The Incidence of Central Nervous System Involvement in AML: A SAL-Tor Vergata Analysis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4236-4236
Author(s):  
Nael Alakel ◽  
Maria Ilaria Del Principe ◽  
Friedrich Stölzel ◽  
Brigitte Mohr ◽  
Uta Oelschlaegel ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Initial Diagnosis ◽  
Chromosome 8 ◽  
Study Group ◽  
Event Free Survival ◽  
Cns Involvement ◽  
Free Survival ◽  
Significant Difference ◽  
The University

Abstract Abstract 4236 Background: Acute myeloid leukemia (AML) involves infrequently the central nervous system (CNS). However, most studies examined paediatric patients. Thus little is known regarding CNS-involvement in adult AML. Therefore, we analyzed the data of patients with AML treated in SAL study group and Tor Vergata study group for CNS involvement. Methods: In this retrospective analysis in adult AML patients included in the prospective AML96- (NCT00180115), AML2003- (NCT00180102), AML60+ trials (NCT00180167) of the SAL study group and patients that were admitted to the University Hospital of Rome Tor Vergata from 2005 to 2011, 3863 patients were evaluated for CNS involvement of AML. The median age of the patients was 49 years (range, 18 –74 years). A total of 30 patients had CNS involvement at time of initial presentation and 30 patients had CNS involvement at first, second or third relapse. CNS involvement was proven depending on morphology and/ or flow cytometry of the Cerebrospinal fluid (CSF). Clinical variables of statistical significance were compared using the χ2-test for dichotomized variables and the Mann-Whitney U-test for continuous variables. The method of Kaplan Meier was used to estimate OS and event-free survival (EFS). Survival distributions were compared using the log-rank test. Results: 21 of 1862 patients (1%) in the AML96-trial, 26 patients of 1182 (2.2%) in the AML2003 trial, 3 of 486 patients (0.6%) in the AML60+ trial, and 10 of 270 patients (3.7%) in the University of Rome Tor Vergata studies had CNS involvement resulting to a total of 60 patients with a combined overall incidence of 1.6%. 30 patients had CNS involvement at the initial presentation and 30 patients at relapse of AML. The majority of patients (n=53, 88%) had de novo AML. Data from the Tor Vergata study group need further analysis therefore in this abstract patients from SAL study group were included. Extramedullary AML other than CNS involvement was observed in 21 patients (42 %) as compared to 246 (7%) in patients without CNS involvement, p < 0.001. Complex aberrant karyotype was not significantly higher in patients with CNS involvement as compared to those without, whereas patients with CNS involvement had a higher tendency for trisomy of chromosome 8 (n=8, 16%) in comparison with patients without CNS involvement (n= 277, 8%), p=0.03. AML FAB M5 occurred more frequently in patients with CNS involvement (n= 15, 30%) as compared to those without (n=459, 13%), p=0.01. Patients with CNS involvement at diagnosis had significantly higher lactate dehydrogenase (LDH) levels (1318 vs. 665 IE/l, p< 0.001) and higher white blood cell count (WBC) (64 vs. 35 Gpt/l, p<0.001). Only 7 of 30 patients (23%) with CNS involvement at initial diagnosis developed relapse and none of them had CNS involvement at the time of relapse, whereas almost all patients with CNS involvement at relapse developed again systemic and CNS-relapse. On the other hand, there was no significant difference in the number of patients who achieved complete remission between these two groups. Comparing patients with CNS involvement with patients without CNS involvement at the initial diagnosis no significant difference in overall survival at 2 years (40% vs. 41%) and event free survival at 2 years (20% vs. 26%) was observed. Conclusion: CNS involvement in AML is a rare entity and it is accompanied with higher incidence of other extramedullary AML. This represents the largest analysis of AML patients with CNS involvement studied in the literature. Factors associated with an increased risk of CNS involvment include: trisomy of chromosome 8, FAB M5, higher LDH levels and higher WBC count at diagnosis. Patients with CNS disease at initial diagnosis of AML have similar survival outcomes as compared to those without CNS disease if treated by intrathecal therapy, whereas extramedullary relapse within the CNS is associated with poor outcome. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Evaluation of The Effectiveness and Side Effects of Radiotherapy in Patients With Primary Nervous System Lymphoma. A Single Center Experience

