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Optimizing Post-Transplant Outcomes for Patients With MDS
Two analyses from the European Society for Blood and Marrow Transplantation ( EBMT ) reported on post-allogeneic hematopoietic cell transplantation ( alloHCT ) among patients with myelodysplastic syndromes ( MDS ), with a goal of identifying patient and procedural factors that could help clinicians better select patients who would benefit most from alloHCT .
Examining Excess Mortality Risk in Post-Transplant MDS In the first study , Johannes Schetelig , MD , MSc , from the University Hospital Dresden in Germany , and colleagues compared outcomes of patients diagnosed with MDS who received alloHCT with matched controls in the general population to define the excess mortality risk associated with the disease . 1
The authors included data from adult patients with MDS who had received a first alloHCT between January 2000 and December 2012 and were registered with the EBMT database . Patients who received unmatched related alloHCT or cord-blood transplantation and those with > 20 percent bone marrow blasts at any point during their treatment history were excluded from the analysis . They then calculated excess mortality in patients with MDS relative to age- , sex- , country- , and calendar year-matched members of the general population .
A total of 3,813 patients were included in the analysis ( 60 % male ), and patients were followed for a median of 49 months ( range not provided ).
The number of alloHCTs performed each year increased substantially during the study period – from 56 in 2000 to 660 in 2012 . The median age at the time of transplant also rose – from 47 years ( range = 18-66 years ) in 2000 to 57 years ( range = 18-74 years ) in 2012 .
Thirty-nine percent of patients had a human leukocyte antigen ( HLA ) -matched sibling donor and 58 percent received reduced-intensity conditioning .
In the overall patient cohort , 5-year overall survival ( OS ) was 46 percent ( 95 % CI 45-48 ) and 10-year OS was 40 percent ( 95 % CI 37-42 ). Age and the presence of excess blasts affected the post-transplant survival outcomes , with 10-year OS probabilities highest in young patients and those with a lower disease burden :
• patients < 55 years of age versus ≥55 years of age : 48 % ( 95 % CI 45-51 ) and 31 % ( 95 % CI 28-34 )
• with versus without excess blasts : 33 % ( 95 % CI 30-37 ) and 46 % ( 95 % CI 43-49 )
Two years after alloHCT , the probability of event-free survival was 52 percent ( 95 % CI 50-54 ). Among patients who were alive at 2 years , the likelihood of surviving to 10 years post-alloHCT was even greater for younger patients and those with a lower disease burden : 82 percent ( 95 % CI 78-86 ) and 65 percent ( 95 % CI 59-72 ) for patients < 55 years of age or ≥55 years of age , and 68 percent ( 95 % CI 62-74 ) and 81 percent ( 95 % CI 77-85 ) for patients with or without excess blasts at alloHCT .
For patients ≥65 years of age , compared with age-matched controls in the general population , the probability of survival at 5 years was 70 percent ( 95 % CI 58-85 ) for older male patients and 88 percent for their matched controls , and 65 percent ( 95 % CI 49- 86 ) and 93 percent for older female patients .
“ Long-term follow-up data derived from the EBMT registry show that patients experience excess mortality , compared with the general population , also beyond the 2-year landmark ,” Dr . Schetelig and co-authors concluded , noting that the post-transplant mortality risk from causes also relevant to the matched population , such as cardiovascular disease , were similar . “ However , for elderly patients this background , mortality should be considered when interpreting results after alloHCT .”
Haplo-Identical and Mismatched Transplant In the second trial , Marie Robin , MD , PhD , from Saint-Louis Hospital in Paris , France , and researchers analyzed outcomes among patients with intermediate- and high-risk MDS who received an alloHCT from an HLA-mismatched related donor or haplo-identical donors , finding similar survival rates between both cohorts . 2 They were also able to identify several factors associated with post-transplant outcome in each group .
Dr . Robin and co-authors included 230 consecutive patients with a primary diagnosis of MDS who received alloHCT from an HLA-mismatched related donor (< 4 mismatches ) and haploidentical donors ( 5 HLA mismatches ) between 2007 and 2014 who were included in the EBMT registry .
The median age at transplant was 56 years ( range = 46-64 years ), and patients had the following MDS classifications , according to 2008 World Health Organization criteria :
• refractory cytopenia with multilineage dysplasia : 31 ( 13.5 %)
• refractory anemia with ring sideroblasts and del5q : 12 ( 5.2 %)
• refractory anemia with excess blasts-1 : 36 ( 15.7 %)
• refractory anemia with excess blasts-2 : 67 ( 29.1 %)
• MDS transformed to acute myeloid leukemia ( AML ): 84 ( 36.6 %)
More than three-quarters of patients ( n = 181 ; 78.7 %) had ≥2 HLA mismatches with the donor , while other patients had only one HLA mismatch ( n = 49 ; 21.3 %). The majority of patients received a reduced-intensity conditioning ( RIC ) regimen pre-transplant ( n = 117 ; 51.5 %), while 62 ( 27.3 %) received a total body irradiation . In vivo T-cell depletion was performed in 105 ( 46.1 %) patients , while ex
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