A single-center study on the distribution and antibiotic resistance of pathogens causing bloodstream infection in patients with hematological malignancies / 中华血液学杂志

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.

Prognostic significance of IKZF1 gene deletions in patients with B-cell acute lymphoblastic leukemia / 中华血液学杂志

Objective: This study aimed to investigate the prognostic significance of IKZF1 gene deletion in patients with acute B lymphoblastic leukemia (B-ALL) . Methods: The clinical data of 142 patients with B-ALL diagnosed in Nanfang Hospital between March 2016 and September 2019 were analyzed. Results: IKZF1 deletion was found in 36.0% of the 142 patients with B-ALL, whereas exon 4-7 deletion was found in 44.0% . White blood cell counts were higher in patients with the IKZF1 deletion (52.0% and 28.3% , P=0.005) ; these patients also experienced worse effects of mid-term induction therapy (40.0% and 70.7% , P<0.001) and had a higher proportion of Philadelphia chromosome-positive (52.0% and 21.7% , respectively, P<0.001) . Univariate analysis revealed that the 3-year overall survival rate (OS) and event-free survival rate (EFS) in the IKZF1 deletion group were significantly lower than the IKZF1 wild-type group [ (37.1±7.3) % vs (54.7±5.4) % , (51.8±7.9) % vs (73.9±4.7) % ; P=0.025, 0.013, respectively]. Multivariable analysis showed that harboring IKZF1 deletion was an adverse factor of EFS and OS (HR=1.744, 2.036; P=0.022, 0.020, respectively) . Furthermore, the IKZF1 deletion/chemotherapy group had significantly lower 3-year OS, EFS, and disease-free survival rates than other subgroups. In the IKZF1 deletion cohort, allo-hematopoietic stem cell transplantation (HSCT) significantly improved OS and EFS compared to non-allo-HSCT[ (67.9±10.4) % vs (31.9±11.0) % , (46.6±10.5) % vs (26.7±9.7) % ; P=0.005, 0.026, respectively]. Conclusion: Pediatric-inspired chemotherapy was unable to completely reverse the negative effect of IKZF1 deletion on prognosis. Pediatric-inspired regimen therapy combined with allo-HSCT, in contrast, significantly improved the overall prognosis of IKZF1 deletion B-ALL.

Clinical Characteristics and Prognosis of Elderly Patients with Medium and High risk Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and prognosis of patients with medium and high risk myelodysplastic syndrome (MDS).@*METHODS@#97 MDS patients above the age of 60 treated in Nanfang Hospital, Southern Medical University from February 2011 to August 2020 were enrolled. The clinical characteristics and prognosis of the MDS patients with medium risk, high risk or very high risk based on IPSS-R category were retrospectively analyzed. According to the difference of treatment regimes, the patients were divided into the transplantation group, chemotherapy group and other treatment group, and the efficacy among the patients in the 3 groups were analyzed.@*RESULTS@#MDS with excess blast (MDS-EB) in the elderly patients with medium and high risk MDS were the most common, 47.4% of the patients with abnormal chromosome karyotypes, and 23.7% with complex karyotypes (≥3). 97.3% of the patients showed at least one gene mutation, and TP53 mutations were detected in nearly 20% of the patients with medium and high risk. Multivariate analysis showed that IPSS-R category and treatment regimes were the factors affecting the prognosis of elderly patients with medium and high risk MDS. The median overall survival (OS) time of the patients in the 3 groups showed significant difference (P=0.012), and the median OS of the patients in the transplantation group was significantly longer than that in the chemotherapy group and other group (P=0.003,P=0.014,respectively), while there was no significant difference in median OS between chemotherapy group and other treatment group (P=0.685).@*CONCLUSION@#Elderly MDS patients with medium and high risk can benefit from allogeneic hematopoietic stem cell transplantation, which will prolong their OS.

