Patients
The clinical characteristics of patients in the MSD-HSCT and haplo-HSCT groups are summarized in table 1 and table 2. No significant difference was observed between the PTCY groups and the control groups in terms of baseline demographics except for stem cell source. Eight patients (40%) of MSD-control group and all patients of haplo-control group received PBSCs and BM, while all patients of PTCY groups received PBSCs and UC-MSCs, except for two patients who suffered from primary graft failure received extra BM from a secondary donor in the haplo-PTCY group. There were 6 males (46.2%) and 13 males (59.1%) in the MSD-PTCY and haplo-PTCY groups and the median ages were 20 (range 9 to 35) and 14 (range 3 to 31) years respectively. One patient of each PTCY group was treated with anti-human lymphocyte immunoglobulin pretransplantation. The remaining patients had previously received treatment with CSA and/or steroids. In addition, two patients (9.1%) had hospital admissions for pulmonary infection requiring treatments prior to admission in the haplo-PTCY group, and one of the two patients had additional fungal sinus infections. Fortunately, the infections of the two patients were controlled after engraftment.


Engraftment
In the MSD-PTCY group, all patients successfully engrafted. The median numbers of infused MNCs and CD34+ cells between the MSD-PTCY and control groups were similar (MNCs: 16.36 (range 12.57 to 23.91) x108/kg vs 14.04 (range 6.33 to 24.95) x108/kg; CD34+ cells: 7.39 (range 4.35 to 18.4) x106/kg vs 5.39 (range 1.02 to 13.37) x106/kg). However, We observed that the times to neutrophil and platelet engraftment were shorter in the MSD-PTCY group than in the control group (11 days (range 10 to 14) vs 13 days (range 10 to 23) and 12 days (range 9 to 15) vs 14 days (range 10 to 45)). The difference in graft rejection between the MSD-PTCY and control groups was not significant(7.7% vs 15.0%). The rates of chimerism at day +30 in the MSD-PTCY and control groups were 100% and 90% respectively, and there was no significant difference.
In the haplo-HSCT groups, the median numbers of infused MNCs and CD34+ cells between the haplo-PTCY and control groups were similar (MNCs: 18.73 (8.41-32.35) x108/kg vs 23.43 (2.02-31.72) x108/kg; CD34+ cells: 7.60 (4.21-19.45) x106/kg vs 8.95 (1.76-22.53) x106/kg). Two patients who suffered from primary graft failure experienced successful engraftment after receiving transplants from haploidentical donors in the haplo-PTCY group. In the haplo-control group, secondary graft failure developed in one patient at 1.5 months after transplantation, and this patient sustained engraftment after undergoing MMUD-HSCT. The times to neutrophil and platelet engraftment were shorter in the haplo-PTCY group than in the control group (12 days (range 9 to 15) vs 13 days (range 11 to 19) and 11.5 days (range 9 to 17) vs 14 days (range 11 to 62)). One patient from each group suffered graft rejection.
Acute and chronic GVHD
The cumulative incidence of aGVHD at day +100 in the MSD-PTCY group was 15.4% (95% CI: 2.2-39.9) compared to 50.0% (95% CI: 26.3-69.8) in the control group (P=0.050) (Fig. 1a). The cumulative incidence of grade II-IV aGVHD in the MSD-PTCY group was lower than that in the control group, 7.7% (95% CI: 0.4-30.3) vs 30.0% (95% CI: 11.8-50.7), but the difference did not reach statistical significance (P=0.122) (Table 3). No patient developed cGVHD in the MSD-PTCY group. In contrast, the 1-year cumulative incidence of cGVHD in the control group was 15.0% (95% CI: 3.5-34.1)(Fig. 1b).

The cumulative incidence of aGVHD at day +100 in the haplo-PTCY group was lower than that in the control group(Table 4), 31.8% (95% CI: 13.8-51.6) vs 60.0% (95% CI: 29.9-80.6), but we observed no significant difference (P=0.165) (Fig. 2a). The cumulative incidences of grade II-IV aGVHD in the haplo-PTCY group was 27.3% (95% CI: 10.8-46.9) compared to 53.3% (95% CI: 24.8-75.3) in the control group(P=0.170). Notably, one patient with grade IV liver aGVHD had intracranial aGVHD, and one patient with aGVHD developed skin cGVHD in the haplo-PTCY group. The 1-year cumulative incidence of cGVHD in the haplo-PTCY and the haplo-control groups was no difference(P=0.600), 18.2% (95% CI: 5.5-36.8) vs 26.7% (95% CI: 7.7-50.7) (Fig. 2b). There was no extensive cGVHD in the haplo-PTCY group, while one patient developed extensive cGVHD in the control group.

