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.

Influence of L-asaraginase and Pegaspargase on Coagulation Function of Adult Patients with Acute Lymphoblastic Leukemia and Analysis of Related Factors / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the coagulation function and relevant factors of adults patients with acute lymphoblastic leukemia treated with pegasparase (PEG-ASP) or L-asaraginase (L-ASP).</p><p><b>METHODS</b>The clinical features of 153 patients with acute lymphoblastic leukemia (ALL) received L-ASP or PEG-ASP in our hospital from January 2010 to January 2015 year were analyzed retrospectively. Among 153 patients, 108 patients received L-ASP treatment and 45 patients received PEG-ASP treatment. The change of coagulation function and the incidence of complications of 2 treated groups were compared, and the influence of differenent using time of L-ASP on above mentioned factors were analyzed.</p><p><b>RESULTS</b>The age, sex, white blood cell count (WBC) at diagnosis, subtype and risk factors of disease, total effective rate and complication rates showed no significant difference in the 2 groups (P > 0.05). The total infusion of fresh frozen plasma (FFP), cryoprecipitate and fibrinogen (FIB) also showed no significant difference (P = 0.12, 0.65, 0.09). FIB levels decreased slower after treatment of PEG-ASP (9.49 vs 6.90) (P = 0.000) than that after treatment of L-ASP. When L-ASP used at interval, FIB level decreased slower than that of continuous use. However, the risk of bleeding is higher when used at interval early (P = 0.01, 0.013).</p><p><b>CONCLUSION</b>Using PEG-ASP can better monitor the coagulation function than L-ASP. L-ASP used at interval can monitor the coagulation function easily, but its early use may cause an increased incidence of complications.</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>

Comparison of clinical implications of p16 deletion in childhood and adult B-lineage acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate and compare the clinical implications of p16 deletion in childhood and adult B-lineage acute lymphoblastic leukemia (B-ALL).</p><p><b>METHODS</b>A total of 129 cases of de novo childhood (73 cases) and adult (56 cases) B-ALL were examined genetically and immunologically using G-banding techniqhe, interphase fluorescence in situ hybridization (I-FISH) and immunophenotyping by flow cytometry, and their clinical data were retrospectively analyzed.</p><p><b>RESULTS</b>Of 73 childhood cases, the prevalences of homozygous deletion, hemizygous deletion and no deletion of p16 were 24.7% (18 cases), 6.8% (5 cases) and 68.5% (50 cases) respectively, and of 56 adult cases, the incidences as of 14.3% (8 cases), 8.9% (5 cases) and 76.8% (43 cases) respectively. The incidence of p16 deletion between the two groups had no significant difference (P = 0.338). In both groups, patients with or without p16 deletion had no significant difference in terms of white blood cells (WBC) count at diagnosis, BM blast percentage, chromosome karyotype, extra-infiltration and CR1 rate. Of note, there were 2 cases, each in childhood and adult, showed no deletion at the time of diagnosis, their p16 deletions occurred at relapse. The deletion of p16 was associated with poor overall survival and event-free survival (EFS) in both childhood and adults. According to the standard of NCI risk stratification, we divided patients of two groups into standard and high risk category respectively, and performed further analysis. The significance of different risk category in children and adults was disparity. The overall survival (OS) rates of deletion and no deletion of p16 were 45.3% and 79.8% (P = 0.006) in children, and 7.7% and 22.6% (P = 0.002) in adults, respectively. EFS rates of deletion and no deletion of p16 were 33.5% and 58.1% (P = 0.008) in children, and 0 and 10.9% (P < 0.01) in adults, respectively. Of the standard risk category in children, OS rates of deletion and no deletion of p16 were 46.8% and 89.3% (P = 0.015) respectively, and EFS rates of deletion and no deletion of p16 as of 40.9% and 82.1% (P = 0.007) respectively. Of the high risk category in children, OS rates of deletion and no deletion of p16 were 41.7% and 67.4% (P = 0.193) respectively, and EFS rates of deletion and no deletion of p16 were 25.0% and 25.6% (P = 0.305) respectively. Of the standard risk category in adults, OS rates of deletion and no deletion of p16 were 20.0% and 46.9% (P = 0.092) respectively, and EFS rates of deletion and no deletion of p16 were 0 and 25.0% (P = 0.062) respectively. Of the high risk category in adults, OS rates of deletion and no deletion of p16 were 0 and 12.4% (P < 0.001) respectively, and EFS rate of deletion and no deletion of p16 was 0 and 4.8%(P < 0.001), respectively.</p><p><b>CONCLUSION</b>This study indicated that deletion of p16 was associated with poor prognosis in both childhood and adult B-ALL, which highlighted an important significance to define the status of p16 in both childhood and adult B-ALL for predicting prognosis and guiding clinical intervention.</p>