Sclerodermatous chronic graft-versus-host disease after hematopoietic stem cell transplantation: incidence, clinical characteristics and risk factors / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the incidence and risk factors of sclerodermatous chronic graft-versus-host disease (ScGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>The clinical data of 259 patients undergoing allo-HSCT in Nanfang Hospital between January, 2012 and December, 2014 were analyzed.</p><p><b>RESULTS</b>Chronic GVHD following allo-HSCT occurred in 134 (51.7%) cases, among whom 22 patients showed sclerodermatous features at a median of 12.5 months (range 4-28 months) after the transplantation. The overall incidence of ScGVHD was 8.49% (22/259) in the recipients and 16.4% (22/134) in those with cGVHD. Univariate analysis showed that the conditioning regimen with total body irradiation (P=0.031), GVHD prophylaxis with MMF (P=0.046), presence of chronic GVHD (P=0.008), and donor lymphocyte infusion (P=0.001) were all closely associated with the occurrence of ScGVHD. Multivariate analysis identified chronic GVHD (RR=3.512, 95%CI: 1.235-9.987, P=0.018) and donor lymphocyte infusion (RR=5.217, 95%CI: 1.698-16.029, P=0.004) as the independent risk factors of ScGVHD.</p><p><b>CONCLUSION</b>ScGVHD following allo-HSCT is not a common complication, and cGVHD and donor lymphocyte infusion are the independent risk factors for ScGVHD.</p>

Clinical analysis of acute heart failure's risk factor for chronic myelogenous leukemia patient during the early stage of allogeneic hematopoietic stem cell transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>The study was to analyze the acute heart failure's risk factors and clinical characteristics for the patient with chronic myelogenous leukemia (CML) during the early stage (within 100 d) of allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>A total of 106 cases of CML received allo-HSCT were retrospectively studied in Nanfang Hospital from May 2003 to May 2013. On the basis of existence or absence of acute heart failure during early stage of allo-HSCT (100 d), the patients were divided into heart failure (15 cases) and control group (91 cases). Using Logistic univariate analysis, Fisher' exact test and Pearson X(2) test, the acute heart failure's risk factors and clinical characteristics of both groups were analyzed.</p><p><b>RESULTS</b>The median occurrence time of acute heart failure was 3 d (1 d before transplantation to 84 d after transplantation). Logistic univariate analysis indicated that the imatinib treatment history and time, and the prophylaxis regimens for GVHD with anti-thymocyte globulin (ATG) were all the poor prognostic factors for acute heart failure. Incidence of hepatic veno-occlusive disease (HVOD), bacterial infection and adverse prognostic events including death in the heart failure group patients were statistically higher than that in control group (P < 0.05).</p><p><b>CONCLUSION</b>Acute heart failure mostly happened in the early stage after allo-HSCT, imatinib treatment and GVHD prophylaxis regimens with ATG are the poor prognostic factors for acute heart failure. The patients of heart failure group seem to have higher incidence of hepatic veno-occlusive disease (HVOD), bacterial infection and deaths.</p>

Clinical observation of mesenchymal stem cell as salvage treatment for refractory acute graft-versus-host disease / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of mesenchymal stem cells (MSCs) on refractory acute graft-versus-host disease (GVHD) failed to second-line immunosuppressive therapy.</p><p><b>METHODS</b>Twenty-two patients with refractory aGVHD received the treatment of first- and/or second-line immunosuppressive agents in combination with MSCs. The MSCs from bone marrow (BM) of HLA-unrelated third-party donors, were used at the median time of 19 (11 - 49) days after aGVHD onset, at a dose of 1×10(6)/kg once with an interval of 14 days. If the symptoms of aGVHD did not improve after continuous infusion four times, MSCs would be discontinued. Meanwhile the proportion of CD3(+)CD4(+), CD3(+)CD8(+) and CD4(+)CD25(+) was detected by flow cytometry (FCM) before and 4 weeks after the MSCs infusion.</p><p><b>RESULTS</b>The median dose of MSC was 4.8 (2.5 - 6.3)×10(6) cell×kg(-1) with a median infusion of 2.5 (1 - 7) times per case. Twelve patients achieved complete response (CR), four partial response (PR) after treatment. The total effective rate was 72.7% (16/22). With a median follow-up of 246.5 (36 - 1116) days post-transplantation, 11 patients survived and 11 died. The causes of death included GVHD(n = 6), infections (n = 3), leukemia relapse (n = 1) and post-transplant lymphoproliferative diseases (n = 1), respectively. The proportion of CD3(+)CD4(+)/CD3(+)CD8(+) was significantly higher at 4th week after MSCs infusion compared to before infusion (1.58 ± 0.54 vs 0.49 ± 0.19, \%t\% = 0.628, P = 0.04). The number of CD4(+)CD25(+) Treg cells had not changed much compared to before infusion (P = 0.606).</p><p><b>CONCLUSION</b>MSCs derived from the BM of a third-party donor are effective to treat aGVHD failed to second-line immunosuppressive therapy after allo-HSCT. MSCs might play a role in aGVHD by regulating the rate of CD3(+)CD4(+)/CD3(+)CD8(+).</p>

