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The current study evaluated factors influencing survival in patients diagnosed with human immunodeficiency virus (HIV)-related primary central nervous system lymphoma (PCNSL), with a focus on the effects of therapeutic radiotherapy (RT) and highly active antiretroviral therapy (HAART).
A retrospective chart review of patients with a diagnosis of HI...
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Context 1
... hundred eight patients were male, with a mean age of 38.0 years (median, 36.6 years; range, 22.0 -63.2 years). Other baseline characteristics are shown in Tables 1 and 2. The original data abstraction identified an additional 14 patients presenting with lymphoma involving the CNS. ...
Context 2
... Improved survival in patients selected for RT may be at least partially attributable to selection bias. Pa- tients who received any RT had a better mean ECOG performance status (P 0.007), fewer previous AIDS- defining illnesses (P 0.04), and a nonsignificant trend toward younger age (P 0.09; Table 1). In the University of California-San Francisco series, there was a significant correlation (P 0.02) between base- line performance status and duration of survival. ...
Similar publications
Primary central nervous system lymphoma (PCNSL) is a frequent complication in acquired immunodeficiency syndrome (AIDS). The objective of this survey was to investigate incidence, clinical features, radiological findings, histologic diagnosis, treatment and outcome for all patients with histologically verified AIDS-related PCNSL diagnosed in Norway...
Over time, the epidemiologic and demographic characteristics of AIDS have changed in the United States, while the use of highly active antiretroviral therapy has changed the natural history of the disease. The goal of the study was to ascertain any changes in the epidemiologic, immunologic, pathologic, or clinical characteristics of AIDS-related ly...
Citations
... Evidence on the benefit of ART in the treatment of HIV-related PCNSL derives from observational studies that showed that early institution of ART after PCNSL diagnosis was independently associated with improved survival. 58,59,181 In a few cases, rapid immune recovery and prolonged tumor regression have been achieved with this sole approach. 182 (Class IV). ...
... months). 58,59,181 On the basis of short response durability and poor survival data, and the high risk of severe neurotoxicity in longer survivors, it is suggested to avoid or reserve palliative WBRT for patients with poor functional status who are not a candidate for chemotherapy (Class IV). For patients with morbidities that preclude safe usage of HD-MTX such as moderate or severe renal insufficiency, treatment decisions must be individualized. ...
The management of primary central nervous system (PCNSL) is one of the most controversial topics in neuro-oncology because of the complexity of the disease and the limited number of controlled studies available. In 2021, given recent advances and publication of practice-changing randomised trials, the European Association of Neuro-Oncology (EANO) created a multidisciplinary task force to update the previously published evidence-based guidelines for immunocompetent adult patients with PCNSL and added a section on immunosuppressed patients. The guideline provides consensus considerations and recommendations for treatment of PCNSL, including intraocular manifestations and specific management of elderly . The main changes from the previous guideline include strenghtened evidence for the consolidation with ASCT in first-line treatment, prospectively assessed chemotherapy combinations for both young and elderly patients, clarification of the role of rituximab even though the data remain inconclusive, of the role of new agents, and the incorporation of immunosuppressed patients and primary ocular lymphoma. The guideline should aid the clinicians in everyday practice and decision making and serve as a basis for future research in the field.
... Survival of patients treated with HAART differed significantly from those receiving no therapy (1093 and 33 days, respectively) [14]. These findings were confirmed in two other retrospectives series [13,34]. ...
Background
AIDS-related primary central nervous system lymphoma (AR-PCNSL) is an AIDS-defining disease that usually occurs when the CD4 count is less than 50 cells/μl. The frequency of the disease has substantially decreased in the era of highly active antiretroviral therapy (HAART). Prognosis is poor with rapid progression leading to death within 2–3 months if left untreated.
