                   AIDS INFORMATION NEWSLETTER
                   Michael Howe, MSLS, Editor
                     AIDS Information Center
                VA Medical Center, San Francisco
                     (415) 221-4810 ext 3305
                          May 31, 1996

               Opportunistic Infections (Part XXV)
          AIDS-Related Lymphoma - Physician Information
          CancerNet from the National Cancer Institute
               Information from PDQ for Physicians
                           May 7, 1996

PROGNOSIS

     The Acquired Immune Deficiency Syndrome (AIDS) was first
described in 1981, and the first definitions included certain
opportunistic infections, Kaposi's sarcoma, and central nervous
system (CNS) lymphomas.  In 1984, a multicentered study described
the clinical spectrum of non-Hodgkin's lymphomas in the populations
at risk for AIDS.[1]  In 1985, the Centers for Disease Control
(CDC) revised the definition of AIDS to include patients with
high-grade B-cell non-Hodgkin's lymphoma in human immunodeficiency
virus (HIV) infected patients.  In 1987, intermediate-grade B-cell
lymphomas were added to the definition of AIDS after several
reports noted an increased incidence of large-cell lymphoma in
patients with AIDS and HIV infection.  The incidence of
non-Hodgkin's lymphoma has increased in an almost parallel course
with the AIDS epidemic and accounts for 3.3% of newly diagnosed
AIDS cases.  Over 200,000 cases of AIDS have been reported to the
CDC.  Of these, 2% were large-cell or immunoblastic lymphomas, 0.7%
were small-noncleaved lymphomas, and 0.6% were primary CNS
lymphomas.  In addition, there appears to be a marked increase in
the incidence of lymphoma in patients with diagnosed AIDS which,
because these are secondary diagnoses, are not included in the CDC
statistics.  Reports from the National Cancer Institute have
estimated the probability of developing a high-grade non-Hodgkin's
B-cell lymphoma in this group of patients to be as high as 19.4%
by 36 months after starting antiretroviral therapy.  Other reports
suggest a relatively constant rate of risk for the development of
non-Hodgkin's lymphoma of 1.6%-2.0% per year in a population with
AIDS or ARC.[2-4]  The diagnosis of AIDS precedes the onset of
non-Hodgkin's lymphoma in approximately 57% of the patients, but
in 30% the diagnosis of AIDS is made at the time of the diagnosis
of non-Hodgkin's lymphoma and HIV positivity.[5]  The geographic
distribution of these lymphomas is also similar to the geographic
spread of AIDS.  Unlike Kaposi's sarcoma, which has a predilection
for homosexual men and appears to be on the decline in incidence,
all risk groups appear to have an excess number of non-Hodgkin's
lymphoma, including intravenous drug users and children of
HIV-positive individuals.
     In general, the clinical setting and response to treatment of
patients with AIDS-related lymphoma is very different from the
non-HIV patient with lymphoma.  The HIV-infected individual with
intermediate- or high-grade lymphoma usually presents with advanced
stage disease that is frequently extranodal.  The clinical course
is more aggressive, and the disease both more extensive and less
responsive to chemotherapy.  Immunodeficiency and cytopenias,
common in these patients at the time of initial presentation, are
exacerbated by the administration of chemotherapy.  Therefore,
treatment of the malignancy increases the risk of opportunistic
infections, which in turn further compromise the delivery of
adequate treatment.
     Prognosis of patients with AIDS-related lymphoma has been
associated with stage (extent of disease, extranodal involvement,
bone marrow involvement), severity of the underlying
immunodeficiency (measured by CD4 lymphocyte count in peripheral
blood), performance status, and prior AIDS diagnosis (history of
opportunistic infection or Kaposi's sarcoma).  Patients with
AIDS-related primary CNS lymphoma appear to have more severe
underlying HIV-related disease than do patients with systemic
lymphoma.  In one report, this was evidenced by patients with
primary CNS lymphoma having a higher incidence of a prior AIDS
diagnosis (73% vs. 37%), lower median number of CD4 lymphocytes
(30/dL vs.  189/dL), and a worse median survival (2.5 months vs.
6.0 months).[6]  This same report showed that patients with poor
risk factors (defined as Karnofsky performance status <70%, history
of prior AIDS diagnosis, and bone marrow involvement) had a median
survival of 4.0 months as compared to a "good prognosis" group
without any of these risk factors with a median survival of 11.3
months.

