Successful Matched Related Bone Marrow Transplantation in a Patient with Autosomal Dominant Interferon Gamma Receptor 1 Deficiency (original) (raw)
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Correction of complete interferon-gamma receptor 1 deficiency by bone marrow transplantation
Blood, 2002
Complete interferon-γ receptor 1 (IFNγR1) deficiency is a primary immunodeficiency disease characterized by high susceptibility to recurrent, severe mycobacterial and other intracellular infections. We here report the first successful treatment of the disorder by bone marrow transplantation (BMT). The 8-year-old girl had suffered from recurrent mycobacterial infections in the past and had developed liver cirrhosis with portal hypertension. For conditioning, fractionated total body irradiation (TBI) was used in combination with cyclophosphamide and antithymocyte globulin (ATG). The patient received red cell–depleted bone marrow from her HLA-identical sister. The transplantation course was uneventful and 4 years later, the child remains in excellent clinical condition and free of mycobacterial infections. She has stable mixed lymphohematopoietic chimerism after repeat T-cell transfusions. Liver disease has not further deteriorated. This experience shows that correction of IFNγR1 defic...
Clinical Infectious Diseases, 2008
Background. Atypical mycobacteria can cause systemic infections in patients with certain types of immunodeficiency. Methods. Clinical samples were decontaminated and cultured to assess the presence of mycobacterial species. Gene sequencing was performed to reveal interferon-g receptor 1 (IFN-gR1) deficiency. Results. The index patient received a diagnosis of dominant IFN-gR1 deficiency during treatment for a serious infection due to atypical mycobacteria. She belongs to a Norwegian multiplex family comprising 3 generations and 5 patients with dominant IFN-gR1 deficiency. Four of these patients have been treated with tuberculostatics because of extensive infection due to atypical mycobacteria, such as Mycobacterium avium-intracellulare, Mycobacterium scrofulaceum, Mycobacterium bovis (bacille Calmette-Guérin), Mycobacterium bohemicum, and Mycobacterium gordonae. Two of the patients have also received subcutaneous injections of IFN-g. One family member with the deficiency has not received treatment and is still healthy at 13 years of age. Conclusions. Serious infection due to atypical mycobacteria should initiate a search for primary immunodeficiencies, particularly IFN-gR1 deficiency. Treatment with IFN-g should be started when serious infection due to atypical mycobacteria is verified and dominant partial IFN-gR1 deficiency is suspected.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2018
Allogenic hematopoietic stem cell transplant (HCT) recipients are at risk of many infections. Nontuberculous mycobacteria (NTM) are increasingly recognized as clinically significant pathogens in this population. We investigated the incidence and risk factors for NTM infection after allogeneic HCT. This retrospective cohort study included all patients with allogeneic HCT at our institution during 2001 to 2013. Patients who developed significant NTM infection (NTM disease) were identified. Multivariable modeling was used to identify risk factors for NTM disease, and a risk score model was constructed to identify high-risk patients. Of 1097 allogeneic HCT patients, 45 (4.1%) had NTM isolated and 30 (2.7%) had NTM disease (28 [93.3%] exclusively pulmonary, 2 [6.7%] pulmonary plus another site). Incidence of NTM infection by competing risk analysis was 2.8% at 5 years (95% CI, 1.9% to 4.0%). The median time to diagnosis was 343 days (range, 19 to 1967). In Fine-Gray proportional hazards ...
British Journal of Haematology, 2002
The timing of transplantation in chronic myeloid leukaemia is still debated and previous treatment with interferon (IFN) alpha has been reported to be deleterious. We have analysed the outcome of 438 allogeneic transplants performed between 1984 and 1995 and reported to the Socie Âte  Franc Ëaise de Greffe de Moelle (SFGM) registry. One hundred and two patients (group I) received IFN for more than 6 weeks (median 9 months) before transplant. Their outcome was compared with 336 other patients (group II) not pretreated with IFN. There were no signi®cant differences between the groups for engraftment and chronic graft-versus-host disease (GVHD) incidence. However, other signi®cant differences included the incidence of acute GVHD ³ 2 at 3 months which was higher in group I (65 10%) than in group II (38 5%; P 0á01). Moreover, diseasefree survival (DFS) and overall survival (OS) at 5 years were signi®cantly shorter for group I than for group II (33 10% vs. 41 6%; P 0á005)(95% CI) and (41 10% vs. 55 6%; P 0á002)(95% CI) respectively. After adjustment for patient and transplant covariables in a multivariate analysis, prior IFN was not found to adversely affect transplant outcome.
