Donor NKG2C homozygosity contributes to CMV clearance after haploidentical transplantation.

CMV infection remains an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several investigators have reported that adaptive NKG2C+ NK cells persistently expand during CMV reactivation. In our study, 2 cohorts were enrolled to explore the relationships among the NKG2C genotype, NKG2C+ NK cell reconstitution, and CMV infection.

Donor activating killer cell immunoglobulin-like receptors genes correlated with Epstein-Barr virus reactivation after haploidentical haematopoietic stem cell transplantation.

Natural killer (NK) cells exert anti-viral effects after haematopoietic stem cell transplantation (HSCT). The balance between inhibition and activation of NK cells determined by the inherited repertoire of killer cell immunoglobulin-like receptors (KIR) genes may influence Epstein-Barr virus (EBV) reactivation after transplantation. To evaluate the relative contributions of KIR genotypes to EBV reactivation, we prospectively enrolled 300 patients with malignant haematological disease who were suitable for haploidentical HSCT.

Comparison of the clinical outcomes between NIMA-mismatched and NIPA-mismatched haploidentical hematopoietic stem cell transplantation for patients with hematological malignancies.

The objective of this study was to compare clinical outcomes between noninherited maternal antigen (NIMA)-mismatched and noninherited paternal antigen (NIPA)-mismatched haploidentical hematopoietic stem cell transplantation (haplo-HSCT) among patients with hematological malignancies and perform a subgroup analysis. We retrospectively analyzed 378 patients with hematological malignancies who received haplo-HSCT from NIMA-mismatched (n = 201) and NIPA-mismatched (n = 177) donors between January 2012 and December 2017. The cumulative incidence of 100-d grades II-IV acute graft-versus-host disease (aGVHD) (19.

Rituximab for desensitization during HLA-mismatched stem cell transplantation in patients with a positive donor-specific anti-HLA antibody.

To define the efficacy of a single dose of 375 mg/m rituximab for DSA-positive patients with 2000 ≤ MFI < 10,000, we enrolled a prospective clinical cohort including patients with positive DSA treated with rituximab (n = 55, cohort A), a matched-pair cohort including cases with negative DSA (n = 110, cohort B) and a historical cohort including subjects with 2000 ≤ MFI < 10,000 without receiving any treatment for DSA (n = 22, cohort C). The incidences of primary poor graft function (PGF) in cohort A and cohort B were 5% and 1% (P = 0.076), respectively, both of which were lower than that in cohort C (27%, P < 0.

Donor and host coexpressing KIR ligands promote NK education after allogeneic hematopoietic stem cell transplantation.

The rate and extent of natural killer (NK)-cell education after hematopoietic cell transplantation correlates with leukemia control. To study the effect of donor and host HLA on NK-cell reconstitution, single killer-cell immunoglobulin-like receptor (KIR)+ NK cells (exhibiting KIR2DL1, KIR2DL2/KIR2DL3, or KIR3DL1 as their sole receptor) were grouped into 4 groups based on the interaction between donor/host HLA and donor inhibitory KIR in 2 cohorts (n = 114 and n = 276, respectively). On days 90 to 180 after transplantation, the absolute number and responsiveness against K562 cells (CD107a or interferon-γ expression) of single-KIR+ NK cells were higher in pairs where donor and host HLA both expressed ligands for donor inhibitory KIRs than in pairs where 1 or both of the donor and recipient HLA lacked at least 1 KIR ligand.

Identification of a novel HLA-B*40 allele, HLA-B*40:451.

HLA-B*40:451 differs from B*40:06:01:01 by a single nucleotide substitution at position 257 of exon 2.

Evaluation of HistoCheck as a Predictor of Clinical Outcomes after Haploidentical Hematopoietic Stem Cell Transplantation.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is available for nearly all patients without matching HLA-related or -unrelated donors. There was not a valid evaluation system to predict the most proper donor. HistoCheck was based on the functional similarity of amino acids to estimate the allogenicity of HLA mismatches with a sequence similarity matching (SSM) score.

Impact of HLA allele mismatch at HLA-A, -B, -C, -DRB1, and -DQB1 on outcomes in haploidentical stem cell transplantation.

The impact of human leukocyte antigen (HLA) allele mismatch on transplant outcomes in haploidentical stem cell transplantation (haplo-SCT) has not been established. We retrospectively studied 595 patients with hematologic malignancy who received haplo-SCT. The impact of multiple HLA allele mismatches (HLA-A, -B, -C, -DRB1, and -DQB1) and each HLA allele mismatch on transplant outcomes was analyzed.

