... followed by high-dose chemotherapy with
autologous stem-cell rescue may be a feasible treatment approach
for primary central nervous system (CNS) lymphoma ...
Nervous System Lymphoma: Results of a Pilot and Phase II Study of
Systemic and Intraventricular Chemotherapy With Deferred
Radiotherapy. J Clin Oncol. 2003 Nov 3 PMID:
14597744 | More
radiotherapy in the outcome of patients with primary CNS lymphoma:
an analysis of the CHOD/BVAM regimen followed by two different
radiotherapy treatments. J Clin Oncol. 2002 Jan 1;20(1):231-6.
PMID: 11773174 - PubMed
Results of intensive chemotherapy followed by
hematopoietic stem-cell rescue in 22 patients with refractory or
recurrent primary CNS lymphoma or intraocular lymphoma.
Cancer. 2004 Feb;91(2):189-92. French PMID:
Primary CNS lymphoma of T-cell origin: a descriptive analysis
from the international primary CNS lymphoma collaborative group.
J Clin Oncol. 2005 Apr 1;23(10):2233-9. PMID:
Prognostic scoring system for primary CNS
lymphomas: the International Extranodal Lymphoma Study Group
experience. J Clin Oncol. 2003 Jan 15;21(2):266-72. PMID:
Initial response to glucocorticoids: an important prognostic
factor in patients with primary CNS lymphoma (PCNSL) - ASCO
with rituximab and temozolomide for central nervous system
lymphomas. Cancer. 2004 Jul 1;101(1):139-45.
15221999 | Related
Trends in survival from primary central nervous system
lymphoma, 1975-1999. Cancer. 2005 Oct 20; PMID:
Prospective trial on topotecan salvage therapy in primary CNS
lymphoma - annonc.oxfordjournals.org
The response rate was 33% with five complete (CR) and four
partial remissions (PR). The median follow-up was 37.7 months.
All complete responders had sustained remissions lasting for
9 to 28 months. The median event-free survival (EFS) was 2.0
months (9.1 months in responders), the overall survival (OAS)
was 8.4 months. CTC grade 3–4 leukopenia occurred in
26% and thrombocytopenia in 11% of the patients. Eight of 12
patients alive without cerebral lymphoma
six months after topotecan exhibited deficits
attributable to late neurotoxicity.
CNS outcomes predicted by gene
expression: Retrospective analysis of P-STAT6 expression as
a predictive marker in primary nervous system lymphoma patients
assigned to high-dose methotrexate -
Feasibility study: Study of
radiolabeled indium-111 and Zevalin in primary central nervous
system lymphoma. Cancer. 2007 Oct 11; PMID:
Brain parenchyma involvement as
isolated central nervous system (CNS) relapse of systemic
non-Hodgkin lymphoma: an International Primary CNS Lymphoma
Collaborative Group report.
Blood. 2007 Oct 25; PMID:
Our results suggest systemic methotrexate is the optimal
treatment for isolated CNS relapse involving the brain parenchyma.
Long-term survival is possible in some patients.
CNS Lymphoma : Methotrexate May Cure up to 20% of Patients
With CNS lymphoma
"In this small, multicenter study we found that at almost 7 years of follow-up, 5 of the original 25 patients were still in remission after treatment with high-dose methotrexate alone and that toxicity was modest," principal investigator Tracy Batchelor, MD, told Medscape Neurology & Neurosurgery.
The study is published in the January 29 issue of Neurology.
Biomarkers: Del(6)(q22) and BCL6 Rearrangements in Primary CNS Lymphoma Are Indicators of an Aggressive Clinical Course.
J Clin Oncol. 2008 Jul 21. PMID: 18645192
Comment: Markers such as these, when validated, can be used
to tailor therapy to the risk of the disease.
RESULTS: The prevalence of del(6)(q22) and BCL6, IGH, and MYC
translocations was 45%,17%, 13%, and 3%, respectively. The
presence of del(6)(q22) and/or a BCL6 translocation was associated
with inferior overall survival (OS; P = .0097). The presence of
either del(6)(q22) alone or a BCL6 translocation alone was also
associated with inferior OS (P = .0087).
Maculopathy in patients with primary CNS lymphoma treated with
chemotherapy in conjunction with blood–brain barrier disruption
Primary Central Nervous System Lymphoma: The Memorial
Sloan-Kettering Cancer Center Prognostic Model.
J Clin Oncol. 2006
Nov 20; PMID:
"The MSKCC prognostic score is a simple, statistically
powerful model with universal applicability to patients with newly
diagnosed PCNSL. We recommend that it be adopted for the
management of newly diagnosed patients and incorporated into the
design of prospective clinical trials."
Primary central nervous system mucosa-associated lymphoid tissue lymphoma: case report and literature review.
Razaq W, Goel A, Amin A, Grossbard ML. Clin Lymphoma Myeloma. 2009
Is Single-Agent Temozolomide the
Treatment of Choice for Recurrent Primary Central Nervous System
The authors conclude that in a heavily
pretreated population, temozolomide shows potential in the
treatment of PCNSL, with modest toxicity. The authors suggest that
temozolomide should be further developed as induction,
consolidation and maintenance therapy for primary lymphomas.
New strategies to deliver anticancer drugs to brain tumors
(technical, Oct 2009) http://bit.ly/37NTog
Temozolomide as salvage treatment in primary brain lymphomas