scholarly journals 262. Epidemiology, Treatment, and Clinical Outcomes of Methicillin-Sensitive Staphylococcus aureus (MSSA) Bacteremia Complicated by Central Nervous System (CNS) Disease within the Veterans Affairs (VA) Healthcare System

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S238-S238
Author(s):  
Jill Provaznik ◽  
Jesse Sutton ◽  
Emily Spivak
Keyword(s):  
Central Nervous System ◽  
Staphylococcus Aureus ◽  
Nervous System ◽  
Clinical Outcomes ◽  
Adverse Drug Events ◽  
Severity Of Illness ◽  
Antibiotic Use ◽  
Cns Involvement ◽  
Cns Disease ◽  
Number Of Patients

Abstract Background The epidemiology of methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia (BSI) complicated by central nervous system (CNS) involvement is not well defined or described. We aimed to identify patients with MSSA BSI with CNS disease using imaging reports and define the epidemiology, characteristics, management, and associated clinical outcomes. Methods We conducted a retrospective study of inpatients (1/1/2014 to 10/31/2019) with MSSA BSI and head imaging (± 7 days of BSI). Imaging reports were categorized into probable, possible, or no CNS involvement. Charts were reviewed to assess source and metastatic sites of infection, severity of illness, and clinical course. Demographics, comorbidities, antibiotic use, and morbidity and mortality were electronically extracted from the corporate data warehouse. Primary antibiotic treatment was defined as the antibiotic received for the highest proportion of treatment course. Results 1852 patients had MSSA BSI and a head imagining performed. 151 (8%) had probable and 56 (3%) had possible CNS involvement. Embolic disease (n=167 [87%]) was the most common type of CNS disease (136 [83%] with probable CNS disease). Overall, high severity of illness defined by ICU admission (52%), vasopressor (7%), or mechanical ventilation (15%) was observed overall and was more common with probable CNS disease. Cefazolin was the most common primary antibiotic (71 [40%]), followed by nafcillin or oxacillin (51 [29%]). 16 (31%) patients had an adverse reaction to nafcillin. 69 (33%) patients died by day 30 and 88 (43%) by day 90. Recurrent CNS infections and bacteremia by day 90 was observed in 11 (6%) and 6 (3%). Conclusion We propose a definition of MSSA bacteremia complicated by CNS disease. CNS disease with MSSA bacteremia is infrequent with the most common manifestation being embolic disease. A significant number of patients with MSSA bacteremia were treated with cefazolin despite evidence of CNS disease. Overall mortality was high. Given higher rates of adverse drug events with nafcillin or oxacillin, comparative effectiveness studies are needed to further define the role of cefazolin for MSSA bacteremia with CNS disease. Disclosures All Authors: No reported disclosures

scholarly journals Frequency and Severity of Central Nervous System Lesions in Hemophagocytic Lymphohistiocytosis

Blood ◽  
1997 ◽  
Vol 89 (3) ◽  
pp. 794-800 ◽  
Author(s):  
Elie Haddad ◽  
Maria-Luisa Sulis ◽  
Nada Jabado ◽  
Stephane Blanche ◽  
Alain Fischer ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Disease Progression ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Systemic Disease ◽  
Neurological Symptoms ◽  
Treatment Modalities ◽  
Remission Induction ◽  
Cns Involvement ◽  
Cns Disease

Abstract We have retrospectively assessed the neurological manifestations in 34 patients with hemophagocytic lymphohistiocytosis (HLH) in a single center. Clinical, radiological, and cerebrospinal fluid (CSF ) cytology data were analyzed according to treatment modalities. Twenty-five patients (73%) had evidence of central nervous system (CNS) disease at time of diagnosis, stressing the frequency of CNS involvement early in the time course of HLH. Four additional patients who did not have initial CNS disease, who did not die early from HLH complications, and who were not transplanted, also developed a specific CNS disease. Therefore, all surviving and nontransplanted patients had CNS involvement. Initially, CNS manifestations consisted of isolated lymphocytic meningitis in 20 patients and meningitis with clinical and radiological neurological symptoms in nine patients. For these nine patients, neurological symptoms consisted of seizures, coma, brain stem symptoms, or ataxia. The outcome of patients treated by systemic and intrathecal chemotherapy and/or immunosuppression exclusively (n = 16) was poor, as all died following occurrence of multiple relapses or CNS disease progression in most cases. Bone marrow transplantation (BMT) from either an HLA identical sibling (n = 6) or haplo identical parent (n = 3) was performed in nine patients, once first remission of CNS and systemic disease was achieved. Seven are long-term survivors including three who received an HLA partially identical marrow. All seven are off treatment with normal neurological function and cognitive development. In four other patients, BMT performed following CNS relapses was unsuccessful. Given the frequency and the poor outcome of CNS disease in HLH, BMT appears, therefore, to be the only available treatment procedure that is capable of preventing HLH CNS disease progression and that can result in cure when performed early enough after remission induction.

