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M.-A. Perales et al.
recipients of haploidentical and MUD transplantations were 42 months (range 12-97) and 47 months (range 5- 124), respectively.
Overall mortality
The risks for overall mortality was higher after trans- plantation of bone marrow or peripheral blood from hap- loidentical compared to MUD after adjusting for HCT-CI score and cytogenetic risk (Table 2 and Figure 1A). Overall mortality risks were higher in patients with a HCT-CI score of 3 or higher compared to score 0-2 (HR 1.39, 95%CI: 1.14-1.68; P=0.001) and poor risk cytogenetics compared to intermediate/good risk cytogenetics (HR 1.46, 95%CI: 1.18-1.81; P=0.001). Donor age was not associated with overall mortality (HR 1.00, 95%CI: 0.98- 1.01; P=0.9). In a subset analysis limited to patients in CR1, overall mortality risk was also higher after hap- loidentical compared to MUD transplant (HR 1.31, 95%CI: 1.01-1.70; P=0.05). Although transplant condi- tioning regimen intensity was not associated with mortal- ity risk (HR 0.88, 95%CI: 0.72-1.08; P=0.2), we tested for an interaction between donor type and conditioning regi- men intensity and found none (P=0.7). An effect of trans- plant center on overall mortality was explored and none was found.
Causes of death differed by donor type (P=0.01); recur- rent disease was the most common cause of death in both treatment groups although this was higher after hap- loidentical (59%) compared to MUD (54%) transplants. Only 2% of deaths after haploidentical transplant was attributed to GvHD compared to 14% after MUD trans- plant. There were no differences in proportion of deaths attributed to graft failure, infection, interstitial pneumoni- tis or organ failure by donor type.
Hematopoietic recovery
The median times to neutrophil and platelet recovery after haploidentical and MUD transplantation was 17
versus 14 days for neutrophils (P<0.001) and 26 versus 17 days for platelets (P<0.001). The day-28 rates of neu- trophil recovery were 89% (95%CI: 84-93) and 98% (95%CI: 97-99) (P<0.001) and the day-100 rates of platelet recovery 89% (95%CI: 84-93) and 96% (95%CI: 95-98) (P=0.004) after haploidentical and MUD transplantation, respectively. The 1-year cumulative incidence of primary or secondary graft failure after haploidentical and MUD transplantation were 11% (95%CI: 7-16) and 9% (95%CI: 7-11) (P=0.4).
Graft-versus-host disease
Compared to MUD transplantation, grade II-IV acute
GvHD was significantly lower after haploidentical trans- plantation (HR 0.53, 95%CI: 0.38-0.75; P<0.001). Independent of donor type, grade II-IV acute GvHD was higher in patients with HCT-CI score of 3 or higher (HR 1.34, 95%CI: 1.06-1.69; P=0.01) and with myeloablative conditioning regimens (HR 1.42, 95%CI:1.14-1.79; P=0.003). The day-100 incidence of grade II-IV acute GvHD after haploidentical and MUD transplantation was 21% (95%CI: 15-27) and 35% (95%CI: 32-39), respective- ly (P<0.001). Chronic GvHD risk was higher after MUD compared to haploidentical donor transplantation when bone marrow was the graft (HR 3.12, 95%CI: 1.75-5.56; P<0.001). The 2-year probability of chronic GvHD follow- ing a bone marrow graft from a haploidentical donor was 15% (95%CI:10-22) compared to 36% (95%CI: 27-46) from a MUD (P<0.001). However, when the graft was peripheral blood, there was no difference in risk of chronic GvHD by donor type (HR 1.08, 95%CI: 0.71-1.69; P=0.7). The 2-year probabilities of chronic GvHD following a peripheral blood graft from haploidentical and MUD were 46% (95%CI: 31-60) and 55% (50-59), respectively (P=0.3). Among patients who developed chronic GvHD, its severity differed by donor type; extensive chronic GvHD was reported in 74% of haploidentical compared to 88% of MUD transplant recipients (P=0.01).
AB
Figure 1. 5-year adjusted probability of overall survival (OS). (A) OS: the 5-year adjusted probability of OS after transplantation of grafts from haploidentical (Haplo) donor (32%, 95%CI: 23-42) and matched unrelated donor (MUD) (42%, 95%CI: 38-47). (B) Leukemia-free survival: the 5-year adjusted probability of disease-free survival after transplantation of grafts from Haplo donor (28%, 95%CI: 20-37) and MUD (36%, 95%CI: 31-41).
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haematologica | 2020; 105(2)