Case description
A 65 years old male presented to medical attention with gait disturbance, weight loss and slight left-sided hemiparesis. Human immunodeficiency virus infection was diagnosed with an initial CD4 count of 116 cells/µl and a viral load of 260,000 copies/ml. Magnetic resonance imaging of the brain revealed three brain lesions involving the right frontal lobe and the left parietal lobe, which on biopsy led to a diagnosis of AR-PCNSL. HAART was initiated with whole-brain radiotherapy (WBRT), and the patient declined systemic chemotherapy. Due to poor performance status, he was transferred to palliative care. Under HAART, he slowly recovered with normalization of CD4 count and undetectable viral load. Medical imaging showed complete remission (CR) of the brain lesions. At 3-year follow-up, the patient remains in CR, but presented mild neurocognitive dysfunction possibly secondary to WBRT.
Conclusion
Nowadays, treatment paradigm parallels that of primary central nervous system lymphoma in the immunocompetent population based on systemic chemotherapy (primarily high-dose intravenous methotrexate and steroids) in association with HAART. The role of WBRT is questionable because of late neurotoxic effects.
... Survival of patients treated with HAART differed signi cantly from those receiving no therapy (1093 and 33 days, respectively) (13). These ndings were con rmed in two other retrospectives series (12,31). ...
Background: Acquired immunodeficiency syndrome (AIDS)-related primary central nervous system lymphoma is an AIDS-defining disease that usually occurs when the CD4 count is less than 50 cells/ml. The frequency of the disease has substantially decreased in the era of highly active antiretroviral therapy (HAART). Prognosis is poor with rapid progression leading to death within 2-3 months if left untreated.
Case description: a 65 years old male presented to medical attention with gait disturbance, weight loss and slight left-sided hemiparesis. Human immunodeficiency virus infection was diagnosed with an initial CD4 count of 116 cells/ml and a viral load of 260’000 copies/ml. Magnetic resonance imaging of the brain revealed three brain lesions involving the right frontal lobe and the left parietal lobe, which on biopsy led to a diagnosis of AIDS-related primary central nervous system lymphoma. HAART was initiated with whole-brain radiotherapy, and the patient declined systemic chemotherapy. Due to poor performance status, he was transferred to palliative care. Under HAART, he slowly recovered with normalization of CD4 count and undetectable viral load. Medical imaging showed complete remission of the brain lesions. At 3-year follow-up, the patient remains in complete remission, but presented mild neurocognitive dysfunction possibly secondary to whole-brain radiotherapy.
Conclusion: Nowadays, treatment paradigm parallels that of primary central nervous system lymphoma in the immunocompetent population based on systemic chemotherapy (primarily high-dose intravenous methotrexate and steroids) in association with HAART. The role of whole-brain radiotherapy is questionable because of late neurotoxic effects.
... Some studies from South-east Asia countries such as Japan and Korea have shown no significant association of PCNSL with AIDS [16,14,15]. A recent study estimated that in USA about 13% of CNS lymphoma cases were associated with AIDS in the period 2001-2007. ...
... The occurrence of Tcell PCNSL is very rare in Western as well as Asian studies [15,17]. A study done in japan of patients with PCNSL between 2000-2004 showed that T-cell PCNSL accounted for 1.7% of all cases [14], whereas a similar study done earlier between 1985-1994 from Japan showed a higher figure of 8.5% [16] From this case presented, the lymphoma is of the B subtype and this is in line with majority of the lesions from several studies discussed above. PCNSL is both a highly radiosensitive and chemosensitive infiltrative tumour. ...
Non-AIDS lymphoma, a type of primary central nervous system (CNS) lymphoma is an uncommon aggressive infiltrative malignant tumour involving several sites in the central nervous system such as the periventricular region and leptomeninges. In this article, the authors presented a 26-year old man with painless progressive right exophthalmos and scalp swelling with no symptoms and signs of intracranial hypertension and hyperthyroidism. Magnetic resonance imaging (MRI) done revealed isointense masses with homogenous brilliant enhancement on contrast administration resembling a meningioma, with a dura tail-like attachment as seen in meningioma. He had surgery for the right orbital tumour and histopathological diagnosis confirmed our suspicion of lymphoma (B type). Steroid was given in the post-operative period which led to significant regression of the tumours, hence its description as 'vanishing tumour'. He is presently receiving a methotrexate-based chemotherapy and subsequently planned for radiotherapy.
