Successful Low Toxicity Hematopoietic Stem Cell Transplantation for High-Risk Adult Chronic Granulomatous Disease Patients

Güngör, Tayfun; Halter, Jörg; Klink, Anne; Junge, Sonja; Stumpe, Katrin D. M.; Seger, Reinhard; Schanz, Urs

doi:10.1097/01.tp.0000163466.73485.5e

Cited by 73 publications

(19 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the RIC regimens performed until now have shown a significant risk of incomplete engraftment with the donor haematopoietic cells or graft rejection and GvHD, particularly if DLI has to be used to ensure engraftment. Nevertheless, the RIC HSCT is usually enough to improve clinical status and resolve the inflammation and infections before the graft rejection [20–22]. Moreover, additional standard myeloablative HSCT could be performed as a salvage therapy if second transplant is required [23].…”

Section: Discussionmentioning

confidence: 99%

Allogeneic Haematopoietic Stem Cell Transplantation as Therapy for Chronic Granulomatous Disease—Single Centre Experience

et al. 2011

View full text Add to dashboard Cite

Chronic granulomatous disease (CGD) is phagocytic cell metabolic disorder resulting in recurrent infections and granuloma formation. This paper reports the favourable outcome of allogeneic transplantation in six high-risk CGD patients. The following donors were used: HLA-matched, related (two) and unrelated (three), and HLA-mismatched, unrelated (one). One patient was transplanted twice using the same sibling donor because of graft rejection at 6 months after reduced-intensity conditioning transplant (fludarabine and melphalan). Myeloablative conditioning regimen consisted of busulphan and cyclophosphamide. Stem cell source was unmanipulated bone marrow containing: 5.2 (2.6–6.5) × 108 nucleated cells, 3.8 (2.0–8.0) × 106 CD34+ cells and 45 (27–64) × 106 CD3+ cells per kilogramme. Graft-versus-host disease prophylaxis consisted of cyclosporine A and, for unrelated donors, short course of methotrexate and anti-T-lymphocyte globulin. Mean neutrophile and platelet engraftments were observed at day 22 (20–23) and day 20 (16–29), respectively. Pre-existing infections and inflammatory granulomas resolved. With the follow-up of 4–35 months (mean, 20 months), all patients are alive and well with full donor chimerism and normalized superoxide production.

show abstract

Section: Discussionmentioning

confidence: 99%

Allogeneic Haematopoietic Stem Cell Transplantation as Therapy for Chronic Granulomatous Disease—Single Centre Experience

et al. 2011

View full text Add to dashboard Cite

show abstract

“…15 (This study included data from 86,640 European ancestry and 9,846 Asian individuals, identifying 231 genome-wide significant independent SNP associations in 200 IBD loci. 6 ) In CGD, even if there is no mucosal inflammation, granulomas are present in gastrointestinal biopsies. 20 Therefore, we included UC risk SNPs in our IBD GRS determinations as patients with CGD-IBD can have a continuous, distal pattern of mucosal inflammation limited to the colon and typical of UC but per IBD phenotyping guidelines, due to the inevitable presence of granulomas, would be called CD (noting that non-CGD patients with a UC pattern always are classified as CD when multiple granulomas are present).…”

Section: Methodsmentioning

confidence: 99%

“…4 Many of those who have inflammation and autoimmune complications of CGD may be on chronic treatment with corticosteroids. CGD can be cured by allogeneic bone marrow transplant (BMT), 6, 7 which is increasingly being offered to patients with minimum residual oxidase activity or who have severe disease.…”

Section: Introductionmentioning

confidence: 99%

Genetic Risk for Inflammatory Bowel Disease Is a Determinant of Crohnʼs Disease Development in Chronic Granulomatous Disease

