Use of alternative donors in HSCT (Europe)

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2 Use of alternative donors in HSCT (Europe) Passweg JR, Baldomero H, Bader P et al (2015) Hematopoietic SCT in Europe 2013: recent trends in the use of alternative donors showing more haploidentical donors but fewer cord blood transplants. Bone Marrow Transplant Apr;50(4):

3 Demographics and outcomes of unrelated CB transplantation in UK Eurocord database All unrelated CB transplants in UK to 31 st December 2012 Children (<18 years) with Paul Veys Adult ( 18 years) with John Snowden Single or double CBT (no experimental) CBT in prospective study (MAC/RIC) removed from analysis of outcomes

4 526 CBT preformed in UK and reported to Eurocord 343 paediatric / 183 adult 489 analysed (*) 335 paediatric 154 adult Adult Paeds * 37 excluded due to experimental CBT or prospective study

5 UK experience of unrelated cord blood transplantation in paediatric patients. Veys P*, Danby R*, Vora A, Slatter M, Wynn R, Lawson S, Steward C, Gibson B, Potter M, de la Fuente J, Shenton G, Cornish J, Gennery A, Snowden JA, Bonney D, Velangi M, Ruggeri A, Gluckman E, Hough R, Rocha V; British Society of Blood and Marrow Transplantation and Eurocord. Br J Haematol Feb;172(3):482-6.

6 Non malignant (n = 168)

7 Overall Survival Non-malignant By diagnosis 75% 75% p = 0.06 Histiocytosis Immune Metabolic BM Failure Metabolic Years Time (Years)

8 Malignant (n = 167)

9 Overall Survival Malignant Acute leukaemia 65% 52% ALL AML Time (Years) Time (Years)

10 Overall Survival TNC dose (x 10 7 /kg) Non-malignant Malignant p = % 59% TNC Q1 TNC Q2-4 p = TNC<Median TNC>Median 65% 41% Time (Years) Time (Years)

11 Overall Survival HLA-matching Non-malignant Malignant p = 0.12 HLA 6/6 HLA 5/6 HLA 4/6 p = HLA 6/6 HLA 5/6 HLA 4/6 75% 48% 33% Time (Years) Time (Years)

12 Non-malignant Univariate Multivariate (Backward)

13 Malignant Univariate Multivariate (Backward)

14 Other outcomes

15 Unrelated Cord Blood Transplantation in adults: evolution, experience and long-term outcomes in the UK National Health Service: a retrospective analysis on behalf of the BSBMT and Eurocord. Snowden JA*, Danby R*, Ruggeri A, Marks DI, Hough RE, Pagliuca A, Potter M, Russell N, Craddock C, Clark A, Miller P, Cook G, Gluckman E, Shaw BE, Rocha V. Br J Haematol Feb;172(3):

16 Summary (n = 154)

17 Overall Survival All cord blood transplants By diagnosis 36% ALL/AML NHL/HL/Myeloma MDS/MP/AA Years Years

18 Overall Survival Disease status at transplant Acute leukaemia only CR1 >=CR2 Active p < p < CR1 >=CR2 Active 56% 38% Years Years

19 Overall Survival T cell depletion (all transplants) Acute leukaemia only T-replete T-deplete p = P = T-replete T-deplete 49% 23% Years Years

20 Univariate Multivariate (Backward)

21 Engraftment Neutrophil Platelet Neutrophil Median 22 days 78% Platelets Median 40 days 65% Days Days

22 GvHD Acute (II-IV) Chronic (all grades) Acute GvHD 29% Chronic GvHD 28% Days Years

23 NRM/Relapse Non-relapse mortality Relapse Non-relpase mortality 37% Relapse 32% Years Years

24 Summary In UK, initial use CB transplantation was slow; peaking around 2010 Encouraging and reassuring outcomes of CBT in UK Comparable (if not superior) to other similar series e.g.1 Eapen 2007 outcomes in 503 children with acute leukaemia 5yr OS for CBT 6/6 = 60% (75%), 5/6 = 45% (48%), 4/6 = 33% (33%) TRM 38% (24%) and relapse 24% (27%) e.g.2 Rocha and Gluckman 2009 outcomes in 279 children with nonmalignant disease 100 month survival 49% (85%) Reflective of lower proportion with BMF, higher cell dose and improved HLA-matching Comparison of CBT vs haploidentical??

25 Prof Vanderson Rocha Prof John Snowden Prof Paul Veys Eurocord Prof Eliane Gluckman Dr Annalisa Ruggeri Chantal Kenzey NHS Blood and Transplant Oxford University Hospitals NHS Trust Dr Andy Peniket Anthony Nolan Prof Alejandro Madrigal Henny Braund