Within 100 days of HSCT, 174 (60%) of the patients developed aGVHD. More patients who developed aGVHD received tissue from an unrelated donor (55.7% vs 37.1%; P =.003), had poor (<80%) Karnofsky performance (56.9% vs 43.1%; P =.029), and were given a prophylaxis of calcineurin inhibitors with methotrexate (79.3% vs 72.4%; P =.037). Development of aGVHD did not vary on the basis of underlying disease (P =.561).
Stratified by status, patients with and without aGVHD remained hospitalized for an average of 28 and 22 days (P <.001), respectively. Compared with patients who did not develop aGVHD, patients with grade I/II disease (n = 118) were hospitalized for 25 days (P =.04), grade III/IV disease (n = 56) for 48 days (P <.001), and patients who had lower gastrointestinal (LGI) aGVHD were hospitalized for 43 days (P <.001).
Few patients without aGVHD were transferred to the intensive care unit (ICU; 6%). Among all patients with aGVHD, transfer to the ICU was not significantly more likely (13.2%; P =.07). However, nearly a quarter of patients with more severe aGVHD (grade III/IV) required transfer to the ICU (22.3%; P =.002).
Mortality was observed among 7.8% of patients without and 14.9% of patients with aGVHD (P =.09). Early mortality occurred among 7.8% of patients without aGVHD, 25.7% of patients with LGI aGVHD (P =.001), and 33.9% of patients with grade III/IV aGVHD (P <.001).
The patients without aGVHD accrued an average cost of $165,622. The increased hospital stays and transfer to ICU resulted in average hospital charges of $226,545 among patients with aGVHD (P <.001). Compared with no disease, increasing severity associated with increased financial burden. Patients with stage I disease had nonsignificantly higher charges ($183,693; P =.44) but patients with stage II ($201,737; P =.04) or stage III/IV ($286,551; P <.001) aGVHD had significantly greater hospital costs.
Among patients with aGVHD, those without GI involvement had average bills of $177,151 which were lower than those with GI involvement ($255,283; P <.001). The treatment of upper GI aGVHD ($203,879) was less costly than LGI aGVHD ($280,290; P =.04).
Overall, increased healthcare costs were associated with grade III/IV aGVHD (cost multiplier [CM], 1.56; 95% CI, 1.39-1.77; P <.001), matched unrelated (CM, 1.5; 95% CI, 1.35-1.67; P <.001) or haploidentical (CM, 1.27; 95% CI, 1.1-1.46; P =.001) donors, noncomplete/nonpartial remission (CM, 1.23; 95% CI, 1.06-1.43; P =.007), high (³3) HCT-specific comorbidity index (CM, 1.18; 95% CI, 1.08-1.28; P <.001), and partial remission (CM, 1.15; 95% CI, 1.02-1.3; P =.022).
Conclusions and Future Perspectives
The most effective means of reducing healthcare utilization burden and cost for patients is also the best method for improving clinical outcomes of HSCT: to develop more efficacious prevention methods and treatments. In recent years, promising results from clinical trials have indicated some new therapeutic strategies may help to avoid development of aGVHD or progression to more severe disease.8
When asked about the future of HSCT, Dr. Farhadfar concluded, “in terms of prevention of acute GVHD, the use of post-transplant cyclophosphamide-based GVHD prophylaxis has been a major advance, allowing the widespread use of haploidentical transplant and decreasing severity of GVHD. In terms of the treatment of acute GVHD, we now have ruxolitinib as an approved agent that was confirmed in a phase 3 trial to be effective for treatment of steroid refractory acute GVHD. I am optimistic in the near future we will have several options to better prevent and treat this disease.”
- Farhadfar N, Leather H, Wang S, et al. Severity of acute graft-versus-host disease and associated healthcare resource utilization, cost and outcomes. Transplant Cell Ther. 2021;27(3S):S1-S488. doi:10.1016/S2666-6367(21)00050-6
- Holtan SG, DeFor TE, Lazaryan A, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125(8):1333-1338. doi:10.1182/blood-2014-10-609032
- Lazaryan A, Weisdorf DJ, DeFor T, et al. Risk factors for acute and chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation with umbilical cord blood and matched sibling donors. Biol Blood Marrow Transplant. 2016;22(1):134-140. doi:10.1016/j.bbmt.2015.09.008
- Holtan SG, Pasquini M, Weisdorf DJ. Acute graft-versus-host disease: a bench-to-bedside update. Blood. 2014;124(3):363-373. doi:10.1182/blood-2014-01-514786
- Nassereddine S, Rafei H, Elbahesh E, et al. Acute graft versus host disease: a comprehensive review. Anticancer Res. 2017;37(4):1547-1555. doi:10.21873/anticanres.11483
- Holtan SG, Hoeschen AL, Cao Q, et al. Facilitating resolution of life-threatening acute GVHD with human chorionic gonadotropin and epidermal growth factor. Blood Adv. 2020;4(7):1284-1295.doi:10.1182/bloodadvances.2019001259
- Stranges E, Russo CA, Friedman B. Procedures With the Most Rapidly Increasing Hospital Costs, 2004–2007: HCUP Statistical Brief #82. Agency for Healthcare Research and Quality; 2009.
- Farhadfar N, Burns LJ, Mupfudze T, et al. Hematopoietic cell transplantation: practice predictions for the year 2023. Biol Blood Marrow Transplant. 2020;27(2):183.e1-183.e7. doi:10.1016/j.bbmt.2020.10.006