Individualised dosing of anti-thymocyte globulin in paediatric unrelated allogeneic haematopoietic stem-cell transplantation (PARACHUTE): a single-arm, phase 2 clinical trial

Admiraal, Rick; Nierkens, Stefan; Bierings, Marc; Bredius, R.G.M.; Vliet, Ineke van; Jiang, Yilin; López-Yurda, Marta; Versluijs, A. Birgitta; Zwaan, C. Michel; Lindemans, Caroline A.; Boelens, Jaap Jan

doi:10.1016/s2352-3026(21)00375-6

Cited by 36 publications

(31 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effectiveness of this individualized dosing regimen was assessed in a cohort of 137 children receiving a cord blood graft and in a prospective, open-label, phase II clinical trial including 58 patients and 112 historical controls. Chance of successful immune recovery was significantly increased in the individualized dosing group in both studies, but no differences were seen between patients with low or high ATG exposure for severe acute GvHD (grade III-IV) and failure of the graft ( Admiraal et al, 2016 ; Admiraal et al, 2022 ).…”

Section: Serotherapymentioning

confidence: 88%

Therapeutic Drug Monitoring of Conditioning Agents in Pediatric Allogeneic Stem Cell Transplantation; Where do We Stand?

et al. 2022

View full text Add to dashboard Cite

Allogeneic hematopoietic stem cell transplantation (HSCT) is an established curative treatment that has significantly improved clinical outcome of pediatric patients with malignant and non-malignant disorders. This is partly because of the use of safer and more effective combinations of chemo- and serotherapy prior to HSCT. Still, complications due to the toxicity of these conditioning regimens remains a major cause of transplant-related mortality (TRM). One of the most difficult challenges to further improve HSCT outcome is reducing toxicity while maintaining efficacy. The use of personalized dosing of the various components of the conditioning regimen by means of therapeutic drug monitoring (TDM) has been the topic of interest in the last decade. TDM could play an important role, especially in children who tend to show greater pharmacokinetic variability. However, TDM should only be performed when it has clear added value to improve clinical outcome or reduce toxicity. In this review, we provide an overview of the available evidence for the relationship between pharmacokinetic parameters and clinical outcome or toxicities of the most commonly used conditioning agents in pediatric HSCT.

show abstract

Section: Serotherapymentioning

confidence: 88%

Therapeutic Drug Monitoring of Conditioning Agents in Pediatric Allogeneic Stem Cell Transplantation; Where do We Stand?

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Delayed CD4 cell reconstitution with higher ATG exposure post HCT infusion has been investigated by Boelens and Admiraal et al in various types of HCT in children using ATG (28). Subsequently, individualized ATG dosing regimen informed by the previous study was tested prospectively in pediatric URD HCT and showed improved early immune reconstitution (95). Similar exposure-response correlation was reported in CD34+ TCD by the same group (96).…”

Section: Optimizing Regimensmentioning

confidence: 81%

T-cell depleted haploidentical hematopoietic cell transplantation for pediatric malignancy

Takahashi

Prockop

2022

Front. Pediatr.

View full text Add to dashboard Cite

Access to allogenic hematopoietic cell transplantation (HCT), a potentially curative treatment for chemotherapy-resistant hematologic malignancies, can be limited if no human leukocyte antigen (HLA) identical related or unrelated donor is available. Alternative donors include Cord Blood as well as HLA-mismatched unrelated or related donors. If the goal is to minimize the number of HLA disparities, partially matched unrelated donors are more likely to share 8 or 9 of 10 HLA alleles with the recipient. However, over the last decade, there has been success with haploidentical HCT performed using the stem cells from HLA half-matched related donors. As the majority of patients have at least one eligible and motivated haploidentical donor, recruitment of haploidentical related donors is frequently more rapid than of unrelated donors. This advantage in the accessibility has historically been offset by the increased risks of graft rejection, graft-versus-host disease and delayed immune reconstitution. Various ex vivo T-cell depletion (TCD) methods have been investigated to overcome the immunological barrier and facilitate immune reconstitution after a haploidentical HCT. This review summarizes historical and contemporary clinical trials of haploidentical TCD-HCT, mainly in pediatric malignancy, and describes the evolution of these approaches with a focus on serial improvements in the kinetics of immune reconstitution. Methods of TCD discussed include in vivo as well as ex vivo positive and negative selection. In addition, haploidentical TCD as a platform for post-HCT cellular therapies is discussed. The present review highlights that, as a result of the remarkable progress over half a century, haploidentical TCD-HCT can now be considered as a preferred alternative donor option for children with hematological malignancy in need of allogeneic HCT.

show abstract

“…Moreover, by individualizing ATG in a prospective clinical trial has shown a significant improvement of immune reconstitution after cord blood transplantation, while not impacting GVHD probability. 16 …”

Section: Discussionmentioning

confidence: 99%

Cord blood transplantation for nonmalignant disorders: early functional immunity and high survival

et al. 2023

View full text Add to dashboard Cite

There is no consensus about the best donor for children with non-malignant disorders and immune deficiencies in the absence of a matched related donor (MRD). We now evaluate the 2-year Overall Survival after Umbilical Cord Blood Transplantation (UCBT) in patients with non-malignant disorders from 2009-2020 enrolled on a prospective clinical trial using either 5/6 or 6/6 umbilical cord blood as cell source. Patients receive a fully ablative busulfan, cyclophosphamide, and fludarabine without serotherapy. 55 children were enrolled, median age 5 mo. (range, 1-111 mo.); PID (45), metabolic (5), HLH (1), and hematologic disorders (4). Twenty-six patients had persistent infections prior to transplant. 19 (34%) were 6/6 matched, 36 (66%) were 5/6 HLA matched. The overall survival (OS) at 2 years was 91% (95% CI:79-96%) with a median follow up of 4.3 years. The median time to neutrophil and platelet recovery were 17 days (range,5-39 days) and 37 days (range,20-92 days), respectively. All but one evaluable patient achieved full donor chimerism. The cumulative incidence of aGvHD grade II-IV by day 100 was 16% (n=9). All patients with viral infections at the time of transplant cleared the infection at a median time of 54 days (range, 44-91 days). All evaluable patients have had correction of their immune or metabolic defect. We conclude that in the absence of a MRD, UCBT following myeloablative conditioning without serotherapy is an excellent curative option in young children with non-malignant disorders. This trial is registered at www.clinicaltrials.gov as NCT00950846.

show abstract

Individualised dosing of anti-thymocyte globulin in paediatric unrelated allogeneic haematopoietic stem-cell transplantation (PARACHUTE): a single-arm, phase 2 clinical trial

Cited by 36 publications

References 27 publications

Therapeutic Drug Monitoring of Conditioning Agents in Pediatric Allogeneic Stem Cell Transplantation; Where do We Stand?

Therapeutic Drug Monitoring of Conditioning Agents in Pediatric Allogeneic Stem Cell Transplantation; Where do We Stand?

T-cell depleted haploidentical hematopoietic cell transplantation for pediatric malignancy

Cord blood transplantation for nonmalignant disorders: early functional immunity and high survival

Contact Info

Product

Resources

About