Leptomeningeal Disease In Patients Research Articles

Factors associated with overall survival in breast cancer patients with leptomeningeal disease (LMD): a single institutional retrospective review.

Breast cancer-related leptomeningeal disease (BC-LMD) is a dire diagnosis for 5-8% of patients with breast cancer (BC). We conducted a retrospective review of BC-LMD patients diagnosed at Moffitt Cancer Center from 2011 to 2020, to determine the changing incidence of BC-LMD, factors which are associated with the progression of BC CNS metastasis to BC-LMD, and factors which are associated with OS for patients with BC-LMD. Patients with BC and brain/spinal metastatic disease were identified. For those who eventually developed BC-LMD, we used Kaplan-Meier survival curve, log-rank test, univariable, and multivariate Cox proportional hazards regression model to identify factors affecting time from CNS metastasis to BC-LMD and OS. 128 cases of BC-LMD were identified. The proportion of BC-LMD to total BC patients was higher between 2016 and 2020 when compared to 2011-2015. Patients with HR+ or HER2 + BC experienced longer times between CNS metastasis and LMD than patients with triple-negative breast cancer (TNBC). Systemic therapy and whole-brain radiation therapy (WBRT) was associated with prolonged progression to LMD in all patients. Hormone therapy in patients with HR + BC were associated with a delayed BC-CNS metastasis to LMD progression. Lapatinib treatment was associated with a delayed progression to LMD in patients with HER2 + BC. Patients with TNBC-LMD had shorter OS compared to those with HR + and HER2 + BC-LMD. Systemic therapy, intrathecal (IT) therapy, and WBRT was associated with prolonged survival for all patients. Lapatinib and trastuzumab therapy was associated with improved OS in patients with HER2 + BC-LMD. Increasing rates of BC-LMD provide treatment challenges and opportunities for clinical trials. Prospective trials testing lapatinib and/or similar tyrosine kinase inhibitors, IT therapies, and combination treatments are urgently needed.

Oncolytic HSV1 targets different growth phases of breast cancer leptomeningeal metastases.

Leptomeningeal metastasis is a fatal complication of breast cancer which results when cancer cells seed in the meninges. Currently there is no cure, limiting survival to less than four months. Treatment options are palliative. We studied a replication conditional Herpes simplex virus 1 (HSV1) in this regard and present the therapeutic efficacy of oncolytic HSV1 on different stages of breast cancer leptomeningeal metastases growth, namely the lag, intermediate, and exponential phases. These phases characterized in a murine model represent the early, intermediate, and late stages of leptomeningeal disease in patients. In this model, virus was introduced into the ventricular system by stereotactic surgery, the same path cancer cells were introduced to create leptomeningeal metastases. Tumor growth was measured with Gd-MRI and virus replication was assessed by FHBG-PET and Fluc bioluminescence. Imaging results were correlated with H&E and HSV-TK immunohistochemical staining. A remarkable growth inhibition was observed when the lag phase was targeted which was associated with multiple virus replication cycles. The onset of debilitating symptoms was delayed, and survival was lengthened by nearly 2 weeks. A growth inhibition similar to the lag phase was observed when the intermediate phase was targeted, associated with robust virus replication. The regression of existing tumor led to a reversal of neurological symptoms, extending survival by nearly one week. A modest response was observed when the lag phase was targeted lengthening survival by 3 days. Oncolytic HSV1 presents a novel treatment option for breast cancer leptomeningeal metastases with potential for targeting different disease stages where virus replication and tumor response can be monitored with molecular imaging techniques that are in the clinic.

LOCL-06 SUPERVISED MACHINE LEARNING IDENTIFIES RISK FACTORS ASSOCIATED WITH LEPTOMENINGEAL DISEASE AFTER SURGICAL RESECTION OF BRAIN METASTASES