Journal of Clinical Immunology, 2014
Interferon-γ receptor 2 (IFN-γR2) deficiency is a rare primary immunodeficiency characterized by predisposition to infections with weakly virulent mycobacteria, such as environmental mycobacteria and BCG vaccines. We describe here two children with IFN-γR2 deficiency, from unrelated, consanguineous kindreds of Arab and Israeli descent. The first patient was a boy who died at the age of 4.5 years, from recurrent, disseminated disease caused by Mycobacterium simiae. His IFN-γR2 defect was autosomal recessive and complete. The second patient was a girl with multiple Rubén Martínez-Barricarte, Orli Megged, Polina Stepensky contributed equally to this work. Jean-Laurent Casanova and Jacinta Bustamante contributed equally to this work.
Immunotherapy, 2012
Interferon-γ receptor-1 (IFNγR1) deficiency is caused by mutations in the IFNγR1 gene and is characterized mainly by susceptibility to mycobacterial disease. Herein, we report an 8-month-old boy with complete recessive IFNγR1 deficiency, afflicted by recurrent mycobacterial diseases with Mycobacterium bovis, Mycobacterium tuberculosis, Mycobacterium avium intracellulare and Mycobacterium fortuitum. Genetic analysis showed a homozygous mutation (106insT) in the IFNγR1 gene leading to complete IFNγR1 deficiency. In addition, he had atypical mycobacterial skin lesions caused by M. avium intracellulare and developed scrotal and lower limb lymphedema secondary to compression of large and fixed inguinal lymphadenopathies. Hematopoietic stem cell transplantation was performed from a matched unrelated donor at 5 years of age; however, he died at 9 months post-transplant. To our knowledge, the patient is the first case with IL-12/IFN-γ pathway defect and severe lymphedema. We have also revie...
Bone Marrow Transplantation, 1998
Timing of transplantation in the chronic phase of chronic myeloid leukemia (CML) and previous treatment with interferon remains controversial. We have tried to discover what influence pretreatment with interferon alpha (IFN-A) has on the results of allogeneic bone marrow transplantation for CML patients treated in a single institution. Fifty-one consecutive patients with chronic phase Ph-positive CML who received an allogeneic bone marrow transplantation from a HLAidentical familial donor were evaluated. Thirty had been treated with IFN-A (IFN+ group) prior to BMT and twenty-one had not (IFN− group). Both groups were homogeneous for clinical characteristics such as age, sex, previous chemotherapy, disease status, and time from diagnosis to transplant. No difference was found in neutrophil and platelet count recovery between the IFN+ and IFN− group. The incidence of acute and chronic GVHD, VOD and severe mucositis was not significantly different. Relapse and both overall survival and DFS were similar for both groups. No adverse effects of prior IFN exposure on the outcome of HLAidentical sibling donor BMT for chronic phase CML patients were found in this study.
Interferon Alpha Treatment of Patients with Impaired Interferon Gamma Signaling
Journal of Clinical Immunology, 2013
Patients with deficiency in the interferon gamma receptor (IFN-γR) are unable to respond properly to IFN-γ and develop severe infections with nontuberculous mycobacteria (NTM). IFN-γ and IFNα are known to signal through STAT1 and activate many downstream effector genes in common. Therefore, we added IFN-α for treatment of patients with disseminated mycobacterial disease in an effort to complement their IFN-γ signaling defect. We treated four patients with IFN-γR deficiency with adjunctive IFN-α therapy in addition to best available antimicrobial therapy, with or without IFN-γ, depending on the defect. During IFN-α treatment, ex vivo induction of IFN target genes was detected. In addition, IFN-α driven gene expression in patients' cells and mycobacteria induced cytokine response were observed in vitro. Clinical responses varied in these patients. IFN-α therapy was associated with either improvement or stabilization of disease. In no case was disease exacerbated. In patients with profoundly impaired IFN-γ signaling who have refractory infections, IFN-α may have adjunctive antimycobacterial effects.