Predictors of cGVHD Outcomes Remain Elusive in Pediatric Hematologic Malignancies

Acute graft-vs-host disease (GVHD) was the only identifiable risk factor for the development of chronic GVHD (cGVHD) in pediatric patients with hematologic malignancies who underwent allogeneic hematopoietic stem cell transplant (HSCT) from matched sibling donors, according to findings from a retrospective analysis presented at the 2025 SOHO Annual Meeting.1

“With increasing survival rates, focus on improving QOL [quality of life] becomes essential. Given that acute GVHD is a major risk factor for cGVHD, predicting occurrence of cGVHD and implementing timely interventions are critical,” Nermeen Alhawary, MD, lead study author and pediatric oncologist in the Department of Pediatric Oncology at the Children’s Cancer Hospital in Cairo, Egypt, and coauthors, wrote in the poster.

Why Study cGVHD Risk Factors and Predictors of Outcomes?

cGVHD remains the primary complication of HSCT and cause of posttransplant morbidity and mortality despite improvements in donor selection, conditioning regimens, graft manipulation, and supportive care. Within the past 10 years, 4 systemic therapies have been approved by the FDA for the treatment of patients with cGVHD, namely ibrutinib (Imbruvica), ruxolitinib (Jakafi), belumosudil (Rezurock), and axatilimab-csfr (Niktimvo).2

However, even with therapeutic intervention, cGVHD has a significant effect on patient QOL, which may be compounded by resulting adverse effects from therapy.1,2 For example, in the pivotal phase 2 AGAVE-201 trial (NCT04710576) of axatilimab, grade 3 or 4 adverse reactions included viral infection (15%), infection (pathogen unspecified, 14%), bacterial infection (8%), diarrhea (5%), fatigue (4%), decreased appetite (4%), musculoskeletal pain (3%), nausea (3%), dyspnea (3%), drug hypersensitivity (3%), pyrexia (1%), edema (1%), headache (1%), and hemorrhage (1%).3

Therefore, it is important to understand the associated risk factors and determinants of outcomes that can help tailor appropriate intervention and treatment.1

How Was the Retrospective Study Designed to Evaluate This Unmet Need?

With this in mind, investigators conducted a retrospective analysis that included 304 patients aged 0.9 to 19.3 years who underwent allogeneic HSCT with either peripheral blood or bone marrow as a stem cell source between January 2007 and December 2020. All patients had received cyclosporine and methotrexate as GVHD prophylaxis.

National Institutes of Health 2014 Consensus Criteria were used to diagnosis and score cGVHD, and univariate and multivariate analyses were performed to ascertain the strength of potential risk factors.

Are There Certain Risk Factors for cGVHD That Can Help Me Predict Outcomes?

A total of 86 patients developed cGVHD; 217 did not, reflecting an incidence rate of 28.3%. Notably, there was no overall survival (OS) difference between the 2 populations (P = .073).

Multivariate logistic regression analysis indicated that neither the source of stem cells (bone marrow vs peripheral blood; OR, 1.36; 95% CI, 0.76-2.41; P = .3) nor the presence of pretransplant fungal infections (21.67%; OR, 0.66; 95% CI, 0.38-1.14; P = .14) were significantly associated with the development of cGVHD. Notably, acute GVHD was significantly associated with the development of cGVHD (OR, 3.68; 95% CI, 2.09-6.51; P < .001).

With respect to predictors of outcome in the 55.8% (n = 48) of patients who experienced severe GVHD, none affected OS, event-free survival, or CIR. Proposed outcome predictors included multiple organ involvement (n = 61; 70.9%), liver involvement (n = 31; 36%), gastrointestinal involvement (n = 19; 22.1%), and lung cGVHD (n = 30; 28.3%). Most patients (n = 65; 75.6%) responded to steroids.

What Additional Research Is Needed to Push This Field Forward?

“Further studies are needed to identify key predictors of long-term outcomes,” the study authors concluded.

Disclosures: None were listed for Alhawary.

References

1. Alhawary N, Hafez H, Hammad M, et al. Risk factors and outcome predictors of chronic GVHD post allogenic HSCT in pediatric cancer patients: a single center experience from a LMIC setting. Clin Lymphoma Myeloma Leuk. 2025;25(suppl 1):S1014. doi:10.1016/S2152-2650(25)02777-6
2. Lee SJ, Zeiser R. FDA-approved therapies for chronic GVHD. Blood. 2025;145(8):795-800. doi:10.1182/blood.2024026633
3. Niktimvo. Prescribing information. Incyte Corporation; 2024. Accessed September 26, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761411s000lbl.pdf