Hematopoietic Stem Cell Transplantation for CD40 Ligand Deficiency: Single Institution Experience

Allewelt, Heather; Martin, Paul L.; Szabolcs, Paul; Chao, Nelson J.; Buckley, Rebecca H.; Parikh, Suhag

doi:10.1002/pbc.25711

Cited by 21 publications

(10 citation statements)

References 37 publications

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“…While the only corrective treatment for HIGM is HSCT, long term data remain limited [8, 29, 30]. The USIDNET Registry currently contains limited information on 13 transplanted subjects.…”

Section: Discussionmentioning

confidence: 99%

Hyper IgM Syndrome: a Report from the USIDNET Registry

et al. 2016

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Purpose The United States Immunodeficiency Network (USIDNET) patient registry was used to characterize the presentation, genetics, phenotypes, and treatment of patients with Hyper IgM Syndrome (HIGM). Methods The USIDNET Registry was queried for HIGM patient data collected from October 1992 to July 2015. Data fields included demographics, criteria for diagnosis, pedigree analysis, mutations, clinical features, treatment and transplant records, laboratory findings, and mortality. Results Fifty-two physicians entered data from 145 patients of ages 2 months to 62 years (median 12 years); 131 were males. Using patients’ age at last entry, data from 2072 patient years are included. Mutations were recorded for 85 subjects; 82 were in CD40LG. Eighteen subjects had non-X-linked HIGM. 40 % had a normal serum IgM and 15 %, normal IgA. Infections were reported for 91 %, with pulmonary, ear, and sinus infections being the most common. 42 % had Pneumocystis jirovecii pneumonia; 6 % had Cryptosporidium. 41 % had neutropenia. 78 % experienced non-infectious complications: chronic diarrhea (n = 22), aphthous ulcers (n = 28), and neoplasms (n = 8) including colon cancer, adrenal adenoma, liver adenocarcinoma, pancreatic carcinoid, acute myeloid leukemia, hepatoma, and, in a female with an autosomal dominant gain of function mutation in PIK3CD, an ovarian dysgerminoma. Thirteen patients had a hematopoietic marrow or stem cell transplant; three had solid organ transplants. Thirteen were known to have died (median age = 14 years). Conclusions Analysis of the USIDNET Registry provides data on the common clinical features of this rare syndrome, and in contrast with previously published data, demonstrates longer survival times and reduced gastrointestinal manifestations.

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“…While the only corrective treatment for HIGM is HSCT, long term data remain limited [8, 29, 30]. The USIDNET Registry currently contains limited information on 13 transplanted subjects.…”

Section: Discussionmentioning

confidence: 99%

Hyper IgM Syndrome: a Report from the USIDNET Registry

et al. 2016

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“…In addition to previously reported results, this suggests that complications, rather than immune reconstitution, present the main problem after HSCT in patients with CD40L‐deficiency 5,8,9 . In view of such promising results, HSCT for patients with CD40L‐deficiency has been increasingly attempted and proven successful, as reported in single‐center experience reports, which provide important case studies for future research on broad cohorts of patients 4‐11 . However, negative results in larger cohorts of patients suggest that transplantations with poor prognosis have not been reported.…”

Section: Discussionmentioning

confidence: 66%

“…We, therefore, found the lowest reported GVHD rate among patients with CD40L‐deficiency. This is attributable to the effects of ATG use, promptly administered HSCTs, the pretransplant conditioning of our patients, and the consequent low risk of toxicity 4‐11 . To our knowledge, haploidentical HSCT performed in twins with unmanipulated bone marrow and GVHD prophylaxis with cyclophosphamide post‐transplant has not previously been reported.…”

Section: Discussionmentioning

confidence: 93%

Hematopoietic stem cell transplantation in CD40 ligand deficiency: A single‐center experience