2020 ◽  
Vol 7 ◽  
Author(s):  
Timur Koca ◽  
Aylin Fidan Korcum ◽  
Yasemin Şengün ◽  
Melek Gamze Aksu ◽  
Mine Genç
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Side Effects ◽  
Disease Free Survival ◽  
Central Nervous System Lymphoma ◽  
Field Size ◽  
High Dose ◽  
Free Survival ◽  
Significant Difference

Aim: In this study, we aimed to evaluate the overall and progression-free survival, the radiotherapy process and the early and late adverse effects in patients who underwent radiotherapy (RT) for primary nervous system lymphoma in our clinic.Method: Between January 2010 and September 2019, 16 patients who received radiotherapy due to primary central nervous system lymphoma in our clinic were examined according to their statistically significant differences in terms of survival and side effects.Results: The median disease-free survival of the patients was 6 months, and the median overall survival was 12.5 months. 18.75% of the patients could not receive chemotherapy but only radiotherapy. Radiotherapy doses were range from 2600 to 5000 cGy. When patients were evaluated in terms of radiotherapy dose, field size and chemotherapy, no statistically significant difference in overall survival was detected. Cognitive disorders were observed as the most common late side effects while the most common acute side effects in patients were headaches.Conclusion: In the treatment of primary central nervous system lymphoma, changes in radiotherapy portals and radiotherapy doses can be predicted in patients who received high-dose methotrexate chemotherapy or not. Furthermore, it has been considered that more comprehensive studies are needed to increase the success of treatment and provide standardization in treatment, especially in patients with elderly and comorbid diseases.

Feline cryptococcosis: a retrospective evaluation

1997 ◽  
Vol 33 (2) ◽  
pp. 118-122 ◽  
Author(s):  
S Gerds-Grogan ◽  
B Dayrell-Hart
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cryptococcus Neoformans ◽  
Clinical Pathology ◽  
Fungal Disease ◽  
University Of Pennsylvania ◽  
Retrospective Evaluation ◽  
Cns Involvement ◽  
The University ◽  
Veterinary Hospital

Cryptococcus neoformans causes the most common form of feline systemic fungal disease. Nineteen cats with cryptococcosis were seen at the Veterinary Hospital of the University of Pennsylvania between April 1986 and May 1995. Compared to other studies, these 19 cases showed increased neurological and ophthalmological involvement. Males were affected more often than females. Season and environment appeared to influence time of onset or presentation to the hospital. Clinical pathology did not show typical changes. It is possible that the organism was present frequently in the urine but was mistaken for fat droplets. Treatment with ketoconazole was unrewarding in cases with central nervous system (CNS) involvement.

scholarly journals Tooth abnormalities in pediatric patients submitted to antineoplastic treatment for central nervous system neoplasms

2016 ◽  
Vol 19 (3) ◽  
pp. 39
Author(s):  
Ornella Florio Demasi ◽  
Marcelo Fava ◽  
Camila Merida Carrillo ◽  
Terezinha Garrett de Freitas Sampaio Amaral ◽  
Vicente Odone Filho
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Pediatric Patients ◽  
Statistical Significance ◽  
Control Group ◽  
Study Group ◽  
Central Nervous System Neoplasms ◽  
Tooth Abnormalities ◽  
Significant Difference ◽  
Nervous System Neoplasms

<strong>Objective</strong>: The aim of this study was to evaluate the frequency of tooth abnormalities in pediatric patients treated for central nervous system neoplasms. <strong>Material and methods: </strong>This cross-sectional study assessed thirty-one patients, median age 14.2 years (range 5 - 25), who were off therapy for at least one year, comparatively with a control group of thirty-one healthy patients matched for age with the study group. Tooth abnormalities were evaluated by panoramic radiographs. <strong>Results: </strong>There was no statistical significant evidence that patients of the study group (age range 5 - 25 years) have more frequency of tooth abnormalities comparatively with controls.   However, in children who were diagnosed before 5 years of age, microdontia was the most common abnormality with statistically significant difference (<em>P=</em>0.037). Root shortening grade III was observed in patients over 10 years of age at the time of radiographic examination, also with statistical significance (<em>P=</em>0.046). <strong>Conclusions: </strong>Tooth abnormalities frequency in patients treated for central nervous system neoplasms is directly related to the age of diagnosis and stage of odontogenesis. Microdontia and reduced root surface areas, the most common abnormalities observed, can lead to future oral health impairment due to malocclusion and less periodontal support. It is important to give parents and patients early orientation about maintenance of good oral hygiene and proper treatment by orthodontics or dentofacial orthopedics.