Central Nervous System Involvement in Adult Acute Lymphoblastic Leukemia (ALL) at Diagnosis and/or at First Relapse: Results from the GET-LALA Group.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4326-4326
Author(s):  
Oumedaly Reman ◽  
Arnaud Pigneux ◽  
Francoise Huguet ◽  
Norbert Vey ◽  
Andre Delannoy ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lymphoblastic Leukemia ◽  
Central Nervous System Involvement ◽  
Unrelated Donor ◽  
Cns Involvement ◽  
Cns Disease ◽  
Cns Relapse ◽  
First Relapse ◽  
B Lineage

Abstract Outcome of adult ALL with central nervous system (CNS) involvement is not clearly defined. We studied 104 patients presenting with CNS involvement at diagnosis among 1493 patients (7%) included into the LALA-87 or LALA-94 trials, and 109 patients (9% of first remitters) presenting CNS disease at the time of first relapse among the 709 relapsing patients (15%) included initially in these trials. Treatment of patients presenting CNS involvement at diagnosis consisted in initial chemotherapy completed by 18 double or triple intrathecal injections associated with 15 to 20 Gy cranial irradiation, followed when possible by intensification by allogeneic or autologous stem cell transplantation (SCT). At diagnosis, 43 patients (41%) presenting with CNS involvement had T-lineage ALL, 53 (51%) had B-lineage ALL (of whom 9 were diagnosed as Philadelphia (Ph) chromosome positive ALL), 8 had undifferentiated ALL or unknown immunophenotype. Eighty-seven of 104 (84%) patients with CNS involvement at diagnosis achieved complete remission (CR). Fifty-three patients underwent SCT (25 allogeneic SCT from matched related or unrelated donor, 28 autologous SCT). Overall survival at 7 years was 34% in those with CNS involvement at diagnosis versus 29% (p = NS) for those without. DFS at 7 years was 35% versus 28% (p = NS). There were no significant differences between patients with CNS involvement and those without CNS involvement regarding T lineage ALL, B lineage ALL (including or not Ph ALL). There were also no significant differences regarding patients who underwent transplantation as consolidation intensification, while in patients receiving only chemotherapy patients without initial CNS involvement had a better outcome (p = 0.01). Among the 709 patients with primary relapse, 66 patients (61%) presented a CNS relapse combined with bone marrow relapse, whereas 17 relapses (15%) and 26 relapses (24%) were CNS relapses combined with another extramedullary relapse or isolated CNS relapses respectively. Median time to relapse was 6.7 months (range, 1–62) in patients with CNS relapse versus 11.2 months (1.7–111) in relapsing patients without CNS involvement. Eleven patients (10%) with CNS relapse had CNS involvement at diagnosis, while 98 patients were diagnosed with CNS disease only at the time of first relapse. Overall, 38 out of 109 patients with CNS relapse (35%) achieved CR. The median OS was 6.3 months. Outcome was similar in terms of CR proportion and OS in relapsing patients without CNS involvement. The 2-year OS rates did not show any difference among patients with CNS relapse who had CNS involvement at diagnosis and those with CNS disease only diagnosed at the time of first relapse.Overall, CNS leukemia in adult ALL is uncommon at diagnosis. Patients have a similar outcome than those who did not present with CNS involvement. However, patients benefit from intensification therapy by autologous or allogeneic SCT. CNS leukemia at first relapse are also uncommon but probably underestimated. Outcome is particularly poor as this of all adult ALL in first relapse.

