Outcomes of Unrelated Donor Hematopoietic Stem Cell Transplantation for Hematological Malignancy: A Single Center’s Experience.
Authors: Huang He , Cai Zhen , Shi Jimin , Luo Yi , Lin Maofang 
Published: October 2019

Unrelated donor allogeneic hematopoietic stem cell transplantation (URD-HSCT) can potentially cure a variety of hematological malignancies. Until now, there were 140 cases of URD-HSCT in our bone marrow transplantation center, and we would retrospectively analyze the results of 128 patients received URD-HSCT between Nov. 1998 and May. 2006. The median age of all patients was 28 years (range 8–52 years), 27 patients with ALL in CR1, 28 patients with AML (26 in CR1 and 2 in CR2), 64 patients with CML (59 in CP, 1 in AP and 4 in BP), 8 patients with MDS, and 1 patient with MM.

113 patients were received Bu/Cy2 regimen as conditioning with busulfan 16mg/kg plus cyclophosphamide 120mg/kg, while other 5 patients with CML were received reduced intensity conditioning (RIC) regimen consisted of fludarabine (30mg/m2/d), busulfan (3.2mg/kg/d, i.v.) and ATG (5mg/kg/d). Graft with a median number of total nucleated cells was 3.45×108/kg (range 1.72–10.50×108/kg), including CD34+ cells 4.77×106/kg (range 0.72–9.92×106/kg) and CFU-GM 2.73×105/kg (range 1.46–7.91×105/kg). 110 patients were given MMF (0.5g/d), combined with CsA (3mg/kg/d) and short course MTX (10mg/m2/d) to prevent aGVHD. 18 patients received additional anti-CD25 monoclonal antibody 50mg/d on day 0, +4. Lipo protaglandin E1 was given to prevent SOS and CMV-PP65 antigen was monitored after the transplantation and ganciclovir was used to prevent CMV infection.

Hemopoietic recovery was observed in 123 evaluable patients, and the median time to achieve ANC>0.5×109/L was 17 days (range 12–31 days), platelets >20×109/L was 24 days (range 8–140 days). aGVHD developed in 69 (56.10%) patients; aGVHD of grade I-II were observed in 53 (43.09%) patients and the severe aGVHD of grade III-IV were observed in 16 (13.01%) patients. cGVHD developed in 53 (46.49%) patients with 46 (40.35%) limited and 7 (6.14%) extensive. In group (n=110) which received MMF combined with CsA and MTX as aGVHD prophylaxis, aGVHD were observed in 60 (54.55%) patients with grade I-II 42.73% and grade III-IV 11.82%. While in group (n=18) which received additional anti-CD25 monoclonal antibody, aGVHD were observed in 7 (46.7%) patients with grade I-II 6 (33.3%) and grade III-IV 3 (16.67%). There was no significant difference between two regimen of aGVHD prophylaxis.

Early TRM of all patients was 10.94% at 100 days after transplant. After a median follow-up of 13.2 months (range 1.3–92 months), clinical relapse were detected in 8 patients. By Kaplan-Meier method, the accumulative probability of 5-year overall survival of all patients was 60.98±4.52%, and which of ALL, AML, CML, MDS were 68.65±9.21%, 61.61±9.74%, 56.95±6.50% and 75.00±15.31%, respectively. 4 of 5 patients received reduced intensity URD-HSCT with follow-up of 7.3 months (range 3.0–10.3 months) experienced successful engraftment, and no aGVHD developed while cGVHD occurred in 2 cases, all patients achieved disease free survival.

To further examined the impact of HLA matching on GVHD and survival, we compared the outcomes of the HLA-matched group (n=82) and HLA 1–2 alleles disparity mismatched group (n=46). aGVHD were observed in 38 (46.34%) patients in HLA-matched group and 31 (67.39%) patients in HLA-mismatched group (P<0.05), respectively. The survival of HLA-matched and HLA-mismatched group were 69.14% and 52.17% (P<0.05) respectively.

URD-HSCT could be one of choice in patients with ALL, AML, CML, MDS, and HLA class I and class II matching would be associated with the outcomes of URD-HSCT.