Efficacy and safety of secondary allogeneic hematopoietic stem cell transplantation in 70 patients with recurrent hematologic malignancies after transplantation / 中华血液学杂志

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.

Clinical features and prognosis of childhood acute myeloid leukemia with myelodysplasia-related changes / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features and prognosis of childhood acute myeloid leukemia with myelodysplasia-related changes (AML-MRC).@*METHODS@#A retrospective analysis was performed on the medical data of 14 children who were diagnosed with AML-MRC from June 2014 to March 2020, including clinical features, laboratory examination results, and prognosis.@*RESULTS@#Among the 14 children with AML-MRC, there were 9 boys and 5 girls, with a median age of 11 years (range: 1-17 years), a median leukocyte count of 8.3×10@*CONCLUSIONS@#Childhood AML-MRC is often observed in boys, and AML-M5 is the most common type based on FAB classification. Such children tend to have a poor prognosis. HSCT is expected to improve the poor prognosis of children with AML-MRC. However due to the small number of cases, it is necessary to increase the number of cases for further observation.

Isolation of mononuclear cells from CNS tissue using Percoll gradients centrifugation / 中国药理学通报

Aim To establish a rapid method to efficiently iso-late mononuclear cells from central nervous system ( CNS) tis-sues of mice that can be effectively utilized for identification of various immune cell populations in a single sample by flow cy-tometry. Methods For defining the feasibility and practicality of the method, wild-type C57BL/6 mice and two mouse models of CNS disease including EAE mice and APP/PS1 mice were used in this study. After the collection and homogenization of the brain and spinal cord tissues respectively, the mononuclear cells were isolated by spinning the 70% -30% Percoll gradients. Cell activities were detected by trypan blue staining, and the im-mune population that infiltrated CNS was identified by flow cy-tometry. Results The results of trypan blue staining showed that the survival rate of the isolated cells was above 90% in all groups. Flow cytometry analysis showed that the relative num- bers of lymphocytes infiltrating CNS of EAE and AD mice in-creased significantly compared with wild-type C57BL/6 mice. In addition, the relative numbers of Th1 and Th17 cell subsets me-diating the inflammatory response also increased significantly, while the decreased regulatory T cells frequency was observed in the two mouse models of CNS disease. Conclusions The cells isolated by the 70% ~30% Percoll gradients centrifugation can be effectively utilized for the identification of various immune cell populations in a single sample by flow cytometry. The meth-od described in this article is simple and rapid in operation and with high survival rate and activity of the cells, which can be ap-plied to the study of the mononuclear cells in CNS.

Clinical pathological analysis of 7 cases of primary tonsil diffuse large B cell lymphoma / 中国实验血液学杂志

Tonsil is the most frequent site of the head and neck non-Hodgkin's lymphoma (NHL), and the diffuse large B cell lymphoma (DLBCL) is the most common pathological type in tonsil NHL. The aim of this study was to investigate the characteristics of clinical manifestation, immunophenotype, prognostic factor of primary tonsil DLBCL and its treatment strategy. The clinical data of 7 newly diagnosed patients with primary tonsil DLBCL from October 2009 to February 2013 were analyzed retrospectively. The results indicated that the pharynx or sore throat as the fist symptom was found in all patients. Out of 7 cases, 3 was in Ann Arbor stage I (42.8%), a case was in stage II (57.1%). Pathological immunohistochemical detection showed that the CD10 positive rate was 100%, BCL-2 positive rate was 83.3%, BCL-6 positive rate was 71.4%, Ki-67 ≥ 70% was 66.7%. They were all sensitive to chemotherapy and radiotherapy. Following up 4 to 40 months, they were all alive. It is concluded that most patients with primary tonsil DLBCL are at early stage, have an obvious characteristics of onset ages, clinical manifestations, pathological histology and achieve better remission through combined chemotherapy and radiotherapy.

Prevalence of EBV infection in patients with allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the prevalence of Epstein Barr Virus (EBV) in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>We retrospectively analyzed the clinical characteristics of 720 patients received allo-HSCT from January 2010 through December 2011 in the Stem Cell Transplant Center of People's Hospital.</p><p><b>RESULTS</b>Of 720 patients (469 male presented and 251 females), with a median age of 30 years (range, 2 to 67 years) old, 66 patients were presented with EBV reactivation. The cumulative incidence of EBV reactivation was (9.3±1.1)%, with a median days of 54.5 (range, 18 to 253 days). During one- year post-transplantation, the cumulative incidences of EBV reactivation in sibling allo-HSCT, haploidentical HSCT and unrelated donor HSCT were (1.3±0.7)%, (13.7±1.7)%, and (9.1±4.4)%, respectively. In patients with haplo-identical HSCT, the cumulative incidences of EBV viremia, probable EBV disease, and post-transplant lymphoproliferative disease (PTLD) were (5.8±1.1)%, (5.7±1.1)%, and (2.3±0.7)%. The mortality was (33.9±5.9)% in all patients with EBV infection: (63.6±15.8)% in PTLD, (42.3±9.9)% in probable EBV disease, (13.8±6.5)% in EBV viremia. By univariate and multivariate analysis, the use of ATG was an independent risk factor for EBV infection.</p><p><b>CONCLUSION</b>EBV reactivation is a common complication in patients with allo- HSCT, especially high mortality in PTLD and probable EBV disease. The use of ATG was an independent risk factor for EBV infection.</p>