Uygun

Karasu

et al. 2020

Pediatric Transplantation

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Deficiency of the CD40L, expressed on the surface of T lymphocytes, is caused by mutations in the glycoprotein CD40L (CD154) gene. Resulting defective humoral and cellular responses cause a clinical presentation that includes recurrent sinopulmonary bacterial infections, opportunistic infections, sclerosing cholangitis, neutropenia, and autoimmune manifestations. HSCT represents the only curative treatment modality. However, the therapeutic decision to use HSCT proves challenging in many cases, mainly due to the lack of a phenotype‐genotype correlation. We retrospectively reviewed patients with CD40L deficiency who were transplanted in Antalya and Göztepe MedicalPark Pediatric HSCT units from 2014 to 2019 and followed by Akdeniz University School of Medicine Department of Pediatric Immunology. The records of eight male cases, including one set of twins, were evaluated retrospectively. As two transplants each were performed on the twins, a total of ten transplants were evaluated. Conditioning regimens were predominantly based on myeloablative protocols, except for the twins, who received a non‐myeloablative regimen for their first transplantation. Median neutrophil and platelet engraftment days were 13 (range 10‐19) and 14 (range 10‐42) days, respectively. In seven of ten transplants, a CMV reactivation was developed without morbidity. None of the patients developed GVHD, except for one mild case of acute GVHD. All patients survived, and the median follow‐up was 852 days. Our data show that HSCT for patients with CD40 ligand deficiency is a potentially effective treatment for long‐term disease control.

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“…HSCT was considered late in the course of CVID when markedly end-organ damage appeared. Previous studies demonstrated that early HSCT prior to end organ damage considerably improves HSCT outcomes [83].…”

Section: Immunoglobulin Replacement Therapy ; a Shot For Prevention Omentioning

confidence: 99%

Toward the stratification and personalization of common variable immunodeficiency treatment

Aryan

Aghamohammadi

Rezaei

2016

Expert Opinion on Orphan Drugs

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INTRODUCTION; Common Variable Immunodeficiency (CVID) represents a heterogeneous group of primary immunodeficiencies characterized by recurrent infections, hypogammaglobulinemia and Downloaded by [University of California Santa Barbara] at 02:16 26 June 2016increased susceptibility to autoimmune diseases and certain malignancies. The list of genetic defects underlying hypogammaglobulinemia is growing every day. AREAS COVERED; In this paper, all identified monogenetic defects underlying CVID were summarized and their similarities and differences were discussed. To date mutation in several genes including ICOS, TNFRSF12, TNFRSF13C, TNFRSF13B, CD19, CD20, CD21, CD81, PI3K, PRKCD and LRBA have been identified to underlie CVID like phenotype. The current standard treatment for CVID is Immunoglobulin substitution. Immunomodulatory drugs for autoimmune phenotypes, HSCT for lymphoid malignancies and impaired cellular immunity are other treatments, while patient selection for these treatments are of utmost importance and justifies individualized patient treatment for CVID.EXPERT OPINION; Genetic testing is expensive and deemed unnecessary in many patients with CVID, however if done it expands our knowledge regarding genetic defects underlying CVID. Currently, CVID is diagnosed and classified based on clinical presentation and laboratory findings. Future studies may help reclassify this heterogeneous group of diseases.

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Hematopoietic Stem Cell Transplantation for CD40 Ligand Deficiency: Single Institution Experience

Abstract: Allogeneic HSCT results in excellent survival and sustained immune reconstitution in patients with CD40 ligand deficiency using both myeloablative and reduced intensity conditioning approaches and various graft sources, including bone marrow, peripheral blood, and umbilical cord blood.

Cited by 21 publications

References 37 publications

Hyper IgM Syndrome: a Report from the USIDNET Registry

Hyper IgM Syndrome: a Report from the USIDNET Registry

Hematopoietic stem cell transplantation in CD40 ligand deficiency: A single‐center experience

Toward the stratification and personalization of common variable immunodeficiency treatment

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