Central Nervous System Involvement in Acute Myeloid Leukemia Patients Undergoing Hematopoietic Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3941-3941
Author(s):  
Merav Bar ◽  
Weigang Tong ◽  
Megan Othus ◽  
Keith R Loeb ◽  
Elihu H. Estey
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Cns Involvement ◽  
Cns Disease ◽  
Extramedullary Disease ◽  
History Of ◽  
Acute Myeloid

Abstract Central nervous system (CNS) involvement is considered rare in adults with acute myeloid leukemia (AML). Therefore the cerebrospinal fluid (CSF) is typically examined only in patients with CNS symptoms. In our institution all AML patients considered candidates for allogeneic hematopoietic cell transplantation (HCT) undergo routine CSF examination as part of pre-transplant evaluation, allowing a relatively unbiased look at the incidence of AML in CSF pre-HCT. The primary objectives of this study were to assess the rate of CNS involvement in AML patients undergoing HCT, evaluate potential risk factors for CNS disease, and examine the effect of CNS involvement on transplant outcome. We retrospectively evaluated 327 adults with AML who underwent ablative HCT between January 2007 and December 2012. Median age was 49 (range 19-73). Twenty eight (8%) patients had favorable karyotype, 215 (66%) had intermediate-risk karyotype, and 84 (26%) had unfavorable karyotype at diagnosis. 206 patients had received a high intensity induction regimen (daily ARA-C dose ≥ 500mg/m2). At time of CSF evaluation pre-HCT, 166 patients were in CR without minimal residual disease (MRD), 65 had CR with MRD, 41 had CRp or CRi, and 54 were in relapse. Median follow-up time was 630 days. 22 patients (7%) had CSF AML involvement, as assessed morphologically or using multiparameter flow cytometry, at their pre-HCT evaluation. 5 of these patients had had prior (treated) CNS AML, 3 had had prior extramedullary disease (EMD) not involving the CNS, and 2 had had both prior CNS and other extramedullary disease (Fig. 1). The incidence of CSF AML at pre-HCT evaluation was 7/20 in patients with past CNS involvement vs. 15/ 307 in patients without history of CNS disease (p <0.001), and was 5/30 in patients with a history of other EMD vs. 17/297 in patients without a history of EMD (p = 0.04). Other covariates associated with CNS AML at pre-HCT evaluation were higher WBC at diagnosis (p <0.001, medians of 34,000 in those with and 5,000 in those without CNS disease) and disease status (p<0.001) with only 2% of patients in CR without MRD had CSF involvement vs. 8% of those with CR with MRD, 7% of those with CRp or CRi, and 19% of those with relapse disease at time of pre-HCT evaluation. Cytogenetics, age, karyotype, and receipt of HiDAC showed no effect on CSF involvement pre-HCT in a univarate analysis. Classification and regression tree (CART) analysis identified 3 risk groups: (1) high = prior CNS disease (20 pts, 35% with CSF involvement at pre-HCT evaluation), (2) intermediate = no prior CNS involvement but in systemic relapse at pre-HCT CSF evaluation (51 pts, 16% with CSF involvement at pre-HCT evaluation), (3) low = no prior CNS disease and either CR (+/- MRD) or CRp/CRi (254 pts, 3% with CSF involvement at pre-HCT evaluation). All 22 patients with CSF involvement at pre-HCT evaluation received CNS-directed treatment (intrathecal chemotherapy +/- intracranial irradiation) and cleared their CNS disease prior to transplant. 18 patients also received CNS-directed therapy after HCT (between 1-6 intrathecal treatments). Nine and 8 patients with prior history of CNS disease, but with no evidence of CSF involvement at time of pre-HCT evaluation, received CNS-directed therapy before and after transplant respectively. Two of 35 patients (6%) with CNS disease at any time pre-HCT had documented CNS disease after transplant. While patients with CSF involvement at pre-HCT evaluation had shorter post-HCT survival (p = 0.002) (Fig. 2), multivariate analysis indicated that this reflected the association of CNS disease with poorer systemic response to therapy and evidence of systemic disease at time of transplant; specifically multivariate hazard rates were 1.48 for CNS involvement vs no CNS involvement (p = 0.17), contrasted with 3.62 for CR with MRD vs CR without MRD (p <0.001) and 3.78 for no CR vs CR without MRD (p <0.001). Tests for interactions indicated that the relatively small effect of CNS disease on survival was similar in patients with CR (+/- MRD), CRp or CRi, or relapse disease at time of CSF evaluation pre-HCT. We conclude that CNS AML involvement pre-HCT is relatively uncommon (7%), is primarily associated with a history of prior CNS disease, and, when controlled, is not an independent factor in determining survival after HCT. Figure 1. CNS and extramedullary disease among 327 AML patients undergoing ablative HCT Figure 1. CNS and extramedullary disease among 327 AML patients undergoing ablative HCT Figure 2. Overall survival since transplant Figure 2. Overall survival since transplant Disclosures No relevant conflicts of interest to declare.

