Current Prophylaxis and Treatment Approaches for Acute Graft-Versus-Host Disease in Haematopoietic Stem Cell Transplantation for Children With Acute Lymphoblastic Leukaemia

Wölfl, Matthias; Qayed, Muna; Benítez‐Carabante, María Isabel; Sýkora, T.; Bönig, Halvard; Lawitschka, Anita; Heredia, Cristina Diaz de

doi:10.3389/fped.2021.784377

Cited by 4 publications

(5 citation statements)

References 189 publications

(250 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar findings from a national study in South Korea reported increased early NRM following allogeneic HCT in AML patients over 20 years of age compared to younger patients [27]. Moreover, a recent review highlighted studies reporting a lower incidence of severe acute GVHD among pediatric recipients compared to adults [28], with GVHD incidence increasing with age within pediatric cohorts [29]. Taken together, these insights demonstrate age-related differences in HCT outcomes and emphasize the importance of tailored approaches for distinct patient groups.…”

Section: Discussionsupporting

confidence: 65%

Hematopoietic Cell Transplantation Trends and Outcomes in Canada: A Registry-based Cohort Study

Seftel,

Pasic,

Parmar

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Hematopoietic cell transplantation (HCT) is an established therapy for hematologic malignancies and serious non-malignant blood disorders. Despite its curative potential, HCT is associated with substantial toxicity and health resource utilization. Effective delivery of HCT requires complex hospital-based care, which limits the number of HCT centers in Canada. In Canada, the quantity, indications, temporal trends, and outcomes of patients receiving HCT are not known. Methods: A retrospective cohort study of first transplants reported to the Cell Therapy Transplant Canada (CTTC) registry between 2000 and 2019. We determined overall survival (OS) and non-relapse mortality (NRM), categorizing the cohort into early (2000-2009) and later (2010-2019) eras to investigate temporal changes. Results: Of 18,046 transplants, 10,475 were allogeneic and 7,571 were autologous. Comparing the two eras, allogeneic transplants increased in number by 22.3%, with greater use of matched unrelated donors in the later era. Autologous transplants increased by 10.9%. Temporal improvements in NRM were observed in children and adults. OS improved in pediatric patients and in adults receiving autologous HCT. In adults receiving allogeneic HCT, OS was stable despite the substantially older age of patients in the later era. Interpretation: HCT is an increasingly frequent procedure in Canada which has expanded to serve older adults. Noted improvements in NRM and OS reflect progress in patient and donor selection, preparation for transplant, and post- transplant supportive care. In allogeneic HCT, unrelated donors have become the most frequent donor source, highlighting the importance of continued growth of volunteer donor registries. These results serve as a baseline measure for quality improvement and health services planning in Canada.

show abstract

Section: Discussionsupporting

confidence: 65%

Hematopoietic Cell Transplantation Trends and Outcomes in Canada: A Registry-based Cohort Study

Seftel,

Pasic,

Parmar

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Steroid-dependent cGvHD may be defined when prednisone doses >0.25 mg/kg per day or >0.5 mg/kg every other day are needed to prevent recurrence or progression of manifestations as demonstrated by unsuccessful attempts to taper the dose to lower levels on at least 2 occasions, separated by at least 8 weeks [ 9 ]. Several second-line treatments have been proposed for SR GvHD in both acute and chronic settings, including anti–TNF-α antibodies, mycophenolate mofetil, methotrexate, anti–IL-2R antibodies, extracorporeal photo apheresis (ECP) [ 2 , 10 – 12 ]. All these immunosuppressive drugs showed suboptimal results and are associated with high rate of complications due to profound immunosuppression [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, a difference between pediatric and adult settings is that younger children present a lower incidence of cGvHD, also related to the limited use of PBSC. Furthermore, a consistent percentage of patients receives transplantation for a non-malignant disease, making the control of transplant related mortality and prevention of severe GvHD a particularly relevant issue in pediatric HCT recipients [ 2 , 12 ]. The aim of this review is to provide a systematic review on current evidence about the use of ruxolitinib for SR GvHD in the pediatric population.…”

Section: Introductionmentioning

confidence: 99%

Ruxolitinib for the treatment of acute and chronic graft-versus-host disease in children: a systematic review and individual patient data meta-analysis