Regimen-Related Toxicities
The incidence of pulmonary infection in the MSD-PTCY group was obviously lower than that in the control group (P=0.022), 7.7% vs 50.0%. Similarly, the incidences of CMV and EBV reactivation in the MSD-PTCY group were significantly lower than those in the control group (CMV: 23.1% vs 65.0%; EBV: 0 vs 60.0%), and there were significant differences between the two groups (P: 0.032 and 0.001, respectively). Although the incidence of hemorrhagic cystitis was lower in the MSD-PTCY group than in the control group (7.7% vs 35.0%), the difference was not significant (P=0.108). One patient suffered from pure red cell aplasia (PRCA) after ABO-compatible HSCT, and hematopoietic recovery occurred eighteen months after transplantation. In the control group, four of twelve patients with EBV reactivation developed posttransplantation lymphoproliferative disorders (PTLD) and three patients were cured through combination therapy with immunosuppressor withdrawal, rituximab and donor lymphocyte infusion (DLI). Another patient experienced an epileptic seizure because of intracranial EBV infection. Furthermore, two patients developed unexplained seizures that were relieved after expectant treatment. Cardiotoxicity and thrombotic microangiopathy (TMA) each developed in one patient. No patient had veno-occlusive disease (VOD).
The incidence of pulmonary infection in the haplo-PTCY group was lower than that in the control group (40.1% vs 60.0%), while the incidence of CMV reactivation in the haplo-HSCT group was higher than that in the control group (81.8% vs 53.3%), but the differences were not statistically significant (P: 0.325, 0.080). The median times to CMV infection were +37 days (range 29 to 46) and +35 days (range 25 to 53) in the haplo-HSCT and the control groups respectively. Two of eighteen patients with CMV infection in the haplo-HSCT group and one of eight patients with CMV infection in the control group developed cytomegalovirus retinitis. The incidence of EBV reactivation in the haplo-HSCT group (22.7%) was obviously lower than that in the control group (80.0%), and the difference was significant (P=0.001). There were no PTLD in the haplo-PTCY group, but three patients developed PTLD based on their seropositive EBV status in the control group. The incidences of hemorrhagic cystitis with BKV seropositivity were similar between the haplo-HSCT group and the control group (31.8% and 26.7%). In the haplo-PTCY group, one of seven patients who were seropositive for BKV progressed to BKV encephalitis and suffered from intracranial fungal infection. In addition, one patient had TMA at day +50. Moreover, posterior reversible encephalopathy syndrome (PRES) developed in four patients in the haplo-PTCY group and in two patients in the control group. None of all patients developed VOD in the two groups.
Survival
The median follow-up time of the MSD-PTCY group was similar to that in the control group, 22 months (range 10 to 36) vs 21.5 months (range 2 to 36). The median follow-up of the haplo-HSCT and the control groups were 11.5 months (range 3 to 27) and 12 months (range 1.5 to 36), respevtively.
All thirteen (100%) patients in the MSD-PTCY group are now alive with normal hematopoiesis. Interestingly, one female is now three months pregnant. The 1-year OS of the MSD-PTCY group was 100% compared to 75.0% (95% CI: 50.0-88.7)% in the MSD-control group (P=0.057) (Fig. 3a). The 1-year EFS of the MSD-PTCY group was 92.3% (95% CI: 56.6-98.9)% compared to 65.0% (95% CI: 40.3-81.5)% in the MSD-control group (P=0.071) (Fig. 3b). In the control group, three patients died from serious pulmonary infection at 2, 3 and 5 months, one patient died of intracranial EBV infection at day +70, and one patient died of TMA at 4 months. In the MSD-PTCY group, twelve of thirteen patients had a follow-up period of more than 12 months at the time of writing. All the patients began to reduce immunosuppressor treatment at 6 months and these agents were withdrawn before 9 months except for the patient with PRCA.
In the haplo-PTCY group, two patients died from intractable pulmonary infection at 3 and 9 months, one patient died of cerebral hemorrhage at 3 months, and one patient died of intestinal GVHD at 7 months. In the control group, two patients died from pulmonary infection at 4 and 6 months, and one patient died of severe intestinal GVHD at 12 months. The cumulative incidence of 1-year OS was 81.8% (95% CI: 58.5-92.8) in the haplo-PTCY group compared to 77.1% (95% CI: 44.2-92.1) in the haplo-control group (Fig. 4a). The 1-year EFS in the haplo-PTCY group vs the control group was 66.9% (95% CI: 39.1-84.2) vs 40.8% (95% CI: 20.5-71.2) (Fig. 4b). However, there was no significant difference in 1-year OS or EFS between the groups. In the haplo-PTCY group, eleven of eighteen living patients had a follow-up period of more than 12 months at the time of writing, those patients began to reduce immunosuppressor treatment at 9 months after HSCT.