HIV-Associated Hodgkin's Disease

     Since 1984, several series of cases of Hodgkin's disease
occurring in patients at risk for AIDS have been published.[7-9] 
However, Hodgkin's disease is still not part of the CDC definition
of AIDS because there has been no clear demonstration yet of its
increased incidence in conjunction with HIV, as is the case for
aggressive non-Hodgkin's lymphoma.  Recently, the CDC in
conjunction with the San Francisco Department of Public Health
reported a cohort study in which HIV-infected men had an excess
risk attributable to the HIV infection of 19.3 cases of Hodgkin's
disease per 100,000 person-years and 224.9 cases of non-Hodgkin's
lymphoma per 100,000 person-years and 224.9 cases of non-Hodgkin's
lymphoma per 100,000 person-years.  Although an excess incidence
of Hodgkin's disease was found in HIV-infected homosexual men in
this report, additional epidemiologic studies will be needed before
the CDC will reconsider Hodgkin's disease as an HIV-associated
malignancy.[10]
     The series referenced above are consistent in identifying
several features of HIV-associated Hodgkin's disease. 
Specifically, HIV-associated Hodgkin's disease presents in a more
aggressive fashion, often with extranodal or bone marrow
involvement.  Most patients in these series had either mixed
cellularity or lymphocyte-depleted Hodgkin's disease, B symptoms,
and a median CD4 count of 300 or less.  Median survival is less
than 1 year.  However, death in these patients was not due to the
Hodgkin's disease (most patients responded to standard treatment
regimens) but rather to opportunistic infections or other
HIV-related malignancies.

References:

  1. Ziegler JL, Beckstead JA, Volberding PA, et al.: Non-Hodgkin's
lymphoma in 90 homosexual men: relation to generalized
lymphadenopathy and the acquired immunodeficiency syndrome. New
England Journal of Medicine 311(9): 565-570, 1984.
  2. Pluda JM, Yarchoan R, Jaffe ES, et al.: Development of
non-Hodgkin lymphoma in a cohort of patients with severe human
immunodeficiency virus (HIV) infection on long-term antiretroviral
therapy.  Annals of Internal Medicine 113(4): 276-282, 1990.
  3. Gail MH, Pluda JM, Rabkin CS, et al.: Projections of the
incidence of non-Hodgkin's lymphoma related to acquired
immundeficiency syndrome. Journal of the National Cancer Institute
83(10): 695-701, 1991. 
  4. Pluda JM, Venzon DJ, Tosato G, et al.: Parameters affecting
the development of non-Hodgkin's lymphoma in patients with severe
human immunodeficiency virus infection receiving antiretroviral
therapy. Journal of Clinical Oncology 11(6): 1099-1107, 1993.
  5. Knowles DM, Chamulak GA, Subar M, et al.: Lymphoid neoplasia
associated with the acquired immunodeficiency sydrome (AIDS): the
New York University Medical Center experience with 105 patients. 
Annals of Internal Medicine 108(5): 744-753, 1988.
  6. Levine AM, Sullivan-Halley J, Pike MC, et al.: Human
immunodeficiency virus-related lymphoma: prognostic factors
predictive of survival. Cancer 68(11): 2466-2472, 1991.
  7. Ree HJ, Strauchen JA, Khan AA, et al.: Human immunodeficiency
virus-associated Hodgkin's disease: clinicopathologic studies of
24 cases and preponderance of mixed cellularity type characterized
by the occurrence of fibrohistiocytoid stromal cells.  Cancer
67(6): 1614-1621, 1991.
  8. Pelstring RJ, Zellmer RB, Sulak LE, et al.: Hodgkin's disease
in association with human immunodeficiency virus infection.  Cancer
67(7):1865-1873, 1991.
  9. Ames ED, Conjalka MS, Goldberg AF, et al.: Hodgkin's disease
and AIDS: twenty-three new cases and a review of the literature.
Hematology/Oncology Clinics of North America 5(2): 343-356, 1991.
 10. Hessol NA, Katz MH, Liu JY, et al.: Increased incidence of
Hodgkin disease in homosexual men with HIV infection.  Annals of
Internal Medicine 117(4): 309-311, 1992.
 11. Levine AM: Acquired immunodeficiency syndrome-related
lymphoma.  Blood 80(1): 8-20, 1992.