Baccelli,

Gottardi,

Muratore

et al. 2024

Bone Marrow Transplant

View full text Add to dashboard Cite

Steroid-refractory graft-versus-host disease (SR-GvHD) represents a major complication of pediatric allogenic hematopoietic stem cell transplantation. Ruxolitinib, a selective JAK 1–2 inhibitor, showed promising results in the treatment of SR-GvHD in adult trial, including patients >12 years old. This systematic review aims to evaluate ruxolitinib use for SR-GvHD in the pediatric population. Among the 12 studies included, ruxolitinib administration presented slight differences. Overall response rate (ORR) ranged from 45% to 100% in both acute and chronic GvHD. Complete response rates (CR) varied from 9% to 67% and from 0% to 28% in aGvHD and cGvHD, respectively. Individual-patient meta-analysis from 108 children under 12 years showed an ORR and CR for aGvHD of 74% and 56%, respectively, while in cGvHD ORR was 78% but with only 11% achieving CR. Treatment-related toxicities were observed in 20% of patients, including cytopenia, liver toxicity, and infections. Age, weight, graft source, previous lines of therapy, and dose did not significantly predict response, while a higher rate of toxicities was observed in aGvHD patients. In conclusion, ruxolitinib shows promising results in the treatment of SR-GvHD in children, including those under 12 years. Specific pediatric perspective trials are currently ongoing to definitely assess its efficacy and safety.

show abstract

“…Allogeneic transplants are quite successful when the donor is a human lymphocyte antigen (HLA)identical twin or matched sibling. On the other hand, patients who receive allogeneic graft from donors who are not HLA-matched siblings are at a greater risk for graft-versus-host disease (GvHD), suboptimal graft function, and delayed immune system recovery 1,2 . There are three main causes of death to be faced by HSCT patients; GvHD, relapse of primary disease and viral infections.…”

Section: Introductionmentioning

confidence: 99%

“…Whereas preemptive therapy involves starting antimicrobial therapy based on screening with a sensitive assay (e.g., polymerase chain reaction) in an attempt to detect viremia to avoid progression early infection to invasive disease. Thus, regular monitoring for CMV, EBV, and ADV is essential in HSCT patients to start pre-emptive treatment timely to prevent asymptomatic infection from progressing to disease and mortality [1][2]8 .…”

Section: Introductionmentioning

confidence: 99%

Monitoring of cytomegalovirus, Epstein-Barr virus and adenovirus infections in hematopoietic stem cell transplant recipients

Şeflek

GÜMÜŞ

Çimentepe

et al. 2023

Cukurova Medical Journal

View full text Add to dashboard Cite

Purpose: Haematopoietic stem cell transplant (HSCT) recipients with iatrogenic immunosuppression are high-risk patients for viral infections. The aim of this study was to investigate the incidence of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (ADV) infections in HSCT recipients. Materials and Methods: We prospectively monitored 35 patients aged 0-17 years who had allogeneic (n=30) and autologous (n=5) HSCT by quantitative real-time polymerase chain reaction tests for CMV, EBV, and ADV. The monitoring was performed one week before HSCT and weekly for the first 100 days, once a month up to one year after HSCT. In addition, seropositivity for viruses was analysed by Enzyme-Linked Immuno Sorbent Assay a week before transplantation. Results: Before transplantation, all 35 (100%) patients who underwent HSCT were CMV IgG positive, 30 (85.7% - 95% CI: 74.1%-97.3%) HSCT recipients were found to be EBV IgG positive. CMV infection was found in 24 (80% - 95% CI: 65.7%-94.3%), ADV infection in 11 (36.7% - 95% CI: 19.4%-53.9%) and EBV infection in 8 (26.7% - 95% CI: 10.8%-42.5%) allogeneic HSCT patients. In this group, CMV DNA viral load in 8 (26.7%) patients, of which one (3.3%) coinfected with EBV DNA and one (3.3%) with ADV DNA, was higher than 1000 copies/mL which was required for pre-emptive treatment. Among 5 autologous HSCT recipients, CMV DNA was detected in 2 patients, EBV DNA in 5 and ADV DNA in 2. Pre-emptive treatment was given to 11 (%31.4 - 95% CI: 16%-46.8%; 6 CMV, 2 EBV, 1 ADV, 1 CMV-EBV and 1 CMV-ADV infection) of 35 patients. Thus, the development of viral disease was prevented in 7 (63.6% - 95% CI: 35.2%-92.1%). Of the total 35 patients, only 2 (5.7% - 95% CI: 0.0%-13.4%) died due to viral infection. Conclusion: Early diagnosis of viral infections by prospective monitoring of viral loads in HSCT patients would be effective in preventing morbidity and mortality by ensuring timely initiation of pre-emptive therapy.

show abstract

Current Prophylaxis and Treatment Approaches for Acute Graft-Versus-Host Disease in Haematopoietic Stem Cell Transplantation for Children With Acute Lymphoblastic Leukaemia

Cited by 4 publications

References 189 publications

Hematopoietic Cell Transplantation Trends and Outcomes in Canada: A Registry-based Cohort Study

Hematopoietic Cell Transplantation Trends and Outcomes in Canada: A Registry-based Cohort Study

Ruxolitinib for the treatment of acute and chronic graft-versus-host disease in children: a systematic review and individual patient data meta-analysis

Monitoring of cytomegalovirus, Epstein-Barr virus and adenovirus infections in hematopoietic stem cell transplant recipients

Contact Info

Product

Resources

About