Pattern of Central Nervous System (CNS) Involvement in Adult Acute Myeloid Leukemia (AML) and Its Impact on Outcome

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2789-2789
Author(s):  
Maria Ilaria Del Principe ◽  
Francesco Buccisano ◽  
Stefano Soddu ◽  
Luca Maurillo ◽  
Mariagiovanna Cefalo ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Newly Diagnosed ◽  
Cns Involvement ◽  
Genetic Characteristics ◽  
Cns Disease ◽  
The Impact ◽  
Acute Myeloid

Abstract Background Routine diagnostic lumbar puncture is not recommended in adult patients with acute myeloid leukemia (AML) without Central Nervous System (CNS) symptoms and little is known about the incidence of CNS involvement and its impact on survival in these patients. Furthermore, several studies have demonstrated that flow cytometry (FCM) is superior to conventional cytology (CC) for detection of CNS involvement in lymphoproliferative disorders but the role of this approach for the investigation of cerebrospinal fluid (CSF) in AML is unknown. Design and Methods The aims of our study were 1) to determine the incidence of occult/manifest CNS disease in a homogenous series of AML patients; 2) to correlate CNS disease with clinico-biologic parameters; 3) to examine the impact of CNS involvement on outcome. CSF samples were collected from 98 newly diagnosed AML patients, 62 males and 36 females, median age 53 years (range 18-75). Sixty-five and 33 patients aged <60 and>60 years, respectively.Seventy-one patients received standard and 22 high-dose-ARA-C-based regimens, 5 supportive care. All of 98 CSF samples were examined by CC whereas 90 (91%) also by FCM. CC positivity was defined as unequivocal morphologic evidence of leukemic blast in CSF and/or white blood cells count (WBCc) ≥ 5/µl with less than 10 erythrocytes/µl. A cluster of at least 10 phenotypically abnormal events was regarded as a proof of FCM positivity. Results Sixty-seven patients were CNS negative (CNS-) while thirty-one (31%) were CNS positive (CNS+). Among the last, 10 (10%) were positive on both CC and FCM (manifest CNS+) and 21 (21%) only on FCM (occult CNS+). There was an equal male/female distribution among CNS- and CNS+ patients, as well as median age (52 years, range, 20-71, vs 56 years, range, 18-75, p=NS) and WBCc(27.5 x109/L, range, 1,20-223 x109/L, vs. 11,6 x109/L, range, 0,70-315 x109/L, p= NS) were similar in both groups. Instead, higher levels of lactate dehydrogenase (LDH) were observed among CNS+ than CNS- patients (p=. 01). Forty-seven patients (48%) had monoblastic/monocytic or myelomonocytic AML and belonging to one of these categories was significantly associated with a condition of CNS positivity (55% vs 45%, P = 002). Cytogenetic/genetic data were available in 82/98 (84%). Twenty-for patients (29%), 33 (39%), 12 (14%) and 12 (14%), belonged to the category of favorable, intermediate-I, intermediate-II, and adverse karyotype, respectively. Cytogenetic/genetic characteristics did not differed significantly between CNS+ and CNS- patients. Overall, response rate was 70%, with complete remission rate being not statistically different between CNS+ and CNS- patients (69% vs 81% p= NS). Five-year DFS and OS were found to be significantly shorter in occult or manifest CNS+ patients than in those CNS- (23% vs 50% p= .03 and 19% vs 46%, p=.02, respectively)(Figure 1A and 1B). The prognostic variables achieving a statistical significance in univariate analysis (CNS status, age , WBCc, favorable vs adverse karyotype) were challenged in a multivariate model to determine to what extent they affected treatment outcome. In multivariate analysis, CNS positivity was found to be independently and significantly associated with a shorter duration of DFS.(p=.03 HR= 0.46). Age >50 years was found to be the only independent prognostic factor affecting OS (p=.01 HR= 2.26). Conclusion Our data suggest that incidence of CNS involvement in newly diagnosed AML pts is higher than expected. Regardless of neurologic symptoms, manifest and occult CNS positivity should always be sought at diagnosis since it may affect outcome and influence therapeutic decision. Further prospective studies on larger series are warranted to confirm this data. Figure 1 DFS and OS based on CNS status Figure 1. DFS and OS based on CNS status Disclosures Lo Coco: Teva: Consultancy, Honoraria, Speakers Bureau; Lundbeck: Honoraria, Speakers Bureau; Novartis: Consultancy; Baxalta: Consultancy; Pfizer: Consultancy.