BACKGROUNDResection of brain metastases (BMs) can help with local disease control, yet predictors of leptomeningeal disease (LMD) after surgery are not well defined. This study examined rates and predictors of LMD in patients who underwent resection of a BM. METHODSA retrospective, single-center study was conducted examining LMD risk for adult patients with a BM that underwent resection with postoperative adjuvant radiation. Logistic regression analyses and a supervised machine learning algorithm (Random forest) were implemented to identify factors within the cohort that were associated with LMD. RESULTSOf the 182 patients in the cohort, 43 patients (23.6%) developed LMD in the postoperative setting with 18 cases of classical LMD (9.9%) and 25 cases of nodular LMD (13.7%). Median censored time to LMD was not reached, and 6-, 12-, and 24-month LMD-free rates from surgery were 93%, 86.3%, and 71.8%, respectively. Median time from surgery to classical and nodular LMD were 13.1 and 9.5 months, respectively (Log-rank p=0.71). Patients diagnosed with classical LMD had worse survival outcomes from LMD diagnosis compared to nodular LMD (2.6 vs 9.7 mo, Log-rank p=0.02), and LMD-subtype was significantly associated with overall survival from the date of surgery (classical vs nodular vs none: 16.1 vs 20 vs 36.7 mo, p <.0001). Random forest analysis identified primary cancer type, absence of extracranial disease, and tumor volume as the top 3 factors associated with LMD. On multivariate regression analysis, absence of extracranial disease at index surgery was associated with any LMD (OR 2.65, 95% CI 1.15-6.10, p=0.02). Treatment with postoperative checkpoint inhibitors, type of radiation, and performing additional craniotomies were not associated with risk of LMD. CONCLUSIONSClassical-type LMD is associated with worse prognosis compared to nodular-type LMD. Absence of extracranial disease at the time of surgery was the most consistent factor associated with LMD on follow-up.

Leptomeningeal Disease in Patients with Histone-Mutant Gliomas (S27.005)

Leptomeningeal Disease in Patients with Histone-Mutant Gliomas (S27.005)

Clinical Problem Solving: A 56-Year-Old Woman With Right Facial Weakness, Numbness, and Diplopia.

We discuss a case of a middle-aged woman with a history of urothelial carcinoma, who presented with subacute progression of double vision, right facial numbness, and back pain. Her MRI brain and spine demonstrated multifocal enhancing lesions at the skull base and throughout the spine. Since her initial serum and cerebrospinal fluid (CSF) studies were unrevealing, she underwent a biopsy of her skull base lesion, which was initially concerning for infection. However, her symptoms worsened despite appropriate antibiotic therapy, necessitating a spinal root biopsy that was consistent with leptomeningeal urothelial carcinoma. Her case illustrates the challenge of accurately diagnosing isolated leptomeningeal metastatic disease, which can be difficult to diagnose from CSF analysis and often requires multiple lumbar punctures to improve sensitivity. While genitourinary cancers rarely metastasize to the CNS, clinicians should retain high suspicion for neoplastic etiologies of leptomeningeal disease in patients with a history of cancer and new neurologic deficits.

Surgical and anatomic factors predict development of leptomeningeal disease in patients with melanoma brain metastases.

Leptomeningeal disease (LMD) is a devastating complication of systemic malignancy, of which there is an unclear etiology. The aim of this study is to determine if surgical or anatomic factors can predict LMD in patients with metastatic melanoma. A retrospective chart review was performed of 1162 patients treated at single institution for melanoma brain metastases (MBM). Patients with fewer than 3 months follow-up or lacking appropriate imaging were excluded. Demographic information, surgical, and anatomic data were collected. Eight hundred and twenty-seven patients were included in the final review. On multivariate analysis for the entire cohort, female gender, dural-based and intraventricular metastasis, and tumor bordering CSF spaces were associated with increased risk of LMD. Surgical resection was not significant for risk of LMD. On multivariate analysis of patients who have undergone surgical resection of a metastatic tumor, dural-based and intraventricular metastasis, ventricular entry during surgery, and metastasis in the infratentorial space were associated with increased risk of LMD. On multivariate analysis of patients who did not undergo surgery, chemotherapy after initial diagnosis and metastasis bordering CSF spaces were associated with increased risk of LMD. In a single-institution cohort of MBM, we found that surgical resection alone did not result in an increased risk of LMD. Anatomical factors such as dural-based and intraventricular metastasis were significant for developing LMD, as well as entry into a CSF space during surgical resection. These data suggest a strong correlation between anatomic location and tumor cell seeding in relation to the development of LMD.