scholarly journals Autologous Stem Cell Transplantation with Thiotepa, Busulfan, and Cyclophosphamide Conditioning in Patients with Primary Central Nervous System Lymphoma: A Remarkable Outcome Form Single-Center Experience

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3462-3462 ◽  
Author(s):  
Seyoung Seo ◽  
Jung Yong Hong ◽  
Dok Hyun Yoon ◽  
Jeong Hoon Kim ◽  
Young Hyun Cho ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Prognostic Score ◽  
Central Nervous System Lymphoma ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Baseline Characteristics

Abstract Introduction High dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) has been adopted as an effective treatment in patients with relapsed or refractory primary central nervous system lymphoma (PCNSL) and also has been proposed as a consolidative treatment option for newly diagnosed PCNSL. HDC-ASCT may overcome chemoresistance mediated by blood-brain barrier by affording higher drug concentrations in the central nervous system. We investigated the feasibility of thiotepa, busulfan, and cyclophosphamide (TBC) conditioning followed by ASCT in patients with PCNSL. Method Between December 2012 and July 2015, a total of 27 patients with PCNSL underwent TBC conditioning followed by ASCT. Those with a complete or partial response after induction chemotherapy or salvage chemotherapy proceeded with TBC conditioning followed by ASCT. TBC conditioning consists of thiotepa 250 mg/m2 on days -9 to day -7, busulfan 3.2 mg/kg on days -6 to day -4 and cyclophosphamide 60 mg/kg on days -3 to day -2. The event free survival (EFS) was defined from the date of transplant to the date of relapse, progression or any cause of death, while overall survival (OS) was calculated from the date of transplant to death. Result Baseline characteristics were summarized in table 1. Twenty patients received TBC conditioning followed by ASCT as a consolidative therapy after high-dose methotrexate-based induction chemotherapy and the other 7 patients received TBC conditioning followed by ASCT after salvage chemotherapy due to relapsed or refractory disease. The median time to neutrophil recovery (absolute neutrophil count >500/uL) and platelet recovery (>20000 x103/uL) were 8 (range, 7-9) and 8 (range, 4-15) days, respectively. All 27 patients experienced febrile neutropenia and 33.3% of patients (9/27) and 7.4% of patients (2/27) had documented bacterial and viral infection, respectively. Commonly observed nonhematologic grade 3 or 4 toxicities were mucositis (63%), diarrhea (59.3%) and nausea (25.9%). The 100-day transplant-related mortality rate was 0%. With median follow-up duration of 27.8 months (range 6.7-42.6), median EFS and OS were not reached. The 2-year EFS and OS estimates were 76.8% (95% CI: 68.4-85.2) and 88.9% (95% CI: 82.9-94.9), respectively (Figure 1). Conclusion ASCT with TBC conditioning appears to be feasible in patients with PCNSL. Although survival outcomes are encouraging, longer follow-up is required. Further studies are warranted to investigate the role of ASCT with TBC conditioning in both clinical settings of consolidative treatment of newly diagnosed PCNSL and salvage treatment of relapsed or refractory PCNSL. Table 1 Baseline characteristics (n=27) *Conventional cytology; flow cytometry not performed $The cutoff for normal CSF protein concentration was 45 mg/dL in patients ¡Â 60 years old and 60 mg/dL in patients more than 60 years old. *MSK RPA, Memorial Sloan-Kettering prognostic score determined by recursive partitioning $Periventricular, basal ganglia, brainstem and cerebellar lesion Table 1. Baseline characteristics (n=27). / *Conventional cytology; flow cytometry not performed. / $The cutoff for normal CSF protein concentration was 45 mg/dL in patients ¡Â 60 years old. / and 60 mg/dL in patients more than 60 years old. / *MSK RPA, Memorial Sloan-Kettering prognostic score determined by recursive partitioning. / $Periventricular, basal ganglia, brainstem and cerebellar lesion Figure 1 Event-free survival and overall survival. Figure 1. Event-free survival and overall survival. Disclosures No relevant conflicts of interest to declare.

scholarly journals Event-free survival at 24 months captures central nervous system relapse of systemic diffuse large B-cell lymphoma in the immunochemotherapy era

2017 ◽  
Vol 183 (1) ◽  
pp. 149-152 ◽  
Author(s):  
Gita Thanarajasingam ◽  
Matthew J. Maurer ◽  
Umar Farooq ◽  
Patrick B. Johnston ◽  
Carrie A. Thompson ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Central Nervous System Relapse ◽  
Event Free Survival ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