Central nervous system involvement in T-cell lymphomas: A single center experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8069-8069 ◽  
Author(s):  
Ronit Gurion ◽  
Jocelyn Maragulia ◽  
Andrew David Zelenetz ◽  
Steven M. Horwitz
Keyword(s):  
Risk Factors ◽  
Central Nervous System ◽  
Nervous System ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cns Involvement ◽  
Cns Disease ◽  
Extranodal Site ◽  
T Cell Lymphomas

8069 Background: Large experiences have reviewed the risk of central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL), but there are limited data on CNS involvement by peripheral T cell lymphomas (PTCL). We characterized the incidence of CNS involvement, risk factors and outcome in a large single institution dataset of PTCL. Methods: Retrospective review of the T-cell lymphoma database at Memorial Sloan Kettering Cancer Center. We identified 232 patients with any subtype of PTCL between 1994-2011 with a minimum 6 months of follow-up or an event defined as relapse or death. We excluded indolent forms of cutaneous T cell lymphoma. Results: Histologies included PTCL-NOS (31%), angioimmunoblastic (16.8%), anaplastic (ALCL), ALK negative (12%), ALCL, ALK positive (6%), extranodal NK/T cell lymphoma (7.3%), adult T cell leukemia/lymphoma (ATLL) (7.3%), and transformed MF (8.6%). Median age was 58 years with 59.9% men. CNS disease was found in 17 patients (7.32%). 8 (47%) had pathologic confirmation and 7 (41.2%) were clinically diagnosed. Two had other diagnoses at biopsy: DLBCL and glioblastoma. Median time to CNS involvement was 2.33 months (range, 0.16 to 103.1). CNS prophylaxis was given to 24 (10.34%), primarily intrathecal methotrexate. There was no difference in CNS involvement in patients who received prophylaxis vs. those who did not: 3/24 (12.5%) vs. 12/208 (5.77%) (p=0.192) respectively. Univariate analysis identified: stage III-IV (p=0.03), bone marrow involvement (p=0.018), >1 extranodal site (p<0.001), and ATLL vs. all other subtypes, 23.5% vs. 6.4% (p=0.003) as risk factors for CNS disease. On multivariate analysis, >1 extranodal site (p=0.004) and high intermediate (H-I) and high (H) IPI (IPI 3-5 & 4-5) were predictive for CNS involvement (p<0.05). The median survival of patients with CNS involvement was 2.628 months. Conclusions: Despite high relapse rates, PTCL carries a low risk of CNS involvement other than the ATLL subtype. As with other aggressive lymphomas, survival of patients with CNS involvement is poor and risk factors include: >1 extra nodal site and H-I-H IPI. In this dataset, prophylactic intrathecal chemotherapy does not appear to reduce the risk of CNS disease.