Huang

Ravin

Paul

et al. 2016

Inflammatory Bowel Diseases

View full text Add to dashboard Cite

Background Approximately one third to one half of children with chronic granulomatous disease (CGD) develop gastrointestinal inflammation characteristic of idiopathic inflammatory bowel disease (IBD), usually Crohn’s disease (CD). We hypothesized that overall IBD genetic risk, determined by IBD genetics risk score (GRS), might in part determine IBD development in CGD. Methods We reviewed medical records to establish IBD diagnoses in CGD subjects seen at NIAID. IBD risk SNP genotypes were determined using the Immunochip and GRS were estimated by Mangrove. Results Among 157 Caucasian CGD patients 55 were confirmed, 78 excluded and 24 were uncertain for IBD. 201 established, independent European IBD risk SNPs passed quality control. After sample quality control and removing non-IBD CGD patients with perianal disease, mean GRS for 40 unrelated CGD-IBD patients was higher than 53 CGD non-IBD patients (in log2-scale 0.08±1.62 vs. −0.67±1.64, p=0.026) but lower than 239 IBD Genetics Consortium (IBDGC) young-onset CD cases (0.76±1.60, p=0.025). GRS for non-IBD CGD was similar to 609 IBDGC controls (−0.69±1.60, p=0.95). Seven established IBD SNPs were nominally significant among CGD-IBD vs. CGD non-IBD, including those near LACC1 (p=0.005), CXCL14 (p=0.007) and TNFSF15 (p=0.016). Conclusions The weight of common IBD risk alleles are significant determinants of IBD in CGD. However, IBD risk gene burden among CGD children with IBD is significantly lower than that in non-syndromic pediatric CD, congruent with the concept that defective superoxide production in CGD is also a major IBD risk factor. Individual IBD genes might interact with the CGD defect to cause IBD in CGD.

show abstract

“…From 1973, when the first CGD bone marrow transplant was performed, until now, 99 transplants, not including cord blood recipients, have been published, with the majority being single case reports. 49–70 However, of the 99 patients transplanted, 50 have occurred in the last 10 years compared to 49 in the prior 27 years. With the advent of non-myeloablative regimens, the risks surrounding transplant have decreased and have permitted transplantation in patients with ongoing infections.…”

Section: Hematopoietic Stem Cell Transplantation For Chronic Granulommentioning

confidence: 99%

Chronic granulomatous disease: Overview and hematopoietic stem cell transplantation

Kang

Marciano

Ravin

et al. 2011

Journal of Allergy and Clinical Immunology

170

137

View full text Add to dashboard Cite

Chronic Granulomatous Disease (CGD) still causes significant morbidity and mortality. The difficulty in considering high-risk yet curative treatments, such as allogeneic bone marrow transplantation, lies in the unpredictable courses of both CGD and bone marrow transplantation in different patients. Some CGD patients may have frequent infections and/or suffer from granulomatous or autoimmune disorders necessitating immunosuppressive therapy, but also experience long periods of relative good health. However, the risk of death is clearly higher in CGD of all types, and the complications of CGD short of death can still cause significant morbidity. Therefore, with recent developments and improvements, bone marrow transplantation, previously considered an experimental or high-risk procedure, has emerged as an important option for patients with CGD. We will discuss the complications of CGD that result in significant morbidity and mortality, in particular the most common infections and autoimmune/inflammatory complications as well as their typical management. We will then discuss the status of bone marrow transplantation.

show abstract

Successful Low Toxicity Hematopoietic Stem Cell Transplantation for High-Risk Adult Chronic Granulomatous Disease Patients

Abstract: This modified reduced intensity conditioning protocol is a promising treatment modality for high-risk adult CGD patients.

Cited by 73 publications

References 40 publications

Allogeneic Haematopoietic Stem Cell Transplantation as Therapy for Chronic Granulomatous Disease—Single Centre Experience

Allogeneic Haematopoietic Stem Cell Transplantation as Therapy for Chronic Granulomatous Disease—Single Centre Experience

Genetic Risk for Inflammatory Bowel Disease Is a Determinant of Crohnʼs Disease Development in Chronic Granulomatous Disease

Chronic granulomatous disease: Overview and hematopoietic stem cell transplantation

Contact Info

Product

Resources

About