Antibiotic Prophylaxis Does Not Impact GVHD Occurrence After Transplant

Omitting the use of prophylaxis antibiotics for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) may reduce the risk of developing graft-versus-host disease, according to new research published in Transplantation and Cellular Therapy.

Researchers at University Hospital Bonn in Bonn, Germany, provided an analysis of patient outcomes at their institution before and after suspending antibiotic prophylaxis for patients undergoing allo-HSCT. Since patients undergoing this procedure are at risk of developing life-threatening blood stream infections, many transplant centers use antibiotic prophylaxis.

GVHD occurs when the donated cells received during allo-HSCT attack the host’s cells. Typically, aGVHD occurs within the first 100 days after the transplant with symptoms mostly affecting skin, gastrointestinal tract or liver. GVHD can be life-threatening, and chronic GVHD, which can appear any time after the transplant and affect skin, mouth, liver, lungs, GI tract, muscles, joints or genitals, is the most common cause of death in patients receiving allo-HSCT.

Once GVHD develops, patients may be prescribed long-term immunosuppressive medicines, Jakafi (ruxolitinib), Rezurock (belumosudil), Imbruvica (ibrutinib) or Niktimvo (axatilimab).

Antibiotic prophylaxis is commonly used among patients undergoing allogeneic hematopoietic stem cell transplantation because they are at risk of developing life-threatening blood stream infections.

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Utilizing antibiotic prophylaxis was thought to prevent the development of acute GVHD (aGVHD) and reduce the frequency of BSI caused by gram-negative bacteria, but the practice is controversial. “…in recent years several clinical studies have indicated a higher risk of multi-resistant bacteria as well as an increase of aGvHD…” after the use of antibiotic prophylaxis.

The researchers’ transplant center suspended use of routine antibiotic prophylaxis starting February 2017 and assessed the impact of this decision. A total of 221 patients who received transplants between December 2012 and June 2020 were included.

The majority (61.1%) of the patients who had a transplant had acute myeloid leukemia or myelodysplastic syndrome, followed by 14.1% with non-Hodgkin lymphoma, 12.2% with myeloproliferative neoplasms, and 9.0% with acute lymphoblastic leukemia. Most (56.6%) of them also received their cells from a matched related donor, while 14.5% received from a mismatched unrelated donor, and 7.7% received a haplo-identical graft.

A total of 101 (45.7%) of patients received antibiotic prophylaxis compared with 120 (54.3%) who did not. Overall, 22 (18.3%) patients without prophylaxis needed treatment in the intensive care unit for severe infections until 30 days after transplant compared with 12 (11.9%) patients who received prophylaxis. However, the researchers noted the difference did not reach statistical significance. There was also a statistically not significant increase of blood stream infections among patients without prophylaxis vs with (29.2% vs 20.8%).

Among the prophylaxis group, 37 (36.6%) patients had no aGVHD. Similarly 43 (35.8%) patients without antibiotic prophylaxis had no aGVHD. While fewer patients on prophylaxis developed low-grade aGVHD, there was a tendency toward reduced severe aGVHD for patients not on prophylaxis. Among patients with antibiotic prophylaxis, 36 (35.6%) developed grade 1-2 aGVHD and 28 (27.7%) developed severe grade 3-4 aGVHD compared with 52 (43.3%) and 25 (20.8%) patients in the non-prophylactic group.

There was no impact on mortality based on prophylaxis regimen. Overall, 15.3% of patients on prophylaxis and 8.3% not on it had relapse-related mortality.

The retrospective, observational nature of the study design means there may be unmeasured confounding effects. The researchers also noted that the 10-year timeframe of the study may be a limitation since progress has been made in the field during that time.

While the findings support evidence that omitting antibiotic prophylaxis is non-inferior to administering prophylaxis, they strongly recommend closely monitoring patients who do not receive antibiotic prophylaxis and intervening quickly if infection is suspected.

“Although the present study cannot distinguish the sole impact of the absence of antibiotic prophylaxis from additional improvements in allo-HSCT with regards towards the trend to a better outcome, it strongly supports larger studies to assess the potential benefits of allo-HSCT without use of antibiotic prophylaxis,” they concluded.