The outcome and safety of mesenchymal stem cells from bone marrow of a third party donor in treatment of secondary poor graft function following allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of bone marrow-derived mesenchymal stem cells (MSC) from a third party donor for secondary poor graft function (PGF) following allogeneic hematopoietic stem cell transplantation(allo-HSCT).</p><p><b>METHODS</b>Five patients with secondary PGF were treated with MSC at a dose of 1 x 10(6)/kg body weight at a median of 47 days (35 to 61) after secondary PGF. MSC were derived from bone marrow (BM) of HLA-disparate third party donors, cultured in vitro and infused without HSC. If absolute neutrophil cell (ANC) and platelet counts (PLT) did not reach the standardization of > 1.5 x 10(9)/L and > 50.0 x 10(9)/L, respectively, within 28-30 days after the first MSC treatment, a second MSC treatment was required.</p><p><b>RESULTS</b>MSC were infused once in one patient and twice in four patients with an interval of 28 to 30 days. All patients obtained ANC and PLT recovery at a median of 34 (25 to 49) days and 47 (26 to 54) days, respectively, without toxic side effects within follow-up periods of median 761 (204-1491) days. Three patients developed Epstein-Barr virus (EBV) reactivation at 42, 48, 108 days after MSC infusion, respectively and two of the three coverted to posttransplant lymphoproliferative disorders (PTLD).</p><p><b>CONCLUSION</b>MSC from a third party donor are effective to patients with secondary PGF following allo-HSCT, whether it might increase the risk of EBV reactivation and EBV-associated PTLD need further observation.</p>

Impact of HLA compatibility on the outcome of allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the influence of HLA compatibility on the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with chronic myeloid leukemia (CML).</p><p><b>METHODS</b>This retrospective study involved 121 CML patients including 90 in chronic phase, 8 in accelerated phase and 23 with blast crisis. Of these patients, 85 received related and 36 had unrelated donor allo-HSCT. The conditioning regimens included total body irradiation with cyclophosphamide in 37 patients, and modified BUCY protocol in 84 patients. Cyclosporine A (CsA) and methotrexate (MTX) were used for graft-versus-host disease (GVHD) prophylaxis in patients undergoing HLA-matched sibling donor transplants. CsA, MTX, antihuman thymocyte globulin and mycophenolate were used in all the patients undergoing HLA-mismatched related donor and unrelated donor transplants. The prognostic factors of CML were evaluated using Cox regression and the cumulative overall survival and the disease-free survival were estimated using Kaplan and Meier survival analysis model.</p><p><b>RESULTS</b>The incidence of II-IV acute GVHD was 26.1% in HLA-matched and 53.3% in HLA-mismatched cases (P=0.006), with a 5-year cumulative incidence of chronic GVHD of 47.4% and 49.6%, respectively (P=0.947). The 5-year cumulative incidences of disease relapse was 16.7% in the total patients, with a 5-year cumulative overall survival (OS) of 70.5% and disease-free survival (DFS) of 63.4%. The 5-year OS was 78.2% in HLA-matched cases, as compared with 47.6% in HLA-mismatched cases. Multivariate analysis with Cox regression model identified HLA mismatch, II-IV acute GVHD, and advanced phase as the risk factors affecting the OS.</p><p><b>CONCLUSION</b>HLA mismatch can significantly increase the incidence of II-IV acute GVHD following allo-HSCT and decrease the long-term survival rate, which is not related to the donor source.</p>

