ASH Clinical News Focus on Myeloid Malignancies | Page 23

vivo T-cell depletion was performed in 34 ( 14.9 %) patients .

The rates of 3-year OS and disease-free survival ( DFS ) were 32 percent ( 95 % CI 26-41 ) and 29 percent ( 95 % CI 23-37 ), respectively . The cumulative incidence of non-relapse mortality ( NRM ) at 3 years was 49 percent ( 95 % CI 41-56 ), and NRM was particularly high in patients who received a myeloablative conditioning regimen , compared with those who received RIC ( 59 % vs . 40 %; p value not provided ), the authors noted .

Rates of grade 2-4 acute graft-versus-host disease ( GVHD ) and chronic GVHD were 31 percent ( 95 % CI 25-38 ) and 30 percent ( 95 % CI 23-36 ), respectively .

When restricting the analysis to patients who received cyclophosphamide as GVHD prophylaxis ( n = 102 ; 44.7 %), rates of 3-year OS and DFS were slightly higher than the overall patient population ( 38 % and 34 %), and the rate of NRM was reduced ( 41 %).

The researchers identified several factors associated with OS , DFS , and NRM , including transformation to AML , not in complete remission at time of transplant , a female donor for a male recipient , myeloablative conditioning regimen , and no use of cyclophosphamide ( TABLE ). The authors attributed the improvement in DFS over time to an increase in the use of prophylactic cyclophosphamide treatment , but noted that rates of NRM remain “ relatively high ,” even with cyclophosphamide treatment .

Authors of both analyses noted that missing data in the registries could have affected the study results .

References

1 . Schetelig J , de Wreede L , van Gelder M , et al . Long-term survival of patients with MDS after allogeneic transplantation : a report from the Chronic Malignancies Working Party of EBMT . Oral abstract presented at the 43rd Annual Meeting of the European Society for Blood and Marrow Transplantation , March 28 , 2017 ; Marseilles , France .

2 . Robin M , Porcher R , Ciceri F , et al . Haplo-identical transplantation ( haplo-HSCT ) in patients with myelodysplastic syndrome ( MDS ): a report from the European Society of Blood and Marrow Transplantation . Oral abstract presented at the 43rd Annual Meeting of the European Society for Blood and Marrow Transplantation , March 28 , 2017 ; Marseilles , France .

Although allogeneic hematopoietic cell transplantation ( alloHCT ) is currently the only curative option for many patients with acute myeloid leukemia ( AML ) or myelodysplastic syndromes ( MDS ), relapse remains the most common cause of morbidity and mortality . In a prospective , open-label , phase II clinical trial , researchers evaluated whether a posttransplant strategy combining prophylactic or preemptive donor lymphocyte infusion ( DLI ) and the hypomethylating agent azacitidine could reduce the risk of post-transplant relapse .

At the European Society for Blood and Marrow Transplantation , lead author Thierry Guillaume , MD , PhD , from the Centre Hospitalier Universitaire in Nantes , France , and colleagues reported that this combination led to a 3-year survival rate of 66 percent and a lower rate of relapse than historical controls .

The trial evaluated relapse rate and disease-free survival in 30 patients ( median age = 58 years ; range = 22-70 years ) with highrisk AML ( n = 20 ) or MDS ( n = 10 ) who received azacitidine and DLI post-alloHCT as prophylactic treatment . The patient ’ s disease status at the time of alloHCT was in first complete remission ( CR ; n = 16 ; 53 %), second CR ( n = 6 ; 20 %), refractory ( n = 5 ; 16 %), and upfront transplantation for MDS ( n = 3 ; 10 %). Cytogenetics were normal or intermediate for 15 patients and unfavorable for 15 patients – eight of whom had complex karyotype .

Azacitidine treatment began between 56 and 112 days post-transplant , at doses of 32 mg / m ² per day administered subcutaneously for 5 days every 28 days for up to 12 cycles ; 10 patients ( 33 %) completing all 12 cycles . However , 20 patients discontinued treatment because of graft-versus-host disease ( GVHD ; n = 11 ), relapse ( n = 5 ), infection ( n = 1 ), sudden death resulting from heart failure ( n = 1 ), or withdrawal of consent ( n = 2 ).

The first DLI was started following three cycles of azacitidine and discontinuation of immunosuppressive prophylaxis as long as the patient had no clinical signs of GVHD , uncontrolled infection , or a recent history of grade > 2 acute GVHD ( aGVHD ). Two additional DLIs were administered after the fifth and seventh cycles of azacitidine ( 8 and 16 weeks after the first DLI ).

DLIs were administered in the following doses : 5x10 6 , 1x10 7 , 5x10 7 CD3 + cells / kg for related donor alloHCTs and 1x10 6 , 5x10 6 , 1x10 7 CD3 + cells / kg for unrelated donor alloHCTs . Forty-one

May 2017 21