CELLULAR CLASSIFICATION

     Almost all AIDS-related non-Hodgkin's lymphoma have been
classified as B-cell, high or intermediate grade, according to the
Working Formulation.[1]

-- Working Formulation --

Low grade
     small lymphocytic, consistent with CLL (SL)
     follicular, predominately small cleaved cell (FSC)
     follicular, mixed small cleaved and large cell (FM)

Intermediate grade
      follicular, predominately large cell (FL)
      diffuse, small cleaved cell (DSC)
      diffuse, mixed, small and large cell (DM)
      diffuse, large cleaved or noncleaved cell (DL)

High Grade
      immunoblastic, large cell (IBL)
      lymphoblastic, convoluted or nonconvoluted cell (LL)
      small noncleaved cell, Burkitt's or non-Burkitt's (SNC)

     The majority of AIDS-related lymphomas are high grade.
Approximately 34%-40% are small-noncleaved (Burkitt's and
non-Burkitt's) lymphoma, 18%-43% are immunoblastic lymphomas, and
22%-36% are intermediate-grade, large-cell lymphomas.[2]
     AIDS-related lymphomas, although usually of B-cell origin as
demonstrated by immunoglobulin heavy chain gene rearrangement
studies, have also been shown to be oligoclonal and polyclonal, as
well as monoclonal in origin.  Chromosomal studies have shown
predictive abnormalities as in other lymphomas of similar
histology.  Molecular genetic studies have shown c-myc
translocation.  Although  HIV does not appear to have a direct
etiologic role, HIV infection does lead to an altered immunologic
milieu.  HIV generally infects T-lymphocytes whose loss of
regulation function leads to hypergammaglobulinemia and polyclonal
B-cell hyperplasia.  B cells are not the target of HIV infection. 
Instead, Epstein-Barr virus (EBV) is thought to be at least a
cofactor in the etiology of some of these lymphomas.  The EBV
genome has been detected in varying numbers of patients with
AIDS-related lymphomas with molecular analysis suggesting that the
cells were infected before clonal proliferation began.[3] 
HIV-related T-cell lymphomas have also been identified and appear
to be associated with EBV infection.[4]

References:

  1. The Non-Hodgkin's Lymphoma Pathologic Classification Project:
National Cancer Institute sponsored study of classifications of
non-Hodgkin's lymphomas: summary and description of a working
formulation for clinical usage.  Cancer 49(10): 2112-2135, 1982. 
  2. Freter CE: Acquired immunodeficiency syndrome-associated
lymphomas. Journal of the National Cancer Institute Monograph 10:
45-54, 1990.
  3. Neri A, Barriga F, Inghirami G, et al.: Epstein-Barr virus
infection precedes clonal expansion in Burkitt's and acquired
immunodeficiency syndrome-associated lymphoma.  Blood 77(5):
1092-1095, 1991.
  4. Thomas JA, Cotter F, Hanby AM, et al.: Epstein-Barr
Virus-related oral T-cell lymphoma associated with Human
Immunodeficiency Virus immunosuppression.  Blood 81(12): 3350-3356,
1993.


STAGE INFORMATION

     Although stage is important in selecting the treatment for
patients with non-AIDS-related non-Hodgkin's lymphoma, the majority
of patients with AIDS-related lymphomas have far advanced disease. 
In general, the Ann Arbor staging system is used, identical to that
for non--AIDS-related non-Hodgkin's lymphomas.

Staging Classification System --

     Stages I, II, III, and IV non-Hodgkin's disease can be
subclassified into A and B categories:  B for those with
well-defined generalized symptoms and A for those without.  The B
designation is given to patients with any of the following:

     * unexplained loss of greater than 10% of body weight in the
     6 months before diagnosis
     * unexplained fever with temperatures above 38 degrees C
     * drenching night sweats

     The designation "E" is used when extranodal lymphoid
malignancies arise in tissues away from the major lymphatic
aggregates.  If pathologic proof of involvement of one or more
extralymphatic sites has been documented, the symbol for the site
of involvement, followed by a plus sign (+), is listed.  Sites are
identified by the following notation:

   N = nodes    H = liver    L = lung    M = marrow
   S = spleen   P = pleura   O = bone    D = skin

-- Stage I --
     Stage I non-Hodgkin's lymphoma means involvement of a single
lymph node region (I), or localized involvement of a single
extralymphatic organ or site (IE).[1,2]

-- Stage II --

     Stage II non-Hodgkin's lymphoma means involvement of two or
more lymph node regions on the same side of the diaphragm (II) or
localized involvement of a single associated extralymphatic organ
or site and its regional lymph nodes with or without other lymph
node regions on the same side of the diaphragm (IIE).[1,2]

