Acknowledgements. Department of Hematological Malignancy and Cellular Therapy, University of Kansas Medical Center

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1 The Addition of Extracorporeal Photopheresis (ECP) to Tacrolimus and Methotrexate to Prevent Acute and Chronic Graft- Versus Host Disease in Myeloablative Hematopoietic Cell Transplant (HCT) Anthony Accurso, MD

2 Acknowledgements Anthony Accurso, Jennifer Bunch, Dean Merkel, Shaun Dejarnette, Omar Aljitawi, Jianghua He, Junqiang Dai, Thomas Yankee, Siddhartha Ganguly, Joseph McGuirk, Sunil Abhyankar Department of Hematological Malignancy and Cellular Therapy, University of Kansas Medical Center Department of Biostatistics, School of Medicine, University of Kansas Medical Center

3 Background agvhd and cgvhd cause significant morbidity any mortality in allogeneic stem cell transplant patients. agvhd 30-50% in HLA identical sibling 50-80% in MUD (Greinix) Greinix et al. Blood :

4 Background cgvhd 20-70% of allo transplant patients (Lee) 40-48% MSD 45-51% MUD (Saber) Fatal 20-40% (Greinix) Lee. Blood : Saber et al. Blood Apr 26; 119(17):

5 Background Treatment Steroids If steroid-refractory, survival is <10% at 5 years No standard therapy for acute No standard second-line therapy» Mycophenylate mofetil» Sirolimus» Rituximab» Monoclonal antibodies Ibrutinib FDA approved for chronic McGuirk et al. Pharmaceuticals (Basel) Jun; 8(2):

6 Background Extracorporeal photopheresis (ECP) Involves removing cells from a patient s body, treating with psoralens, exposing to UV light. Lymphocytes undergo apoptosis Reinfused apoptotic lymphocytes have tolerogenic effect on antigen-presenting cells. Decreased cytokine production (Bladon)

7 Background Extracorporeal photopheresis (ECP) Response rate in cgvhd 50-80% (Bredeson). May take 8-12 weeks for response to manifest (Flowers, Beaton). Limited data regarding peri-transplant prophylactic ECP Suggest reduced incidence of GVHD and possibly improved survival (Shaughnessy, Miller).

8 Background

9 Methods Single-center prospective cohort study conducted at Kansas University Cancer Center. Patients undergoing myeloablative allogeneic HSCT for treatment of hematological malignancy between January 2011 and July 2012.

10 Patients Majority of patients treated for AML Lymphoma CML Study candidates signed a written informed consent, which was approved by the Institutional Review Board (IRB) at KUMC.

11 Patients Inclusion criteria Patients undergoing myeloablative allogeneic stem cell transplant at KUMC for hematologic malignancy Exclusion criteria Patients who may not be able to tolerate ECP Patients who have received Rituximab monoclonal antibody therapy in the past 3 months.

12 Protocol Myeloablative conditioning Busulphan and cyclophosphamide Cyclophosphamide and total body irradiation (TBI). GVHD Prophylaxis Tacrolimus or cyclosporine Methotrexate ATG allowed for unrelated donors

13 Protocol Two ECP treatments prior to conditioning regimen (7-14 days prior to cells). 8 additional treatments between day 0-100

14 Protocol Patients assessed weekly until day 100 At least once every three months after day 100.

15 cgvhd Assessment

16 cgvhd Assessment

17 cgvhd Assessment

18 cgvhd Assessment

19 Results Six patients received part of the prescribed protocol. All patients who received any ECP were included in the analysis.

20 Results Explanations for patients receiving partial ECP protocol Early death from RSV pneumonia 2 treatments Relapsed AML 5 treatments CMV 2 treatments Pleural effusion from dasatinib 4 treatments

21 Results Explanations for patients receiving partial ECP protocol Progressive disease 1 treatment Acute GVHD and CMV 2 treatments

22 Table 1

23 Results 10 total agvhd events (62.5%) 7 Grade 2 (43%) 3 Grade 3-4 (18.8%) 1 Grade 3 (6.3%) 2 Grade 4 (12.5%) 1 death

24 Results 6 total cgvhd events (37.5%) 5 mild-moderate (31.3%) 1 mild 4 moderate 1 severe (6.2%)

25 Results

26 Results

27 Results

28 Toxicity No major adverse effects reported. Additional transfusion needs were minimal. 4 of 16 patients received blood products that would not otherwise have been indicated. 6 total units prbc 2 total units platelets

29 Discussion Small pilot study is too small to draw conclusions about efficacy. Acute and chronic GVHD rates were within range of previously-recorded outcomes in our cohort (majority MUD, ¼ mismatched). GVHD severity was relatively mild. AML patient outcomes were particularly encouraging.

30 Discussion Our data, along with previously reported data, suggest that large randomized controlled trial is justified. ECP was well-tolerated and increased transfusions minimally.

31 Thank you!