No Survival Improvement for Central Nervous System Multiple Myeloma By the Use of Novel Anti-Myeloma Agents: The Greek Myeloma Study Group Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4752-4752
Author(s):  
Eirini Katodritou ◽  
Evangelos Terpos ◽  
Sosana Delimpasi ◽  
Argiris Symeonidis ◽  
Panagiotis Repousis ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Multiple Myeloma ◽  
Nervous System ◽  
Conflicts Of Interest ◽  
Median Number ◽  
Novel Agents ◽  
Study Group ◽  
Newly Diagnosed ◽  
Cns Involvement ◽  
Cox Regression Analysis

Abstract Multiple myeloma of the central nervous system (CNSMM) is a rare and severe clinical entity. The efficacy of novel agents in this setting has not been sufficiently explored. Our aim was to describe the incidence, characteristics and outcome of CNSMM in the era of novel agents, to search for prognostic factors of post CNSMM survival and explore the efficacy of novel agent-based combinations (NAC). Data were provided by 8 Centers of the Greek Myeloma Study Group from January 2000 to December 2013. Documentation of CNSMM required: biopsy that proved CNSMM or MRI/CT findings consistent with CNSMM or detection of plasma cells (PCs) and/or monoclonal immunoglobulin (MC) in the cerebrospinal fluid (CSF). Response to CNSMM treatment was defined as improvement/normalization of at least one of the aforementioned variables. Twenty-four (M/F: 10/14; median age: 63.5 years, range 24-97 years) of 3107 newly diagnosed symptomatic MM patients, who were diagnosed in the same centers during the same period of time, developed CNSMM (0.8%); 2 of them were newly diagnosed and 22 had received previous therapies (6/22 had CNS involvement as the sole feature of MM). Fourteen patients had IgG MM, 2 IgA, 3 light chain, 1 IgD and 4 non-secretory MM. The median time to CNSMM diagnosis was 28.5 months (range: 0-98 months). Clinical manifestations included: visual disturbances/diplopia (37%), paresis/paraplegia (29%), lethargy/confusion (25%), headache (16%) and cranial nerve palsy (12%). MRI or CT documentation was available in 20/24 patients and revealed parenchymal lesions (35%), leptomeningeal lesions (10%), direct MM extension (20%), parenchymal/leptomeningeal (10%), parenchymal/direct MM extension (15%) or leptomeningeal/direct MM extension (10%). Diagnostic lumbar puncture was performed in 17 patients and in 10/17 PCs were detected in the CSF (median number of PCs/μL was 172.5/μL, range: 5-2550/μL). LDH and albumin in the CSF was high in all patients, while MC was detected in the CSF of 4 patients. Sixteen patients (67%) had additional extramedullary disease (EMD) or plasma cell leukemia (PCL) prior to CNSMM diagnosis (plasmacytomas: 9 patients, PCL primary/secondary: 3/3 patients, EMD/PCL: 1 patient). Molecular cytogenetics were available in 12/24; 4 patients had high risk cytogenetics. Patients who developed CNSMM after frontline therapy (n=22) had higher LDH at the time of CNS involvement compared to initial MM diagnosis (267 U/L vs 191 U/L; p=0.02). NAC had been given in 17/22 (77%) such patients prior to CNSMM diagnosis (bortezomib-based: 17, IMiD-based: 13, both: 13). The median number of previous MM treatment lines in these patients was 3 (range: 1-5). Treatment of CNSMM included NAC (bortezomib-based 9 and IMiD-based 3 patients), chemotherapy alone (7 patients) and only intrathecal infusions (ITI) with MTX or AraC (3 patients); 7 patients received both systematic therapy and ITI. Additional radiotherapy (RT) was given to 8 patients; one patient underwent ASCT consolidation. Regarding CNSMM response, 10/22 treated patients had improvement or normalization of initial CNS findings and 6 of them relapsed. At the time of evaluation, 2 patients were alive and 22 patients had died (MM progression: 13, sepsis: 6, cerebral hemorrhage: 2, leishmaniasis: 1 and CNSMM progression: 1). The median post CNSMM survival was 3 months (95% CI: 1.9-4.1). The median post CNSMM survival for patients treated with NAC vs. others was 4 (95% CI: 0-8.6) vs. 2 months (95% CI: 0.7-3.3), respectively (p>0.05). Additional RT did not improve survival (p>0.05). In the cox regression analysis, prior treatment with NAC and presence of EMD/PCL prior to CNSMM diagnosis marginally predicted for shorter post CNSMM survival (p=0.05 and 0.068, HzR: 3.03 and 2.57, respectively). The median post CNSMM survival for previously NAC-exposed patients was 2 months (95% CI: 1-2.9) vs. 6 months (95% CI: 0.8-11) for NAC-naive patients (p=0.03), while that of patients with prior EMD/PCL was 2 months (95% CI: 1.3-2.6) vs. 8 months (95% CI: 0-18) of the others (p=0.06). In the era of novel agents the incidence of CNSMM remains low, but yet outcome is extremely poor. In our study, treatment with NAC ± RT and ITI did not offer any survival advantage. Treatment with NAC and presence of EMD/PCL prior to CNSMM diagnosis seems to predict for shorter post CNSMM survival. Patients with EMD/PCL should be monitored more firmly in order to detect early manifestations of CNSMM. Disclosures No relevant conflicts of interest to declare.

