Abstract

Allogeneic hematopoeitic cell transplantation (alloHCT) is a curative therapy for severe/very severe aplastic anemia (sAA) in adult. alloHCT from haplo-identical family donor (HD) is an alternative approach while alloHCT from matched sibling donor (MSD) is the choice of therapy. Our previous study suggested that alloHCT from matched unrelated donor (MUD) were comparable with MSD when pre-transplantation conditions were well-matched. It means poor outcome of MUD might come from poor pre-transplantation clinical factors such as delayed alloHCT. Same will be applied to HD. In this study we compared HD with alternative donors (AD; MUD or mismatched family donor) by matched case study.

We selected AD cases from KSBMT2007-01 study population who had comparable pre-transplantation clinical factors with HD by propensity-score matching. Pre-tranplatation clinical factors such as age, ATG conditioning or ABO-compatibility were matched. Therefore 48 AD cases were selected for the comparison with 16 HD cases.

Male (p=0.009) and female to male transplantation (p=0.002) were more frequent in HD. AD received prior immune suppression therapy (IST) frequently (p=0.092). Cyclophosphamide (p<0.001) and total body irradiation (p=0.055) were frequent in AD while fludarabine (p=0.006) and busulfan (p<0.001) were common in HD as a conditioning regimen. Bone marrow was used frequent in AD (60.4%; p<0.001) and peripheral blood was used in all HD (100%; p<0.001) as stem cell source. Despite this differences, ATG as prior IST (p=0.769), ABO compatibility (p=0.111), T-cell ex vivo depletion (0%, both), age at diagnosis (p=0.622), age at alloHCT (p=0.400), time from diagnosis to alloHCT (p=0.822), unit of red blood cell transfusion prior to alloHCT (p=0.655), unit of platelet cell transfusion prior to alloHCT (p=0.604) and infused CD34+ cell dose (p=0.087) were similar. All transplantation outcomes except for extensive chronic graft versus host disease (GvHD) were similar. The frequencies of hepatic sinusoidal obstruction syndrome (p=1.000), acute GvHD (p=0.769), grade 3/4 acute GvHD (p=0.258), chronic GvHD (p=0.173), extensive GvHD (p=0.099), primary neutrophil engraftment failure (p=1.000), secondary graft failure (p=1.000), platelet engraftment failure (p=0.505), all graft failure (p=0.745) were similar (Table 1). Time to neutrophil engraftment was faster in HD (p=0.003) while cumulative incidence of platelet engraftment (p=0.505), acute GvHD (p=0.378), grade 3/4 acute GvHD (p=0.255), chronic GvHD (p=0.202), extensive GvHD (p=0.918) were similar. Overall survival was also similar between AD and HD (p=0.730; Figure 1).
Table 1

Transplantation outcomes

Clinical factorsAlternative donors (n=48)Haplo-identical donors (n=16)P-value
SOS 2 (4.2%) 0 (0%) 1.000 
Acute GvHD 19 (39.6%) 43.8%) 0.769 
Grade 3/4 2 (4.2%) 2 (12.5%) 0.258 
Chronic GvHD 9 (18.8%) 6 (37.5%) 0.173 
Extensive 4 (8.3%) 4 (25.0%) 0.099 
Engraftment failure    
Neutrophil, primary 5 (10.4%) 2 (12.5%) 1.000 
Neutrophil, secondary 6 (12.5%) 2 (12.5%) 1.000 
Platelet 9 (22.0%) 5 (31.3%) 0.505 
Any 12 (25.0%) 5 (31.3%) 0.745 
Time to ANC>500/μL, days°× 18 (15.4-20.6) 13 (11.2-14.8) 0.003 
Time to platelet>20K/μL, day°×s 25 (21.4-28.6) 15 (5.7-24.3) 0.772 
CI of aGvHD, days°× 86 (19.4-152.6) 0.378 
CI of grade 3/4 aGvHD, days°× 0.255 
CI of cGvHD, months°× 10.4 (0-35.3) 0.202 
CI of extensive cGvHD, months°× 9.5 (5.1-13.9) 7.3 (1.9-12.8) 0.918 
Clinical factorsAlternative donors (n=48)Haplo-identical donors (n=16)P-value
SOS 2 (4.2%) 0 (0%) 1.000 
Acute GvHD 19 (39.6%) 43.8%) 0.769 
Grade 3/4 2 (4.2%) 2 (12.5%) 0.258 
Chronic GvHD 9 (18.8%) 6 (37.5%) 0.173 
Extensive 4 (8.3%) 4 (25.0%) 0.099 
Engraftment failure    
Neutrophil, primary 5 (10.4%) 2 (12.5%) 1.000 
Neutrophil, secondary 6 (12.5%) 2 (12.5%) 1.000 
Platelet 9 (22.0%) 5 (31.3%) 0.505 
Any 12 (25.0%) 5 (31.3%) 0.745 
Time to ANC>500/μL, days°× 18 (15.4-20.6) 13 (11.2-14.8) 0.003 
Time to platelet>20K/μL, day°×s 25 (21.4-28.6) 15 (5.7-24.3) 0.772 
CI of aGvHD, days°× 86 (19.4-152.6) 0.378 
CI of grade 3/4 aGvHD, days°× 0.255 
CI of cGvHD, months°× 10.4 (0-35.3) 0.202 
CI of extensive cGvHD, months°× 9.5 (5.1-13.9) 7.3 (1.9-12.8) 0.918 

°× Median (95% confidence interval), calculated by Gray's test

Abbreviations: SOS, sinusoidal obstruction syndrome; aGvHD, acute graft-versus-host disease; cGvHD, chronic graft-versus-host disease; ANC, absolute neutrophil count, CI, cumulative incidence

Figure 1

Overall survival

Figure 1

Overall survival

In conclusion, alloHCT from HD in sAA is comparable with alloHCT from AD when pre-transplantation clinical factors were similar although extensive chronic GvHD seemed frequent in HD. Therefore alloHCT from sAA could be alternative approach of alloHCT from MUD in adult sAA.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.