-- Stage III --
     Stage III non-Hodgkin's lymphoma means involvement of lymph
node regions on both sides of the diaphragm (III) that may also be
accompanied by localized involvement of an extralymphatic organ or
site (IIIE), involvement of the spleen (IIIS), or both
(IIIS+E).[1,2]

-- Stage IV --
     Stage IV non-Hodgkin's lymphoma means disseminated
(multifocal) involvement of one or more extralymphatic sites with
or without associated lymph node involvement, or isolated
extralymphatic organ involvement with distant (nonregional) nodal
involvement.[1,2]]

     A number of factors important for determining prognosis are
not included in the staging system for non-Hodgkin's lymphomas. 
All of these factors should be considered when selecting treatment. 
Prognosis is related to the severity of the underlying immune
deficiency (CD4 lymphocyte count), the presence or history of
opportunistic infections (prior AIDS-defining illness), bone marrow
involvement, performance status, and presence of extranodal
disease.[3]  Typically, AIDS-related lymphomas are widespread with
extranodal disease at the time of presentation.  The most common
extranodal sites are the gastrointestinal (GI) tract, central
nervous system, bone marrow, and liver.  In one series, the largest
group of patients had both extranodal and nodal disease (43%), but
one-third of the patients presented with extranodal disease
only.[4]  In a second series, 87% of the patients had extranodal 
disease at presentation.[5]  Two-thirds of patients are stage IV
at diagnosis.  In addition, unusual presentations include
involvement of the rectum, heart, pericardium, pulmonary
parenchyma, bile ducts, mouth, and subcutaneous and soft tissues. 
The clinical features of AIDS-related lymphomas correlate with
histopathology.  The majority of small-noncleaved cell (Burkitt's)
lymphomas present with Stage IV disease, mostly because of bone
marrow involvement.  This compares to approximately 40% stage IV
presentation by the immunoblastic and large-cell lymphomas.  A
particular prevalence for GI involvement by immunoblastic and
large-noncleaved cell lymphoma types has also been noted.[6]  While
high-risk behavior should be looked for in every patient, HIV
testing should probably be done with any Burkitt's lymphoma or the
atypical presentation of extranodal lymphoma involving rare sites,
i.e., rectum, GI tract, bone, or orbit.  Similarly, malignant
lymphoma should be considered in any HIV-infected patient with
progressive lymphadenopathy; tumors at any site; CNS symptoms; or
unexplained wasting, fever, or abdominal pain.

References:

  1. American Joint Committee on Cancer:  Manual for Staging of
Cancer. Philadelphia: JB Lippincott Company, 3rd ed., 1988.
  2. The Non-Hodgkin's Lymphoma Pathologic Classification Project:
National Cancer Institute sponsored study of classifications of
non-Hodgkin's lymphomas: summary and description of a working
formulation for clinical usage.  Cancer 49(10): 2112-2135, 1982. 
  3. Levine AM, Sullivan-Halley J, Pike MC, et al.: Human
immunodeficiency virus-related lymphoma: prognostic factors 
predictive of survival. Cancer 68(11): 2466-2472, 1991.
  4. Kaplan LD, Abrams DI, Feigal E, et al.: AIDS-associated
non-Hodgkin's lymphoma in San Francisco.  Journal of the American
Medical Association 261(5): 719-724, 1989.
  5. Knowles DM, Chamulak GA, Subar M, et al.: Lymphoid neoplasia
associated with the acquired immunodeficiency sydrome (AIDS): the
New York University Medical Center experience with 105 patients. 
Annals of Internal Medicine 108(5): 744-753, 1988.
  6. Raphael BG, Knowles DM: Acquired immunodeficiency
syndrome-associated non-Hodgkin's lymphoma.  Seminars in Oncology
17(3): 361-366, 1990.


