Early lymphocyte recovery predicts superior overall survival after unmanipulated haploidentical blood and marrow transplant for myelodysplastic syndrome and acute myeloid leukemia evolving from myelodysplastic syndrome.

We investigated whether early lymphocyte recovery, after unmanipulated, haploidentical, blood and marrow transplant (HBMT), affected clinical outcomes in 78 patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia evolving from MDS. Lymphocyte recovery was based on the absolute lymphocyte count on day 30 (ALC-30). Patients with high ALC-30 (≥ 300 cells/μL) had lower relapse rates (13.

Ceruloplasmin is a potential biomarker for aGvHD following allogeneic hematopoietic stem cell transplantation.

Acute graft-versus-host-disease (aGvHD) is the major cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recently, diagnostic biomarkers for aGvHD have been shown to play important roles in evaluating disease status and mortality risk after allo-HSCT. To identify plasma biomarkers for aGvHD with high sensitivity and specificity, a quantitative proteomic approach using 8-plex isobaric tags for relative and absolute quantitation (8-plex iTRAQ) was employed to screen differentially expressed proteins in peripheral blood before and after the onset of aGvHD.

Donor lymphocyte infusions for relapse after allogeneic transplantation: when, if and for whom?

Donor lymphocyte infusion (DLI) using unstimulated leukapheresis is one of the most effective treatment strategies for patients with hematological malignancies; its graft-versus-leukemia effects make it especially effective in chronic myeloid leukemia patients who relapsed after allogeneic stem cell transplantation (allo-HSCT). However, DLI application is limited by the development of graft-versus-host disease and aplasia, and thus cannot be routinely applied for prophylaxis. Therefore, important questions remain to be answered, such as when, and whom to DLI? Recent advances enable DLI using allografts of granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells; allodepleted donor T cells; and infusions of donor-derived, ex vivo-expanded, CD8(+) cytotoxic T lymphocyte, which can decrease relapse and improve transplant outcomes.

Haploidentical bone marrow transplantation without T-cell depletion.

Approaches for haploidentical bone marrow transplantation (BMT) without T-cell depletion have been designed using new transplant strategies, including anti-thymocyte globulin (ATG) preparative regimens, granulocyte colony-stimulating factor-primed grafts, post-transplantation rapamycin, or high-dose cyclophosphamide (Cy) in combination with other immunosuppressive agents for graft-versus-host disease (GVHD) prophylaxis. These strategies ensured fast hematologic engraftment across the human leukocyte antigen (HLA) barrier with an acceptable incidence of GVHD. Long-term follow-up results from different transplant centers suggest that unmanipulated transplantation may provide an alternative strategy in the haploidentical setting without requiring the technical expertise and cost of ex vivo T-cell depletion.

[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.

Haploidentical hematopoietic stem cell transplantation with unmanipulated granulocyte colony stimulating factor mobilized marrow and blood grafts.

Purpose Of Review: This article summarizes recent improvements and progress with unmanipulated haploidentical blood and marrow transplantation (HBMT) and discusses the difference in outcomes between patients receiving HBMT and those receiving unmanipulated granulocyte colony stimulating factor (G-CSF) mobilized haploidentical peripheral blood (G-PB) grafts as allografts.

Recent Findings: Long-term follow-up confirmed that unmanipulated HBMT is a promising protocol that can be successfully extended to treat severe aplastic anemia. Recent observations regarding immune recovery, infections, and strategy for modified donor lymphocyte infusions have provided insight into the prevention of infections and the decrease in relapse after HBMT.

Characteristics and influencing factors of CD19+ B cell reconstitution in patients following haploidentical/mismatched hematopoietic stem cell transplantation.

In patients undergoing hematopoietic stem cell transplantation (HSCT), B cells exert important, prolonged effects that provide protection from infection. In this study, we analyzed characteristics and influencing factors of CD19+ B cell reconstitution in 83 patients who underwent unmanipulated haploidentical/mismatched blood and bone marrow transplantation. Of these patients, 45 % showed a normal CD19+ B cell count at +360 days.

The superiority of haploidentical related stem cell transplantation over chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia in first complete remission.

We report the results of a prospective, patient self-selected study evaluating whether haploidentical related donor stem cell transplantation (HRD-HSCT) is superior to chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia (AML) in first complete remission (CR1). Among totally 419 newly diagnosed AML patients, 132 patients with intermediate- and high-risk cytogenetics achieved CR1 and received chemotherapy alone (n = 74) or HSCT (n = 58) as postremission treatment. The cumulative incidence of relapse at 4 years was 37.

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.

Characterization of CD3+CD4-CD8- (double negative) T cells reconstitution in patients following hematopoietic stem-cell transplantation.

Background: CD3+CD4-CD8-double negative (DN) T cells, as a distinct subset of regulatory T cells (Tregs), played a pivotal role in patients following hematopoietic stem-cell transplantation.

