Researchers at the University of Minnesota have published two multicenter studies, both in Bone Marrow Transplantation, highlighting the critical unmet medical need for early intervention and disease management of acute graft-versus-host disease (aGVHD) and steroid-refractory and steroid-dependent aGVHD. While HCT is a potentially curative treatment for certain hematological malignancies, aGVHD can occur and can result in poor clinical outcomes. Patients who are non-responsive to first-line corticosteroids (known as steroid-refractory) will have continued aGVHD progression and higher mortality. Moreover, patients may also experience steroid dependence and be unable to taper steroid use without worsening symptoms of GVHD. These studies sought to improve knowledge on aGVHD in the current real-world clinical settings by examining current regimens, stem cell sources, steroid dependency status, and aGVHD treatment options.

Disease progression, treatments, hospitalization, and clinical outcomes in acute GVHD: a multicenter chart review

The first study examined outcomes among patients with acute GvHD at 11 large academic community transplant centers. Data were collected for 475 patients who underwent HCT (median age at HCT was 55). The most prevalent underlying malignancies were acute myeloid leukemia (38.7%), acute lymphoid leukemia (15.8%), and myelodysplastic syndrome (14.9%). The most common HCT graft source was peripheral blood (67.7%) and the majority of patients were given a calcineurin inhibitor (tacrolimus or cyclosporine) and an additional immunosuppressive agent such as methotrexate, mycophenolate, sirolimus, or antithymocyte globulin.

Among the patients in this study, aGVHD recurred in 41.9% (grades III–IV), with recurrence being managed by increasing corticosteroid dose in 51.3%. Chronic GVHD occurred in 40.2% of patients. At a median follow-up of 524 days since acute GVHD diagnosis, 52.8% of patients died, and of the surviving patients, 23.4% of patients had an increase in steroid dose and 44.4% were unable to reduce their doses below 10 mg/day.

Mortality rates were increased in patients who had high-grade aGVHD or progressed to a higher grade from diagnosis. Patients with a grade II diagnosis that progressed had a 25.1% increase in mortality, and those with a grade III diagnosis that progressed increased by 20.1%. These finding highlight the need for effective, safe, and early treatments for aGVHD.    

Disease progression, hospital readmissions, and clinical outcomes for patients with steroid-refractory acute graft-versus-host disease: A multicenter, retrospective study

In the second study, researchers from the same group conducted an analysis of 168 patients who developed grades II–IV aGVHD after their first allogeneic HCT and were either steroid-refractory (n = 113) or -dependent (n=55). The most common type of underlying malignancies in these patients were acute myeloid leukemia (35.1%), myelodysplastic syndrome (19.0%), and acute lymphoid leukemia (16.1%). The main stem cell source was peripheral blood (73.8%). The most commonly used transplant conditioning regimens were high-dose myeloablative regimens among patients who were steroid-refractory (51.3%) and reduced-intensity regimens among patients who were steroid-dependent (47.3%).

Most patients (64.9%) had grades I–II aGVHD at diagnosis. During follow-up, 49.4% of patients progressed to a higher grade and at the time of maximum aGVHD, most patients (66.1%) had grade III or IV disease. Recurrence was related to steroid dose reduction in 80.0% of cases, including patients who were steroid-refractory and steroid-dependent. Approximately a quarter (26.8%) of all patients later developed chronic GVHD (similar for both groups).

More than half of the patients (56.5%) required hospital readmission through 100 days post-HCT with an extended length of stay. The primary reasons for hospital readmission among patients who were steroid-refractory and steroid-dependent, respectively, were aGVHD (53.5% and 39.4%) and infection (13.9% and 25.2%). Half of patients (50.6%) experienced ≥1 infection that was confirmed and required treatment between diagnosis of aGVHD and 100 days post-HCT. In conclusion, this study recommends that more successful strategies are needed for prevention of steroid-refractory and -dependent aGVHD and that additional second line and later treatment options would be needed for patients who have progressed on steroids.

Reference:

Holtan, S.G., Yu, J., Choe, H.K. et al. Disease progression, treatments, hospitalization, and clinical outcomes in acute GVHD: a multicenter chart review. Bone Marrow Transplant 57, 1581–1585 (2022). https://doi.org/10.1038/s41409-022-01764-w

Holtan, S.G., Yu, J., Paranagama, D. et al. Disease progression, hospital readmissions, and clinical outcomes for patients with steroid-refractory acute graft-versus-host disease: A multicenter, retrospective study. Bone Marrow Transplant 57, 1399–1404 (2022). https://doi.org/10.1038/s41409-022-01736-0

Tags: patient care, GVHD, HCT, Regimen, Research, Transplant, Mortality, aGVHD, cell therapy, grafts, diagnosis, steroid, malignancies, immunosuppressive, transplatation, peripheral blood, treatments, survival rate, progression, acute graft-versus-host disease, graft-versus-host, acute myeloid leukemia, recurrence