Predicted indirectly recognizable HLA epitopes are not associated with clinical outcomes after haploidentical hematopoietic stem cell transplantation.

Haploidentical stem cell transplantation (haplo-SCT) provides an alternative method to cure patients with malignant and nonmalignant hematologic diseases who lack a human leukocyte antigen (HLA) matched related or unrelated donor. HLA disparity between donor and patient was the main reason causing lots of clinical immune response. The aim of this study was to investigate whether indirect recognition of mismatched HLA could predict the clinical outcomes in haplo-SCT.

Recipient-donor KIR ligand matching prevents CMV reactivation post-haploidentical T cell-replete transplantation.

Licensed natural killer (NK) cells have been demonstrated to have anti-cytomegalovirus (CMV) activity. We prospectively analysed the human leucocyte antigen typing of donor-recipient pairs and the killer cell immunoglobulin-like receptor (KIR) typing of donors for 180 leukaemia patients to assess the predictive roles of licensed NK cells on CMV reactivation post-T-cell-replete haploidentical stem cell transplantation. Multivariate analysis showed that donor-recipient KIR ligand graft-versus-host or host-versus-graft direction mismatch was associated with increased refractory CMV infection (Hazard ratio = 2·556, 95% confidence interval, 1·377-4·744, P = 0·003) post-transplantation.

miR-153-3p, a new bio-target, is involved in the pathogenesis of acute graft-versus-host disease via inhibition of indoleamine- 2,3-dioxygenase.

Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Therefore, seeking reliable biomarkers and delineating the potential biological mechanism are important for optimizing treatment strategies and improving their curative effect. In this study, using a microRNA polymerase chain reaction (PCR)-based chip assay, microRNA-153-3p (miR-153-3p) was screened and selected as a potential biomarker of aGVHD.

Donor-specific anti-human leukocyte antigen antibodies were associated with primary graft failure after unmanipulated haploidentical blood and marrow transplantation: a prospective study with randomly assigned training and validation sets.

Background: Small studies suggest an association of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) with primary graft failure (GF) following haploidentical stem cell transplantation, but primary graft rejection (GR) was not discriminated from primary poor graft function (PGF). In this study, we aimed to determine the association of DSAs with primary GF, including GR and PGF, in patients who underwent unmanipulated haploidentical blood and marrow transplantation.

Methods: A total of 345 subjects were prospectively recruited and randomly selected as training group (n = 173) and validation group (n = 172).

Who is the best donor for a related HLA haplotype-mismatched transplant?

The best donor for a related donor for a human leukocyte antigen (HLA) haplotype-mismatched transplant for hematological neoplasms is controversial. We studied outcomes in 1210 consecutive transplant recipients treated on a uniform protocol. Younger donors and male donors were associated with less nonrelapse mortality (NRM; hazard ratio [HR] = 0.

[Cytomegalovirus-specific T cells immune reconstitution after human leukocyte antigen matched sibling donor allogeneic bone marrow plus peripheral blood hematopoietic stem cell transplantation].

Objective: To investigate the regular pattern of Cytomegalovirus (CMV)-specific T cells (CTL) immune reconstitution after human leukocyte antigen (HLA) matched sibling donor allogeneic bone marrow(BM) plus peripheral blood hematopoietic stem cell (PBSC) transplantation.

Methods: CTL from seventeen patients after transplantation was detected by flow cytometry, the IFN-γ secretion ability of CTL by enzyme-linked immunospot (ELISPOT) assay, and clonal analysis of TCR Vβ subfamily by gene scan assays. The relationship between CTL reconstitution and CMV infection was studied.

Immune reconstitution following unmanipulated HLA-mismatched/haploidentical transplantation compared with HLA-identical sibling transplantation.

In this study, we prospectively investigated the immune reconstitution in patients with hematological malignancies after human leukocyte antigen (HLA)-mismatched/unmanipulated haploidentical transplantation (50 cases) and HLA-matched transplant (25 cases). Transplant-related mortality, relapse, leukemia-free survival, and overall survival were similar between the two transplant strategies, although the cumulative incidence of CMV antigenemia was significantly higher in haploidentical recipients than in HLA-matched recipients (49.9 ± 7.

The effect of HLA disparity on clinical outcome after HLA-haploidentical blood and marrow transplantation.

The relative importance of various human leukocyte antigen (HLA) loci has not been established for unmanipulated HLA-mismatched/haploidentical transplantation. To address this question, we analyzed the impact of HLA-A, HLA-B, HLA-DRB1, HLA-DRB3, HLA-DRB4, and HLA-DRB5 on the outcome of HLA-haploidentical transplantation. Four hundred and eighty-one donor-recipient pairs were fully typed before transplantation.

