A research team conducted a study to identify possible risk factors for graft rejection in patients treated with hematopoietic stem cell transplantation (HCT) for bone marrow failure. Results of the study were presented at the 2021 American Society of Pediatric Hematology/Oncology (ASPHO) meeting by Anthony Sabulski, MD, of the Cincinnati Children’s Hospital Medical Center in Cincinnati, Ohio, and colleagues.

The study included patients who had been treated with HCT for severe aplastic anemia, Fanconi anemia, or Fanconi anemia-like disease. Blood samples from patients with graft rejections occurring within 2 months of HCT were compared with those of a control group. The control group had similar disease characteristics and fever but no graft rejection within 2 months of HCT. Samples were collected at 3 time points, including at baseline, on day 7, and at the time of fever.

A total of 22 patients were evaluated, and 7 patients experienced graft rejection. The median time to graft rejection after HCT was 21 days (range, 13-47). While fevers were present in patients included in each group, those with graft rejection had higher maximum temperatures (median 105.6°F) than control patients did (median 103.3°F; P =.0015).

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The maximum temperature of patients with graft rejection occurred later (median day 13) than it did for febrile control patients (median day 6; P =.0027). In addition during the time of fever, patients with graft rejection showed higher levels of the markers CXCL9 (P =.0012), BAFF (P =.0022), and sC5b-9 (P =.0266) than did febrile control patients.

On day 7, there were also higher levels of CXCL9 and BAFF in the patients with graft rejection than in the control patients, but these differences were not statistically significant. At this time point, median CXCL9 levels were 94 pg/mL in those who developed graft rejection and 44 pg/mL in controls (P =.12). Median BAFF levels were 5240 pg/mL in patients who developed graft rejection and 4708 pg/mL in the control group (P =.07).

The research team considered elevations in fever, CXCL9, BAFF, and sC5b9 to serve as warnings that graft rejection may occur, and they suggested that a high fever after day 7 warrants monitoring for graft rejection. The researchers also noted that the mechanism of inflammatory activity is unclear, and they discussed a possible role for T-cell production of interferons in this process.


Sabulski A, Myers KC, Duell A, Teusink-Cross A, Davies SM, Jodele S. Clinical and laboratory markers of impending graft rejection in pediatric hematopoietic stem cell transplant for bone marrow failure. Poster presented at: 2021 American Society of Pediatric Hematology/Oncology meeting; April 21-23, 2021; virtual.