Background: Regarding standardization of treatment, classification, and pathophysiology of peripheral T- and NK-cell neoplasias the current knowledge is markedly behind that of B-cell lymphomas, which are approximately 10 times more frequent. In May 2000, the study group 'Peripheral T- and NK-cell Neoplasias' was founded in Frankfurt/M. This group decided on a clinical protocol and a scientific program for research on the pathophysiology of these entities. Rationales for the therapeutic regimen are the efficacy of cyclophosphamide and doxorubicine as shown in protocols for treatment of high grade lymphoma, the synergism of cyclophosphamide and fludarabine, and reports demonstrating the efficacy of fludarabine in T-cell neoplasias. Patients and Methods: Patients will be treated with a combination of fludarabine (30 mg/m2 days 1–3), cyclophosphamide (1000 mg/m2 day 1) doxorubicine (25 mg/m2 day 2+3) (FCD). For patients ≧65 years a dose-reduced FCD regimen will be administered. In patients included in the treatment study and additionally in patients with indolent disease not requiring therapy, scientific projects on the biology of peripheral T- and NK-cell neoplasias will be performed. Conclusions: Expected conclusions of the projected study are the establishment of treatment and diagnostic standards, and improvement of classification of these entities by clinical, morphologic and biologic parameters.
To compare MOG positive and negative patients with ADEM as relates to demographic features, neuroimaging and laboratory features, hospital course, treatments, and relapse rate.
Background:
MOG antibody disease is an increasingly recognized etiology for acute disseminated encephalomyelitis (ADEM). ADEM is a condition that predominately affects children and presents with multifocal neurological symptoms and encephalopathy. Positive MOG antibodies strongly argues against later development of multiple sclerosis or NMOSD. The distinguishing characteristics of ADEM, as defined by MOG positive or negative status has not been well studied.
Design/Methods:
Children with the initial diagnosis of ADEM were consented to participate in a study of ADEM related outcomes. Their demographic features, clinical presentation, laboratory and imaging results, and clinical course are presented, highlighting differences in MOG positive and negative cohorts.
Results:
37 children in the study were assessed for MOG IgG. 18 children were MOG positive (49%) and 19 children were MOG negative (51%). Average age and race/ethnicity were similar between cohorts but the MOG positive group showed equal male/female ratio while MOG negative cohort showed male predominance (74%). The MOG negative cohort had greater number of individuals with normal nucleated cells in CSF (0–5 cells/mm3) than MOG positive cohort: 7/19 (37%) vs 2/18 (11%). Neuroimaging features, need for ICU stay and acute rehabilitation were similar between cohorts. A greater number of MOG positive patients required ICP management (4/18 vs 1/19) and one MOG positive child died. 6/18 (33%) MOG positive patients had relapses compared to 3/19 (16%) MOG negative patients. 90% of the 29 patients who had neuropsychological testing scored within the normal range.
Conclusions:
MOG antibody disease is a common cause of ADEM though the characteristics of MOG positive and negative ADEM patients have not been well described. This study compares these populations from our tertiary center's cohort of ADEM patients enrolled in an ADEM study. Disclosure: Dr. Wang has nothing to disclose. Patricia Plumb has nothing to disclose. Dr. Harder has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis Pharmaceuticals. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Greenberg has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Horizon. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi/Genzyme. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant. Dr. Greenberg has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech/ROche. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Signant-2022. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IQVIA. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Greenberg has received personal compensation in the range of $0-$499 for serving as a Consultant for Intervenn. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. Dr. Greenberg has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for TWI. Dr. Greenberg has stock in GenrAb. The institution of Dr. Greenberg has received research support from CLENE Nanomedicine. The institution of Dr. Greenberg has received research support from Anokion. The institution of Dr. Greenberg has received research support from Regeneron. Dr. Greenberg has received intellectual property interests from a discovery or technology relating to health care. Dr. Greenberg has received publishing royalties from a publication relating to health care. Dr. Greenberg has a non-compensated relationship as a Scientific Board with Siegel Rare Neuroimmune Association that is relevant to AAN interests or activities.