Myelomatous Involvement Of The Central Nervous System: Mayo Clinic Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3119-3119 ◽  
Author(s):  
Jonas Paludo ◽  
Utkarsh Painuly ◽  
Shaji Kumar ◽  
Francis Buadi ◽  
Suzanne R Hayman ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
High Risk ◽  
Mayo Clinic ◽  
Plasma Cells ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Cns Involvement ◽  
Cns Disease ◽  
True Incidence

Abstract Background Limited data exist with respect to outcome and optimal therapeutic strategies in patients with central nervous system (CNS) involvement in multiple myeloma (MM). We present a single center experience of patients with myelomatous CNS involvement in newly diagnosed and relapsed / refractory MM. Methods Of 4060 patients with MM seen at Mayo Clinic, Rochester, MN between January, 1st 1998 and December, 31st 2012, 26 patients had identifiable CNS involvement confirmed by biopsy / presence of plasma cells in the cerebrospinal fluid (CSF) and/or identification of intraparenchymal or meningeal involvement by imaging (MRI/CT). Patients were risk stratified by mSMART (Mayo Stratification for Myeloma And Risk-adapted Therapy) criteria. Overall survival (OS) from diagnosis and the time of CNS involvement was calculated using the Kaplan-Meier method. Results Myelomatous CNS involvement occurred in 26 (0.6%) patients with MM of whom 3 were newly diagnosed. The median time to detection of CNS involvement was 24 months (range: 0-125) from diagnosis of MM. Median age at CNS myeloma diagnosis was 58 years (range 37-80) and 73% were male. Abnormally high LDH was observed in 11 out of 22 patients at the time of CNS involvement. Lumbar puncture was performed on 16 patients, 13 (81%) of whom had plasma cells in the CSF detected by cytology/flow-cytometry. Two patients, without evidence of plasma cells, had abnormally high CSF protein and 1 had normal CSF analysis. Of the 25 patients who underwent MRI, 16 (64%) had at least one of the following significant abnormalities; intraparenchymal disease (37%), leptomeningeal enhancement (68%) or direct extension of MM (31%). The neurological symptoms at or after diagnosis of CNS myeloma included headache (38%), cranial nerve palsy (38%), visual disturbance (38%), gait disturbance (35%), paresthesias (35%), limb weakness (31%), confusion (30%), nausea/vomiting (15%), dysarthria (12%), seizures (8%) and urinary incontinence (4%). Fluorescent in-situ hybridization (FISH n=7), cytogenetics (n=8) and/or plasma cell labeling index (PCLI n=12) were available in 18 patients prior to the diagnosis of CNS disease. Ten (56%) out of those 18 patients had high-risk features at least by one criterion. At the time of CNS involvement, six additional patients demonstrated high risk features [5 by PCLI (≥ 3%) and 1 by FISH]. Overall, 16 out of 26 (62%) patients were classified as high risk by mSMART criteria prior to or at the time of CNS involvement. Four (27%) out of 15 had a deletion p53 or monosomy 17 chromosomal abnormality. Median OS was 42 (95% CI, 19-55) months from the diagnosis of MM and 3 months (95% CI: 1-7.9) from the time of CNS involvement (Figure). OS of patients with high risk features was significantly worse (27 months) compared to standard risk disease (67 months, p=0.02) from diagnosis of MM. Eighteen patients received radiation therapy for CNS myeloma. Five of those patients also received intrathecal (MTX and ARA-C) therapy. One patient received intrathecal and systemic chemotherapy. Four patients did not receive any treatment. Novel agents, including bortezomib (23%), thalidomide (15%), and pomalidomide (4%) were administered to the patients post diagnosis of CNS disease. Six (23%) patients underwent autologous stem cell transplant post diagnosis of CNS disease with a median OS of 19 months (95% CI: 10-122 months) from the time of CNS involvement. Conclusion CNS involvement is a rare complication of MM that portends a poor survival outcome. It is likely that the rates in this study are an underestimate of the true incidence due the perceived futility of CNS directed therapy in this disease. Among those recognized, high-risk genetic and markers of increased proliferative activity, including deletion p53 / monosomy 17 and elevated PCLI (≥ 3%) appear to cluster in this cohort. Current therapeutic approaches are largely ineffective in managing this aggressive subset of myeloma patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals RARE-42. INCIDENCE AND BEHAVIOR OF CENTRAL NERVOUS SYSTEM INVOLVEMENT IN PATIENTS WITH HODGKIN’S LYMPHOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi230-vi230
Author(s):  
Carlos Eduardo Silva Correia ◽  
Rachna Malani ◽  
Lisa DeAngelis ◽  
Alison Moskowitz
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Median Time ◽  
Hodgkin’S Lymphoma ◽  
Systemic Disease ◽  
Hodgkin's Lymphoma ◽  
Leptomeningeal Disease ◽  
High Dose ◽  
Cns Involvement ◽  
Cns Disease