Effect of granulocyte colony stimulating factor on myeloid-derived suppressor cells in the bone marrow and peripheral blood: a preliminary study / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of granulocyte colony stimulating factor (G-CSF) on myeloid-derived suppressor cells (MDSCs) in the bone marrow and peripheral blood, and explore the relationship between MDSC and graft-versus-host disease (GVHD).</p><p><b>METHODS</b>Bone marrow, peripheral blood and peripheral blood stem cells were obtained from 12 healthy hemopoietic stem cell donors before and on day 5 after G-CSF mobilization. Flow cytometry was employed to examine the number of MDSC, and the relationship between MDSC number and the incidence of GVHD was analyzed.</p><p><b>RESULTS</b>In normal physiological conditions, MDSC could be detected in the peripheral blood and bone marrow with a cell percentages of (1.35±0.35)% and (2.44±1.11)%, respectively, showing a significantly higher cell percentage in the bone marrow (P=0.015). On the 5th day after G-CSF mobilization, the percentage of MDSCs increased to (4.01±1.82)% in the peripheral blood and to (4.38±2.19)% in the bone marrow, showing no significant difference between them (P=0.083). The mobilization caused a significant increase in the number of MDSCs in the peripheral blood (P=0.047) but not in the bone marrow (P=0.761). The number of MDSCs in the collected samples showed a significant inverse correlation to the incidence of GVHD (P=0.048).</p><p><b>CONCLUSIONS</b>MDSCs are present in the peripheral blood and bone marrow of healthy donors, with a greater number in the bone marrow. G-CSF can mobilize the MDSCs from the bone marrow to the peripheral blood to increase number of MDSCs in the peripheral blood, which may contribute to a lowered incidence of GVHD in hematopoietic stem cell transplantation (HSCT).</p>

The incidence and risk factors of late-onset non-infectious pulmonary complications after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the incidence and the risk factors of late-onset non-infectious pulmonary complications (LONIPC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Clinical data from 144 patients who underwent allo-HSCT and survived more than 3 months at our institution between January 2003 and August 2006 were collected, and the incidence and its risk factors of LONIPC were reviewed retrospectively.</p><p><b>RESULTS</b>With a median follow-up time of 1149 (103 - 2151) d, 24 patients (16.7%) fulfilled the diagnostic criteria for LONIPC. The median time to diagnosis of LONIPC was 235 days after transplantation (range, 116 - 950 days). Three variables were associated with LONIPC on univariate analysis: CMV antigenaemia (P = 0.000), grade II-IV aGVHD (P = 0.026) and cGVHD (P = 0.002). By using a Binary Logistic regression model for multivariate analysis, cGVHD (OR = 18.804, P = 0.004) and CMV antigenaemia (OR = 14.376, P = 0.000) were the risk factors of LONIPC.</p><p><b>CONCLUSION</b>LONIPC is one of the major complications after allo-HSCT and cGVHD and CMV antigenaemia are the risk factors for developing LONIPC.</p>

Quantitative real-time PCR for detecting the expression levels of TCR Vgamma subfamilies in patients with graft-versus-host disease following allogenic hematopoietic stem cell transplantation / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of T cell receptor (TCR) Vgamma genes in patients with graft-versus-host disease (GVHD) after allogenic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>The expression levels of the TCR Vgamma I-III genes in peripheral blood mononuclear cells (PBMNCs) from 18 patients with GVHD following allo-HSCT were determined using real-time fluorescence quantitative PCR, with 12 healthy individuals serving as the normal controls.</p><p><b>RESULTS</b>The expression level of TCR Vgamma II gene in the PBMNCs from patients with GVHD was significant lower than that in the normal controls. The expression patterns of TCR Vgamma I-III subfamilies also underwent alterations in patients with GVHD, and the expression level of TCR Vgamma II gene was significantly lower than that of TCR Vgamma I gene or TCR Vgamma III gene.</p><p><b>CONCLUSION</b>The low expression of TCR Vgamma II subfamily might be related to the pathogenesis of GVHD in patients receiving allo-HSCT.</p>

