Reduced GVHD Prophylaxis Possible in Pediatric Acute Leukemia

Muna Qayed, MD

The risk for graft-vs-host disease (GVHD) is low in children aged 2 to 12 years with acute leukemia, suggesting these patients may be good candidates for reduced preventative measures.

In a retrospective analysis of data on 476 patients collected in the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, investigators determined that, compared to patients aged 13 to 18 years, patients aged 2 to 12 years had a lower risk for grade 2 to 4 acute GVHD (hazard ratio [HR], 0.42; 95% CI, 0.26-0.70; P = .0008), grade 3/4 acute GVHD (HR, 0.24; 95% CI, 0.1-0.56; P = .001), and chronic GVHD (HR, 0.32; 95% CI, 0.19-0.54; P <.001).

Patients younger than 18 years with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) in first or second complete remission (CR) who received myeloablative, T cell-replete matched sibling donor bone marrow transplantation and calcineurin inhibitor-based GVHD prophylaxis from 2000 to 2013 were included in the analysis. Patients who received a lymphocyte depleting antibody (ATG/Campath) within the conditioning regimen were excluded.

“Our results indicate that children aged 2 to 12 years are at very low risk for GVHD. In this age group, the cumulative incidence of grade 3/4 acute GVHD was only 3% and chronic GVHD, most of which was mild, was only 8%,” first author Muna Qayed, MD, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, and coinvestigators wrote. “Remarkably, in our dataset, there were no cases of grade 3/4 in this age group out of 120 [hematopoietic cell transplantations (HCTs)] performed after 2004.”

Median patient age at the time of allogeneic HCT was 10.1 years. The majority of patients (47%) had AML in first CR and 8% had AML in second CR. About 20% of patients had ALL in first CR and 24% had ALL in second CR. Investigators divided patients into 3 groups using grade 3/4 acute GVHD as the primary outcome: <2 years (n = 60), 2 to 12 years (n=255), and 13 to 17 years (n = 162).

Most patients (73%) received cyclosporine and methotrexate for GVHD prophylaxis, with similar frequencies across the 3 age groups. In the youngest age group, 76% of patients received busulfan-based conditioning, whereas roughly half of the patients in the other age groups received TBI-based conditioning. Total nucleated cell (TNC) dose was higher for the youngest age group. Among the <2-year age group, 41% received a TNC dose >5 x 108/kg, whereas 14% of patients aged 2 to 12 years, and 6% of patients aged 13 to 17 years received that dose.

Qayed et al found that the 4-year risk for GVHD has declined in this population since 2000. The risk for grade 2 to 4 acute GVHD was lower for children undergoing transplantation from 2005 to 2008 (HR, 0.36; 95% CI, 0.2-0.65; P = .0007), and 2009 to 2013 (HR, 0.24; 95% CI, 0.11-0.53; P = .0004), compared with 2000 to 2004.

Similarly, the risk of grade 3/4 acute GVHD was lower for children undergoing transplantation from 2005 to 2008 (HR, 0.23; 95% CI, 0.08-0.65; P = .0056) and 2009 to 2013 (HR, 0.16; 95% CI, 0.04-0.67; P = .0126) compared with 2000 to 2004.

The cumulative incidence of grade 3/4 acute GVHD was 7% for all patients at 100 days (95% CI, 5-10). Children aged 2 to 12 years developed significantly less grade III/IV acute GVHD (3%), compared with children younger than 2 years (9%) and with those older than 13 years (14%; P <.001).

After adjusting for year of transplant, children aged 2 to 12 years also had significantly less risk for grade 3/4 acute GVHD (HR, 0.23; 95% CI, 0.1-0.54; P = .001) compared to children 13 years or older.

The cumulative incidence of chronic GVHD at 1 year posttransplant for all age groups was 16% (95% CI, 13-20). Chronic GVHD was 10% for children aged 2 to 12 years, 15% in children younger than 2 years (15%), and 27% in children aged 13 years or older (27%; P <.001).

Children aged 2 to 12 years were at significantly lower risk for chronic GVHD (HR, 0.32; 95% CI, 0.19-0.54; P <.001) compared with children 13 or older. Children younger than 2 years were also at lower risk (HR, 0.36; 95% CI, 0.16-0.82; P = .0156), but the result was not statistically significant.

Overall survival (OS) was 81% (95% CI, 78-85) at 1 year posttransplant. Transplant-related mortality was 2% (95% CI, 1-3) at 100 days and 4% (95% CI, 3-6) at 1 year. By multivariate analyses, there was no difference in OS, relapse-free survival, or leukemia-free survival between the age groups.

Qayed M, Wang T, Hemmer MT, et al. Influence of age on acute and chronic GVHD in children receiving HLA-identical sibling BMT for acute leukemia: implications for prophylaxis [published online November 16, 2017]. Biol Blood Marrow Transplant. doi: 10.1016/j.bbmt.2017.11.004.