mycophenolic-acid and Immunologic-Deficiency-Syndromes

Topics: Humans; Iatrogenic Disease; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Lymphoproliferative Disorders; Myasthenia Gravis; Mycophenolic Acid

In this study, our aim was to compare the outcomes of everolimus versus mycophenolate mofetil plus standard-dose tacrolimus immunosuppression in patients who received de novo kidney transplant at our center in Fukuoka, Japan.. In this retrospective, observational, single-center, inverse probability of treatment weighting analysis study, 225 recipients who underwent kidney transplant at our center between January 2013 and December 2018 were included. The variables considered were recipient age/sex, duration of dialysis, cytomegalovirus mismatch (seronegative recipient and seropositive donor), cause of end-stage renal disease, donor age/sex, and number of HLA mismatches.. Our analyses included 85 transplant recipients in the everolimus group and 141 transplant recipients in the mycophenolate mofetil group (n = 226 overall). There were no significant differences between the groups at 1 year for incidence of patient death and allograft loss, biopsy-proven acute rejection, BK virus-associated nephropathy, surgical complications, delayed graft function, and posttransplant diabetes mellitus. Incidence of cytomegalovirus infection and estimated glomerular filtration rate were significantly lower in the everolimus group than in the mycophenolate mofetil group. Posttransplant triglyceride and low-density lipoprotein were higher in the everolimus group than in the mycophenolate mofetil group. Multivariate ordered logistic analysis showed that older donor age and an acute rejection episode, but not induction with everolimus or mean tacrolimus trough concentration throughoutthe firstpostoperative year,were significant risk factors for severity of interstitial fibrosis/tubular atrophy at the 1-year protocol biopsy (P = .004 and P < .001,respectively).. Short-term outcomes with everolimus plus standard-dose tacrolimus in recipients of de novo kidney transplant were comparable to those with mycophenolate mofetil plus standard-dose tacrolimus.

Topics: Everolimus; Female; Graft Rejection; Humans; Immunologic Deficiency Syndromes; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Retrospective Studies; Tacrolimus; Treatment Outcome

Allogeneic bone marrow transplantation (alloBMT) is the only cure for many primary immune deficiency disorders (PIDD), primary immune regulatory disorders (PIRD), and inherited bone marrow failure syndromes (IBMFS).. We report the results of 25 patients who underwent alloBMT using reduced intensity conditioning (RIC), alternative donors, and post-transplantation cyclophosphamide (PTCy). In an attempt to reduce regimen-related toxicities, we removed low-dose TBI from the prep and added mycophenolate mofetil and tacrolimus for graft-versus-host disease (GVHD) prophylaxis for all donor types in the latter 14 patients. Donors were haploidentical related (n = 14), matched unrelated (n = 9), or mismatched unrelated (n = 2). The median age was 9 years (range 5 months-21 years).. With a median follow-up of 26 months (range 7 months-9 years), the 2-year overall survival is 92%. There were two deaths, one from infection, and one from complications after a second myeloablative BMT. Three patients developed secondary graft failure, one at 2 years and two at >3 years, successfully treated with CD34 cell boost in one or second BMT in two. The remaining 20 patients have full or stable mixed donor chimerism and are disease-free. The incidence of mixed chimerism is increased since removing TBI from the prep. The 6-month cumulative incidence of grade II acute GVHD is 17%, with no grade III-IV. The 1-year cumulative incidence of chronic GVHD is 14%, with severe of 5%.. This alloBMT platform using alternative donors, RIC, and PTCy is associated with excellent rates of engraftment and low rates of GVHD and non-relapse mortality, and offers a curative option for patients with PIDD, PIRD, and IBMFS.. ClinicalTrials.gov Identifier: NCT04232085.

Topics: Adolescent; Adult; Bone Marrow Failure Disorders; Bone Marrow Transplantation; Child; Child, Preschool; Cyclophosphamide; Disease-Free Survival; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Deficiency Syndromes; Infant; Infant, Newborn; Male; Mycophenolic Acid; Tacrolimus; Tissue Donors; Transplantation Conditioning; Young Adult

Immunoglobulin replacement therapy is recommended in case of severe hypogammaglobulinemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the supposed increased risk of infection in case of hypogammaglobulinemia has not been confirmed in allo-HSCT. In this study, we assessed the relationship between the gamma globulin level and the risk of infection during the 100 days following the allo-HSCT.. We gathered the weekly laboratory tests from day 7 to day 100 of 76 allograft patients, giving a total of 1 044 tests. 130 infections were documented clinically, by imaging, or microbiologically.. Average gamma globulin levels between D-7 and D100 did not differ between patients with or without infection (642 ± 232 and 671 ± 246 mg/dL, respectively, P = .65). Gamma globulin level <400 mg/dl was not associated with the occurrence of infection between the test studied and the next one (aOR 1.33 [0.84-2.15], P = .24). The gamma globulin level was not predictive of bacterial or fungal infections (AUC 0.54 [95%CI: 0.47-0.61]) nor of viral reactivations (AUC 0.51 [95%CI: 0.43-0.60]).. This confirmed that the humoral deficiency is a minor part of the immune deficiency in the 100 days post-transplant. This questions the relevance of the indications of immunoglobulin substitution during this period.