Identification of acute lymphoctic leukemia extramedullary relapse and PTLD after allo-HSCT by monitoring sex chromosome chimeric status with FISH / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the role of monitoring sex chromosome chimeric status by fluorescence in situ hybridization (FISH) in the identification of leukemic extramedullary relapse and post-transplant lymphoproliferative disease (PTLD) in acute lymphocytic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Six ALL patients who received sex-mismatched allo-HSCT and manifested extravisceral lymphadenectasis or local lump were investigated. The sex chromosome chimeric status in tumor tissues and bone marrows (BM) were monitored by FISH, and EBV-RNA in the tumor tissues were detected by in situ hybridization (ISH).</p><p><b>RESULTS</b>The sex chromosomes in BM of all 6 patients were 100% donor-derived. Among the sex chromosome chimeric status of tumor tissues, three patients were mainly recipient-derived, and the percentage of sex chromosomes derived from recipients were 100%, 100% and 98.0%, respectively, and then they were diagnosed leukemic extramedullary relapse. The other 3 patients were donor-derived, the percentage was 98.5%, 96.0% and 91.5%, respectively, and were diagnosed PTLD. EBV-RNA and latent membrane protein (LMP-1) were positive in 2 patients with PTLD and negative in the other 4 patients. One patient with extramedullary relapse obtained partial remission, one with PTLD gained complete remission, and the others died eventually after therapy.</p><p><b>CONCLUSION</b>Monitoring the sex chromosome chimeric status by FISH is an effective method to distinguish leukemic extramedullary relapse from PTLD in ALL received sex-mismatched donor HSCT.</p>

Study on relationship between chemical castration and thymic function following hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the impact of luteinizing hormone-releasing hormone (LHRH) on the protection of thymic function after allogenic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Murine model of MHC mismatched allogeneic HSCT (C57BL/6-->BALB/c) was established. The severity of acute graft-versus-host-disease (GVHD) was assessed according to a clinical scoring system. The intra-cellular levels of IFN gamma, TNFalpha and IL-1 beta in thymocyte were analyzed by protein array and thymic function by quantification of signal-joint TCR rearrangement excision circles (sjTRECs).</p><p><b>RESULTS</b>All recipients in group A (allogeneic mice), B (allogeneic LHRH castrated-mice) and C (syngenic mice) achieved hematopoietic reconstitution. White blood cell (WBC) over 1.0 x 10(9)/L in groups A, B and C were on day (11.2 +/- 1.4), day (9.8 +/- 0.6) and day (9.7 +/- 0.7), respectively (P = 0.003, 0.002). The onset of acute GVHD in group B was (14.1 +/- 0.7) d and in group A was (11.4 +/- 1.2) d (P = 0.000). All mice in groups A and B developed acute GVHD. No mice occurred aGVHD in group C. The average scores of acute GVHD in groups A and B were (9.1 +/- 0.7) and (5.1 +/- 1.0), respectively (P = 0.000). The levels of IFN gamma, TNFalpha and IL-1 beta in control group were (2.3 +/- 2.5) ng/ml, (1.7 +/- 1.1) pg/ml and (1.8 +/- 1.2) pg/ml, respectively. The IFN gamma levels in groups A, B and C were (10.5 +/- 2.1) ng/ml, (6.7 +/- 2.1) ng/ml and (5.2 +/- 3.3) ng/ml, TNFalpha levels were (7.0 +/- 2.6) pg/ml, (4.3 +/- 0.8) pg/ml and (3.0 +/- 1.8) pg/ml, and IL-1 beta levels were (24.9 +/- 9.0) pg/ml, (17.4 +/- 3.9) pg/ml and (10.8 +/- 3.1) pg/ml, respectively. There were significant differences in the levels of cytokines between group A and the control group (P = 0.000, 0.000, 0.000). The levels of cytokines in group B were significantly higher than those in control group (P = 0.000, 0.003, 0.000). The levels of IFN gamma and IL-beta in group C were significantly higher than those of in control group (P = 0.015, 0.013), and so did in group A than in group B (P = 0.002, 0.002, 0.004), and in group A than in group C (P = 0.000, 0.000, 0.000). The analysis of linear regression showed that the average levels of IFN gamma and TNFalpha paralleled with aGVHD scores (r(2) = 0.359, P = 0.045; r(2) = 0.228, P = 0.019). The average sjTRECs copies/1000 PBMNCs were (39.4 +/- 44.7) in the control group and (12.3 +/- 13.0), (58.0 +/- 71.8) and (19.6 +/- 14.6) in groups A, B and C, respectively. There was no significant difference in the multiple comparisons of peripheral blood levels of sjTRECs among these four groups (P = 0.468).</p><p><b>CONCLUSION</b>IFN gamma, TNFalpha and IL-1 beta might be involved in the damage to the thymus by acute GVHD. Sex steroid inhibitor can not only reduce the severity of thymic damage after allo-HSCT, but also reduce the severity of aGVHD and the mechanism might be associated with the reduction of intra-cellular levels of IFN gamma in thymocyte.</p>

