Characteristics of patients and donors
In total, 26 patients were divided into the 60-70 year old group and the >70 year old group (Table 1). 84.6% of donors were related to patients. The donors of the 60~70 year old group were much younger than those of the >70 year old group (p = 0.0006). Compared to the >70 year old group, more patients in the 60-70 year old group received more than 3 courses of MST therapy (p = 0.0008). In summary, except for donor age and MST courses, there were no significant differences in most characteristics between the two age groups.
Response to induction chemotherapy
The CR rate of all patients was 84.6%, in which 2 patients achieved CR after 2 courses of induction chemotherapy (Table 2). A total of 94.1% of patients from the 60~70 year old group and 66.7% of patients from the >70 year old group achieved CR. There was no significant difference in overall CR rates between the two age groups. All patients with standard risk achieved CR, but 76.5% of patients with high risk achieved CR.
Total death rate, early death rate and causes of death
In this study, the total death rate and the early death rate were 57.7% and 15.4%, respectively (Table 2). The total death rate of the 60-70 year old group was much lower than that of the > 70 year old group (p = 0.002). In total, 30.8% of patients died of relapse, 15.4% died of severe infection, and 11.5% died of organ failure. Fewer patients died of severe infection in the 60-70 year old group than those in the >70 year old group (p = 0.008).
Haematopoietic recovery and adverse events
The median neutrophil and platelet recovery times were 12 days and 14 days after induction chemotherapy, respectively. The adverse events of the patients are summarized in Supplementary Table 1. The constipation rate of the >70 year old group was significantly higher than that of the 60-70 year old group (p = 0.002). The pulmonary infection rate of the >70 year old group was higher than that of the 60-70 year old group (p = 0.009).
OS and LFS
The median follow-up time was 20.5 months (range, 1-135 months). In particular, 10 patients were still alive with CR on December 31, 2019, and the median OS was 64 months. The OS rate of all patients was 41.3% (Table 2). The OS rate of the 60-70 year old group was significantly higher than that of the >70 year old group (p< 0.0001). The Kaplan–Meier analyses showed that patients from the 60-70 year old group, the standard risk group and the group receiving more than 3 courses of MST had much longer OS times than their corresponding groups (p < 0.0001, p = 0.0155, and p = 0.0009) (Figure 1 A, C and D).
The LFS rate was 52.4% (Table 2). All 10 leukaemia-free patients were from the 60-70 year old group. Therefore, the LFS rate of the 60-70 year old group was higher than that of the >70 year old group (p< 0.0001). In the Kaplan–Meier analysis, patients from the 60-70 year old group and the group receiving more than 3 courses of MST had much longer LFS times than their corresponding groups (p < 0.0001 and p = 0.0056) (Figure 2 A and D).
Relapse and nonrelapse mortality
During follow-up, 38.5% of patients experienced relapse (Table 2). The median relapse time of these 8 patients was 8.5 months (range, 4-20 months). The relapse rate of the 60-70 year old group was lower than that of the >70 year old group (21.0% vs. 83.3%, p = 0.0002). Thirty percent of patients died of nonrelapse diseases, including 5 patients with severe pulmonary infection, 1 patient with cerebral haemorrhage and 1 patient with acute GVHD (Table 2). Compared to the >70 year old group, the 60-70 year old group had a much lower cumulative incidence of NRM (18.1% vs. 100%, p = 0.0296).
Donor microchimerism and GVHD
96.2% of patients had negative donor microchimerism. Only one 62-year-old female patient was diagnosed with severe acute GVHD with high fever, rash, diarrhoea and severe hyperbilirubinemia, and mixed donor chimerism was detected after 4 courses of MST therapy. The donor of the patient was her 28-year-old daughter. The patient was infused with MNCs (3.84×108/kg), CD34+ (3.21×106/kg) and CD3+ (0.76×108/kg) in each course of MST therapy. The chimaerism rate increased from negative to 7.973%, reaching 25.809% after one week. The patient failed to respond to anti-GVHD treatment and died of multiorgan failure at Day 44 after the fourth MST.
Univariate Cox proportional regression analyses
Univariate Cox proportional regression analysis showed that patient age, donor age, risk and the number of courses of MST therapy might be factors for OS (Supplementary Figure 1A). Patient age, risk and the number of courses of MST therapy might be factors for LFS (Supplementary Figure 1B). Patient age and the infused MNC dose might be factors affecting the cumulative incidence of relapse (Supplementary Figure 1C). The number of courses of MST therapy might affect the cumulative incidence of NRM (Supplementary Figure 1D).