Topics: Aged; Bacterial Infections; Cyclosporine; Female; gamma-Globulins; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulins, Intravenous; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Leukemia; Lymphoma; Male; Middle Aged; Mycophenolic Acid; Mycoses; Myeloablative Agonists; Myelodysplastic Syndromes; Opportunistic Infections; Prognosis; ROC Curve; Transplantation Conditioning; Transplantation, Homologous; Virus Activation

Gain of function (GOF) mutations in PIK3CD gene encoding PI3K p110δ were recently associated with a novel combined immune deficiency characterized by recurrent sinopulmonary infections, CD4 lymphopenia, reduced class-switched memory B cells, lymphadenopathy, cytomegalovirus and/or epstein-Barr virus (EBV) viremia, and EBV-related lymphoma. A subset of affected patients also had elevated serum IgM.. We report a patient who was diagnosed with systemic lupus erythematosus (SLE) at a young age and was recently found to carry heterozygous mutations in PIK3CD. The patient not only presented with recurrent sinopulmonary infections, CD4 lymphopenia, lymphadenopathy, EBV viremia, and elevated serum IgM, but also met classification criteria of SLE based on persistent proteinuria and hematuria, leukopenia and anemia, low level of serum complement, and positive autoantibody for antinuclear antibodies.. Activated PI3Kδ syndrome.. Oral prednisolone and hydroxychloroquine combined with mycophenolate mofetil was given to the patient. He was currently receiving intravenous immunoglobulin per month in association with hydroxychloroquine, low-dose prednisolone, and mycophenolate mofetil.. At present, the level of complement restored to normal, hematuria and proteinuria disappeared, and liver function returned to normal.. SLE may be a novel phenotype of GOF mutation in PI3CKD gene (GOF PIK3CD).

Topics: Adolescent; Antibodies, Antinuclear; Asian People; Class I Phosphatidylinositol 3-Kinases; Complement System Proteins; Enzyme Inhibitors; Epstein-Barr Virus Infections; Gain of Function Mutation; Glucocorticoids; Herpesvirus 4, Human; Humans; Hydroxychloroquine; Immunoglobulins, Intravenous; Immunologic Deficiency Syndromes; Lupus Erythematosus, Systemic; Male; Mycophenolic Acid; Phenotype; Prednisolone; Primary Immunodeficiency Diseases

The autoimmune manifestations of primary immunodeficiencies, such as autoimmune lymphoproliferative syndrome (ALPS) and common variable immunodeficiency (CVID), often constitute a great therapeutic challenge and have a significant impact on patients' morbidity and mortality. The most common autoimmune presentations are autoimmune cytopenias, but organ-related autoimmunity is also frequently observed. From a pulmonology perspective, granulomatous/lymphocytic interstitial lung disease (GLILD) is a severe immunological complication which significantly worsens the clinical outcome of these patients and for which there are currently few guidelines or protocols for treatment. We present three cases where the use of Mycophenolate in the context of autoimmune cytopenias proved beneficial also on the lung disease.

Topics: Adolescent; Autoimmune Diseases; Autoimmunity; Child, Preschool; Female; Humans; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Lung Diseases; Male; Mycophenolic Acid; Treatment Outcome; Young Adult

