Using Extracorporeal Photopheresis in the Treatment of Graft-Versus-Host Disease

Akhil Kumar, MD
Published: Thursday, Jun 30, 2011

Management of GVHD

The management of a patient who has developed acute GVHD primarily includes steroids, and the durable remission rate with steroids in acute GVHD ranges from 24% to 40%.1,2,3,4 The second-line agents, such as cyclosporine, are generally less successful. A prospective phase II trial of ECP in steroidrefractory GVHD or steroid-dependent GVHD showed complete resolution of GVHD in 82% of patients with cutaneous involvement, 61% with liver involvement, and 61% with gut involvement (Table 1).5  Patients were treated on 2 consecutive days (1 cycle) at 1- to 2-week intervals until improvement and thereafter every 2 to 4 weeks until maximal response. An analysis of the relationship of response of acute GVHD to transplant-related mortality and survival was also conducted. The 4-year survival for those in whom acute GVHD had a complete resolution was 59%, which compares very favorably to the 11% of those who did not achieve complete resolution of acute GVHD. Overall, the study confirmed that ECP allows for accelerated tapering of corticosteroids, which had a significantly favorable impact on transplant-related mortality (Figure 1).

Figure 1: Relationship of Complete Resolution with ECP to Long-Term Survivala

Figure 1: survival probably higher year after year after transplantation with ECP

ECP indicates extracorporeal photophoresis; CR, complete resolution.
aAdapted from reference 5.

The treatment of chronic GVHD is determined in part by the severity of the disease. The severity is graded as either limited or extensive and is based on the clinical severity and target organs affected. Treatment is individualized and commonly includes combination of steroids with other immunosuppressants, such as cyclosporine or azathioprine. Patients with limited chronic GVHD have a favorable prognosis even without therapy, while those who have extensive GVHD, particularly those with multiorgan involvement, have poor longterm outcomes. There are numerous studies that have shown significant clinical benefit of ECP in chronic GVHD.6,7,8 The phase II study by Alcindor and colleagues included 25 patients with chronic GVHD who were treated with ECP either weekly or on 2 consecutive days once every 2 weeks. Skin improvement was shown in 71% of patients and response rates were similar in patients who were treated early (<18 months from transplant) versus late (>18 months from transplant). Steroid sparing or tapering of immunosuppression was seen in more than 80% of the patients. A correlation of the response rates with various baseline clinical characteristics is provided in Table 2.

Table 2: Correlation Between Response to ECP and Baseline Clinical Characteristicsa

Table 2: Prognostic Variable, Group, response and P Value

ECP indicates extracorporeal photophoresis.
aAdapted from reference 6.

Conclusion

The data in both acute and chronic GVHD largely are case series or single-center phase II studies. Though these data have the limitation of selection bias, the responses seen are generally very impressive in patients who are refractory to conventional measures. There are also several advantages of ECP when compared to conventional therapies. There is selective benefit in GVHD without the increased rates of infection and malignant disease relapse associated with the use of conventional immunosuppressants. In responding patients, ECP treatment can lead to a reduction and, often, a cessation of treatment with corticosteroids and other immunosuppressive agents. ECP is associated with few acute side effects from the therapy itself; these effects include occasional hypotensive episodes, mild pyrexia, and general tiredness and lethargy. There are no reported long-term side effects of this treatment, despite more than 5 years of follow-up in many patients. Analysis of survival data reveals increased survival in patients who respond. This confirms that the benefit of controlling GVHD is not lost through toxicity of the therapy or disease relapse, which are major problems with alternative therapies.


Reference

  1. Weisdorf D, Haake R, Blazar B, et al. Treatment of moderate/severe acute graftversus- host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome. Blood. 1990;75(4): 1024-1030.
  2. Martin PJ, Schoch G, Fisher L, et al. A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. Blood. 1990;76(8):1464-1472.
  3. Martin PJ, Schoch G, Fisher L, et al. A retrospective analysis of therapy for acute graftversus- host disease: secondary treatment. Blood. 1991;77(8):1821-1828.
  4. Antin JH, Chen HR, Couriel DR, et al. Novel approaches to the therapy of steroid-resistant acute graft-versus-host disease. Biol Blood Marrow Transplant. 2004;10(10):655-668.
  5. Greinix HT, Knobler RM, Worel N, et al. The effect of intensified extracorporeal photochemotherapy on long-term survival in patients with severe acute graft-versus-host disease. Haematologica. 2006;91(3):405-408.
  6. Alcindor T, Gorgun G, Miller KB, et al. Immunomodulatory effects of extracorporeal photochemotherapy in patients with extensive chronic graft-versus-host disease. Blood. 2001;98(5):1622-1625.
  7. Gonzalez Vicent M, Ramirez M, Sevilla J, Abad L, Diaz MA. Analysis of clinical outcome and survival in pediatric patients undergoing extracorporeal photopheresis for the treatment of steroid-refractory GVHD. J Pediatr Hematol Oncol. 2010;32(8):589-593.
  8. Jagasia MH, Savani BN, Stricklin G, et al. Classic and overlap chronic graft-versus-host disease (cGVHD) is associated with superior outcome after extracorporeal photopheresis (ECP). Biol Blood Marrow Transplant. 2009. 15(10):1288-1295.



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