Methods: This study examines the behavior of CD3+CD4-CD8- double negative (DN) T cells in 73 patients at days 30, 60, 90 and 180 after allo-HSCT.

Results: There was no significant difference in neutrophil and platelet engraftment between the higher and lower absolute counts of 30days DN Tregs (p=0.

Allogeneic bone marrow transplantation compared to peripheral blood stem cell transplantation for the treatment of hematologic malignancies: a meta-analysis based on time-to-event data from randomized controlled trials.

Controversy remains regarding the transplant outcomes of human leukocyte antigen-identical related bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) for the treatment of patients with hematological malignancies. To provide an estimate of the effect of BMT and PBSCT on clinical outcomes in patients with hematological malignancies, we conducted a meta-analysis based on time-to-event data from 17 randomized controlled trials. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL), from 1972 through July 2010, and conference proceedings through July 2009 and reference lists, without any language restriction, of randomized trials that compared the transplant outcomes after BMT and PBSCT in patients with hematological malignancies were searched for details.

Conflicting impact of alloreactive NK cells on transplantation outcomes after haploidentical transplantation: do the reconstitution kinetics of natural killer cells create these differences?

Partially HLA-mismatched related, or HLA-haploidentical, donor stem cell transplantation (SCT) is a feasible therapeutic option for advanced hematologic malignancy patients who lack an HLA-matched related or unrelated donor. Natural killer (NK) cells, a major cell type of the innate immune system, express surface receptors that regulate potent effector functions, such as cytolytic activity and the release of cytokines, and play a central role in the inflammatory response and immunoregulation. Conflicting results have been reported regarding the impact of NK cell alloreactivity on the outcome of haploidentical SCT in leukemic patients.

The impact of graft composition on clinical outcomes in pediatric patients undergoing unmanipulated HLA-mismatched/haploidentical hematopoietic stem cell transplantation.

Objective: In pediatric patients, the association of graft composition with clinical outcomes after unmanipulated haploidentical hematopoietic stem cell transplantation has not been well defined. Therefore, the impact of graft composition on transplant outcomes was evaluated.

Methods: We examined the absolute numbers and relative proportions of CD3+, CD4+, CD8+, CD14+, and CD34+ cells contained in allografts of 103 children who underwent unmanipulated HLA-mismatched/haploidentical hematopoietic stem cell transplantation (HSCT) without in vitro T cell depletion.

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.

Use of G-CSF-stimulated marrow in allogeneic hematopoietic stem cell transplantation settings: a comprehensive review.

In recent years, several researchers have unraveled the previously unrecognized effects of granulocyte colony-stimulating factor (G-CSF) on hematopoiesis and the immune cell functions of bone marrow in healthy donors. In human leukocyte antigen-matched or haploidentical transplant settings, available data have established the safety of using G-CSF-stimulated bone marrow grafts, as well as the ability of this source to produce rapid and sustained engraftment. Interestingly, G-CSF-primed bone marrow transplants could capture the advantages of blood stem cell transplants, without the increased risk of chronic graft-versus-host disease that is associated with blood stem cell transplants.

Unmanipulated HLA-mismatched/haploidentical blood and marrow hematopoietic stem cell transplantation.

Extensive ex vivo T cell-depleted or unmanipulated haploidentical transplantation provides benefits of rapid and near universal donor availability for patients without HLA-identical sibling donors or those who urgently need transplant. However, CD34 selected haplotype mismatched transplantation was limited by delayed immune reconstitution (IR), although this protocol has now been an acceptable approach. Recently, Peking University researchers developed a novel approach to HLA-mismatched/haploidentical blood and marrow transplantation without in vitro T cell depletion (GIAC protocol).

[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.

[Factors influencing engraftment in hematological patients after human leukocyte antigen matched sibling allogeneic blood and marrow transplantation].

Objective: To investigate the factors influencing engraftment in patients with hematological diseases after human leukocyte antigen matched sibling allogeneic blood and marrow transplantation.

Methods: One hundred and fifty-seven patients with hematological diseases who underwent allogeneic blood and marrow transplantation were enrolled in this study. The cell compositions in allografts were determined using multi-color flow cytometry.

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.

The impact of CD34+ cell dose on platelet engraftment in pediatric patients following unmanipulated haploidentical blood and marrow transplantation.

Objective: Unmanipulated haploidentical blood and marrow transplantation has been developed as an alternative transplant strategy for pediatric patients with hematological diseases. The aim of this study was to investigate the effects of donor and recipient characteristics on hematopoietic recovery in pediatric patients following unmanipulated haploidentical transplantation.

Methods: Factors correlating with hematopoietic recovery in 133 pediatric patients after unmanipulated haploidentical transplantation were analyzed retrospectively.

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.