The immunosuppressive therapy with everolimus (ERL) after heart transplantation is characterized by a narrow therapeutic window and a substantial variability in dose requirement. Factors explaining this variability are largely unknown.. Our aim was to evaluate factors affecting ERL metabolism and to identify novel metabolites associated with the individual ERL dose requirement to elucidate mechanisms underlying ERL dose response variability.. We used liquid chromatography coupled with mass spectrometry for quantification of ERL metabolites in 41 heart transplant patients and evaluated the effect of clinical and genetic factors on ERL pharmacokinetics. Non-targeted plasma metabolic profiling by ultra-performance liquid chromatography and high resolution quadrupole-time-of-flight mass spectrometry was used to identify novel metabolites associated with ERL dose requirement.. The determination of ERL metabolites revealed differences in metabolite patterns that were independent from clinical or genetic factors. Whereas higher ERL dose requirement was associated with co-administration of sodium-mycophenolic acid and the CYP3A5 expressor genotype, lower dose was required for patients receiving vitamin K antagonists. Global metabolic profiling revealed several novel metabolites associated with ERL dose requirement. One of them was identified as lysophosphatidylcholine (lysoPC) (16:0/0:0). Subsequent targeted analysis revealed that high levels of several lysoPCs were significantly associated with higher ERL dose requirement.. For the first time, this study describes distinct ERL metabolite patterns in heart transplant patients and detected potentially new drug-drug interactions. The global metabolic profiling facilitated the discovery of novel metabolites associated with ERL dose requirement that might represent new clinically valuable biomarkers to guide ERL therapy.

Topics: Adult; Aged; Biomarkers; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP3A; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Everolimus; Female; Heart Transplantation; Humans; Immune Tolerance; Immunologic Deficiency Syndromes; Immunosuppression Therapy; Immunosuppressive Agents; Lysophosphatidylcholines; Male; Metabolomics; Middle Aged; Molecular Targeted Therapy; Mycophenolic Acid; Tandem Mass Spectrometry

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is characterized by severe systemic autoimmunity caused by mutations in the forkhead box protein 3 (FOXP3) gene. Hematopoietic cell transplantation is currently the only viable option for long-term survival, but patients are frequently very ill and may not tolerate traditional myeloablative conditioning regimens.. Here we present the outcome of hematopoietic cell transplantation using a low-intensity, nonmyeloablative conditioning regimen in 2 patients with IPEX syndrome and significant pretransplant risk factors.. Two high-risk patients with IPEX syndrome received HLA-matched related bone marrow or unrelated peripheral blood stem cell grafts following conditioning with 90 mg/m(2) fludarabine and 4 Gy total body irradiation. Postgrafting immunosuppression consisted of mycophenolate mofetil and cyclosporine. Immune reconstitution and immune function was evaluated by measurement of donor chimerism, regulatory T-cell numbers, absolute lymphocyte subsets, and T-cell proliferation assays.. Both patients experienced minimal conditioning toxicity and successfully engrafted after hematopoietic cell transplantation. With a follow-up of 4 and 1 years, respectively, patients 1 and 2 have full immune function and normal FOXP3 protein expression.. A low-intensity, nonmyeloablative conditioning regimen can establish stable engraftment and correct the life-threatening immune deficiency and enteropathy of IPEX syndrome despite the presence of comorbidities that preclude conventional hematopoietic cell transplantation.

Topics: Adolescent; Cell Separation; Child; Cyclosporine; Flow Cytometry; Forkhead Transcription Factors; Genetic Diseases, X-Linked; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Infant; Male; Mycophenolic Acid; Myeloablative Agonists; Reverse Transcriptase Polymerase Chain Reaction; Syndrome; Transplantation Conditioning; Vidarabine; Whole-Body Irradiation

The authors report on a 55-year-old female patient after R1 resection of a malignant thymoma with spindle type epithelial cells (WHO type A, Masaoka stage III) referred for further therapy of an ulcerative colitis. At that time, both adjuvant radiation and cytostatic therapy were not applicable due to severe activity of the ulcerative colitis. Under immunosuppressive treatment with azathioprine and steroids, the patient developed cytomegalovirus (CMV) enteritis which was triggered by therapy-induced leukopenia. After a switch from azathioprine to mycophenolatmofetil (MMF) treatment and administration of cidofovir because of nonresponse to ganciclovir and incompatibility of foscarnet sodium (Foscavir), the patient clinically improved. In addition, the patient was treated with immunoglobulins every 3-4 weeks because of antibody deficiency. At present, 3.5 years after R1 resection, the patient still has no clues of a remaining tumor mass under current immunosuppressive therapy. Ulcerative colitis is also in complete remission stage.. This case indicates the very rare features of a syndrome with thymoma and antibody deficiency which was first described by Robert Good. Furthermore, the impact of immunosuppressive therapy and management of opportunistic infections on the course of this disease is obvious.

Topics: Agammaglobulinemia; Antiviral Agents; Azathioprine; Cidofovir; Colitis, Ulcerative; Cytomegalovirus Infections; Cytosine; Enteritis; Female; Humans; Immunization, Passive; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Leukopenia; Middle Aged; Mycophenolic Acid; Neoplasm Staging; Opportunistic Infections; Organophosphonates; Postoperative Complications; Syndrome; Thymectomy; Thymoma; Thymus Neoplasms