<div>Abstract<p>Chromosomal breakpoints affecting immunoglobulin (<i>IG</i>) loci are recurrent in many subtypes of B-cell lymphomas. However, despite the predominant B-cell origin of the Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL), the presence of chromosomal translocations in <i>IG</i> loci has not yet been systematically explored. Therefore, we have investigated a series of cHL for chromosomal breakpoints in the <i>IGH</i> (<i>n</i> = 230), <i>IGL</i> (<i>n</i> = 139), and <i>IGK</i> (<i>n</i> = 138) loci by interphase cytogenetics. Breakpoints in the <i>IGH, IGL</i>, or <i>IGK</i> locus were observed in the HRS cells of 26 of 149 (17%), 2 of 70, and 1 of 77 evaluable cHLs, respectively. The <i>IG</i> partners could be identified in eight cHLs and involved chromosomal bands 2p16 (<i>REL</i>), 3q27 (<i>BCL6</i>, two cases), 8q24.1 (<i>MYC</i>), 14q24.3, 16p13.1, 17q12, and 19q13.2 (<i>BCL3/RELB</i>). In 65 of 85 (76%) cHLs evaluable for an <i>IGH</i> triple-color probe, the HRS cells showed evidence for a (partial) deletion of the <i>IGH</i> constant region, suggesting the presence of class switch recombination (CSR). Furthermore, analyses with this probe in cases with <i>IGH</i> breakpoints indicated that at least part of them seem to be derived from CSR defects. Our results show that chromosomal breakpoints affecting the <i>IG</i> loci are recurrent in cHL. (Cancer Res 2006; 66(21): 10332-8)</p></div>
PURPOSE Infants treated for CNS malignancies experience a significantly poorer response to treatment and are particularly at risk for neuropsychological deficits. The literature is limited and inconsistent regarding cognitive outcomes among this group. We investigated predictors of cognitive outcomes in children treated for brain tumors during infancy as part of a large, prospective, multisite, longitudinal trial. PATIENTS AND METHODS One hundred thirty-nine infants with a newly diagnosed CNS tumor were treated with chemotherapy, with or without focal proton or photon radiation therapy (RT). Cognitive assessments were conducted at baseline, 6 months, 1 year, and then annually for 5 years. The median length of follow-up was 816 days (26.8 months). Neurocognitive testing included assessment of intellectual functioning (intellectual quotient [IQ]), parent ratings of executive functioning and emotional and behavioral functioning, and socioeconomic status. RESULTS At baseline, IQ, parent-reported working memory, and parent-reported adaptive functioning were worse than normative expectations. Baseline cognitive difficulties were associated with younger age at diagnosis and lower socioeconomic status. Linear mixed models did not demonstrate a decline in IQ over time. There were increased parent-reported attention and executive problems over time. Increased concerns were related to supratentorial tumor location and CSF diversion. There were no differences in cognitive outcomes based on treatment exposure (chemotherapy-only v chemotherapy with RT and proton v photon focal RT). CONCLUSION Even before adjuvant therapy, young children with brain tumors experience cognitive difficulties that can affect quality of life. Changes in cognitive functioning over time were dependent on tumor location and surgical factors rather than adjuvant therapy. These findings may serve to guide treatment planning and indicate targets for cognitive monitoring and intervention.
Abstract: Objectives : Classical mantle cell lymphoma (MCL) and its blastoid variant (MCL‐BV) are characterized by an extremely poor prognosis. Long‐time survivors are rare, only very few patients with an overall survival over 10 years have been reported. We present a case of a 41‐year‐old male with a 12 yr history of MCL stage I to show, that very late relapses in MCL are possible and may present as a transformation into an aggressive blastoid variant and to illustrate the value of quantitative minimal residual disease (MRD) monitoring for treatment guidance. Methods : Diagnostic lymph node and bone marrow samples were investigated by immunohistochemistry. Clonality analysis was performed by immunoglobulin heavy chain gene (IGVH) and t(11;14) PCR. The MRD assessment was done by real‐time quantitative PCR (RQ‐PCR) on available follow‐up samples. Results : By histologic review and sequencing of the clonal IGVH and t(11;14) PCR products we demonstrated a common clonal origin of the leucemic MCL‐BV and the classical MCL diagnosed 12 yr earlier. Quantitative MRD assessment revealed significant MRD levels after intensive conventional chemotherapy including Rituximab. Therefore, treatment was early intensified by myeloablative radio‐chemotherapy and allogeneic peripheral stem cell transplantation from an unrelated HLA‐identical donor. This did not translate into a sustained remission as reflected by persisting MRD levels after transplantation and the patient died from rapid progressive disease 3.5 months after transplant. Conclusion : This report presents a rare case of long‐term survivor of MCL with a progression of the original MCL cell clone to MCL‐BV and demonstrates the clinical value of quantitative MRD assessment for optimized therapeutic management.