Detection of the JAK2 gene mutation in familial myeloproliferative neoplasm and its clinical significance / 中华血液学杂志

<p><b>OBJECTIVE</b>To comprehend the abnormalities of JAK2, c-mp, EPOR, MPW515L/K and TET2 genes in patients with familial myeloproliferative neoplasm (MPN) and their relatives, and to explore mechanism of MPN pathogenesis.</p><p><b>METHODS</b>The complete blood counts of 2 brothers diagnosed with MPN in out hospital and their family members (15 persons in together) were performed, and bone marrow (BM) examinations in patients with abnormal blood count were performed PCR, DNA sequencing were used to evaluate the expression of related genes.</p><p><b>RESULTS</b>The elder brother was diagnosed with essential thrombocythemia (ET), the younger one was polycythemia vera (PV), and others had no clinical manifestation. The third MPN patient was diagnosed based on the blood count and BM examination. The PCR and sequencing results showed that there was JAK2V617F mutation in 3 patients, the elder brother was homozygous, the younger and their father were heterozygous. There were no BCR/ABL fusion gene and c-mp, EPOR, MPW515L/K, TET2 gene mutation in any member. By sequencing the full-length cDNA of familia JAK2 gene, we found that G380A heterozygous mutation was detected in 2 patients, which changed glycine at 127 into aspartic acid, C489T mutation was detected in 13 patients, G2490A mutation in 14, but both of them were synonymous mutations.</p><p><b>CONCLUSIONS</b>JAK2V617F is one of the important indicators to diagnose MPN. The JAK2V617F mutation of this family involves two generations. For newly diagnosed MPN patients, their family members should consider screening, so some familial patients can be diagnosed as early as possible. Gene mutation besides JAK2V627F can be detected by sequencing the full-length of JAK2 gene.</p>

Simultaneous analysis of telomere length and cell surface antigen in leukemia by multicolor Flow-FISH / 中国实验血液学杂志

This study was purposed to explore the feasibility of simultaneous analysis of telomere length and cell surface antigen by multicolor Flow-FISH to assess minimal residual disease (MRD) in leukemia. The telomere length in 34 leukemia patients versus 20 normal controls was compared by using Flow-FISH, and the relationship between telomere length and therapeutic effect and prognosis was analyzed preliminarily. As for those patients with follow-up samples, the changes of telomere length combined with surface antigen in different courses of disease were observed by multicolor Flow-FISH. The results indicated that the telomere length of de novo patients was significantly shorter than that of controls except the patients in chronic myeloid leukemia-chronic phase (CML-CP). The shorter telomere, the lower complete remission (CR) rates were observed in acute leukemia cases and the shorter duration of CP before onset of blast phase (BP) occurred in CML cases. The acute leukemia patients showed longer telomere and fewer cells expressed the related antigen after CR. The telomere length of cases with continued CR remained at normal level during remission, and there was no increased expression of the specific antigen. However, the telomere of relapsed cases shortened again after relapse with elevated specific antigen expression. In the relapsed cases, the telomere of related antigen positive cells shortened ahead of telomere length change of the whole cells and morphologic change of bone marrow cells. It is concluded that analysis of telomere length by flow-FISH manifests the significance for monitoring disease conditions, estimating prognosis and guiding therapy in all kinds of leukemia. The simultaneous analysis of telomere length and cell surface antigen by multicolor flow-FISH may monitor abnormal clone or clonal evolution to predict recurrence more sensitively and specifically, and may provide a promising and widely applicable method for monitoring MRD in leukemia.

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>

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>