Use of alternative donors in HSCT (Europe)

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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. 2015 Apr;50(4):476-82. 2.

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

526 CBT preformed in UK and reported to Eurocord 343 paediatric / 183 adult 489 analysed (*) 335 paediatric 154 adult 90 80 70 60 Adult Paeds 50 40 30 20 10 0 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 * 37 excluded due to experimental CBT or prospective study

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. 2016 Feb;172(3):482-6.

Non malignant (n = 168)

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

Malignant (n = 167)

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

Overall Survival TNC dose (x 10 7 /kg) Non-malignant Malignant p = 0.01 80% 59% TNC Q1 TNC Q2-4 p = 0.008 TNC<Median TNC>Median 65% 41% Time (Years) Time (Years)

Overall Survival HLA-matching Non-malignant Malignant p = 0.12 HLA 6/6 HLA 5/6 HLA 4/6 p = 0.004 HLA 6/6 HLA 5/6 HLA 4/6 75% 48% 33% Time (Years) Time (Years)

Non-malignant Univariate Multivariate (Backward)

Malignant Univariate Multivariate (Backward)

Other outcomes

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. 2016 Feb;172(3):478-81.

Summary (n = 154)

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

Overall Survival Disease status at transplant Acute leukaemia only CR1 >=CR2 Active p <0.0001 p <0.0001 CR1 >=CR2 Active 56% 38% Years Years

Overall Survival T cell depletion (all transplants) Acute leukaemia only T-replete T-deplete p = 0.004 P = 0.004 T-replete T-deplete 49% 23% Years Years

Univariate Multivariate (Backward)

Engraftment Neutrophil Platelet Neutrophil Median 22 days 78% Platelets Median 40 days 65% 0 20 40 60 80 100 Days 0 20 40 60 80 100 Days

GvHD Acute (II-IV) Chronic (all grades) Acute GvHD 29% Chronic GvHD 28% 0 20 40 60 80 100 Days Years

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

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??

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