Matched versus Haploidentical Hematopoietic Stem Cell Transplantation as Treatment Options for Primary Immunodeficiencies in Children

Holzer, Ursula; Döring, Michaela; Eichholz, Thomas; Ebinger, Martin; Queudeville, Manon; Turkiewicz, Dominik; Schwarz, Klaus; Handgretinger, Rupert; Lang, Peter; Toporski, Jacek

doi:10.1016/j.bbmt.2020.09.010

Cited by 8 publications

(9 citation statements)

References 27 publications

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“…TCRαβ + /CD19 + depleted haploHSCT compares favorably with other types of transplants from related 58 and unrelated donors in the pediatric NMD setting. 33,59 Moreover, despite being characterized by high initial costs, mainly related to the process and consumables to perform TCRαβ + /CD19 + depletion, a pharmacoeconomic analysis suggests that this approach may be cost-effective as compared with HSCT from MUD.…”

Section: Discussionmentioning

confidence: 99%

TCRαβ/CD19 depleted HSCT from an HLA-haploidentical relative to treat children with different nonmalignant disorders

et al. 2022

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Several non-malignant disorders (NMDs), either inherited or acquired, can be cured by allogeneic hematopoietic stem cell transplantation (HSCT). Between January 2012 and April 2020, 70 consecutive children affected by primary immunodeficiencies, inherited/acquired bone marrow failure syndromes, red blood cell disorders or metabolic diseases, lacking a fully-matched donor or requiring urgent transplantation, underwent TCRαβ/CD19-depleted haploidentical HSCT from an HLA-partially matched relative as part of a prospective study (#NCT01810120). Median age at transplant was 3.5 years (range 0.3-16.1); median time from diagnosis to transplant was 10.5 months (2.7 for SCID patients). Primary engraftment was obtained in 51 patients, while 19 and 2 patients experienced either primary or secondary graft failure (GF), the overall incidence of this complication being 30.4%. Most GFs were observed in children with disease at risk for this complication (e.g., aplastic anemia, thalassemia). All but 5 patients experiencing GF were successfully retransplanted. Six patients died of infectious complications (4 had active/recent infections at time of HSCT), the cumulative incidence of transplant-related mortality (TRM) being 8.5%. Cumulative incidence of grade I-II acute GvHD was 14.4% (no patient developed grade III-IV acute GVHD). Only one patient at risk developed mild chronic GvHD. With a median follow-up of 3.5 years, the 5-year probability of overall and disease-free survival was 91.4% and 86.8%, respectively. In conclusion, TCRαβ/CD19-depleted haploidentical HSCT from an HLA-partially matched relative is confirmed to be an effective treatment for children with NMDs. Prompt donor availability, low incidence of GvHD and TRM make this strategy an attractive option in NMDs patients.

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Section: Discussionmentioning

confidence: 99%

TCRαβ/CD19 depleted HSCT from an HLA-haploidentical relative to treat children with different nonmalignant disorders

et al. 2022

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“…This resulted in the availability of a donor for almost all patients as well as the ability to proceed to HCT without major delays and potentially before the deterioration of the clinical status of the patient. The experience of HHCT in patients with IEIs is now being reported by multiple groups [32–34,35 ▪▪ ,36–40,41 ▪▪ ,42 ▪▪ ,43–46]. Two main platforms aimed at reducing GVHD-associated morbidity and mortality have been applied in this setting: in-vivo T-cell depletion of a T-cell replete graft with posttransplant high-dose cyclophosphamide (PT-Cy), which was developed by the Johns Hopkins Group [31,33] and ex-vivo T-cell depletion of the graft before infusion [32,41 ▪▪ ,42 ▪▪ ,43–46].…”

Section: Haploidentical Hematopoietic Cell Transplantationmentioning

confidence: 99%

“…The experience of HHCT in patients with IEIs is now being reported by multiple groups [32–34,35 ▪▪ ,36–40,41 ▪▪ ,42 ▪▪ ,43–46]. Two main platforms aimed at reducing GVHD-associated morbidity and mortality have been applied in this setting: in-vivo T-cell depletion of a T-cell replete graft with posttransplant high-dose cyclophosphamide (PT-Cy), which was developed by the Johns Hopkins Group [31,33] and ex-vivo T-cell depletion of the graft before infusion [32,41 ▪▪ ,42 ▪▪ ,43–46]. Tables 2 and 3 detail the HHCT outcomes in patients with IEIs from recent reports.…”

Section: Haploidentical Hematopoietic Cell Transplantationmentioning

confidence: 99%

“…Haploidentical transplantation was also used as a salvage therapy after graft rejection or poor graft function with declining donor chimerism results [34,35 ▪▪ ,42 ▪▪ ,43]. This is a special niche for HHCT that needs to be further explored and heavily relies on the value of rapid donor availability.…”

Section: Haploidentical Hematopoietic Cell Transplantationmentioning

confidence: 99%

“…HLA-matched related donor transplantation continues to be the gold standard [8,9]. The development of in-vivo and ex-vivo T-cell depletion techniques of the graft have made HHCT possible and is now considered a valid option for these patients [31–34,35 ▪▪ ,36–40,41 ▪▪ ,42 ▪▪ ,43–46]. Autologous gene therapy is available for a handful of IEIs and offers an option to alternative donor transplantation through well designed clinical trials, which have started to deliver impressive results [57–65].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pediatric immune deficiencies: current treatment approaches

Gonzalez¹

2021

Current Opinion in Pediatrics

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Purpose of reviewTo summarize the currently available definitive therapies for patients with inborn errors of immunity (IEIs) with a strong focus on recent advances in allogeneic hematopoietic cell transplantation (HCT) and gene therapy, including the use of alternative donors, graft manipulation techniques, less toxic approaches for pretransplant conditioning and gene transfer using autologous hematopoietic stem cells. Recent findingsIn the absence of a matched sibling or a matched related donor, therapeutic alternatives for patients with IEIs include alternative donor transplantation or autologous gene therapy, which is only available for selected IEIs. In recent years, several groups have published their experience with haploidentical hematopoietic cell transplantation (HHCT) using different T-cell depletion strategies. Overall survival and event free survival results, although variable among centers, are encouraging. Preliminary results from autologous gene therapy trials with safer vectors and low-dose busulfan conditioning have shown reproducible and successful results. Both strategies have become valid therapeutic options for patients with IEIs. A new promising and less toxic conditioning regimen strategy is also discussed. SummaryDefinitive therapies for IEIs with HCT and gene therapy are in stage of evolution, not only to refine their efficacy and safety but also their reach to a larger number of patients.

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Improving Outcomes with Haploidentical Stem Cell Transplantation [HaploSCT] in Children Using Post-transplant Cyclophosphamide: a Single Center Experience

George,

Kulkarni,

Lionel

et al. 2023

Indian J Hematol Blood Transfus

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Matched versus Haploidentical Hematopoietic Stem Cell Transplantation as Treatment Options for Primary Immunodeficiencies in Children

Cited by 8 publications

References 27 publications

TCRαβ/CD19 depleted HSCT from an HLA-haploidentical relative to treat children with different nonmalignant disorders

TCRαβ/CD19 depleted HSCT from an HLA-haploidentical relative to treat children with different nonmalignant disorders

Pediatric immune deficiencies: current treatment approaches

Improving Outcomes with Haploidentical Stem Cell Transplantation [HaploSCT] in Children Using Post-transplant Cyclophosphamide: a Single Center Experience

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