Role of membrane-bound human leukocyte antigen G in inducing immune tolerance after allogeneic hematopoietic stem cell transplantation / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the role of human leukocyte antigen G (HLA-G) in the better effect of allogenetic bone marrow transplantation than that of peripheral blood stem cell transplantation.</p><p><b>METHODS</b>Flow cytometry was used to detect the expression of membrane-bound HLA-G (mHLA-G) on donor peripheral blood (PBC) or bone marrow (BM) mononuclear cells. The levels of soluble HLA-G (sHLA-G) in the plasma and bone marrow fluid were determined using enzyme-linked immunosorbent assay (ELISA) before and after granulocyte colony-stimulating factor (G-CSF) mobilization.</p><p><b>RESULTS</b>The mean levels of mHLA-G after G-CSF mobilization in the PBC and BM were significantly higher than that before G-CSF mobilization (P=0.001 and 0.000), but the plasma levels of sHLA-G showed no significant changes after the mobilization (P=0.279). The mean levels of sHLA-G in the BM fluid significantly increased (P=0.002) to a level higher than that in the PBC after G-CSF mobilization (P=0.004).</p><p><b>CONCLUSION</b>HLA-G plays an important role in immune tolerance after hematopoietic stem cell transplantation with G-CSF mobilization.</p>

Effects of graft compositions on hematopoietic reconstitution and graft-versus-host disease in related donor peripheral blood stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the effects of graft composition on hematopoietic reconstitution and graft-versus-host disease (GVHD) in HLA-identical related donor peripheral blood stem cell transplantation (PBSCT) for hematological malignancies.</p><p><b>METHODS</b>The relationship between the number of graft composition and their hematopoietic reconstitution and GVHD in 107 patients with hematological malignancies undergoing HLA-identical related donor PBSCT was retrospectively analyzed.</p><p><b>RESULTS</b>None of the graft composition numbers had correlation with the time of neutrophil reconstitution. There was a negative correlation between the number of mononuclear cells (MNCs) or CD34+ cells and the time of platelet reconstitution (P < 0.05) with the absolute correlation coefficients below 0.4, and so did between the number of CD34+ or CD34+ CD38- cells and the development of acute GVHD (P < 0.05) and their absolute correlation coefficients. Each lymphocyte subset number had no correlation with acute GVHD. There was a positive correlation between the number of CD25+ CD4+, CD3+ or CD4+ CD3+ cells or CD4+ /CD8+ ratio and the development of chronic GVHD (P < 0.05). And the correlation coefficients all exceeded 0.4, more over, CD25+ CD4+ cells number reached up to 0.78. CD34+, CD34+ CD38- cells number had no correlation with chronic GVHD.</p><p><b>CONCLUSION</b>In HLA-identical related donor PBSCT, further increasing infused MNC, CD34+, CD34+ CD38- cells can no more accelerated hematopoietic reconstitution after these cells attained their threshold values, otherwise the incidence of cGVHD might increase due to the increase of the accompanied lymphocytes.</p>

