scholarly journals Endocrine Complications in Children and Adolescents With Non-Central Nervous System Solid Tumors

2021 ◽  
Vol 12 ◽  
Author(s):  
Yena Lee ◽  
Juhee Shin ◽  
Yunha Choi ◽  
Hyery Kim ◽  
Kyung-Nam Koh ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Regression Analysis ◽  
Solid Tumors ◽  
Growth Failure ◽  
Hematopoietic Stem ◽  
Cox Regression Analysis ◽  
Primary Gonadal Failure ◽  
Gonadal Failure ◽  
Endocrine Complications

BackgroundDue to remarkable progress in cancer treatment, endocrine complications are now the major medical issues facing childhood cancer survivors. Although non-central nervous system solid tumors (NCSTs) account for approximately 40% of all pediatric cancers, there have been few studies on endocrine complications associated with NCSTs. This study investigated endocrinopathies following the treatment of pediatric NCSTs.Design and settingRetrospective study in a single academic center.MethodsThis study analyzed 253 survivors of childhood NCSTs who were diagnosed between January of 2000 and December of 2018. The medical charts were reviewed regarding the frequency of endocrinopathies and treatment modalities. The hazard ratios were assessed by multivariable Cox regression analysis. The final height-SDS were analyzed by multivariable linear regression analysis.ResultsThere were 76 patients (30%) that developed at least one endocrine complication. Forty-four patients (17.4%) experienced endocrine complications within five years of their cancer diagnosis. The most common endocrine complication was growth failure (n = 35), followed by obesity (n = 18), and primary gonadal failure (n = 16). High cumulative doses of alkylating agents increased the risk of developing at least one endocrine complication. Hematopoietic stem cell transplantation was an important risk factor for primary gonadal failure.ConclusionsThis study described the comprehensive endocrine outcomes, including growth failure, obesity, primary gonadal failure, primary hypothyroidism, dyslipidemia, and osteoporosis, following the treatment of childhood NCSTs. As endocrinopathies occurred within five years of primary tumor diagnosis, surveillance for endocrine dysfunction is required for early intervention and management.

scholarly journals CENTRAL NERVOUS SYSTEM INVOLVEMENT IN ADULT ACUTE LYMPHOBLASTIC LEUKEMIA: DIAGNOSTIC TOOLS, PROPHYLAXIS AND THERAPY

2014 ◽  
Vol 6 (1) ◽  
pp. e2014075 ◽  
Author(s):  
Maria Ilaria Del Principe ◽  
Luca Maurillo ◽  
Francesco Buccisano ◽  
Giuseppe Sconocchia ◽  
Mariagiovanna Cefalo ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Intrathecal Injection ◽  
False Negative ◽  
Diagnostic Tools ◽  
Positive Finding ◽  
Cns Involvement ◽  
Hematopoietic Stem

In adult patients with acute lymphoblastic leukemia (ALL), Central Nervous System (CNS) involvement is associated with a very poor prognosis. The diagnostic assessment of this condition relies on the use of neuroradiology, conventional cytology (CC) and flow cytometry (FCM). Among these approaches, which is the gold standard it is still a matter of debate. Neuroradiology and CC have a limited sensitivity with a higher rate of false negative results. FCM demonstrated a superior sensitivity over CC, particularly when low levels of CNS infiltrating cells are present. Although prospective studies of large series of patients are still awaited, a positive finding by FCM appears to anticipate an adverse outcome even if CC shows no infiltration. Current strategies for adult ALL CNS-directed prophylaxis or therapy involve systemic and intrathecal chemotherapy and radiation therapy. Actually, early and frequent intrathecal injection of cytostatic combined with systemic chemotherapy is the most effective strategy to reduce the frequency of CNS involvement. In patients with CNS overt ALL, at diagnosis or upon relapse, allogenic hematopoietic stem cell transplantation might be considered. This review will discuss risk factors, diagnostic techniques for identification of CNS infiltration and modalities of prophylaxis and therapy to manage it. 

scholarly journals Neoplastic Meningitis from Solid Tumors: A Prospective Clinical Study in Lombardia and a Literature Review on Therapeutic Approaches

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
A. Silvani ◽  
M. Caroli ◽  
P. Gaviani ◽  
V. Fetoni ◽  
R. Merli ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Solid Tumors ◽  
Antitumor Agents ◽  
Palliative Radiotherapy ◽  
Symptomatic Treatment ◽  
Diagnostic Techniques ◽  
Prospective Clinical Study ◽  
Pattern Of Care ◽  
Bulky Disease

