31 research outputs found
Clinical considerations in the hematopoietic stem cell transplant management of primary immunodeficiencies
No full textImproved outcome of HSCT in STAT1 gain-of-function disease following JAK inhibition bridging.
No full textGermline gain-of-function (GOF) mutations in signal transducer and activator of transcription 1 () are associated with infections, including chronic mucocutaneous candidiasis and autoimmunity. Morbidity is high, and disease manifestations can be life-threatening. Curative allogeneic hematopoietic stem cell transplantation (HSCT) historically has had poor outcomes. We identified 36 patients with STAT1 GOF disease, receiving 40 HSCT procedures in 2010-2023, in a combined effort of the EBMT-IEWP and the PIDTC. Median age at first transplant was 11 years (range 1 - 33). Indications for HSCT were combined immunodeficiency, severe and/or refractory infections, and autoimmunity. Acute GvHD occurred in 22/40 HSCT procedures; 5 patients suffered from grade III/IV acute GvHD. One patient had chronic GvHD. Overall survival was 72.2%, and event-free survival was 55.6%, markedly improved from an earlier report on HSCT for STAT1 GOF disease. Patients with an HCT-CI score of 1 or higher had worse outcome. Pre-treatment with Janus kinase (JAK) inhibitors was associated with better event-free survival
Hematopoietic stem cell transplantation in a patient with type 1 mosaic variegated aneuploidy syndrome
No full textAbstract Background Mosaic variegated aneuploidy (MVA) syndrome is a chromosomal instability disorder that leads to aneuploidies of different chromosomes in various tissues. Type 1 MVA (MVA1) is caused by mutations in the budding uninhibited by benzimidazoles 1 homolog beta (BUB1B) gene. The main clinical features of MVA1 syndrome are growth and mental retardation, central nervous system anomalies, microcephaly, and predisposition to cancers. There have been no reports of hematopoietic stem cell transplantation (HSCT) in MVA patients. Results We report an 11-year old boy diagnosed with MVA1 syndrome. The BUB1B gene mutations c.498_505delAAACTTTA and c.1288 + 5G > A were detected using the next generation sequencing (NGS) method. The patient presented with cytopenia soon after birth, but remained stable until 9 years of age, when he developed myelodysplastic syndrome associated with monosomy of chromosome 7. Due to severe dependence on blood transfusions, a TCRαβ+/CD19+ depleted HSCT was performed from a matched unrelated donor (MUD) using a treosulfan-based reduced intensity conditioning (RIC) regimen. The engraftment occurred, and no severe toxicity was observed soon after the HSCT, but on day + 47, graft rejection was detected. It was followed by prolonged pancytopenia and sepsis with multi-organ Enterococcus faecium infection, which led to the patient’s death on day + 156 after HSCT. Conclusions In conclusion, we demonstrate that RIC HSCT with TCRαβ+/CD19+ depletion was well tolerated and resulted in complete hematologic recovery in our MVA1 patient, but, unfortunately, it was followed by rapid graft rejection. This fact needs to be taken into consideration for HSCT in other MVA patients
Haematopoietic stem cell transplantation for CTLA-4 insufficiency across Europe: an EBMT Inborn Errors Working Party study
No full textSingle-Center Experience of Unrelated and Haploidentical Stem Cell Transplantation with TCRαβ and CD19 Depletion in Children with Primary Immunodeficiency Syndromes
No full textAbstractThe transplantation of stem cells from a matched unrelated donor (MUD) or a haploidentical mismatched related donor (MMRD) is a widely used variant of curative treatment for patients with primary immunodeficiency (PID). Currently, different strategies are used to reduce the risk of post-transplant complications and enhance immune reconstitution. We report the preliminary results of MUD and MMRD transplantation with TCRαβ/CD19 depletion in patients with PID (trial registered at www.clinicaltrials.gov as NCT02327351). Thirty-seven PID patients (median age, 2.6 years; range, .2 to 17) were transplanted from MUDs (n = 27) or haploidentical MMRDs (n = 10) after TCRαβ+/CD19+ graft depletion. The median numbers of CD34+ and TCRαβ+ cells in the graft were 11.7 × 106/kg and 10.6 × 103/kg, respectively. Acute graft-versus-host disease (GVHD) was observed in 8 patients (22%), without a statistically significant difference between MUDs and MMRDs; 7 of these patients had grade II acute GVHD and responded to first-line therapy, whereas 1 patient had grade IV acute GVHD with transformation to extensive chronic GVHD. Primary and secondary graft failure (nonengraftment or rejection) was observed in 10 patients (27%), 9 of whom were treated with 1 alkylating agent in the conditioning regimen. All these patients were successfully retransplanted with different rescue protocols. Preliminary data on immune reconstitution were very encouraging. Most patients had significant numbers of T lymphocytes detected on the first assessment (day +30) and more than 500 T cells/μL, on day +120. Based on our preliminary data, no significant difference was seen between MMRD and MUD hematopoietic stem cell transplantation (HSCT). With a median follow-up period of 15 months, the cumulative probabilities of overall patient survival and transplant-related mortality were 96.7% and 3.3%, respectively. Based on the results, the ability to control the main post-transplant complications and the immune reconstitution rates are the main factors leading to successful outcome in patients with PID after TCRαβ+-depleted HSCT