TREATMENT OPTION OVERVIEW

     The treatment of AIDS-related lymphomas presents the challenge
of integrating therapy appropriate for the stage and histologic
subset of malignant lymphoma with the limitations imposed by HIV
infection, to date an incurable illness.  Patients with HIV
positivity and underlying immunodeficiency have poor bone marrow
reserve, thereby compromising the potential for dose intensity.
There is a risk of intercurrent opportunistic infection, which may
also lead to a decrease in drug delivery.  Furthermore,
chemotherapy itself compromises the immune system increasing the
likelihood of opportunistic infection.  In general, response rates
are lower than for a non-HIV population.  Complete responses occur
but tend to be of shorter duration with frequent relapses.  The
question is whether the curative potential of high-dose
chemotherapy is so compromised by the treatment-related morbidity
and mortality, that low-dose chemotherapy should be used.  Most
studies have used a lower dose intensity, and delays in treatment
have been common.  In the initial reports of AIDS-related lymphomas
approximately half of the evaluable patients achieved a complete
remission with combination chemotherapy, but of these,
approximately half subsequently relapsed.  One-half of the deaths
were from progressive lymphoma.  Although the other half died of
opportunistic infections, a significant percentage of this group
had active lymphoma at the time of death.  Since the initial
studies, several investigators have attempted to use intensive
chemotherapy regimens.  In general, these have not improved
survival.  Median overall survival for treated patients is
approximately 6 months.  The patients with the more favorable
outcomes and prolonged survival tend to have less disease (stage
I or II), no systemic symptoms, good performance status, and no CNS
or bone marrow involvement.  Therefore, chemotherapy should be
individualized for patients with good prognostic features who may
tolerate more aggressive therapy than those with poor prognostic
features.


AIDS-RELATED PERIPHERAL/SYSTEMIC LYMPHOMA

     As noted above, the treatment of AIDS-related lymphomas
involves overcoming several problems.  These are all aggressive
lymphomas, which by definition are diffuse large-cell/immunoblastic
lymphoma or small-noncleaved cell lymphoma. These lymphomas
frequently involve the bone marrow and central nervous system and
therefore are usually in an advanced stage.  In addition, the
immunodeficiency of AIDS and the leukopenia commonly seen with HIV
infection makes the use of immunosuppressive chemotherapy
difficult.
     A large number of retrospective studies, and more recently
several prospective studies, have been reported using regimens such
as CHOP and m-BACOD as are commonly employed with non-AIDS
aggressive lymphomas.  In general, these studies have combined the
various histologic subsets of AIDS-related systemic peripheral
lymphomas.  Unlike the non--HIV-related lymphomas, investigators
have treated diffuse large-cell/immunoblastic lymphoma as they have
small-noncleaved cell lymphoma.  These studies have shown that
complete remissions are possible, although the responses are often
of short duration and relapses are frequent.  The patients who go
into remission are more likely to have less disease, no bone marrow
or CNS involvement, no prior AIDS-defining illness, and a better
performance status.  Central nervous system relapses are common
such that the use of prophylactic intrathecal chemotherapy is
considered relatively standard.[1]  Overall complete responses have
been seen in approximately 50% of patients.  The complete response
rate and survival is higher in patients with diffuse large-cell
lymphoma.  Whether patients with small-noncleaved cell and
immunoblastic lymphoma have a worse prognosis is unclear and varies
from one series to another.[2]  The most appropriate treatment
regimen for patients with AIDS-related lymphoma is not known.
Delays in therapy and dose reductions are often necessary, and some
investigators have advocated using lower-dose chemotherapeutic
regimens.  In addition, more aggressive chemotherapy has been
reported to be associated with a shortened survival for
AIDS-related lymphomas.[3]  Therefore, the prognostic features
related to the underlying immune deficiency and marrow compromise
seem to outweigh the lymphoma-specific related prognostic
indicators.
     One recent report used a low dose modification of the m-BACOD
regimen as well as intrathecal cytarabine.  Pneumocystis
prophylaxis was employed and zidovudine was instituted after
completion of 4-6 cycles of chemotherapy.  The results were
comparable to the reports above.[4]  Median duration of survival
was 6.5 months in the patients evaluable for response and 15 months
in the patients with complete response.  Another report
incorporated hematopoietic growth factor (GM-CSF) into a regimen
using CHOP.[5]  Compared to a control group, patients receiving
GM-CSF tolerated the chemotherapy better as evidenced by higher
nadirs and fewer complications of neutropenia, fever, and
hospitalization.  In addition, fewer reductions in chemotherapy
dosages and less frequent delays in chemotherapy administration
were noted.  Although complete responses were achieved in 70% of
patients, the small numbers in the study did not allow for adequate
comparison of prognostic factors to determine if dose intensity was
useful.  A phase I study of m-BACOD and GM-CSF has been recently
reported in which the use of hematopoietic growth factor permitted
administration of full doses of chemotherapy.[6]  To determine if
dose intensity is important in AIDS-related lymphoma, the AIDS
clinical trial units (ACTG) are currently comparing low-dose to
standard-dose chemotherapy in this group of patients.