LMD-19. Anatomic and Surgical Factors Predict Development of Leptomeningeal Disease in Patients with Metastatic Melanoma

BackgroundLeptomeningeal disease (LMD) is a devastating complication of systemic malignancy, portending a poor prognosis with an estimated median survival of 4–6 weeks if left untreated. Several reports have suggested surgical resection, particularly piecemeal resection, as a potential causative factor. Herein, we explore if surgical and anatomical factors are correlated with development of LMD in patients with melanoma brain metastases.MethodsPatients treated at our institution between 1999–2019 for primary melanoma with brain metastasis were compiled into a database based on ICD9/10 coding. 1,079 patients with melanoma brain metastases and appropriate imaging were identified, and 834 patients with a minimum of 3 months’ follow up were included. Patients were dichotomized by development of LMD or lack thereof. General demographic information, surgical and anatomic data, and ventricular access during surgery were investigated as possible correlative factors for the development of LMD.ResultsOn univariate analysis, female gender (p=0.033), presence of dural metastasis (p=0.018), presence of periventricular lesions (p<.001), presence of intraventricular lesions (p<.001), and ventricular access during surgery (p<.001) were significantly associated with LMD. Patients undergoing surgery, or those undergoing surgery without ventricular access, were not at higher risk of LMD. Administration of immunotherapy, either as first-line or salvage therapy, did not impact rates of LMD. On multivariate analysis, female gender (p=.033), presence of periventricular lesions (p<.001), presence of intraventricular lesions (p<.002), and presence of dural metastasis (p=0.032) were significantly associated with development of LMD. In patients who had surgery, iatrogenic ventricular access (p<.001) was significantly correlated with LMD.ConclusionsIn a retrospective cohort of patients with melanoma metastatic to the brain, those patients with pre-existing lesions in contact with the CSF space are more likely to develop LMD than those who do not. In addition, iatrogenic access to the CSF space during surgery is highly correlated with LMD development.

Metastatic Melanoma With Leptomeningeal Disease.

Leptomeningeal disease in patients with melanoma historically portends a grim prognosis, with median survival measured in weeks to months. The advent of effective immunotherapy and targeted agents may modify the outcome of such patients. This case report describes a 43-year-old patient diagnosed with stage IIIa BRAF-positive cutaneous melanoma in 2012 who subsequently developed leptomeningeal involvement as her sole site of melanotic metastasis. She received multiple systemic therapies and radiotherapy and survived 2.5 years after her diagnosis with central nervous system involvement. This case report highlights the importance of a multidisciplinary team and the advent of effective agents, which offers the potential for significantly improved outcomes for patients with metastatic melanoma involving the central nervous system.

11. ASSOCIATION OF TUMOR EXPOSURE TO CEREBROSPINAL FLUID SPACES TO LEPTOMENINGEAL DISEASE IN PATIENTS WITH BRAIN METASTASES

BACKGROUNDDevelopment of leptomeningeal disease in patients with brain metastases is associated with extremely poor survival. Identification of the underlying pathogenesis of leptomeningeal disease is unknown.METHODSThis retrospective case control study included consecutive adult patients with at least one cerebral metastasis from a known extracranial primary solid malignancy and at least 3 month follow up (n=366). Patients were treated with radiotherapy with or without surgical resection and primary outcome was development of leptomeningeal disease.RESULTSThe overall rate of leptomeningeal disease was 15.0%. Rates of development of leptomeningeal disease correlated with the presence of a dural based lesion (65.7% vs. 9.7%; P<0.0001), intraventricular lesion (29.4% vs. 14.3%; P=0.0897), and with dural based lesions with sulcal or cortical enhancement (100% vs. 12.9%; P<0.0001). Rates of developing leptomeningeal disease were not independently associated with surgical resection (17.2% vs. 14.2%; P=0.4859), however did occur significantly more often with piecemeal, as opposed to en bloc, resection (31.3% vs. 8.1%; P=0.0138) or when the ventricle was entered (61.5% vs. 18.9%; P<0.0001).CONCLUSIONSMetastases that are in contact with cerebrospinal fluid spaces are associated with a higher rate of subsequent leptomeningeal disease, with or without surgical resection. Future studies should investigate the use of neoadjuvant radiation, whole brain radiation therapy or adherence to strict surgical technique in high risk brain metastasis patients to mitigate this probability.

