Umbilical cord blood transplantation without in vivo T-cell depletion for children with MHC class II deficiency

Elfeky, Reem; Silva, Juliana M Furtado; Chiesa, Robert; Rao, Kanchan; Lucchini, Giovanna; Amrolia, Persis; Worth, Austen; Gaspar, Bobby; Qasim, Waseem; Veys, Paul

doi:10.1016/j.jaci.2017.10.051

Cited by 8 publications

(5 citation statements)

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“…Thirty-four patients have been reported previously. 15,21,22 Among the 155 grafts, 38 were in patients with SCID, and 117 were in patients with non-SCID PIDs. Table I shows a full list of patients' diagnoses.…”

Section: Patients' Characteristicsmentioning

confidence: 99%

New graft manipulation strategies improve the outcome of mismatched stem cell transplantation in children with primary immunodeficiencies

Elfeky

Shah

Unni

et al. 2019

Journal of Allergy and Clinical Immunology

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Background: Mismatched stem cell transplantation is associated with a high risk of graft loss, graft-versus-host disease (GvHD), and transplant-related mortality. Alternative graft manipulation strategies have been used over the last 11 years to reduce these risks. Objective: We investigated the outcome of using different graft manipulation strategies among children with primary immunodeficiencies. Methods: Between 2006 and 2017, 147 patients with primary immunodeficiencies received 155 mismatched grafts: 30 T-cell receptor (TCR) ab/CD19-depleted grafts, 43 cord blood (CB) grafts (72% with no serotherapy), 17 CD34 1 selection with Tcell add-back grafts, and 65 unmanipulated grafts. Results: The estimated 8-year survival of the entire cohort was 79%, transplant-related mortality was 21.7%, and the graft failure rate was 6.7%. Posttransplantation viral reactivation, grade II to IV acute graft-versus-host disease (aGvHD), and chronic graft-versus-host disease (cGvHD) complicated 49.6%, 35%, and 15% of transplantations, respectively. Use of TCRab/ CD19 depletion was associated with a significantly lower incidence of grade II to IV aGvHD (11.5%) and cGvHD (0%), although with a greater incidence of viral reactivation (70%) in comparison with other grafts. T-cell immune reconstitution was robust among CB transplants, although with a high incidence (56.7%) of grade II to IV aGvHD. Stable full donor engraftment was significantly greater at 80% among TCRab 1 /CD19 1-depleted and CB transplants versus 40% to 60% among the other groups. Conclusions: Rapidly accessible CB and haploidentical grafts are suitable alternatives for patients with no HLA-matched donor. Cord transplantation without serotherapy and TCRab 1 / CD19 1-depleted grafts produced comparable survival rates of around 80%, although with a high rate of aGvHD with the former and a high risk of viral reactivation with the latter that need to be addressed.

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Section: Patients' Characteristicsmentioning

confidence: 99%

New graft manipulation strategies improve the outcome of mismatched stem cell transplantation in children with primary immunodeficiencies

Elfeky

Shah

Unni

et al. 2019

Journal of Allergy and Clinical Immunology

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“…Elfeky et al have reported on the use of unrelated cord blood transplantation without serotherapy in 6 patients with MHC class II deficiency, 5 of whom had chronic norovirus infection (48). Other active infections at the time of transplant included: CMV viremia, Pneumocystis jiroveci pneumonia, Echovirus meningitis, and RSV pneumonitis.…”

Section: Hematopoietic Stem Cell Transplantation For Individual Primamentioning

confidence: 99%

Hematopoietic Stem Cell Transplantation in Primary Immunodeficiency Diseases: Current Status and Future Perspectives