Outcomes of HLA-mismatched HSCT with TCRαβ/CD19 depletion or post-HSCT cyclophosphamide for inborn errors of immunity
No full text: HLA-mismatched transplants with either in vitro depletion of CD3+TCRαβ/CD19 (TCRαβ) cells or in vivo T-cell depletion using post-transplant cyclophosphamide (PTCY) have been increasingly used for patients with inborn errors of immunity (IEI). We performed a retrospective multicenter study via the EBMT registry on 306 children with IEI undergoing first transplant between 2010-2019 from an HLA-mismatched donor using TCRαβ (n=167) or PTCY (n=139). Median age at HSCT was 1.2 years (range, 0.03-19.6 years). The 3-year overall survival (OS) was 78% (95% confidence interval (CI), 71-84%) after TCRαβ and 66% (57-74%) after PTCY (p=0.013). Pre-HSCT morbidity score (hazard ratio (HR) 2.27, 1.07-4.80, p=0.032) and non-Busulfan/Treosulfan conditioning (HR 3.12, 1.98-4.92, p<0.001) were the only independent predictors of unfavorable OS. The 3-year event-free survival (EFS) was 58% (50-66%) after TCRαβ and 57% (48-66%) after PTCY (p=0.804). Cumulative incidence of severe acute GvHD was higher after PTCY (15%, 9-21%) than TCRαβ (6%, 2-9%, p=0.007), with no difference in chronic GvHD (PTCY, 11%, 6-17%; TCRαβ, 7%, 3-11%, p=0.173). The 3-year GvHD-free EFS was 53% (44-61%) after TCRαβ and 41% (32-50%) after PTCY (p=0.080). PTCY had significantly higher rates of veno-occlusive disease (14.4% versus TCRαβ 4.9%, p=0.009), acute kidney injury (12.7% versus 4.6%, p=0.032) and pulmonary complications (38.2% versus 24.1%, p=0.017). Adenoviraemia (18.3% versus PTCY 8.0%, p=0.015), primary graft failure (10%, versus 5%, p=0.048), and second HSCT (17.4% versus 7.9%, p=0.023) were significantly higher in TCRαβ. In conclusion, this study demonstrates that both approaches are suitable options in IEI patients, although characterized by different advantages and outcomes
Multicenter Experience of Hematopoietic Stem Cell Transplantation in WHIM Syndrome
No full text\ua9 2021, The Author(s). Purpose: WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is a rare disease, caused by CXCR4 gene mutations, which incorporates features of combined immunodeficiency, congenital neutropenia, and a predisposition to human papillomavirus infection. Established conventional treatment for WHIM syndrome does not fully prevent infectious complications in these patients. Only single case reports of hematopoietic stem cell transplantation (HSCT) efficacy in WHIM have been published. Methods: To summarize current information on HSCT efficacy in disease treatment, seven pediatric patients with WHIM syndrome who underwent allogeneic HSCT were identified in five centers worldwide. Results: All patients presented early after birth with neutropenia. Two of seven patients exhibited severe disease complications: poorly controlled autoimmunity (arthritis and anemia) in one and progressive myelofibrosis with recurrent infections in the other. The remaining patients received HSCT to correct milder disease symptoms (recurrent respiratory infections, progressing thrombocytopenia) and/or to preclude severe disease course in older age. All seven patients engrafted but one developed graft rejection and died of infectious complications after third HSCT. Three other patients experienced severe viral infections after HSCT (including post-transplant lymphoproliferative disease in one) which completely resolved with therapy. At last follow-up (median 6.7 years), all six surviving patients were alive with full donor chimerism. One patient 1.4 years after HSCT had moderate thrombocytopenia and delayed immune recovery; the others had adequate immune recovery and were free of prior disease symptoms. Conclusion: HSCT in WHIM syndrome corrects neutropenia and immunodeficiency, and leads to resolution of autoimmunity and recurrent infections, including warts
A Conditioning Regimen with Plerixafor Is Safe and Improves the Outcome of TCRαβ+ and CD19+ Cell-Depleted Stem Cell Transplantation in Patients with Wiskott-Aldrich Syndrome
No full textCorrection to: An International Survey of Allogeneic Hematopoietic Cell Transplantation for X-Linked Agammaglobulinemia (Journal of Clinical Immunology, (2023), 43, 8, (1827-1839), 10.1007/s10875-023-01551-2)
No full text\ua9 The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2026.Table 1 carried an erratum. The reference numbers were incorrect. The corrected table is on the next page. The original version has been corrected
