Management of Acute Graft-Versus-Host Disease in Children
Section snippets
Diagnosis and classification of acute GVHD
Historically, GVHD was categorized as acute or chronic based on time of presentation; GVHD before day 100 was known as acute, and after day 100 it was known as chronic. This classification was based on patients transplanted with HLA-identical sibling bone marrow (BM) after receiving myeloablative conditioning. In the last 20 years, HSCT has become more complex, particularly with the use of different stem cell sources (reviewed by Peters and colleagues elsewhere in this issue), and the
Primary (initial) treatment of aGVHD
Patients with aGVHD have traditionally continued on GVHD prophylaxis, most commonly a calcineurin inhibitor (CNI), and in some cases the CNI is combined with mycophenolate mofetil (MMF) or sirolimus. Additional therapy depends on the initial grade of aGVHD, the particular organs involved, and is discussed later.
Modification of the Starting Dose of MP for Patients with Grade II aGVHD
An important goal of therapy is to minimize complications associated with high-dose glucocorticoid therapy. Therefore, some centers have attempted to begin treatment with MP-equivalent doses less than 2 mg/kg for milder GVHD within the spectrum of aGVHD manifestations that warrant systemic therapy as shown by a large retrospective study of 733 patients.21 This approach requires further validation, particularly for patients with grades III to IV aGVHD who were not well represented in this study.
Monitoring of response and tapering glucocorticoids
All patients with aGVHD should be monitored closely. If aGVHD progresses within 3 to 4 days or no improvement is observed after 5 to 7 days of MP treatment then the GVHD is considered to be steroid refractory (SR-GVHD) and second-line therapy is required as discussed later. Progression is defined as worsening GVHD in 1 or more organ with or without amelioration in any organ.
If on the other hand, GVHD symptoms have resolved after 5 to 7 days of MP therapy, it is reasonable to attempt a taper of
Treatment of steroid-resistant acute GVHD and outcomes
Approximately half of patients with aGVHD respond to treatment with steroids as initial therapy, with approximately one-third of patients having a durable response.18, 19, 20, 46 Factors most commonly associated with a favorable response include HLA matching for the GVHD vector, use of related donor grafts, and early onset of GVHD.18 Failure of primary therapy (steroid-resistant [SR-aGVHD]) has been defined operationally as the progression of aGVHD symptoms beyond 3 to 4 days after starting MP.
Antimicrobial prophylaxis and supportive care
AGVHD is by itself profoundly immunosuppressive as are the therapies used to treat it, leading to an extraordinarily high risk for opportunistic infections and sepsis. Breakdown of skin and intestinal epithelia that occurs in more severe aGVHD forms adds to this risk. High-dose prednisone increases the risk for cytomegalovirus (CMV) reactivation.41 Similarly, invasive aspergillosis occurs more frequently in patients who develop CMV disease and in patients receiving higher doses of prednisone.43
Summary
AGVHD remains a major cause of morbidity and mortality after allogeneic HSCT in children. Currently, first-line aGVHD therapy relies on glucocorticoid-induced inhibition of inflammation and donor T cell alloreactivity, usually in combination with 1 or more of the agents chosen for aGVHD prophylaxis. Newer approaches are needed to improve the overall 50% or less durable response rates that have been achieved with systemic glucocorticoids. Because promising agents in small single-center studies
Acknowledgments
This work was supported by grant no. CA18029 from the National Institutes of Health.
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Cited by (33)
Granulocyte Colony-Stimulating Factor Is Safe and Well Tolerated following Allogeneic Transplantation in Patients with Sickle Cell Disease
2022, Transplantation and Cellular TherapyCitation Excerpt :ANC recovery was a criterion for discharge from the HSCT unit according to the standard of care. Data were collected on the severity and nature of adverse events (Common Terminology Criteria for Adverse Events 4.0 [CTCAE 4.03]), engraftment, acute GVHD (aGVHD), chimerism, and outcomes until day +100 [21]. Between January 2004 and December 2019, a total of 62 SCD patients underwent HSCT at 12 centers.
Prevention and Treatment of Acute Graft-versus-Host Disease in Children, Adolescents, and Young Adults
2020, Biology of Blood and Marrow TransplantationCitation Excerpt :While clinical trials are increasingly being conducted to test new approaches based on recent advances in GVHD biology, there remains a need for greater inclusion of pediatric patients to advance novel strategies for acute GVHD. Nearly all published studies on GVHD management focus on adults [3], with assumptions of efficacy extrapolated to pediatric patients without evidence-based data or pediatric pharmacokinetic or dose-finding studies [19]. A search of ClinicalTrials.gov was performed on September 19, 2019.
Investigating the self-perceived educational priorities of haematology nurses
2019, European Journal of Oncology NursingCitation Excerpt :One example being GvHD - a cause of significant morbidity and mortality post allogeneic SCT in children. Identification of this topic as an educational priority for respondents working with paediatric and AYA patients may also reflect the diversity of strategies in GvHD management as optimal therapies are not yet established (Carpenter and MacMillan, 2010). Given the increasing number of survivors, it is not surprising that one of the top 5 educational priorities was that of long-term side effects.
Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Children and Adolescents with Fanconi Anemia
2017, Biology of Blood and Marrow TransplantationCitation Excerpt :To circumvent this, we have instituted administration of methylprednisolone (1 mg/kg/day) for 2 weeks with the earliest sign of neutrophil recovery with the intent to dampen inflammatory response. GVHD is an important determinant of morbidity and mortality after transplantation for nonmalignant diseases [32]. We used 50 mg/kg of PT-CY for FA to reduce exposure to an alkylating agent [9] and have shown previously that 60 mg/kg of CY is well tolerated in FA [33].
Gastrointestinal tract and liver graft-versus-host disease in pediatric patients with hematopoietic progenitor cell transplantation at a tertiary care center in Mexico
2018, Revista de Gastroenterologia de Mexico
This work was supported by Grant No. CA18029 from the National Institutes of Health.