scholarly journals Influence of Nucleated Cell Dose on Overall Survival of Unrelated Cord Blood Transplantation for Patients with Severe Acquired Aplastic Anemia: A Study by Eurocord and the Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation

2011 ◽  
Vol 17 (1) ◽  
pp. 78-85 ◽  
Author(s):  
Regis Peffault de Latour ◽  
Duncan Purtill ◽  
Annalisa Ruggeri ◽  
Guillermo Sanz ◽  
Gerard Michel ◽  
...  
Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3394-3394
Author(s):  
John A Snowden ◽  
Robert Danby ◽  
Annalisa Ruggeri ◽  
David I Marks ◽  
Rachael E Hough ◽  
...  

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.


Blood ◽  
2013 ◽  
Vol 121 (6) ◽  
pp. 1059-1064 ◽  
Author(s):  
Thomas Daikeler ◽  
Myriam Labopin ◽  
Annalisa Ruggeri ◽  
Alessandro Crotta ◽  
Mario Abinun ◽  
...  

Key Points Autoimmune diseases do occur after CBT in approximately 5% of patients. Of these, AIHA or ITP were observed the most often and were treated with prednisone, CSA, and RTX.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 155-155
Author(s):  
Frederic Baron ◽  
Ruggeri Annalisa ◽  
Eric Beohou ◽  
Myriam Labopin ◽  
Guillermo Sanz ◽  
...  

Abstract BACKRGOUND. Non-relapse mortality (NRM) is the first cause of treatment failure after unrelated cord blood transplantation (UCBT) following myeloablative conditioning (MAC). In the last decade, reduced-intensity conditionings (RIC) for UCBT have been developed with the aim of reducing NRM and allowing older patients and those with medical comorbidities to benefit from UCBT. The aim of our retrospective registry study was to compare outcomes of acute leukemia (AL) adult patients given UCBT after either RIC or MAC regimens. Regimens were classified as MAC or RIC based on EBMT criteria. PATIENTS AND METHODS. Data from 1352 adult (> 18 yrs) patients with AL (acute myeloid leukemia [AML; n=894] or acute lymphoblastic leukemia [ALL; n=458]) given a first single or double UCBT from 2004 to 2013 at EBMT-affiliated centers were included in this retrospective study. RESULTS. 518 patients were given UCB after RIC, while 834 patients were administered MAC. The most frequently used conditioning regimens combined either TBI, cyclophosphamide and Flu (TCF regimen, given in 22% of MAC vs 75% of RIC recipients, P<0.001), or thiotepa, Bu and Flu (TBF, given in 32% of MAC vs 6% of RIC recipients, P<0.001). In comparison to MAC recipients, RIC recipients were almost 2 decades older (median age 52.5 vs 33.7 yrs, P<0.001), were more often transplanted for AML (80% vs 57%, P=0.001), received more frequently 2 cord blood units (61 vs 32%, P<0.001), received more frequently units with > or = 2 HLA-mismatches (69% vs 58%, P<0.001), received more TNC (median 3.5x10E7 vs 2.9x10E7, P<0.001), and received less frequently ATG in the conditioning (23% versus 57%). Disease status at UCBT was comparable in both groups (51% of patients in CR1 and 17% >CR). Median follow-up for survivors was 25 months. In univariate analyses, in comparison to patients given MAC, RIC recipients had a similar rate of neutrophil engraftment (89.5 vs 89%, P=0.7), and a similar incidence of grade II-IV acute (34% vs 29%, P=0.1) and chronic (22% vs 26%, P= 0.22) GVHD. In contrast, at 2-yr, RIC recipients had a higher incidence of disease relapse (41 vs 24%, P<0.001) but a lower NRM (19 vs 37%, P<0.001), translating to similar leukemia-free survival (LFS, 40% vs 38%, P=0.6) but better overall survival (OS, 47 vs 42%, P=0.01) than MAC recipients (Figure 1). Further, among ALL patients, the use of TCF regimen (n=159) was associated lower NRM (21 vs 40% at 2-yr, P<0.001), lower relapse incidence (24 vs 34%, P=0.07), and better OS (63 vs 34%, P<0.001) and LFS (55 vs 27%, P<0.001). We performed separate multivariate analyses (MVA) for patients with AML and ALL. In MVA for AML patients, the use of RIC regimen was associated with a higher incidence of relapse (HR=1.6, P=0.005) but a suggestion for lower NRM (HR=0.7, P=0.1) translating to similar OS (HR=1.0, P=0.9) and LFS (HR=1.1, P=0.3). Similarly, in MVA for ALL patients, the use of RIC regimen was associated with a higher incidence of relapse (HR=2.0, P=0.002) but a lower NRM (HR=0.6, P=0.04) translating to similar OS (HR=0.8, P=0.2) and LFS (HR=1.1, P=0.5). Further, interestingly, conditioning with TCF-based regimen was associated with a lower incidence of relapse (HR=0.5, P=0.004) translating into better OS (HR=0.6, P=0.013) and LFS (HR 0.6, P=0.002) in ALL patients in MVA adjusted for conditioning intensity (RIC vs MAC). CONCLUSIONS. These data suggest that LFS and OS might be as good with RIC than with MAC in adults AL patients offered UCBT. These observations could serve as basis for future prospective randomized studies. Figure 1. Unadjusted UCBT outcomes in patients transplanted following RIC versus MAC. Figure 1. Unadjusted UCBT outcomes in patients transplanted following RIC versus MAC. Disclosures Milpied: Celgene: Honoraria, Research Funding. Sierra:Amgen: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Mohty:Janssen: Honoraria; Celgene: Honoraria. Schmid:Neovii: Consultancy; Janssen Cilag: Other: Travel grand.


Sign in / Sign up

Export Citation Format

Share Document