References:

  1. Gill PS, Levine AM, Krailo M, et al.: Aids-related malignant
lymphoma: results of prospective treatment trials.  Journal of
Clinical Oncology 5(9): 1322-1328, 1987.
  2. Pedersen C, Gerstoft J, Lundgren JD, et al.: HIV-associated
lymphoma: histopathology and association with Epstein-Barr virus
genome related to clinical, immunological and prognostic features. 
European Journal of Cancer 27(11): 1416-1423, 1991.
  3. Kaplan LD, Abrams DI, Feigal E, et al.: AIDS-associated 
non-Hodgkin's lymphoma in San Francisco.  Journal of the American
Medical Association 261(5): 719-724, 1989.
  4. Levine AM, Wernz JC, Kaplan L, et al.: Low-dose chemotherapy
with central nervous system prophylaxis and zidovudine maintenance
in AIDS-related lymphoma: a prospective multi-institutional trial. 
Journal of the American Medical Association 266(1): 84-88, 1991.
  5. Kaplan LD, Kahn JO, Crowe S, et al.: Clinical and virologic
effects of recombinant human granulocyte-macrophage colony
stimulating factor in patients receiving chemotherapy for human
immunodeficiency virus-associated non-Hodgkin's lymphoma: results
of a randomized trial.  Journal of Clinical Oncology 9(6): 929-940,
1991.
  6. C Walsh: Colony-stimulating factors in the treatment of
HIV-associated non-Hodgkin's lymphoma.  Oncology (Huntington NY)
3(10): 79-86, 1989.


AIDS-RELATED PRIMARY CNS LYMPHOMA

     Until the 1980s, primary CNS lymphoma was a rare disease. 
Recently, there has been a dramatic increase in primary CNS
lymphoma in association with AIDS.[1]  Primary CNS lymphoma
accounts for approximately 0.6% of initial AIDS diagnoses and is
the second most frequent CNS mass lesion in adults with AIDS.  As
with other AIDS-related lymphomas, these are usually aggressive
B-cell neoplasms, either diffuse large-cell or diffuse
immunoblastic NHL.  However, unlike AIDS-related systemic lymphomas
in which 30%-50% of tumors are associated with EBV, AIDS-related
primary CNS lymphoma has been reported to have a 100% association
with EBV.[2]  This indicates a pathogenetic role for EBV in this
disease.  These patients usually have evidence of far advanced
AIDS, are severely debilitated, and present with focal neurologic
symptoms such as seizures and paralysis.  Computed tomography scans
show contrast-enhancing mass lesions, which cannot be distinguished
from other CNS diseases occurring in AIDS patients such as
toxoplasmosis.[3]  Diagnosis is made by biopsy.  Primary CNS
lymphoma is often identified as a terminal manifestation of AIDS
or on postmortem examination.
     Radiation therapy alone has usually been used in this group
of patients.  With doses in the 3500-4000 cGy range, median
survival has been only 72-119 days.[3-5]  Survival is longer in
patients with better performance status and absence of
opportunistic infection.  Most patients respond to treatment with
partial improvement in neurologic symptoms.  When autopsies have
been performed, patients have been shown to die of opportunistic
infections as well as tumor progression.  Treatment of these
patients is also complicated by other AIDS-related CNS infections
including subacute AIDS encephalitis, CMV encephalitis, and
toxoplasmosis encephalitis.

References:

  1. Ziegler JL, Beckstead JA, Volberding PA, et al.: Non-Hodgkin's
lymphoma in 90 homosexual men: relation to generalized
lymphadenopathy and the acquired immunodeficiency syndrome.  New
England Journal of Medicine 311(9): 565-570, 1984.
  2. MacMahon EM, Glass JD, Hayward SD, et al.: Epstein-Barr virus
in AIDS-related primary central nervous system lymphoma.  Lancet
338(8773): 969-973, 1991.
  3. Goldstein JD, Dickson DW, Moser FG, et al.: Primary central
nervous system lymphoma in acquired immune deficiency syndrome: a
clinical and pathologic study with results of treatment with
radiation.  Cancer 67(11): 2756-2765, 1991.
  4. Baumgartner JE, Rachlin JR, Beckstead JH, et al.: Primary
central nervous system lymphomas: natural history and response to
radiation therapy in 55 patients with acquired immunodeficiency
syndrome.  Journal of Neurosurgery 73(2): 206-211, 1990.
  5. Remick SC, Diamond C, Migliozzi JA, et al.: Primary central
nervous system lymphoma in patients with and without the acquired
immune deficiency syndrome: a retrospective analysis and review of
the literature.  Medicine 69(6): 345-360, 1990.

Date Last Modified: 05/96