Neoplastic dissemination to the leptomeninges is an increasingly common occurrence in patients with both haematological and solid tumors arising outside the central nervous system. Both refinement of diagnostic techniques (Magnetic resonance imaging) and increased survival in patients treated with targeted therapies for systemic tumors account for this increased frequency. Cerebrospinal fluid cytological analysis and MRI confirm clinical diagnosis based on multifocal central nervous system signs/symptoms in a patient with known malignancy. Overall survival in patients with leptomeningeal neoplastic dissemination from solid tumors is short, rarely exceeding 3-4 months. However, selected patients may benefit from aggressive therapies, Apart from symptomatic treatment, intrathecal chemotherapy is used, with both free (methotrexate, Thiotepa, AraC) and liposomal antitumor agents (liposomal AraC). Palliative radiotherapy is indicated only in cases of symptomatic bulky disease, surgery is limited to positioning of Ommaya recervoirs or C5F shunting. We report clinical data on a cohort of 26 prospectively followed patients with neoplastic leptomeningitis followed in Lombardia, Italy, in 2011. Prognostic factors and pattern of care are reported.

scholarly journals PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMAS

2015 ◽  
Vol 14 (2) ◽  
pp. 77-84
Author(s):  
Adriana Octaviana Dulamea ◽  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Treatment Strategies ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Diagnostic Methods ◽  
Hematopoietic Stem ◽  
Whole Brain Radiation ◽  
Author Review ◽  
Immunocompetent Patients

Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin B-cell lymphoma with characteristic clinical behavior, biological features and poor prognosis despite complex treatment. PCNSL has a median survival of 17 to 45 months in immunocompetent patients, and only 20-30% of cases can be cured successfully. Clinical outcome has improved since the advances in combination chemotherapy protocols, addition of whole brain radiation therapy, encouraging responses of rituximab administration in refractory PCNSL and autologous hematopoietic stem-cell transplantation as consolidative therapy. The author review the recent data on pathogenesis, diagnostic methods and treatment strategies of PCNSL in immunocompetent patients.

scholarly journals Central Nervous System Complications after Allogeneic Hematopoietic Stem Cell Transplantation: The Role of Calcineurin Inhibitors

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4601-4601
Author(s):  
Elisa Sala ◽  
Stephanie von Harsdorf ◽  
Verena Wais ◽  
Thanh Mai Anne Nguyen ◽  
Raphael Beck ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Research Funding ◽  
Calcineurin Inhibitors ◽  
Neurological Manifestations ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Prophylaxis Therapy

Abstract Introduction Despite its curative potential, the outcome after allogeneic hematopoietic stem cell transplantation (SCT) strongly depends on transplant-related mortality. Neurological complications, especially those affecting the central nervous system (CNS), are often associated with a significant rate of morbidity. Commonly used immunosuppressive drugs are calcineurin inhibitors (CNI) such as cyclosporinA (CsA) and tacrolimus (TAC) which are associated with an increased risk of neurotoxicity. So far no direct comparison between CsA and TAC has been performed to identify the better option in terms of "neurologic tolerability" in the setting of SCT. Patients and Methods We performed a retrospective analysis of consecutive patients (pts) who underwent SCT for different hematological malignancies and developed one or more CNS complications between 1999 and 2018 at the University Hospital of Ulm (Germany) and received CsA or TAC as Graft versus Host Disease (GvHD) prophylaxis/therapy. During post transplant follow up, in case of neurological manifestations, neurological evaluation, brain imaging (CT-scan or MRI), electroencephalography and, if necessary, a lumbar puncture (including microbiological analysis) were performed. Results We identified 60 out of 1256 pts who experienced a total of 79 CNS complications. Pts' characteristics are listed in Table 1. Seventy-four of 79 (94%) complications occurred in pts receiving CNI (n=58/60 pts): 51/74 (69%) were detected during or after TAC administration, while in 23/74 cases (31%) CsA was used. No statistically significant differences were observed in the two subgroups with regard to conditioning regimen (myeloablative vs reduced intensity), donor type (matched related vs matched unrelated vs mismatched related), and incidence of severe GvHD (both acute and chronic). In both cohorts early complications (within 1 month after SCT) were mostly represented by vascular events and metabolic encephalopathy (sepsis or chemotherapy-related). As intermediate complications (2-6 months after SCT) we observed a trend towards increased infections of herpes encephalitis in the TAC cohort (p=0.08), CNI-neurotoxicity and CNS symptoms due to severe transplant-associated microangiopathy (TMA). As late effects (>1 year (y) after SCT) we detected secondary CNS neoplasms, CNS relapse or neurologic effects of chronic GvHD. Comparing the time of onset of all complications, we observed a median time of 6 months after SCT in the TAC-cohort (range: day -1 - 13y) and of 11 months in the CsA-cohort (range: day 0 - 4y). The frequency of the different types of CNS complications was similar in the two cohorts with exception for the occurrence of neurological manifestations related to TMA (Figure 1), which was statistically significant higher (p=0.01) in pts receiving TAC. These changes were reversible in 33% of cases (4/12) after discontinuation of TAC (which, at the time of TMA onset, was within or below the therapeutic ranges in 91% of cases) or after specific treatment (e.g. Eculizumab, plasma exchange). Conclusions Our data suggest a possible increment of neurologic complications in pts undergoing GvHD prophylaxis/therapy with TAC, especially related to the development of severe TMA, which is known to promote mental status changes. Although these findings need to be further explored and validated in larger prospective cohorts, they could have clinical relevance, such as avoiding TAC in pts at high risk of developing TMA as well as a stricter TMA monitoring in pts undergoing GvHD prophylaxis with TAC to minimize the development of severe TMA forms with neurological involvement. Disclosures Döhner: Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Pfizer: Research Funding; Agios: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Jazz: Consultancy, Honoraria; Celator: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Jazz: Consultancy, Honoraria; Astex Pharmaceuticals: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; AROG Pharmaceuticals: Research Funding; Astellas: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria, Research Funding; Celator: Consultancy, Honoraria; Astex Pharmaceuticals: Consultancy, Honoraria; Bristol Myers Squibb: Research Funding; AROG Pharmaceuticals: Research Funding; Astellas: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Bristol Myers Squibb: Research Funding; Seattle Genetics: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Agios: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Pfizer: Research Funding.

