Abstract
Introduction: Chronic graft-versus-host disease (cGVHD) is a major cause of morbidity and non-relapse mortality in allogeneic haematopoietic stem cell transplant patients (Allo-HSCT). Extracorporeal Photopheresis (ECP) is now an established second-line treatment for steroid-refractory cGVHD. Here we report a large, multi-centre case series of 115 patients treated with ECP for cGVHD. To the best of our knowledge, this is the largest reported series of patients receiving fortnightly ECP for cGVHD.
Method:A retrospective case note audit identified 115 consecutive Allo-HSCT patients who commenced fortnightly ECP for cGVHD between 2007 and 2016 at The Christie and Central Manchester NHS Foundation Trusts. cGVHD was classified and graded using the National Institutes of Health (NIH) consensus response criteria.
Results: Median age when starting ECP was 49 years (range 18-75). 61% patients were male (n=70) and 39% Female (n=45). Underlying disease groups undergoing Allo-HSCT included Acute Leukaemia/Myelodysplastic Syndrome (n=69; 60%), Lymphoma (10%; n=12), Chronic leukaemia (13%; n=15) Myeloma (14%; n=16) and Aplastic Anaemia (3%; n=3). 24% of patients had myeloablative conditioning (n=27) and 76% had reduced-intensity conditioning (n=88). 61% (n=70) received stem cells from Voluntary Unrelated Donors (VUD) and 39% (n=45) Siblings (Sib). Patients received post Allo-HSCT GvHD prophylaxis with Calcineurin inhibitors, either alone, or in combination with Methotrexate and/or Mycophenolate Mofetil. Median time to stopping Calcineurin inhibitor post Allo-HSCT was 12 months (range 0-88). 14 patients received Donor Lymphocyte Infusions (DLI).
Median time to development of GvHD post Allo-HSCT was 5 months (range 0-33). 94% developed cutaneous cGVHD (n=108), 32% oral cGVHD (n=37), 23% gut cGVHD(n=27), 24% liver cGVHD (n=28), 11% lung cGVHD (n=13) and 26% ocular cGVHD (n=30). 49% (n=57) patients had sclerodermoid disease. 37% (n=43) had one, 31% (n=36) two, 21% (n=24) three, 9% (n=10) four and 2% (n=2) five organ involvement. All 115 patients had been previously treated with immunosuppressive drugs - 109 Prednisolone; 73 Calcineurin Inhibitors; 60 Mycophenolate mofetil and other (ATG, n=1; Basiliximab, n=1; Methotrexate, n=6; Rituximab, n=10; and Thalidomide, n=18). Median duration of ECP treatment was 12 months (range 1-27 months).
Response to ECP was assessed using NIH Criteria - 29% (n=33) Complete Response (CR), 19% (n=22) Partial Response (PR), 16% (n=18) Stable Disease (SD), 11% (n=13) Progressive Disease (PD), 17% (n=19) Death and 9% (n=10) Other. As a result of ECP treatment 26% (n=30) were able to stop steroid treatment while the remaining 74% were able to reduce their steroid dose. There was no overall difference in response between the two centres. Patients with cutaneous and oral cGVHD were more likely to achieve a PR or better (cutaneous p=0.03; oral p=0.05) but there was no difference with other organ involvement. The chance of response was not influenced by the number of organs involved.
Median Overall Survival (OS) from the date of Allo-HSCT was 110 months (range 8-221). OS was not influenced by age, donor type, diagnostic group (Acute Leukaemia/Myelodysplastic Syndrome, Lymphoma, Chronic Leukaemia, Myeloma and Aplastic Anaemia), gender or the number and type of organs involved. The only exception was oral cGVHD which was associated with a lower OS (p=0.03). Patients with cGVHD achieving a CR/PR with ECP treatment, had a significantly better OS (40 months vs. median not reached, p<0.0001).
Conclusion: ECP is an effective second line treatment for steroid-refractory and steroid-dependent cGVHD with a 50% response rate. This is not affected by the underlying diagnostic group or pattern of organ involvement, however patients with cutaneous and oral cGVHD seem to respond better. As response to ECP translates into better OS, this most likely reflects the reduction in immunosuppressive related complications. Therefore it is worth considering the use ECP treatment early in the management of cGVHD.
Disclosures
Routledge: Celgene: Honoraria; Jazz Pharmaceuticals: Honoraria; Gilead: Honoraria. Dignan:Jazz: Honoraria; Adienne: Speakers Bureau; Therakos/Mallinckrodt: Honoraria, Research Funding, Speakers Bureau; Gilead: Other: Cl for GvHD Study. Bloor:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Gilead: Honoraria; GSK: Consultancy, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees. Tholouli:Johnson and Johnson: Speakers Bureau; MSD: Speakers Bureau; Celgene: Honoraria; Giles: Speakers Bureau; Amgen: Honoraria, Speakers Bureau.
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