scholarly journals Studies on the Use of "Prophylactic" Intrathecal Amethopterin in Childhood Leukemia

Blood ◽  
1970 ◽  
Vol 36 (1) ◽  
pp. 55-60 ◽  
Author(s):  
DAVID K. MELHORN ◽  
SAMUEL GROSS ◽  
BARRY J. FISHER ◽  
ARTHUR J. NEWMAN
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Leukemia ◽  
Lumbar Puncture ◽  
Childhood Leukemia ◽  
Initial Diagnosis ◽  
Initial Evaluation ◽  
Frequency Of Occurrence ◽  
Cns Involvement ◽  
Central Nervous System Infiltration

Abstract Central nervous system infiltration was studied in a group of 47 children with acute leukemia. CNS involvement was found to occur more frequently and appear more rapidly in patients who presented with elevated peripheral WBC counts. CNS infiltration not suspected clinically was identified by spinal fluid examination in a significant minority of children at the time of the initial diagnosis of leukemia, indicating that lumbar puncture should be a routine part of the initial evaluation of patients with acute leukemia. Intrathecal amethopterin administered "prophylactically" at the time of initial diagnosis of leukemia did not prevent or decrease the frequency of occurrence of CNS infiltration. However, it did delay the onset of CNS involvement in patients with elevated WBC counts. Intrathecal amethopterin administered before the onset of CNS infiltration appears to be useful in delaying morbidity resulting from CNS involvement in children who present with elevated peripheral WBC counts.

Predictive factors for oligometastatic versus non-oligometastatic involvement of the central nervous system by brain metastases from breast cancer.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 123-123 ◽  
Author(s):  
S. Garg ◽  
J. C. Marsh ◽  
R. D. Rao ◽  
K. L. Griem
Keyword(s):  
Breast Cancer ◽  
Central Nervous System ◽  
Nervous System ◽  
Brain Metastases ◽  
Initial Diagnosis ◽  
Breast Cancer Patients ◽  
Cns Involvement ◽  
Cancer Subtypes ◽  
Oligometastatic Disease ◽  
The Central Nervous System

123 Background: To assess rates of oligometastatic (1-3 metastases) versus non-oligometastatic (4 or more) involvement of the central nervous system (CNS) from breast cancer and determine whether rates vary for different breast cancer subtypes. Methods: We reviewed records of 65 patients with brain metastases from breast cancer. Fisher’s Exact Test compared incidence of oligometastatic versus nonoligometastatic CNS involvement and presence of visceral metastatic disease between groups. Paired Student's t test compared mean age and interval from initial diagnosis to development of brain metastases. Results: 25 patients (38.5%) developed oligometastatic and 40 (61.5%) developed non-oligometastatic CNS disease. Subtypes predictive of oligometastatic disease included ER+ (p .04) and PR+ (p .008). Subtypes predictive of non-oligometastatic disease included HER2+ (p .05). HER2+ patients trended toward a lower incidence of visceral metastases compared to ER+ or PR+ patients (p .07). Non-oligometastatic and HER2+ patients developed brain metastases sooner after initial diagnosis (p .046 and .03, respectively). Conclusions: ER+ breast cancer patients are more likely to develop oligometastatic CNS involvement and may be excellent candidates for stereotactic radiosurgery (SRS) alone. HER+ patients are likely to develop non-oligometastatic CNS involvement and may be better treated initially with whole brain radiotherapy (WBRT) even with apparent initial oligometastatic CNS involvement.

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