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

Abstract

Acute graft-versus-host disease (aGvHD) continues to be a leading cause of morbidity and mortality following allogeneic haematopoietic stem cell transplantation (HSCT). However, higher event-free survival (EFS) was observed in patients with acute lymphoblastic leukaemia (ALL) and grade II aGvHD vs. patients with no or grade I GvHD in the randomised, controlled, open-label, international, multicentre Phase III For Omitting Radiation Under Majority age (FORUM) trial. This finding suggests that moderate-severity aGvHD is associated with a graft-versus-leukaemia effect which protects against leukaemia recurrence. In order to optimise the benefits of HSCT for leukaemia patients, reduction of non-relapse mortality—which is predominantly caused by severe GvHD—is of utmost importance. Herein, we review contemporary prophylaxis and treatment options for aGvHD in children with ALL and the key challenges of aGvHD management, focusing on maintaining the graft-versus-leukaemia effect without increasing the severity of GvHD.

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

“…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.…”

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

“…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 ].…”

“…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.…”

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

“…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.…”

“…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 .…”