Predictors of Leptomeningeal Disease after Hypofractionated Stereotactic Radiotherapy for Intact and Resected Brain Metastases

Hypofractionated stereotactic radiotherapy (HSRT) for patients with resected or large intact brain metastases is increasing in clinical practice; however, reporting on patterns of failure, specifically leptomeningeal disease (LMD) is lacking. In this study we identify patterns of LMD and determine predictors for developing LMD in patients with intact or resected brain metastases treated with 5-fraction HSRT. A single-institution retrospective review of a prospective database identified patients receiving HSRT for intact brain metastases or surgical cavities. Patient, tumor, and treatment factors were extracted. Patterns of LMD were stratified into four groups based on their radiographic presentation: focal classical, diffuse classical, focal nodular and diffuse nodular. Univariate and multivariable analyses were conducted to determine potential predictors for developing LMD. HSRT was delivered to 320 intracranial lesions (57% intact and 43% surgical cavities) in 235 patients with a median follow-up of 13.4 months (range, 0.8 to 60 months). The most common dose regimen was 30Gy in 5 fractions (65%). Overall, the incidence of developing LMD was 19% and the most common radiographic presentation of LMD was a diffuse nodular pattern (44%). The 6-month and 1-year rates of LMD were 7.5% and 12%, respectively. On multivariable analysis for the entire cohort, cavity lesions were statistically significant predictors of LMD compared with intact metastases (24% vs. 7%; hazard ratio=0.47; p=0.01). For cavities alone, radiosensitive tumors (including non-small cell lung, small cell and breast cancer) were the only statistically significant predictor of LMD (p=0.030), with a trend towards significance observed for increasing maximum tumor diameter (p=0.050). From the date of LMD diagnosis, the median overall survival (OS) for the entire cohort was 3.8 months (range, 0.2 to 20.8 months). The 6-month and 12-month OS rates were 42% and 15%, respectively. No statistically significant difference in OS was observed between the four patterns of LMD (p=0.203) or between nodular and classical patterns (p=0.267). For patients treated with HSRT, surgical cavities are at increased risk of developing LMD compared to intact brain metastases. Our findings suggest that despite the ability of HSRT to safely escalate tumor dose compared with single-fraction SRS, it may still be insufficient to mitigate the heightened risk of LMD observed with surgical cavities. Further research is required to determine optimal strategies to reduce LMD rates.

Radiographic Appearance of Leptomeningeal Disease in Patients with EGFR Mutated Non-Small Cell Lung Carcinoma Treated with Tyrosine Kinase Inhibitors – A Case Series (P2.6-032)

Radiographic Appearance of Leptomeningeal Disease in Patients with EGFR Mutated Non-Small Cell Lung Carcinoma Treated with Tyrosine Kinase Inhibitors – A Case Series (P2.6-032)

Association of Neurosurgical Resection With Development of Pachymeningeal Seeding in Patients With Brain Metastases

Neurosurgical resection represents an important management strategy for patients with large, symptomatic brain metastases and increasingly is followed by stereotactic radiation as opposed to whole-brain radiation. Whether neurosurgical resection is associated with tumor spread beyond the resection site and adjuvant stereotactic radiation field remains unknown. To characterize the association and incidence of pachymeningeal seeding with neurosurgical resection in patients with brain metastases treated with adjuvant stereotactic radiation. Retrospective cohort study of a consecutive sample of patients with newly diagnosed brain metastases managed with neurosurgical resection and stereotactic radiation (n = 318) vs radiation alone (n = 870) between 2001 and 2015. Incidence of pachymeningeal seeding (dural and/or outer arachnoid) and leptomeningeal disease in patients treated with neurosurgical resection and stereotactic radiation vs radiation alone and the risk factors and outcomes associated with pachymeningeal seeding in patients treated with neurosurgical resection followed by stereotactic radiation. In 1188 patients with newly diagnosed brain metastases, 133 men and 185 women (mean [SD] age, 58.9 [11.5] years) underwent neurosurgical resection. Resection was found to be associated with pachymeningeal seeding (36 of 318 patients vs 0 of 870 patients; P < .001) but not leptomeningeal disease (hazard ratio [HR], 1.14; 95% CI, 0.73-1.77; P = .56). In total, 36 (8.4%) of 428 operations were complicated by pachymeningeal seeding, with a higher incidence noted with resection of previously irradiated vs unirradiated metastases (HR, 2.39; 95% CI, 1.25-4.57; P = .008). Patients with pachymeningeal seeding had relatively low rates of subsequent development of new brain metastases and leptomeningeal disease (8 [16%] of 51 and 6 [13%] of 48, respectively). Among patients with pachymeningeal seeding, neurologic death primarily owing to progressive pachymeningeal disease accounted for 26 (72%) of 36 deaths, but when treated with salvage radiation, 49.1% of patients survived 1 year or longer. In the era of omission of adjuvant whole-brain radiation after neurosurgical resection, pachymeningeal seeding beyond the stereotactic radiation field represents a notable oncologic event that often proves difficult to salvage. However, in some patients, disease control can be achieved with radiotherapeutic approaches.