... HIV-related PCNSL is typically a large cell lymphoma with immunoblastic and more aggressive features [4]. The presentations of PCNSL in both immunocompromised and immunocompetent patients is similar, with signs of a focal mass lesion in 70% and 61.3% of patients, respectively [5]. Seizures are less common than with other types of brain tumors probably because PCNSL involves predominantly subcortical white matter rather than epileptogenic gray matter. ...
... In immunocompetent PCNSL patients, lesions are solitary in 65% of cases and are located in the cerebral hemisphere (38%), thalamus or basal ganglia (16%), corpus callosum (14%), periventricular region (12%), and cerebellum (9%) [6]. HIV-related PCNSL is solitary in 48.6% of cases and is localized to the cerebral cortex in 65%, the periventricular region in 56%, the basal ganglia in 33%, the cerebellum in 7%, and the brainstem in 4% [5]. CEMRI brain is the imaging of choice. ...
Abstract Background Primary central nervous system lymphoma (PCNSL) is an uncommon extranodal non-Hodgkin lymphoma. This tumor is common in the fifth to seventh decade and is located commonly in the periventricular region and in the cerebral hemisphere. Corpus callosum is a rare site. We report a case of diffuse large B cell lymphoma with corpus callosum and contralateral side involvement in immunocompetent patient. Case presentation A 50-year-old male was admitted with complaints of headache with one episode of generalized seizure. On examination, the patient was neurologically intact. CEMRI (contrast-enhanced magnetic resonance imaging) brain showed heterogenous enhancing mass lesion in the left frontal and basifrontal region with involvement of rostrum and body of corpus callosum with patchy areas of diffusion restriction and choline peak on MRS (magnetic resonance spectroscopy). Intraoperatively yellowish brown tumor was seen in the left basifrontal and frontal region with involvement of corpus callosum and extension to opposite side. Microscopic and IHC (immunohistochemistry) examination was suggestive of diffuse large cell lymphoma. Postoperative period was uneventful. The patient received chemoradiotherapy in postoperative period. The patient is asymptomatic 6 months after surgery. Conclusion Primary CNS lymphoma is a rare tumor, and corpus callosum with contralateral side involvement is rare.
... Primer SSS lenfoması olan 248 hastalık bir seride 43% oranında nöropsikiyatrik bulgular, 33% oranında artmış kafa içi basınç bulguları, 14% oranında nöbet ve 4% oranında oküler bulgular saptanmıştır (11). HIV ile ilişkili 111 hastayı içeren diğer bir seride ise 43.2% oranında baş ağrısı, 21.6% oranında nöbet ve 18% oranında ataksi saptanmıştır (12). ...
... HIV ilişkili olan primer SSS lenfomalarında ise lezyonlar 52% oranında multipl olarak saptanırlar. Bunların yerleşim bölgeleri ise sırasıyla beyin hemisferleri (65%), periventriküler alan (56%), bazal ganglionlar (33%), serebellum (7%) ve beyin sapı (4%) olarak tespit edilirler (12). İzole spinal kord tutulumları ise çok nadirdir ve 1% oranından bile az olarak saptanırlar. ...
... These mainly reflect patient characteristics (e.g. age, performance score), [5,9,10,12,13] type or severity of immunosuppression (e.g. CD4 + T-cell counts at diagnosis, duration of immunosuppression, type of transplant) [5,[13][14][15], and treatment [10,12,13,16]. ...
... age, performance score), [5,9,10,12,13] type or severity of immunosuppression (e.g. CD4 + T-cell counts at diagnosis, duration of immunosuppression, type of transplant) [5,[13][14][15], and treatment [10,12,13,16]. To our knowledge, no molecular or imaging related predictors of survival have been identified. ...
... age, performance score), [5,9,10,12,13] type or severity of immunosuppression (e.g. CD4 + T-cell counts at diagnosis, duration of immunosuppression, type of transplant) [5,[13][14][15], and treatment [10,12,13,16]. To our knowledge, no molecular or imaging related predictors of survival have been identified. ...