Central Nervous System Complications after Allogeneic Hematopoietic Stem Cell Transplantation in Children

2019 ◽  
Vol 142 (4) ◽  
pp. 217-223
Author(s):  
Peng Ke ◽  
Xiebing Bao ◽  
Jihao Zhou ◽  
Qian Zhu ◽  
Juan Zhuang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Impact On Survival ◽  
Poor Outcomes

Central nervous system complications (CNSCs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are common and may be a significant source of morbidity and mortality. We performed a retrospective study of 153 pediatric patients who underwent allo-HSCT to determine CNSC type, incidence, and impact on survival. A total of 34 patients (22.2%) developed CNSCs. The cumulative incidence of CNSCs at 100 days and 3 years was 18.30 and 22.73%, respectively. The most common CNSC was calcineurin inhibitor (CNI)-associated neurotoxicity (50.0%). Risk factors for CNSCs were the time from diagnosis to HSCT ≥4.8 months (p = 0.032) and the development of acute graft-versus-host disease (aGVHD) grade III–IV (p = 0.002). CNSCs after allo-HSCT negatively impacted overall survival (hazard ratio [HR] 1.97, p = 0.043) and nonrelapse mortality (HR 4.84, p < 0.001). In conclusion, CNSCs after allo-HSCT are associated with poor outcomes; patients with severe aGVHD and/or late transplantation should be given more attention.

scholarly journals GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies

2020 ◽  
Vol 21 (17) ◽  
pp. 6213
Author(s):  
Andrés Felipe Leal ◽  
Eliana Benincore-Flórez ◽  
Daniela Solano-Galarza ◽  
Rafael Guillermo Garzón Jaramillo ◽  
Olga Yaneth Echeverri-Peña ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Protein Transport ◽  
Current Knowledge ◽  
Sandhoff Disease ◽  
Substrate Reduction Therapy ◽  
Hematopoietic Stem ◽  
Enzyme Replacement ◽  
Central Nervous System Dysfunction ◽  
Gm2 Gangliosidoses

GM2 gangliosidoses are a group of pathologies characterized by GM2 ganglioside accumulation into the lysosome due to mutations on the genes encoding for the β-hexosaminidases subunits or the GM2 activator protein. Three GM2 gangliosidoses have been described: Tay–Sachs disease, Sandhoff disease, and the AB variant. Central nervous system dysfunction is the main characteristic of GM2 gangliosidoses patients that include neurodevelopment alterations, neuroinflammation, and neuronal apoptosis. Currently, there is not approved therapy for GM2 gangliosidoses, but different therapeutic strategies have been studied including hematopoietic stem cell transplantation, enzyme replacement therapy, substrate reduction therapy, pharmacological chaperones, and gene therapy. The blood–brain barrier represents a challenge for the development of therapeutic agents for these disorders. In this sense, alternative routes of administration (e.g., intrathecal or intracerebroventricular) have been evaluated, as well as the design of fusion peptides that allow the protein transport from the brain capillaries to the central nervous system. In this review, we outline the current knowledge about clinical and physiopathological findings of GM2 gangliosidoses, as well as the ongoing proposals to overcome some limitations of the traditional alternatives by using novel strategies such as molecular Trojan horses or advanced tools of genome editing.

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