[Association of HLA DRB1 polymorphism with susceptibility to myelodysplastic syndrome and aplastic anemia in Chinese Han population].

Objective: To investigate the association of the HLA-DRB1 polymorphism with susceptibility to myelodysplastic syndrome (MDS) and aplastic anemia (AA) in Chinese Han population.

Methods: The polymorphism of HLA-DRB1 alleles in 242 patients with MDS, 115 patients with AA and 2264 umbilical cord blood control samples were tested by polymerase chain reaction-sequence specific primer (PCR-SSP).

Results: Compared with normal controls, the frequency of HLA-DRB1*15 was significantly increased in the MDS group and AA group (22.

Clinical impact of absolute lymphocyte count on day 30 after unmanipulated haploidentical blood and marrow transplantation for pediatric patients with hematological malignancies.

Currently, limited information is available regarding the effects of early lymphocyte recovery on transplant outcomes in pediatric patients with hematological malignancies after unmanipulated haploidentical transplantation. In this study, we evaluated the association of Day 30 absolute lymphocyte count (ALC-30) with transplant outcomes in 60 consecutive pediatric patients with hematological malignancies receiving T-cell-repleted transplantation from an haploidentical related donors. After median follow-up of 36 months (range, 1.

[Determination of optimal time to second allogeneic peripheral blood stem cell harvest from healthy donors].

Objective: To investigate the optimal time for second allogeneic peripheral blood stem cell grafts (PBSC) harvest from healthy donors after in vivo recombinant human granulocyte colony-stimulating factor application (rhG-CSF).

Methods: Thirty-eight healthy donors of second collection (group A) were treated with subcutaneous rhG-CSF \[5 microgxkg(-1)xd(-1)\] for five consecutive days and followed by leukapheresis on day 5 and 6. The control group (group B) was thirty-eight healthy donors who had received a first PBSC collection previously.

Influence of lymphocyte recovery on outcome of haploidentical transplantation for hematologic malignancies.

Unmanipulated human leukocyte antigen (HLA)-mismatched/haploidentical blood and marrow transplantation is an established treatment for patients without HLA-matched related or unrelated donors. However, the prognostic significance of early lymphocyte recovery in this transplant setting is not defined. In this study, we investigated the association of day 30 absolute lymphocyte count (ALC-30) with outcome after unmanipulated HLA-mismatched/haploidentical transplantation.

[Modulation of adhesion molecule expression on T cells in bone marrow after in vivo rhG-CSF application].

The aim of study was to investigate the modulation effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on adhesion molecule expression of memory T lymphocyte in the bone marrow grafts. rhG-CSF was administered in 41 donors by subcutaneous injection for 5 consecutive days. Bone marrow grafts were collected on day 4.

Expression profiles of adhesion molecules on naïve T cells in bone marrow grafts of healthy donors treated with granulocyte colony-stimulating factor.

Background And Objectives: Adhesion molecules on T cells were implicated in the process of leukocyte migration and GVHD. The aim of this study was to investigate the profiles of adhesion molecule expression on naïve T cells in bone marrow grafts of healthy donors treated with G-CSF.

Methods: The expression of four adhesion molecules, including VLA-4, ICAM-1, L-selectin, and LFA-1, on naïve T cells in G-CSF-primed bone marrow grafts (G-BM) from 35 healthy donors was analyzed using flow cytometry.

Expression of CD62L on donor CD4(+) T cells in allografts: correlation with graft-versus-host disease after unmanipulated allogeneic blood and marrow transplantation.

Introduction: The aim of this study was to investigate the association of donor CD4(+) T cells expressing CD62L with transplant outcomes.

Materials And Methods: We report a prospective analysis of 31 patients who were treated with a Bu/Cy regimen, followed by unmanipulated blood and marrow transplantation.

Results: Median number (range) of CD4(+)CD62L(+), CD4(+)CD45RA(+)CD62L(+), and CD4(+)CD45RO(+)CD62L(+) cells infused were 0.

[Peripheral monocyte counts at first collection of allo-grafts predicts amount of CD34(+) cells in mixture of rhG-CSF primed bone marrow and mobilized peripheral stem cell grafts].

This study was purposed to investigate the relation of monocyte counts in peripheral blood (PB) at the first collection of allograft to the amount of CD34(+) cells in the mixture of recombinant human granulocyte colony-stimulating factor (rhG-CSF)-primed bone marrow graft (G-BM) and rhG-CSF mobilized peripheral stem cell grafts (G-PB). 70 healthy donors were treated with rhG-CSF [5 microg/(kg.d)] injected subcutaneously for 5 consecutive days.