Background
Immunodeficiency is a major risk factor for primary central nervous system lymphoma (PCNSL), but data on the disease in immunocompromised hosts are scarce. We aimed to define clinical and imaging features and determine prognostic factors for immunodeficiency-associated PCNSL.
Methods
All PCNSL cases seen at Yale-New Haven Hospital between 2002 and 2017 were retrospectively screened for immunodeficiency. For patients with immunosuppression, biopsies were evaluated and clinical data were collected. Predictors of survival were identified using Kaplan–Meier survival analysis and log-rank test. p values < 0.05 were considered significant.
Results
23 patients with immunodeficiencies were identified: eleven on immunosuppressants after solid organ transplantation, seven with human immunodeficiency virus infection, and five on immunosuppressive treatment due to various autoimmune disorders. PCNSL cases were largely Epstein-Barr-Virus positive (78%), histologically classified as diffuse large B cell lymphomas (87%), and showed peripheral contrast enhancement (81%) and corresponding heterogeneous diffusion-weighted imaging patterns (DWI) on magnetic resonance imaging (MRI) (71%). Median overall survival was 31 months. Age > 60 years at diagnosis (p < 0.01), peripheral enhancement of the mass on MRI (p = 0.04), heterogeneous DWI patterns (p = 0.04), and clonal immunoglobulin heavy chain gene rearrangement (IgHR) (p = 0.03) were found to be negative prognostic markers.
Conclusions
Immunodeficiency-associated PCNSL presents with similar clinical, pathological and imaging features. Age > 60 years, clonal IgHR, heterogeneous DWI pattern and peripheral enhancement on MRI may serve as predictors of less favorable outcome.
... Brain biopsy, the gold standard for PCNSL diagnosis, was obtained from 36 patients; deep-seated AR-PCNSL in a highly functional brain area precluded potentially dangerous biopsy or delayed diagnosis for 15. In that frequent real-life setting (table e-1), the following 3 validated surrogate criteria enabled diagnosis 8,13,14,19,[22][23][24] : compatible MRI with diffusion and perfusion sequences and spectroscopy, positive EBV-DNA PCR of CSF, and unresponsiveness to 2 to 3 weeks of ToxE treatment without corticosteroids. The date of histologic results or CSF EBV PCR positivity yielding a definitive or highly probable diagnosis, respectively, dated PCNSL diagnosis. ...
... For the 15 patients without histology, multivariate analyses found time interval between AIDS diagnosis and PCNSL diagnosis .6 months (odds ratio 7.35, p 5 0.002) to be independently associated with worse OS. DISCUSSION AR-PCNSL remains a leading cause of mortality in the modern cART era, [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] with the highest 2-year mortality rate (76%-84%) 30 among all cancers in PLHs. In contrast, our cohort's mortality was 52%, with 5.7-year median OS and 48% 5-year OS; the 69% TTP plateau for the whole cohort (i.e., PCNSL-specific mortality) stabilized after 10 months. ...
... Our patients' clinical and radiologic AR-PCNSL characteristics were comparable to those reported previously. 2,6,[9][10][11][12][13]17,19,[22][23][24] The main difference was our unrestricted, systematic, standardized administration of specific HD-MTX (3 g/m 2 ), the backbone of IP-PCNSL therapy conferring the best survival advantage. 1 That dose was chosen on the basis of convergent findings, notably in PLHs, 23 and in agreement with recommendations for IPs .60 years and observations suggesting potentially accelerated PLH brain aging. ...
Objective:
To assess the characteristics and outcomes of patients with AIDS-related primary CNS lymphoma (AR-PCNSL) in the combined antiretroviral therapy (cART) era systematically treated with high-dose methotrexate (HD-MTX).
Methods:
We retrospectively analyzed (intention-to-treat analysis) 51 consecutive patients with AR-PCNSL (median age 39 years) who were diagnosed from 1996 to 2014 and treated with a median of 6 (range 1-15) infusions of HD-MTX (3 g/m(2)) combined with cART.