Association of the ratio of regulatory and effector T cells with recurrence and chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the association of the ratio of regulatory and effector T cells with recurrence and chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Thirty patients with hematological malignancies who underwent allo-HSCT were classified as recurrence with cGVHD (n=4), non-recurrence with cGVHD (n=14), recurrence without cGVHD (n=5) and non-recurrence without cGVHD (n=7). The different percentage of CD4⁺CD25⁻CD69⁺ regulatory T cells in bone marrow and CD4⁺CD25⁺FoxP3⁺ regulatory T cells, Th1 cells and Th17 cells in peripheral blood were analyzed by flow cytometry.</p><p><b>RESULTS</b>There were no significant differences in all these T-cell subsets among different groups (P>0.05). While the ratio of CD4⁺CD25⁻CD69⁺ regulatory T cells and Th1 cells (0.211±0.177) in 9 recurrence patients was significant higher than that (0.133±0.160) in 21 non-recurrence patients (P=0.033). The ratio were also significance between recurrence without cGVHD and non-recurrence without cGVHD patients (0.167±0.073 vs 0.073±0.057, P=0.048), and between recurrence with cGVHD and non-recurrence without cGVHD patients (0.218±0.113 vs 0.073±0.057, P=0.024). Furthermore, the ratio of CD4⁺CD25⁺FoxP3⁺ regulatory T cells and Th17 cells was significant lower (1.975±2.045) in 18 cGVHD patients than that of 12 without cGVHD patients (3.198±1.132, P=0.010), and the ratio was also significant lower in non-recurrence patients with cGVHD (1.695±1.178) than that of without cGVHD (3.446±1.376, P=0.028).</p><p><b>CONCLUSION</b>Our results show that the ratio of CD4⁺CD25⁻CD69⁺ regulatory T cells and Th1 cells raise in recurrence patients, and the ratio of CD4⁺CD25⁺FoxP3⁺ regulatory T cells and Th17 decrease in cGVHD patients, which suggest that the ratio of regulatory and effector T cells had association with recurrence and cGVHD in patients with allo-HSCT.</p>

Reconstitution kinetics of T helper cells subsets post unmanipulated allogeneic blood and marrow transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the differences of the T helper cell reconstitution kinetics between HLA matched or HLA mismatched allo-HSCT through exploring the reconstitution kinetics of CD4+ CD25+Foxp3+ cells (CD4+ Treg), CD8+CD25+Foxp3+ cells (CD8+Treg), CD4+CD25-CD127+ conventional T cells (Tcon) and the secretion of IL-17a and IFN-γ in CD4+ T cells (Th17 and Th1 cells) or CD8+ T cells (Tc17 and Tc17 cells) post allogeneic hematopoietic stem cells transplantation (allo-HSCT).</p><p><b>METHODS</b>From December 2011 to October 2012, the peripheral blood (PB) of 20 patients undergoing HLA matched (10 patients) or mismatched (10 patients) allo- HSCT without acute graft-versus-host disease (aGVHD) and of 10 related healthy donors were collected to analyze the expression of CD25+Foxp3+, IL-17a, IFN-γ and CD127 expression through 8-colour Flow cytometer.</p><p><b>RESULTS</b>(1) The reconstitution kinetics of CD3+ T cells, CD4+ T cells, CD8+ T cells absolute numbers were comparable within 2 month post HLA matched and mismatched transplantation. (2)The absolute numbers of CD4+ Treg cells[+30 d, 8.46 (0.36-27.41) cells/μl 1.10 (0.04-8.03) cells/μl, P<0.05; +60 d, 8.50 (1.16-36.20) cells/μl vs 2.73 (0.34-6.84) cells/μl, P<0.05], Tcon cells[+30 d, 72.69 (3.85-211.73) cells/μl vs 13.41 (0.48-96.17) cells/μl, P<0.05; +60 d, 100.85 (16.28-267.20) cells/μl vs 47.75 (6.34-143.04) cells/μl, P<0.05], as well as Th17 cells[+30 d, 2.34 (0.02-6.87) cells/μl vs 0.20 (0.02-1.34) cells/μl, P<0.05; + 60 d, 1.90 (0.36- 7.82) cells/μl vs 0.46 (0.03-1.39) cells/μl, P<0.05]and Tc17 cells[+ 30 d, 1.08 (0.07-15.03) cells/μl vs 0.25 (0.01- 0.81) cells/μl, P<0.05;+60 d, 1.85 (0.63-26.57) cells/μl vs 0.46 (0.01-3.66) cells/μl, P<0.05]within 2 month post HLA matched HSCT were significantly higher than those post HLA- mismatched HSCT. However, the absolute numbers of Th1 cells or Tc1 cells within 2 month post HLA-matched or HLA-mismatched HSCT were comparable. (3) The ratio of Th1 and Th17 cells, or the ratio of Tc1 and Tc17 cells were significantly higher within 2 month post HLA-mismatched allo-HSCT compared to those post HLA-matched HSCT.</p><p><b>CONCLUSION</b>The reconstitution kinetics of T helper cells subset were different at early stage post HLA-matched or HLA-mismatched allo-HSCT, which might be help to explain the different rate or the different involved organ of the acute graft-versus-host diseases (aGVHD) post HLA-matched or -mismatched allo-HSCT.</p>

