Dataset Information

Reticular dysgenesis: international survey on clinical presentation, transplantation, and outcome.

ABSTRACT: Reticular dysgenesis (RD) is a rare congenital disorder defined clinically by the combination of severe combined immunodeficiency (SCID), agranulocytosis, and sensorineural deafness. Mutations in the gene encoding adenylate kinase 2 were identified to cause the disorder. Hematopoietic stem cell transplantation (HSCT) is the only option to cure this otherwise fatal disease. Retrospective data on clinical presentation, genetics, and outcome of HSCT were collected from centers in Europe, Asia, and North America for a total of 32 patients born between 1982 and 2011. Age at presentation was <4 weeks in 30 of 32 patients (94%). Grafts originated from mismatched family donors in 17 patients (55%), from matched family donors in 6 patients (19%), and from unrelated marrow or umbilical cord blood donors in 8 patients (26%). Thirteen patients received secondary or tertiary transplants. After transplantation, 21 of 31 patients were reported alive at a mean follow-up of 7.9 years (range: 0.6-23.6 years). All patients who died beyond 6 months after HSCT had persistent or recurrent agranulocytosis due to failure of donor myeloid engraftment. In the absence of conditioning, HSCT was ineffective to overcome agranulocytosis, and inclusion of myeloablative components in the conditioning regimens was required to achieve stable lymphomyeloid engraftment. In comparison with other SCID entities, considerable differences were noted regarding age at presentation, onset, and type of infectious complications, as well as the requirement of conditioning prior to HSCT. Although long-term survival is possible in the presence of mixed chimerism, high-level donor myeloid engraftment should be targeted to avoid posttransplant neutropenia.

SUBMITTER: Hoenig M

PROVIDER: S-EPMC5445572 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Reticular dysgenesis: international survey on clinical presentation, transplantation, and outcome.

Hoenig Manfred M Lagresle-Peyrou Chantal C Pannicke Ulrich U Notarangelo Luigi D LD Porta Fulvio F Gennery Andrew R AR Slatter Mary M Cowan Morton J MJ Stepensky Polina P Al-Mousa Hamoud H Al-Zahrani Daifulah D Pai Sung-Yun SY Al Herz Waleed W Gaspar Hubert B HB Veys Paul P Oshima Koichi K Imai Kohsuke K Yabe Hiromasa H Noroski Lenora M LM Wulffraat Nico M NM Sykora Karl-Walter KW Soler-Palacin Pere P Muramatsu Hideki H Al Hilali Mariam M Moshous Despina D Debatin Klaus-Michael KM Schuetz Catharina C Jacobsen Eva-Maria EM Schulz Ansgar S AS Schwarz Klaus K Fischer Alain A Friedrich Wilhelm W Cavazzana Marina M

Blood 20170322 21

Reticular dysgenesis (RD) is a rare congenital disorder defined clinically by the combination of severe combined immunodeficiency (SCID), agranulocytosis, and sensorineural deafness. Mutations in the gene encoding adenylate kinase 2 were identified to cause the disorder. Hematopoietic stem cell transplantation (HSCT) is the only option to cure this otherwise fatal disease. Retrospective data on clinical presentation, genetics, and outcome of HSCT were collected from centers in Europe, Asia, and ...[more]

PMID: 28331055

Similar Datasets

Project description:BackgroundThe long-term outcomes of both pancreas and islet allotransplantation have been compromised by difficulties in the detection of early graft dysfunction at a time when a clinical intervention can prevent further deterioration and preserve allograft function. The lack of standardized strategies for monitoring pancreas and islet allograft function prompted an international survey established by an International Pancreas and Islet Transplant Association/European Pancreas and Islet Transplant Association working group.MethodsA global survey was administered to 24 pancreas and 18 islet programs using Redcap. The survey addressed protocolized and for-cause immunologic and metabolic monitoring strategies following pancreas and islet allotransplantation. All invited programs completed the survey.ResultsThe survey identified that in both pancreas and islet allograft programs, protocolized clinical monitoring practices included assessing body weight, fasting glucose/C-peptide, hemoglobin A1c, and donor-specific antibody. Protocolized monitoring in islet transplant programs relied on the addition of mixed meal tolerance test, continuous glucose monitoring, and autoantibody titers. In the setting of either suspicion for rejection or serially increasing hemoglobin A1c/fasting glucose levels postpancreas transplant, Doppler ultrasound, computed tomography, autoantibody titers, and pancreas graft biopsy were identified as adjunctive strategies to protocolized monitoring studies. No additional assays were identified in the setting of serially increasing hemoglobin A1c levels postislet transplantation.ConclusionsThis international survey identifies common immunologic and metabolic monitoring strategies utilized for protocol and for cause following pancreas and islet transplantation. In the absence of any formal studies to assess the efficacy of immunologic and metabolic testing to detect early allograft dysfunction, it can serve as a guidance document for developing monitoring algorithms following beta-cell replacement.

