Transplantation in CTCL using TLI/ATG Conditioning

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1 Transplantation in CTCL using TLI/ATG Conditioning Liam Smyth Heidelberg (Germany), September 24-26, 2015 #EBMTLymphoma

2 65 year old male Case Report Presented in yrs ECOG 0/1 Erythrodermic skin rash Skin biopsy consistent with CTCL PUVA/Bexarotene Electron Beam Therapy CHOPx6 2 2

3 2006 Case Report Desquamating skin rash Weight loss Anorexia Circulating Sezary Cells Alemtuzumab 2011 Recurrence of erythrodermic skin reaction Alemtuzumab 3 3

4 2014 Case Report Progression of erythroderma Further weight loss Alemtuzumab Bortezomib Lenalidomide August 2014 Referred to our institution for consideration for SCT 4 4

5 SCT Referral Clinical Ongoing clinical deterioration Weight loss Anorexia ECOG 1-2 Erythroderma with desquamation Palpable bilateral Supraclavicular, Axillary and Inguinal Adenopathy?Reactive No organomegaly Investigations Lymphocytes 4.0 x10 9 /l Rising LDH Circulating Sezary Cells 5 5

6 Skin 6 6

7 Role of Allogeneic SCT in CTCL Allo SCT should be considered for patients with advanced disease who fail to respond to all primary therapies Allo Vs Auto SCT in patients with MF Significant difference in 5yr OS 79% Vs 36% at 5 yrs Substantial GvL effect in Primary CTCL Severe GvHD remains a limiting factor Optimal conditioning therapy and timing of SCT unknown 7 7

8 Rationale for ATG/TLI Conditioning Disappointing results from previous RIC transplantation strategies, with/without T cell depletion using ATG or alemtuzamab Morbidity/mortality from GvH or infection despite good CR rates Risk-adapted Strategy using Stanford approach Pre-treatment with TSEBT for debulking pre-sct ECP for persistent MRD Positivity at D

9 TLI/ATG (Stanford) Conditioning D-35 to D-2 D-11 to D-7 D-4 to D-2 D-3 D-1 D0 D+28 TSEBT 100cGy (4X/Wk) TLI 80 cgy ATG 1.5mg/kg TLI 80 cgy Start CSA TLI 80 cgy x2 PBSCT Start MMF Check PB for Circulating Sezary cells ECP Wkly x4 ECP q2 Wkly x4 ECP Monthly x4 9 9

10 TSEBT Extensive skin involvement Cytoreduction pre transplant 100cGy Fractions to total of cGy to affected area TLI 10 times in 80cGy fractions 4 Radiation fields Conditioning 2 Anterior and 2 Posterior Include all major lymphoid organs Spleen, Thymus & Lymph nodes 10 10

11 Conditioning ATG Thymoglobulin 1.5mg/kg/d for 5 days Standard prophylaxis pre-medication 11 11

12 Ciclosporine GvHD Prophylaxis 5mg/Kg BD D-3 to D+56 Tapered post D+56 Chimerism result Mycophenolate Mofetil 15mg/Kg Sib BD; D0 to D27 MUD TDS; D0 to D40 Tapered by 10% weekly til discontinued Typically by D

13 Laboratory follow up Total and CD3 Chimerism Peripheral Blood D+28; +56; +90; +180; +270; then annually Bone Marrow D+90; +180; Flow cytometry for Sezary cell detection D+28; 3, 6, 9, 12 and 24 months ECP if persistant Sezary cells at day 28 Clinical Response Post Transplant Monitoring Documentation of clinical response at 3, 6, 9, 12 and 24mth Documentation of tumour burden in skin, Lymph nodes and Blood 13 13

14 Clinical Progress Neutropenic Fever D+6 No significant toxicities Engraftment Plts >50x10 9 /l - D+11 Neuts >0.5x10 9 /l - D+20 Discharge to Day Care follow-up D

15 D+28 MRD Positive Chimerism Total = 89% CD3 = 72% Clinical Progress ECP As per Protocol ECP Wkly x4 ECP q2 Wkly x4 ECP Monthly x

16 Clinical Progress Day post D+28 D+60 D+90 D+91 BMT MRD Positive Negative Negative Total Chimerism CD3 Chimerism 89% (PB) 98% (PB) 100% (PB) 100% (BM) 72% (PB) 99% (PB) 100% (PB) 16 16

17 Clinical Progress 17 17

18 TLI/ATG a conditioning regimen appears promising in this patient cohort Less toxicity Conclusions Risk adapted strategy Favourable reduction in GvHD rate whilst maintaining GvL effect Further clinical trials required to confirm favourable outcome of TLI/ATG conditioning in CTCL 18 18

19 Acknowledgements St. James s Hospital Dublin, Ireland Prof E Vandenberghe Dr CL Bacon Dr C Gillham Prof L Barnes Ms E Higgins (Transplant Co-Ordinator) Ms E Rowan (CNS) Ms M Moran (CNS) Belfast City Hospital, Northern Ireland Dr H McCarty EBMT LWP Group 19 19