Whether a graft-versus-graft (GVG) response in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) is associated with an enhanced graft-versus-leukemia (GVL) effect remains highly controversial. Furthermore, it is unknown if the GVG response overwhelms the impact of refractory acute leukemia. We aimed to compare the characteristics and therapeutic outcomes between patients undergoing a modified haploidentical cord blood (cord-haplo) HSCT protocol (n = 97) and those undergoing haploidentical HSCT (n = 42) for refractory acute leukemia. A reliable and stable predominant haploidentical donor chimerism was established. The 2-year relapse rate was more favorable in patients undergoing cord-haplo HSCT than in those undergoing haploidentical HSCT (25.9% versus 53.2%; P = .007), as was progression-free survival (PFS; 35.5% versus 17.9%; P = .049). Meanwhile, nonrelapse mortality at 2years was not significantly different (38.0% versus 24.6%; P = .367). We also found that a higher number of mutual haploidentical donor-mismatched antigens, a concept similar to HLA mismatching, was associated with better disease control. Multivariate analysis identified cord-haplo HSCT as an independent significant predictor of reduced relapse (hazard ratio [HR], .44; P = .028) and improved PFS (HR, .58; P = .033), as was chronic graft-versus-host disease (GVHD) (relapse: HR, .42; P  = .013; PFS: HR, .63: P = .052). However, the incidences of neutrophil and platelet engraftment, GVHD, and virus reactivation were comparable in the 2 groups. This study demonstrates that cord-haplo HSCT significantly enhances the GVL effect and improves PFS, providing a reliable and efficient therapeutic platform for patients with refractory acute leukemia.

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Clonal expansion of T cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been observed, but their characteristics remain to be fully elucidated. We report here that CD8(+) T cells were the dominant T lymphocytes seen and T-cell repertoire diversity decreased dramatically during the first 3 months after allo-HSCT. Patients with GVHD grade II - IV had significantly lower T-cell repertoire diversity compared with non-GVHD patients. TCR beta variable gene (TCRBV) subfamily 8, 5.1, 5.2, 4, and 13 were the five most frequently expanded subfamilies among these patients. Among the 49 over-expanded clones identified, clonotype "TCR3-5" and "TCR18-5" were isolated from four patients with HLA-A2 allele and skin GVHD. Their frequencies correlated well with skin symptoms (i.e. rash). Moreover, they were detected in donors but not detected in recipients before transplantation. Lastly, three common TCRBV CDR3 motifs shared by T cells related with GVHD were discovered: TGDS, GLAG, and GGG. These findings suggest that TCR spectratyping is helpful for revealing GVHD-related T cells and may have utility in early diagnosis.

To explore the efficacy, and safety of the intensive conditioning regimen consisting of cladribine, cytarabine (Ara-C), and granulocyte colony-stimulating factor (G-CSF) plus modified busulfan (Bu) combined with cytoxan (Cy) (BuCy), prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with refractory, or relapsed acute myeloid leukemia (R/R AML).Thirty-Six R/R AML patients scheduled to receive allo-HSCT were consecutively, enrolled in this prospective study, and treated using intensive conditioning regimen consisting of CLAG plus modified BuCy. Median follow-up duration was 11.25 (range 0.5 – 21.0) months and the last follow up date was August 15, 2017.All patients (100%) achieved white blood cell (WBC) recovery within a median time of 16.00 (13.25 – 18.00) days, and 34 of them (94%) attained platelet (PLT) recovery within a median time of 13.50 (9.25 – 19.75) days. Incidence of acute graft-versus-host disease (aGVHD) was 50.00%, with median time of 71.50 (41.00 – 401.25) days. Three patients developed Grade I; nine, Grade II; 5, Grade III; and 1, Grade IV aGVHD. The incidence of chronic GVHD (cGVHD) was 44.40%, with median time of 255.00 (120.00 – 390.00) days. Four patients developed limited cGVHD, and 12, extensive cGVHD. One-year accumulating leukemia free survival (LFS), and overall survival (OS) rates between 52.9 ± 8.8% to 69.4 ± 7.7%, respectively. Eighteen (50%) patients were infected with cytomegalovirus; 2 (5.6%), with Epstein-Barr virus (EBV), 7 (19.4%), with hemorrhagic cystitis; 13 (36.1%), with bacteria; and 8 (22.2%), with fungus.Intensive conditioning regimen of CLAG plus modified BuCy for allo-HSCT may be effective and well-tolerated in R/R AML patients.

Cytomegalovirus (CMV) infection is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT); however, we have little information on the clinical association of various human leukocyte antigen (HLA) alleles with CMV infection. We reviewed medical records of 60 patients who underwent allo-HSCT. The effect of the 7 most frequent HLA alleles on the incidence of CMV infection and disease was analyzed, including HLA-A*02, A*11, A*24, B*13, B*40(60), DRB1*15, and DRB1*09. All the patients were monitored for CMV infection at least once weekly within 3 months. CMV infection was found in 38 (63.3%) patients on a median of day 36 (range: 16-89). Diagnosis of CMV disease was established in 6 (10.0%) patients, comprising pneumonia (n = 2), enterocolitis (n = 2), and hemorrhagic cystitis (n = 2). CMV disease was successfully treated using ganciclovir or foscarnet combined with immune globulins in 4 patients. The other 2 patients died without improvement of CMV disease. In multivariate analysis, grade II-IV acute graft-versus-host disease (aGVHD), CMV seronegative donors, and HLA-DRB1*09 were associated with increased incidence of CMV infection and disease after allo-HSCT. We suggest that more cautions should be taken to prevent CMV infection in patients with HLA-DRB1*09 after allo-HSCT.