Abstract INTRODUCTION Central nervous system (CNS) involvement from Hodgkin’s Lymphoma (HL) is rare, with a reported incidence of 0.07–0.5%. There is a paucity of data regarding its natural history and management. METHODS In this retrospective single-institution review, we analyzed all adult patients with HL for CNS involvement (parenchymal or meningeal), who were evaluated at Memorial Sloan Kettering Cancer Center from January 2008 until December 2018. RESULTS A total of 3478 patients with HL were identified, and CNS involvement was found in 10 patients (0.3%). All patients were symptomatic from CNS disease. Four patients had a synchronous presentation. The other 6 patients had a median time from systemic diagnosis to CNS involvement of 8 years (2.5–14). Two patients had radiographic evidence of leptomeningeal disease, however 4 had positive cerebrospinal fluid (CSF) cytology. At time of CNS involvement, 2 patients had confirmed transformation to Non-Hodgkin-Lymphoma on biopsy. 2 patients had EBV-positive HL. One patient died before treatment. Five patients received high-dose methotrexate (HD-MTX) for CNS disease. Of these patients, 1 died during treatment, 2 had partial responses, and 2 had complete response of both systemic and CNS disease; to date they are in remission. Three patients had varied responses to immunotherapy and cytotoxic chemotherapy. Removal of an immunosuppressive agent resolved disease in one EBV-positive patient. Median overall survival (OS) from diagnosis of HL was 10.6 years (1.1–21.2), and OS from time to CNS involvement was 6 years (0.2–15). CONCLUSION The median time from diagnosis to CNS involvement, and OS from time of CNS involvement are higher than previously reported, which may be related to newer therapies for systemic disease. Neuroimaging should be used in conjunction with CSF for diagnostic accuracy. HD-MTX can be used to treat CNS and refractory systemic disease, as historically used for the latter.

scholarly journals Central Nervous System (CNS) Infiltration Assessment Using Cerebrospinal Fluid Flow Cytometry in Hematologic Malignancies: A Single Center Retrospective Analysis of Clinical Outcomes

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5773-5773
Author(s):  
Eduardo Cerello Chapchap ◽  
Carolina Feres ◽  
Laiz Cameirão Bento ◽  
Daniela Schimidell ◽  
Rodolfo Patussi Correia ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Flow Cytometry ◽  
Overall Survival ◽  
Nervous System ◽  
Clinical Outcomes ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Hematologic Malignancies ◽  
Clinical Approach ◽  
Cns Disease