Effect of donor CD4+CD25+ regulatory T cells on hematopoietic and immune reconstitution, GVHD and disease-free survival after allogeneic hematopoietic stem cell transplantation / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of donor CD4+;CD25+; regulatory T cells (TReg) on hematopoietic reconstitution, immune reconstitutuion and graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Thirty patients were divided into high TReg group (TReg> or =10.0 x 10(6) cells/kg, n=13) and low TReg group (TReg<10.0 x 10(6) cells/kg, n=17) according to the number of TReg in the grafts. Flow cytometry (FCM) was used to detect the TReg percentage in the grafts and recipients peripheral blood T lymphocyte subsets and TReg at different time points after allo-HSCT. The hematopoietic reconstitution, immune reconstitution, TReg reconstitution, incidence of GVHD and disease-free survival were compared between the two groups.</p><p><b>RESULTS</b>The high and low TReg groups showed similar WBC reconstitution time (+8.62-/+2.29 vs +8.88-/+2.71 days, P=0.778) and platelet reconstitution time (+12.69-/+5.74 vs +15.18-/+6.71 days, P=0.613). In high TReg group, the reconstitutions of CD4+;CD3+; and CD45RO+;CD4+; T cells on day 15 and CD3+; and CD4+;CD3+; T cells on day 30 were significantly accelerated in comparison with those of the low TReg group (with P values of 0.039, 0.024, 0.014, 0.020, respectively). TReg reconstitution 15 and 180 days following the surgery was significantly faster in high TReg group than in low TReg group (P=0.013, 0.005, respectively). The incidence of acute GVHD in high TReg group (61.54%) was obviously lower than that in low TReg group (94.12%, P=0.027). A negative correlation was found between the number of infused donor TReg and the severity of acute GVHD (rs=-0.393, P=0.032). The one-year disease-free survival rates of the high and low TReg groups were (60.40-/+16.10)% and (72.00-/+12.00)%, respectively, showing no significant difference between the two groups (P=0.818).</p><p><b>CONCLUSION</b>Donor TReg may promote immunological reconstitution and TReg reconstitution, and decrease the incidence of acute GVHD after allo-HSCT.</p>

Influence of donor T(reg) cells on GVHD and hematopoietic reconstitution after allogeneic bone marrow transplantation in mice / 中国实验血液学杂志

In order to explore the influence of purified donor regulatory T cells (T(Reg) cells) infused after allogeneic bone marrow transplantation (allo-BMT) on GVHD and hematopoietic reconstitution of mice, an allo-BMT model of C(57)BL/6-->BALB/c mice was established. CD4(+)CD25(+)T(Reg) cells were purified through bead-magnetic activated cells separated from donor mice peripheral blood. The recipient mice were randomly divided into three groups: CD4(+)CD25(+) T cells, CD4(+)CD25(-) T cells and RPMI 1640 culture medium. These cells and RPMI 1640 were infused into recipient mice by caudal veins at about 6 to 8 hours after allo-BMT respectively. Incidence of GVHD, pathological lesion of liver, spleen, small intestine, survival time and hematopoietic reconstitution in the recipients were observed after allo-BMT. The results showed that the time for WBC > 1.0 x 10(9)/L was (8.14 +/- 3.26) days, (17.62 +/- 5.71) days, (19.81 +/- 6.77) days and the time for Plt > 20.0 x 10(9)/L was (5.29 +/- 1.34) days, (8.97 +/- 3.44) days, (9.52 +/- 3.92) days in T(Reg) positive cell group, T(Reg) negative cell group and the blank control group respectively, and the recovery times of WBC and Plt in T(Reg) positive cell group were faster than that in T(Reg) negative cell group and the blank control group (P < 0.05). The scores of GVHD were (1.33 +/- 0.58), (1.80 +/- 0.27), (1.93 +/- 0.45) in three groups of mice at about 15 days after allo-BMT, respectively, the GVHD in T(Reg) positive cell group was slighter than that in T(Reg) negative cell group and the blank control group (P < 0.05). It was found that GVHD pathologic manifestations of the liver, spleen and small intestine in T(Reg) positive cell group were slighter in a certain extent than those in other two groups at about (25 - 30) days after allo-BMT. The mean survival time in three groups was (41.45 +/- 17.88) days, (18.75 +/- 14.39) days and (25.67 +/- 16.84) days after allo-BMT, respectively, which in the T(Reg) positive cell group was significantly longer than that in other two groups (P < 0.05). It is concluded that donor-T(Reg) cell infusion can mitigate the GVHD so as to reach hematopoietic reconstitution and prolong survival time after allo-BMT in mice.