et al. 2019

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Primary immunodeficiencies (PID) are disorders that for the most part result from mutations in genes involved in immune host defense and immunoregulation. These conditions are characterized by various combinations of recurrent infections, autoimmunity, lymphoproliferation, inflammatory manifestations, atopy, and malignancy. Most PID are due to genetic defects that are intrinsic to hematopoietic cells. Therefore, replacement of mutant cells by healthy donor hematopoietic stem cells (HSC) represents a rational therapeutic approach. Full or partial ablation of the recipient's marrow with chemotherapy is often used to allow stable engraftment of donor-derived HSCs, and serotherapy may be added to the conditioning regimen to reduce the risks of graft rejection and graft versus host disease (GVHD). Initially, hematopoietic stem cell transplantation (HSCT) was attempted in patients with severe combined immunodeficiency (SCID) as the only available curative treatment. It was a challenging procedure, associated with elevated rates of morbidity and mortality. Overtime, outcome of HSCT for PID has significantly improved due to availability of high-resolution HLA typing, increased use of alternative donors and new stem cell sources, development of less toxic, reduced-intensity conditioning (RIC) regimens, and cellular engineering techniques for graft manipulation. Early identification of infants affected by SCID, prior to infectious complication, through newborn screening (NBS) programs and prompt genetic diagnosis with Next Generation Sequencing (NGS) techniques, have also ameliorated the outcome of HSCT. In addition, HSCT has been applied to treat a broader range of PID, including disorders of immune dysregulation. Yet, the broad spectrum of clinical and immunological phenotypes associated with PID makes it difficult to define a universal transplant regimen. As such, integration of knowledge between immunologists and transplant specialists is necessary for the development of innovative transplant protocols and to monitor their results during follow-up. Despite the improved outcome observed after HSCT, patients with severe forms of PID still face significant challenges of short and long-term transplant-related complications. To address this issue, novel HSCT strategies are being implemented aiming to improve both survival and long-term quality of life. This article will discuss the current status and latest developments in HSCT for PID, and present data regarding approach and outcome of HSCT in recently described PID, including disorders associated with immune dysregulation.

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“…One hundred forty-seven patients have been previously reported. [25][26][27][28][29] Transplants (441/474) were evaluable for the study. For the excluded patients (33/474), the median day to mortality was 15 days.…”

Section: Patient Characteristicsmentioning

confidence: 99%

New insights into risk factors for transplant-associated thrombotic microangiopathy in pediatric HSCT

Elfeky¹,

Lucchini

Lum

et al. 2020

Blood Advances

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This study aimed to identify a risk profile for development of transplant-associated thrombotic microangiopathy (TA-TMA) in children undergoing hematopoietic stem cell transplantation (HSCT). Between 2013 and 2016, 439 children underwent 474 HSCTs at 2 supraregional United Kingdom centers. At a median of 153 days post-HSCT, TA-TMA occurred among 25 of 441 evaluable cases (5.6%) with no evidence of center variation. Sex, underlying disease, intensity of the conditioning, total body irradiation–based conditioning, the use of calcineurin inhibitors, venoocclusive disease, and viral reactivation did not influence the development of TA-TMA. Donor type: matched sibling donor/matched family donor vs matched unrelated donor vs mismatched unrelated donor/haplo-HSCT, showed a trend toward the development of TA-TMA in 1.8% vs 6.1% vs 8.3%, respectively. Presence of active comorbidity was associated with an increased risk for TA-TMA; 13% vs 3.7% in the absence of comorbidity. The risk of TA-TMA was threefold higher among patients who received >1 transplant. TA-TMA rates were significantly higher among patients with acute graft-versus-host disease (aGVHD) grades III to IV vs aGVHD grade 0 to II. On multivariate analysis, the presence of active comorbidity, >1 transplant, aGVHD grade III to IV were risk factors for TA-TMA (odds ratio [OR]: 5.1, 5.2, and 26.9; respectively), whereas the use of cyclosporine A/tacrolimus-based GVHD prophylaxis was not a risk factor for TA-TMA (OR: 0.3). Active comorbidity, subsequent transplant, and aGVHD grades III to IV were significant risk factors for TA-TMA. TA-TMA might represent a form of a vascular GVHD, and therefore, continuing control of aGVHD is important to prevent worsening of TA-TMA associated with GVHD.

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Umbilical cord blood transplantation without in vivo T-cell depletion for children with MHC class II deficiency

Cited by 8 publications

References 10 publications

New graft manipulation strategies improve the outcome of mismatched stem cell transplantation in children with primary immunodeficiencies

New graft manipulation strategies improve the outcome of mismatched stem cell transplantation in children with primary immunodeficiencies

Hematopoietic Stem Cell Transplantation in Primary Immunodeficiency Diseases: Current Status and Future Perspectives

New insights into risk factors for transplant-associated thrombotic microangiopathy in pediatric HSCT

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