Prognostic significance of serum immunoglobulin paraprotein in chronic lymphocytic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the incidence of serum immunoglobulin (Ig) paraprotein in chronic lymphocytic leukemia (CLL), and to explore its clinical associated laboratory features and prognostic implication.</p><p><b>METHODS</b>Serum protein electrophoresis and immunofixation electrophoresis were performed by automatic electrophoresis apparatus to identify serum Ig paraprotein. Immunonephelometry was used to measure serum Ig levels.</p><p><b>RESULTS</b>Out of 101 CLL patients, serum Ig paraprotein detection was found in 20 (19.8%) cases, 13 (12.9%) patients with IgG paraprotein, 7 (6.9%) patients with IgM paraprotein and 1(1.0%) patient with IgA paraprotein. Among these 20 cases, 1 patient had both IgG and IgM paraprotein, 2 patients had both κ and λ light chains. The incidence of serum IgG paraprotein was high in the group of advanced Binet stage (P = 0.032) and high level of thymidine kinase 1 (TK1) (P = 0.013). The incidence of serum IgM paraprotein was high in the group of advanced Binet stage (P = 0.037), high level of TK1 (P = 0.017) and cytogenetic abnormalities of del(11q22.3) (P = 0.006). With a median follow-up of 30 months (range 1 - 101 months), 66 patients received therapy after initial diagnosis. Survival analysis showed that the patients with serum Ig paraprotein had significantly shorter treatment-free survival (TFS) times than the patients without serum Ig paraprotein (P = 0.024). And the patients with serum IgM paraprotein had significantly shorter treatment-free survival (TFS) times than the patients without serum Ig paraprotein (P = 0.013). However, serum Ig paraprotein or IgM paraprotein was not independent prognostic factor.</p><p><b>CONCLUSION</b>Serum Ig paraprotein can be detected in a subset of patients with CLL, which could be of value as a prognostic factor in CLL.</p>

Thiazolidinediones combined with metformin in treatment of polycystic ovary syndrome: A systematic review / 第二军医大学学报

Objective: To assess the efficacy and safety of thiazolidinediones combined with metformin in treatment of polycystic ovary syndrome. Methods: Electronic database searching was performed on Medline, Cochrane Library, EMbase, EBSCO, ScienceDirect, OVID, Springer LINK, Wiley, Chinese biology and medicine (CBM), China National Knowledge Infrastructure (CNKI), and Chongqing VIP Database; meanwhile, unpubished literature, conference papers and dissertations were also searched manually. The data included those from the establishment to November 2009. Randomized or clinical controlled trials concerning the thiazolidinediones and metformin combination therapy for PCOS were selected and assessed for the methodological quality, and Meta-analysis was performed using statistical software Revman 5. 0. Results: Five randomized controlled trials met the inclusion criteria and were included. Compared to metformin group, thiazolidinediones combined with metformin significantly improved insulin resistance(P<0.000 01, WMD=-0.21, 95%CI[-0.27, -0.15]) and ovulation rates (P=0.003, OR=2.76, 95%CI[1.14, 5.42]). There was no difference in WHR(P=0.51, WMD=0.02, 95%CI[-0.04, 0.08]) and serum testosterone(P=0.20, WMD=-31.14, 95%CI[-79.21, 16.92]) between the combination and metformin groups. However, single metformin therapy was shown to have more benefit in ameliorating BMI(P=0. 02, WMD=0.54, 95% CI[0.08, 1.00]) than the combination group. There were no serious adverse events during the treatment. Conclusion: Thiazolidinediones combined with metformin can greatly improve of insulin resistance and ovulation rates in PCOS women; besides, it is comparatively safe.