Comparison of clinical outcomes between unrelated donor peripheral blood stem cell transplantation and bone marrow transplantation for leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the hemopoietic reconstitution, immune reconstitution, infection, incidence of graft-versus-host disease (GVHD) and clinical outcome between unrelated donor peripheral blood stem cell (PBSC) transplantation and bone marrow (BM) transplantation for leukemias.</p><p><b>METHODS</b>The clinical results of 21 leukemia patients receiving G-CSF mobilized PBSC graft from unrelated donors were compared with that of 32 patients receiving unrelated BM transplants.</p><p><b>RESULTS</b>Compared with BM grafts, the PBSC graft contained significantly more nucleated cells (P = 0.000), and resulted in a significantly shorter time-to-neutrophil (12.43 +/- 3.67 vs 16.16 + 2.99 days) and platelet engraftment (14.67 +/- 6.19 vs 21.23 +/- 8.25 days), (P = 0.000 and 0.003, respectively). T cell reconstitution between the two groups differed little after transplantation. The incidences of early-stage infection (42.86% vs 53.13%), the probabilities of acute graft-versus-host disease (aGVHD) (61.90% vs 71.88%), the grades III to IV aGVHD (23.81% vs 15.63%), the chronic GVHD (47.06% vs 43.48%) and the probabilities of relapse (6.90% vs 12.50%) between PBSC and BM groups all has no statistical significance (NS). The 2-year disease free survival (DFS) rates of the two groups were (50.14 +/- 12.00) % and (59.81 +/- 8.99)%, respectively also have no NS.</p><p><b>CONCLUSION</b>G-CSF-mobilized unrelated donor PBSCs engraft more rapidly in the recipients as compared with conventional BM grafts. The T cell reconstitution, the incidence of infection, the incidence and severity of aGVHD and cGVHD, and the 2-year DFS rates between the two groups all have no significant differences.</p>

A comparative study of unrelated donor bone marrow transplantation and peripheral blood stem cell transplantation for their therapeutic effects on leukemia / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the effect of unrelated donor bone marrow (BM) transplantation and peripheral blood stem cell (PBSC) transplantation in light of hemopoietic reconstitution, immune reconstitution, infection, incidence of graft-versus-host disease (GVHD) and other complications in patients with leukemia.</p><p><b>METHODS</b>The clinical outcomes of 16 patients receiving unrelated PBSC graft mobilized by granulocyte colony-stimulating factor (G-CSF) were compared with 30 patients receiving unrelated BM transplantation.</p><p><b>RESULTS</b>Engraftment was achieved in 97.83% of the total patients. Compared with BM transplantation group, PBSC graft contained significantly more nucleated cells (P=0.000), resulting in a significantly shorter time-to-neutrophil (16.21-/+3.09 vs 12.81-/+4.15 days, P=0.003) and platelet engraftment (20.31-/+7.19 vs 15.50-/+6.91 days, P=0.035). T cell reconstitution differed little between the two groups at different time points after transplantation. The incidences of early-stage infection were 37.50% and 50.00% (P=0.644) in the PBSC and BM groups, respectively. In PBSC and BM groups, the incidences of grades I to IV acute GVHD (aGVHD) were 56.25% and 70.00% (P=0.456), 18.75% and 13.79% (P=0.661) for grades III to IV aGVHD, and 30.77% and 36.36% (P=0.413) for chronic GVHD (cGVHD), respectively. The nonrelapse transplant-related mortality (TRM) rates were 18.75% in PBSC group and 33.33% in BM group (P=0.295). The relapse occurred in 18.75% and 6.90% (P=0.226) of the patients in the two groups, respectively, and the 2-year disease-free survival (DFS) rates were 62.19% and 56.23% (P=0.615), respectively.</p><p><b>CONCLUSION</b>G-CSF-mobilized PBSCs allow more rapid engraftment in unrelated donor recipients in comparison with conventional BM, but T cell reconstitution and the incidence of infection between the two groups differ little, nor are there significant differences in the incidence or severity of aGVHD and cGVHD, nonrelapse TRM or 2-year DFS rates between the two groups.</p>