Efficacy and immunologic effects of extracorporeal photopheresis plus interleukin-2 in chronic graft-versus-host disease

Roger Belizaire, Haesook T. Kim, Samuel J. Poryanda, Nikola V. Mirkovic, Evelyn Hipolito, William J. Savage, Carol G. Reynolds, Marie J. Fields, Jennifer Whangbo, Tomohiro Kubo, Sarah Nikiforow, Edwin P. Alyea, Philippe Armand, Corey S. Cutler, Vincent T. Ho, Bruce R. Blazar, Joseph H. Antin, Jerome Ritz, Robert J. Soiffer, John Koreth

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Chronic graft-versus-host disease (cGVHD) affects >50% of hematopoietic stem cell transplant patients. Extracorporeal photopheresis (ECP), an immunomodulatory therapy, provides clinical benefit in steroid-refractory (SR) cGVHD, possibly via regulatory T (T reg) and natural killer (NK) cell expansion. We demonstrated that low-dose interleukin-2 (IL2) led to clinical improvement in SR-cGVHD and stimulated preferential T reg and NK-cell expansion with minimal effect on conventional T (T con) cells. We evaluated the effect of ECP (weeks 1-16) plus IL2 (1 × 10 6 IU/m 2, weeks 9-16) in 25 adult patients with SR-cGVHD in a prospective phase 2 trial. Objective responses occurred in 29% and 62% of evaluable patients at weeks 8 (ECP alone) and 16 (ECP plus IL2), respectively. Eight weeks of ECP alone was associated with a marked decline in CD4 + T con ( P = .03) and CD8 + T cells ( P = .0002), with minimal change in T reg cells, T reg:T con cell ratio, or NK cells. Adding IL2 induced an increase in T reg cells ( P < .05 at weeks 9-16 vs week 8), T reg:T con cell ratio ( P < .0001 at weeks 9-16 vs week 8), and NK cells ( P < .05 at weeks 9-16 vs week 8). Patients responding to ECP alone had significantly fewer CD4 + T con and CD8 + T cells at baseline compared with patients who responded after IL2 addition and patients who did not respond; neither T reg nor NK cells were associated with response to ECP alone. Altogether, ECP plus IL2 is safe and effective in patients with SR-cGVHD. ECP and IL2 have distinct immunologic effects, suggesting different therapeutic mechanisms of action. This trial was registered at www.clinicaltrials.gov as #NCT02340676.

Original languageEnglish (US)
Pages (from-to)969-979
Number of pages11
JournalBlood Advances
Volume3
Issue number7
DOIs
StatePublished - Apr 9 2019

Bibliographical note

Publisher Copyright:
© 2019 by The American Society of Hematology.

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural

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