INTRODUCTION: The detection of central nervous system (CNS) disease in hematologic malignancies is important to guide optimal therapeutic approach, refine prognosis and understand patient`s unexplained neurologic symptoms. Newer flow cytometry (FC) techniques are emerging, also there are increasingly reports of higher accuracy than routine cytospin. Moreover, these are becoming incorporated more frequently in clinical work up practices. However, there is still uncertainty on clinical approach of CNS-positive patients, detected only by FC. OBJECTIVE: To analyze accuracy and clinical outcomes of CNS disease by cytopsin or FC in patients with hematologic malignancies. MATERIAL AND METHODS: FC cerebrospinal samples and medical charts of 84 consecutive patients evaluated for CNS infiltration by hematologic malignancies from January/2014 to December/2016 were reviewed. Statistical analysis were done with SPSS and STATA softwares. RESULTS: Baseline patients characteristics were: male (62%), median age 53 years; non-hodgkin lymphoma (52%), Acute Lymphoblastic Leukemia (26%), Acute Myeloblastic Leukemia (15,5%), Multiple Myeloma (6,5%); CNS-positivity rates according to each technique were: Cytopsin-/FC- (71,4%), Cytospin+ (14,3%), Cytospin-/FC+ (14,3%); CNS-disease was detected by FC in 32,3%, while for cytospin was 16,7%. Overall survival was 71,4% and relapse rate 38,1% at 2,5 years of median follow-up. Relapsed (HR: 2,76 p0,023) and CNS-positivity (HR: 2,01 p0,037) patients were significantly associated with an inferior overall survival. Also, progression free survival (PFS) of Cytospin-/FC+ was significantly inferior than CNS-negative subgroup (HR: 2,93 p0,022). CONCLUSION: FC sensitivity appears to be higher than classicaly cytospin methods to detect CNS disease, also CNS-positivity was associated with a worse prognosis, as well as in the subset of patients Cytospin-/FC+. Further studies with a more homogeneous cohort and larger sample sizes are needed to validate our findings. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals Isolated CNS Hemophagocytic Lymphohistiocytosis in Children:What We Know, What We Don't Know ?

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4190-4190
Author(s):  
Selin Aytac ◽  
Gunay Balta ◽  
Baris Kuskonmaz ◽  
Tekin Aksu ◽  
Fatma Visal Okur ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Allogeneic Bone Marrow Transplantation ◽  
Central Nervous System Involvement ◽  
Allogeneic Bone ◽  
Cns Involvement ◽  
Nerve Paralysis ◽  
System Involvement ◽  
Number Of Patients

Abstract The presence of central nervous system involvement has a profound impact on the prognosis, treatment, and clinical outcome of the primary hemophagocytic lymphohistiocytosis (pHLH). However, isolated CNS-HLH is a challenging disease with a high mortality and morbidity , possibly resulting from a spsecific neuroinflammation that leads to isolated disease only without systemic activation under some additional genetic modifiers. In this study, we retrospectively reviewed our isolated CNS-HLH cases and there were 73 patients (36 male, 37 female) with a median age of 20 months (range, 1- 226 months) diagnosed as primary hemophagocytic lymphohistiocytosis at Hacettepe University Faculty of Medicine, between January 2005 and June 2021. Among these, 39 (53%) patients had central nervous system involvement either on admission or during the recurrence. On admission, the number of patients who had both CNS and sytemic involvement was 19 (49%), moreover 2 had CNS infiltration both initially and during the course of relapse. 8 patient did show CNS involvement only during the relapse. Ten (25%) patients (5 male, 5 female) with isolated CNS involvement are the main subject of this study and none of them had infectious trigger. What we know is they were presented with mostly unexplained neurological findings and /or cranial nerve paralysis. In this group median age at presentation was 101 months ( range 6 - 180 months). They all had primary HLH associated patogenic mutation and in some of them diagnosed was also confirmed by brain biopsy. Neither family history and /or consanguinity nor HLH criteria are fullfilling in this devastating disorder. Cranial MRI gives many clues during admission in experienced hands. Two of our published cases were initially diagnosed as lymphomatoid granulomatosis and acute disseminated encephalomyelitis ; they were diagnosed as hemophagocytic lymphohistiocytosis after developing systemic symptoms 3 and 12 months later. Interestingly 6 of 10 patients in this group never developed systemic symptomps, 7 patients underwent allogeneic bone marrow transplantation. Spinal cord involvement was determined in 8 patients(20%), including 4 at diagnosis and 4 during follow up ; including one previously published case, 4 out of 8 had isolated cases did show spinal involvement as well. Even though few number of cases with isolated CNS-HLH has been reported in the recent years, we believe that the number of such cases is not limited to those who have been reported because it is rather difficult to diagnose patients with isolated CNS symptoms, which leads to misdiagnosis and/or mistreatment. What we don't know is how to specifically treat patients with CNS directed therapy, and exactly which mutations are associated with isolated CNS-HLH or whether there is a known tendency in this group and perhaps unknown mutations ? Does it have a facilitating effect ? Disclosures No relevant conflicts of interest to declare.

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