Abstract
In the UK, unrelated cord blood transplantation (UCBT) has been used increasingly in adults since 2000. National guidelines were published in 2009 (Shaw et al, 2009) and two national prospective clinical trials have been established (EUDRACT registrations; RIC 2004-003845-41 and MAC 2009-011818-21). However, national trends and outcomes have never been comprehensively appraised. We have therefore analysed the demographic data and outcomes in adults (>18 years) undergoing UCBT in 23 UK transplant centres from 2000-2012 using the BSBMT and Eurocord databases.
From the first adult UCBT in 2000 to the end of 2102 there were a total of 176 centre UCBT registrations with corresponding cord blood bank data, including 28 patients in the national prospective clinical trials which have been excluded from any further analysis. Outcomes were analysed for 148 patients with a median age of 40.8 (range 18-72) years, with acute leukaemia (n=80), myeloproliferative disorders/myelodysplastic syndrome (MDS) (n=43), lymphoproliferative diseases (n=20) or bone marrow failure (n=5). Half the activity was between 2000-2008 and half between 2009-2012, reflecting a greater than doubling of activity in recent years. Various conditioning regimens were used, with the majority receiving a reduced intensity conditioning regimen. Most patients (72%) received double cord blood units (dCBU) and the remainder a single CBU. Recorded median total cell dose infused was 3.61 x107/kg (range 0.41-34.35) for total nucleated cell count (TNC) and 1.69 x105/kg (range 0.13-14.97) for CD34+ cells. Engraftment of neutrophils to >0.5 x109/L occurred at a median of 22 (range 3-52) days and platelets to >20 x109/L at a median of 39 (range 10-117) days. Overall survival at 1 year was 46.4% (CI 38.8-55.5%) and 2 years was 40% (CI 32-49%), with an overall median survival of 27.1 (range 3.2-83.7) months. The incidence of grade II to IV acute graft-versus-host disease (GVHD) was 17.6% (CI 11.5-24.8%) and chronic GVHD at 1 year was 11.4% (CI 6.7-17.6%). In patients treated for malignant disease with remission status available (n=137), cumulative incidence of relapse was 11.0% (CI 6.4-16.9%) at 100 days and 24.6% (CI 17.5-32.4%) at 1 year, and treatment related mortality was 22.6% (CI 16.0-30.0%) at 100 days and 34.6% (CI 26.5-42.7%) at 1 year. In univariate analysis, overall survival (OS) at 2 years was strongly related to stage of disease; 54% for early (CR1, chronic phase, MDS subtype-RA, good remission) versus 47% for intermediate (CR2, accelerated phase, MDS transformation, PR) versus 21% for advanced (non-remission, other subtypes of MDS) (p=0.0001). There was no impact of gender, age, diagnosis, intensity of conditioning regimen, use of serotherapy in the conditioning regimen, CBU number, TNC or CD34+ dose, HLA or ABO matching, or year of UCBT (2000-08 versus 2009-12) on OS. In a subgroup analysis of acute leukaemia, the relationship between 2 year OS and disease status was stronger; 60% for early versus 43% for intermediate versus 0% for advanced (p=0.000008), with improved survival outcomes with the use of dCBU over single unit UCBT (50% vs 34%), although this did not achieve significance (p=0.15).
This retrospective national analysis supports the evolution of UCBT as an effective treatment in adults without an otherwise available donor. Outcomes are comparable to similar patient groups treated with unrelated blood and marrow transplantation. The best outcomes are achieved in early and intermediate risk disease. The benefit of national guidelines is supported by more than doubling of activity since publication in 2009 without deterioration in outcomes. Whether the national prospective clinical trials will deliver improved UK outcomes will be determined following initial analysis in 2014.
Reference
Shaw BE, et al. Recommendations for a standard UK approach to incorporating umbilical cord blood into clinical transplantation practice: conditioning protocols and donor selection algorithms. Bone Marrow Transplantation 2009;44:7-12
Disclosures:
Gluckman: Cord use: Honoraria; gamida: Honoraria.
Anatomy of a Successful Practice-Changing Study: A Blood and Marrow Transplantation Clinical Trials Network-National Cancer Institute Cooperative Group Collaboration