Project description:BackgroundThe insula is a small but complex structure located in the depth of the sylvian fissure, covered by the frontal, parietal and temporal operculum. Ischemic strokes limited to the insula are rare and have not been well studied. Our objective is to better define the clinical presentation and outcome of insular ischemic strokes (IIS).MethodsWe reviewed the institutional prospective, consecutive stroke database from two centers to identify patients with IIS seen between 2008 and 2010. We also searched the Medline database using the keywords insula(r), infarction and stroke to identify previously published IIS cases confirmed by MRI. Minimal extension to an adjacent operculum or subinsular area was accepted. Clinicoradiological correlation was performed by distinguishing IIS involving the anterior (AIC) or posterior insular cortex (PIC). We collected clinical, demographic and radiological data. The outcome was determined using the modified Rankin Scale (mRS).ResultsWe identified 7 patients from our institutions and 16 previously published cases of IIS. Infarcts were limited to the AIC (n = 4) or the PIC (n = 12) or affected both (n = 7). The five most frequent symptoms were somatosensory deficits (n = 10), aphasia (n = 10), dysarthria (n = 10), a vestibular-like syndrome (n = 8) and motor deficits (n = 6). A significant correlation was found between involvement of the PIC and somatosensory manifestations (p = 0.04). No other statistically significant associations were found. IIS presentation resembled a partial anterior circulation infarct (n = 9), a lacunar infarct (n = 2) or a posterior circulation infarct (n = 2). However, most cases presented findings that did not fit with these classical patterns (n = 10). At the 6 month follow up, mRS was 0 in 8/23 (35%) patients, 1-2 in 7/23 (30%) and unknown in 8/23 (35%).ConclusionsIIS presentation is variable. Due to the confluence of functions in a restricted region, it results in multimodal deficits. It should be suspected when vestibular-like or motor but especially somatosensory, speech or language disturbances are combined in the same patient. The outcome of IIS is often favorable. Larger prospective studies are needed to better define the clinical presentation and outcome of IIS.

Project description:ImportanceAcute rejection is one of the most frequent complications in facial transplantation, with potentially severe consequences for the recipient if overlooked. Clinical signs, such as erythema or edema, are helpful to diagnose acute rejection in the early follow-up stage; however, it is not well known whether these clinical signs remain reliable markers of acute rejection beyond the second posttransplant year.ObjectiveTo determine the diagnostic value of clinical signs of acute rejection after facial transplantation over time.Design, setting, and participantsA retrospective, single-center cohort study was conducted of patients who underwent facial transplantation at Brigham and Women's Hospital between April 2009 and October 2014, with up to an 8-year follow-up. Medical records were reviewed until September 30, 2017. The medical records from 104 encounters with 7 patients who underwent partial or full facial transplantation were analyzed for symptoms of rejection, immunosuppressive therapy, and histopathologic findings.Main outcomes and measuresThe occurrence of 5 clinical signs of acute rejection were evaluated: erythema, edema, exanthema, suture line erythema, and mucosal lesions. Odds ratios (ORs) were calculated to determine the statistically significant association of these signs with the histopathologic diagnosis of rejection. In addition, tacrolimus blood levels, as a surrogate marker of immunosuppressive therapy, were evaluated.ResultsOf the 7 patients included in the study, 5 were men. The mean follow-up was 66 months (range, 35-101). Of 104 clinical encounters, 46 encounters (44.2%) represented rejection episodes and 58 encounters (55.8%) represented no-rejection episodes. Beyond 2 years posttransplantation, only erythema (OR, 6.53; 95% CI, 1.84-20.11; P = .004) and exanthema (OR, ∞; 95% CI, 2.2-∞; P = .004) were demonstrated to be reliable clinical signs of acute rejection in facial transplantation. There was also a statistically significant association of subtherapeutic tacrolimus levels with late rejection episodes (OR, 3.79; 95% CI, 1.25-12.88; P = .03). In addition, the occurrence of subclinical rejection was more frequent during later follow-up times (7 [24.1%] late rejections vs 1 [5.9%] early rejection). Five of 8 subclinical rejections (62.5%) were associated with subtherapeutic tacrolimus levels.Conclusions and relevanceClinical signs of acute rejection in facial transplantation appear to be of limited diagnostic value, particularly after the second postoperative year. Until alternative biomarkers for rejection are identified, protocol skin biopsies will remain necessary for guiding assessments of allograft rejection.Level of evidence3.

Dataset Information

Reticular dysgenesis: international survey on clinical presentation, transplantation, and outcome.

Publications

Reticular dysgenesis: international survey on clinical presentation, transplantation, and outcome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets