Abstract

Haploidentical hematopoietic stem cell transplantation (HSCT) is globally used. Results from small sample of haploidentical HSCT for patients with myelodysplastic syndrome (MDS) are encouraging, which need to be confirmed. And the risk factors established in HLA-identical sibling or unrelated transplant need to be explored in haploidentical setting. With this aim, we conducted a disease-specific multi-center study using haploidentical donor for MDS patients with larger sample-size and longer follow-up.

We analyzed outcomes of 139 MDS patients including those with transformation to acute myeloid leukemia (tAML). Median follow-up time for surviving patients was 41 months. Eighty-seven percent of the patients had advanced disease. The 28-d cumulative incidence of neutrophil recovery was 94%, Risk factor analysis showed that disease duration, family relationship (maternal donor to be the lowest) and number of cells infused significantly affected myeloid recovery. The 100-d cumulative incidences of grades II to IV aGVHD and of grades III to IV aGVHD were 29% and 8%, respectively. The 3-y cumulative incidence of cGVHD was 37%. Risk factor analysis showed that disease duration and family relationship (50% vs 26% with maternal donor compared with others, P = .03) significantly affected 100d aGVHD incidence. The 5-year cumulative incidence of relapse (CIR) for the entire group was 9%. The 5-year CIR, by disease stage, was 20% for tAML, 6% for RAEB (13% after 7 years post-HSCT), and 0% for RA/RARS [refractory anemia/refractory anemia with ringed sideroblasts] patients (P = .06). Among patients with tAML, the incidence of relapse was not reduced in patients who had received induction chemotherapy before HSCT. The 5-year OS and DFS for the entire group was 59% and 59%. Factors significantly affected DFS were time from diagnosis to transplant (P = .03), transplant year (P = .05) and occurrence of grades III to IV aGVHD (P = .006).

Additionally, outcomes were compared with results in 109 patients who received transplants from HLA-identical siblings during the same period, and a multivariate analysis failed to show significant differences in relapse, non-relapse-mortality or survival rates between the 2 cohorts. DFS correlated significantly with disease stage (P = .008), patient age (P = .04), time from diagnosis to transplant (P = .02), transplant year (P = .03) and grades III to IV aGVHD (P < .001). The data suggest that similar survival can be achieved with haploidentcial HSCT in comparison with HLA-identical siblings. For both cohorts, transplantation outcomes improved when transplanted early in the disease course. (This study was registered as NCT01793675 at www. Clinicaltrial.gov)

Table.

Multivariate analysis for relapse, NRM and DFS

Outcome Hazard ratio (95%Confidence interval) 
Relapse   
HID vs ISD 0.48(0.21-1.09) 0.08 
Other significant factors   
IPSS risk  <0.001 
Low to Int-1 0.10(0.02-0.42) 0.003 
Int-2 0.18(0.06-0.54) 0.002 
High 1.0 
Disease-free survival   
HID vs ISD 1.04 (0.66-1.65) 0.85 
Other significant factors   
Disease stage  0.008 
RA/RARS 0.18 (0.04-0.71) 0.004 
RAEB 0.35 (0.19-0.63) 0.001 
tAML untreated 0.47 (0.22-1.00) 0.052 
tAML response 0.56 (0.16-1.94) 0.36 
tAML no response 1.0  
Patient age <50 vs >50 0.58(0.35-0.97) 0.04 
Disease duration 1.01(1.00-1.02) 0.02 
Grades ¢'-¢'aGVHD no vs yes 0.18(0.09-0.35) <0.001 
Transplant year 2010 pre vs post 1.75 (1.07-2.86) 0.03 
Non-Relapse-Mortality   
HID vs ISD 1.35 (0.76-2.38) 0.29 
Other significant factors   
Patient age <50 vs >50 0.44(0.23-0.83) 0.008 
Disease duration 1.01(1.00-1.02) 0.01 
Grades ¢';-¢';aGVHD no vs yes 0.13(0.06-0.27) <0.001 
Transplant year 2010 pre vs post 1.84 (1.01-3.36) 0.04 
Stem cell source  0.048 
BM 2.91(0.93-9.06) 0.053 
PB 0.63(0.24-1.66) 0.36 
BM+PB 1.0 
   
Outcome Hazard ratio (95%Confidence interval) 
Relapse   
HID vs ISD 0.48(0.21-1.09) 0.08 
Other significant factors   
IPSS risk  <0.001 
Low to Int-1 0.10(0.02-0.42) 0.003 
Int-2 0.18(0.06-0.54) 0.002 
High 1.0 
Disease-free survival   
HID vs ISD 1.04 (0.66-1.65) 0.85 
Other significant factors   
Disease stage  0.008 
RA/RARS 0.18 (0.04-0.71) 0.004 
RAEB 0.35 (0.19-0.63) 0.001 
tAML untreated 0.47 (0.22-1.00) 0.052 
tAML response 0.56 (0.16-1.94) 0.36 
tAML no response 1.0  
Patient age <50 vs >50 0.58(0.35-0.97) 0.04 
Disease duration 1.01(1.00-1.02) 0.02 
Grades ¢'-¢'aGVHD no vs yes 0.18(0.09-0.35) <0.001 
Transplant year 2010 pre vs post 1.75 (1.07-2.86) 0.03 
Non-Relapse-Mortality   
HID vs ISD 1.35 (0.76-2.38) 0.29 
Other significant factors   
Patient age <50 vs >50 0.44(0.23-0.83) 0.008 
Disease duration 1.01(1.00-1.02) 0.01 
Grades ¢';-¢';aGVHD no vs yes 0.13(0.06-0.27) <0.001 
Transplant year 2010 pre vs post 1.84 (1.01-3.36) 0.04 
Stem cell source  0.048 
BM 2.91(0.93-9.06) 0.053 
PB 0.63(0.24-1.66) 0.36 
BM+PB 1.0 
   

Disclosures

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.