Ventricular violation increases the risk of leptomeningeal disease in cavity-directed radiosurgery treated patients

Stereotactic radiosurgery is increasingly used in patients with limited brain metastases and good baseline performance to avoid the toxicities of whole brain radiotherapy (WBRT). Patients with resected brain metastases are undergoing cavity-directed radiosurgery, withholding WBRT. Multiple institutions have published concerning incidences of leptomeningeal disease (LMD) when using this approach. We assess the risk of LMD in patients treated with this approach and identify risk factors for developing LMD. We identified 58 patients treated at our institution with cavity-directed SRS without WBRT for brain metastases between 2009 and 2015. Fifty-one (87.9%) had adequate follow-up for analysis, and 50 were treated to 30 Gy in 5 fractions to the resection cavity and are analyzed here. Patient demographics, tumor characteristics, and clinical outcomes were evaluated. With a median follow-up of 12.9 months (range, 1.9–63.2), the 1-year and 2-year incidences of LMD were 20 and 24%, respectively. The median time from SRS to the development of LMD was 6.0 months (range, 0.7–14.5). On multivariate analysis, ventricle violation during surgery (HR = 7.1, P = .030) and number of metastases (HR = 1.9, P = .034) were associated with an increased risk of LMD. One-year and 2-year leptomeningeal failure-free survival was 76 and 64%, and 1-year and 2-year survival of the entire cohort was 56 and 32%, respectively. LMD incidence is relatively high in patients receiving postoperative cavity-directed SRS. Ventricular violation during surgery causes a significantly higher risk of LMD, and consideration of WBRT, greater SRS target volumes, or preoperative treatment in these patients may be warranted.

Medical management of brain metastases and leptomeningeal disease in patients with breast carcinoma.

Breast cancer is the most common malignancy among women and accounts for the second highest number of cancer-related deaths. With patients surviving longer due to advances in systemic control, the incidence of CNS involvement is increasing; however, the management of CNS metastases has not undergone parallel advancements. The blood-brain barrier limits the efficacy of most systemic chemotherapies, and the utilization of surgery and radiation beyond first-line therapy is limited. We will explore the recent developments in the medical management of breast cancer brain metastasis. Beyond traditional chemotherapy, we will also discuss targeted therapies and immunotherapies which may provide a survival benefit to this population and thus, offer further treatment options and a path for future research and treatment advances.

Surgical Resection and Posterior Fossa Location Increase the Incidence of Leptomeningeal Disease in Patients Treated with Stereotactic Radiosurgery for Brain Metastases

Surgical Resection and Posterior Fossa Location Increase the Incidence of Leptomeningeal Disease in Patients Treated with Stereotactic Radiosurgery for Brain Metastases

Stereotactic radiosurgery for focal leptomeningeal disease in patients with brain metastases.

Leptomeningeal disease (LMD) is well described in patients with brain metastases, presenting symptomatically in approximately 5% of patients. Conventionally, the presence of LMD is an indication for whole brain radiation therapy (WBRT) and not suitable for stereotactic radiosurgery (SRS). The purpose of the study was to evaluate the local control and overall survival of patients who underwent SRS to focal LMD. We reviewed our prospective registry and identified 32 brain metastases patients with LMD, from a total of 465 patients who underwent SRS between 2013 and 2015. Focal LMD was targeted with SRS in 16 patients. The median imaging follow-up time was 7 months. The median volume of LMD was 372mm3 and the median margin dose was 16Gy. Five patients underwent prior WBRT. Histology included non-small cell lung (8), breast (5), melanoma (1), gastrointestinal (1) and ovarian cancer (1). Follow-up MR imaging was available for 14 patients. LMD was stable in 5 and partially regressed in 8 patients at follow-up. One patient had progression of LMD with hemorrhage 5 months after SRS. Seven patients developed distant LMD at a median time of 7 months. The median actuarial overall survival from SRS for LMD was 10.0 months. The 6-month and 1-year actuarial overall survival was 60% and 26% respectively. Six patients underwent WBRT after SRS for focal LMD at a median time of 6 months. Overall, focal LMD may be may be treated successfully with radiosurgery, potentially delaying WBRT in some patients.

Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases

We sought to determine the risk of leptomeningeal disease (LMD) in patients treated with stereotactic radiosurgery (SRS) targeting the postsurgical resection cavity of a brain metastasis, deferring whole-brain radiation therapy (WBRT) in all patients. We retrospectively reviewed 175 brain metastasis resection cavities in 165 patients treated from 1998 to 2011 with postoperative SRS. The cumulative incidence rates, with death as a competing risk, of LMD, local failure (LF), and distant brain parenchymal failure (DF) were estimated. Variables associated with LMD were evaluated, including LF, DF, posterior fossa location, resection type (en-bloc vs piecemeal or unknown), and histology (lung, colon, breast, melanoma, gynecologic, other). With a median follow-up of 12 months (range, 1-157 months), median overall survival was 17 months. Twenty-one of 165 patients (13%) developed LMD at a median of 5 months (range, 2-33 months) following SRS. The 1-year cumulative incidence rates, with death as a competing risk, were 10% (95% confidence interval [CI], 6%-15%) for developing LF, 54% (95% CI, 46%-61%) for DF, and 11% (95% CI, 7%-17%) for LMD. On univariate analysis, only breast cancer histology (hazard ratio, 2.96) was associated with an increased risk of LMD. The 1-year cumulative incidence of LMD was 24% (95% CI, 9%-41%) for breast cancer compared to 9% (95% CI, 5%-14%) for non-breast histology (P=.004). In patients treated with SRS targeting the postoperative cavity following resection, those with breast cancer histology were at higher risk of LMD. It is unknown whether the inclusion of whole-brain irradiation or novel strategies such as preresection SRS would improve this risk or if the rate of LMD is inherently higher with breast histology.

Detection of Monoclonal B-Cell Populations by Polychromatic Flow Cytometry in Cerebrospinal Fluid Specimens From Patients With Demyelinating Disease

Flow cytometric immunophenotyping is an established method for the detection of occult leptomeningeal disease in patients with aggressive B-cell non-Hodgkin lymphoma, and is increasingly being used in the evaluation of patients without an established diagnosis of lymphoma who present with signs and/or symptoms referable to the central nervous system. However, the specificity of flow cytometric immunophenotyping …

Detection of B‐cell populations with monotypic light chain expression in cerebrospinal fluid specimens from patients with multiple sclerosis by polychromatic flow cytometry

Flow cytometric immunophenotyping is an established method for the detection of occult leptomeningeal disease in patients with aggressive B-cell non-Hodgkin lymphoma, and is increasingly being used in the evaluation of patients without an established diagnosis of lymphoma who present with signs and/or symptoms referable to the central nervous system. However, the specificity of flow cytometric immunophenotyping in the identification of monoclonal B-cell populations in cerebrospinal fluid (CSF) has not been systematically evaluated. We searched a consecutive series of CSF specimens submitted to our laboratory for polychromatic (8-color) flow cytometric immunophenotyping between June, 2010 and December, 2012 for cases in which a B-cell population with monotypic immunoglobulin light chain expression was detected in patients without clinical or radiographic evidence of lymphoma. A B-cell population with monotypic light chain expression was identified in CSF specimens from three patients whose subsequent clinical and radiologic evaluation provided no evidence for lymphoma. In all three patients, a diagnosis of multiple sclerosis was ultimately rendered upon completion of the clinical evaluation. We conclude that the detection of a B-cell population with monotypic light chain expression in CSF by polychromatic flow cytometry is not diagnostic of occult leptomeningeal involvement by a B-cell non-Hodgkin lymphoma. Moreover, these findings suggest that monotypic B-cell populations detectable by polychromatic flow cytometry may be prevalent in patients with multiple sclerosis, and highlight the importance of clinicopathologic correlation in this application of polychromatic flow cytometry.

XVI. CNS prophylaxis in aggressive lymphomas: for whom and how

Dissemination in the central nervous system (CNS) in patients with aggressive lymphoma is a relatively rare but a frequently deadly complication that occurs between 5 (diffuse large B-cell lymphoma, DLBCL) and 30% (Burk itt lymphoma, BL and B-cell lymphoblastic lymphoma, B-LL) [1] in different subtypes of non-Hodgkin lymphoma (NHL). However, although a CNS prophylaxis is normally included into treatment regimens for BL and B-LL, in other NHL a prophylactic treatment is not systematically warranted because it may increase the toxicity of systemic chemotherapy.