Results:
Median all-patients' and survivors' follow-up lasted 23 (range 0-186) and 76 (range 23-186) months, respectively. At PCNSL diagnosis, 83% of the patients were on cART, median plasma HIV load was 175,600 copies/mL, and median CD4+ T-cell count was 24/μL. Median Eastern Cooperative Oncology Group performance status was 2 (range 1-4). Median overall survival (OS) was 5.7 years, with 5- and 10-year rates of 48% and 41%. Median time to progression was not reached (69% at 10 months). PCNSL was the direct cause of 14 deaths, all observed within the 10 months after its diagnosis: 6 patients died before HD-MTX could be administered, 4 had refractory disease, and 4 relapsed. Multivariate analyses retained time interval between AIDS diagnosis and PCNSL diagnosis, age at AR-PCNSL diagnosis, and deep brain structure involvement as independent OS-predictive factors. To restore effective immune function, cART tailored to HIV genotypes was started and combined with HD-MTX; no interactions and no immune reconstitution inflammatory syndrome occurred. No patient died of acute treatment-related toxicity, and 21 of 51 (41%) patients experienced grade 3/4 toxicity.
Conclusions:
Combined short-term HD-MTX monochemotherapy and optimal cART simply and effectively treat AR-PCNSL, achieving long-term survival with few relapses.
Classification of evidence:
This study provides Class IV evidence that short-term HD-MTX monochemotherapy improves long-term survival of patients with AIDS with primary CNS lymphoma receiving cARTs.
... Similarly, it is not yet known whether rituximab and combination chemotherapy are more effective when given with or without radiation therapy (Kansara et al, 2015;Holdhoff et al, 2014). There are even less data pertaining to the benefit of rituximab in the immuno-compromised population with PCNSL (Newell et al, 2004). As such, we sought to: (i) identify whether evolving patterns of care in a 'realworld' setting have impacted outcomes in newly diagnosed PCNSL; (ii) consider if such practice patterns offer reasonable outcomes in the immuno-compromised subset; and (iii) determine whether 'real-world' practice patterns and clinical outcomes are comparable to those reported in recent clinical trials. ...
Patients with primary central nervous system lymphoma (PCNSL) treated in the ‘real-world’ setting do not represent those treated on clinical trials and might not be treated similarly. We studied characteristics and variability in care for 113 newly diagnosed PCNSL patients treated at 5 institutions in the Chicago area between 2000 and 2012. In 111 patients, single modality therapy with a high dose methotrexate (HD-MTX) regimen +/− rituximab, was most commonly employed (n = 65), and 34 underwent radiotherapy (+/− systemic therapy). Fifty-eight of 108 patients received rituximab. Twenty-nine of 110 patients (26%) received intrathecal chemotherapy (ITC). Overall response rate was 80% (47% complete responses). With a median follow-up of 18·7 months, median overall survival (OS) was 65·2 months. In univariate analysis, HD-MTX (median OS 72·7 vs. 2·7 months, P < 0·001) and rituximab (median not reached versus 28·4 months, P = 0·005) impacted OS favourably. This significance was sustained regardless of immune status and in multivariate analysis. Whole brain radiotherapy (WBRT) resulted in a trend for improved OS as compared with systemic therapy alone (P = 0·09), while ITC did not impact survival. Clinical practice has evolved to exclude WBRT and ITC while incorporating rituximab with clinical outcomes comparable in immuno-competent/compromised patients and similar to those achieved in recent clinical trials.
... It can induce and simultaneously overcome the p27KIP1-mediated inhibition of cell growth. In addition, EBV leads to the expression of activation-induced cytidine deaminase (AID) and DNA polymerase-n (Pol n), and these factors are associated with the mutation of two oncogenes (Bcl-6 and p53) that are associated with PCNSL [18][19][20][21][22]. ...
... Of note, the cause of death was mainly related to infectious complication of AIDS but not to the neurologic disease. Since the development of HAART, there are cumulating studies showing an improved overall survival of AIDS patients including AIDS-PCNSL patients treated with WBRT, especially in complete responders (Hoffmann et al. [48], Newell [22], Skiest and Crosby [49], Nagai et al. [50 ]). Performance status, CR and HAART appeared as good prognostic factors in these latter studies [22,43-49,50 ,51 ]. ...
