Current status of diagnosis and treatment of chronic lymphocytic leukemia in China: A national multicenter survey research / 中华血液学杂志

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.

First-dose response of part-time versus full-time occlusion therapy for the treatment of amblyopia in children / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the efficacy of the first follow-up visit after daily partial or full-day occlusion of the dominant eye in patients with unilateral amblyopia and assess the maximum efficacy produced by different amounts of occlusion.METHODS: A retrospective clinical study was conducted on 135 cases of unilateral amblyopia cured in our hospital's outpatient clinic from January 2020 to December 2021. They were divided into 2h/d occlusion group, 6h/d occlusion group and all-day occlusion group according to the duration of occlusion, with fine sight training of amblyopic eyes. The effect of the first dose(baseline visual acuity-first review visual acuity), cured visual acuity, stereo vision at the first review and cure time of amblyopic eyes were recorded. The factors affecting the first dose effect in patients with unilateral amblyopia were also analyzed.RESULTS: All patients had a baseline visual acuity of 0.4(0.22, 0.52), a first follow-up visual acuity of 0.22(0.15, 0.3), a first-dose effect of 0.1(0.08, 0.18), and a visual acuity of 0(-0.08, 0.05)when amblyopia cured. The first-dose effects were 0.08(0.07, 0.12)for patients in the 2h/d occlusion group, 0.18(0.08, 0.3)for the 6h/d occlusion group, and 0.10(0.08, 0.18)for the all-day occlusion group. The most significant first-dose effect was the 6h/d occlusion group(P<0.05); Analysis of different influencing factors showed that the highest values of the first-dose effect of 6h/d occlusion were in the 3-6 years group, 7-12 years group, female group, strabismic amblyopia group and mild to moderate group(P<0.05); Furthermore, the first dose effect of the 6h/d occlusion was positively correlated with cure time of amblyopic eyes(rs=0.334, P=0.038). At the first follow-up, 21 cases(53.8%)had improved Titmus stereo visual acuity in the 6h/d occlusion group, which was higher than that in the 2h/d and all-day occlusion groups [16 cases(41.0%), 13 cases(22.8%), P<0.017].CONCLUSIONS: For monocular amblyopia, the first-dose effect of 6h/d occlusion treatment was the most significant, and the recovery of stereopsis was the best.

Evaluation of GELTAMO-IPI for Patients with Diffuse Large B-cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To evaluate the prognostic value of GELTAMO-IPI for patients with diffuse large B-cell lymphoma (DLBCL).@*METHODS@#The clinical data of 238 newly diagnosed DLBCL patients treated in Shanxi Cancer Hospital from September 2011 to March 2016 were collected retrospectively, the risk stratification and prognostic evaluation of the patients were analyzed according to GELTAMO-IPI. Progression-free survival (PFS) and overall survival (OS) of the patients were analyzed by the Kaplan-Meier method, COX regression analysis was used to compare the risk of death and progress in each risk group. Harrell's C statistics was used to compare the prognostic stratification ability of each model.@*RESULTS@#The 3-year OS rate statistics showed that both IPI and GELTAMO-IPI could distinguish low risk group and Low-intermediate risk group, but the prognosis stratification ability of IPI was better (IPI: HR=5.085, P0.05). GELTAMO-IPI could distinguish High-intermediate risk group from high risk group (GELTAMO-IPI: HR=2.966, P50%). The results of Harrell's C statistics showed the C-index of IPI and GELTAMO-IPI was 0.687 and 0.721 (P<0.001); the C-index of the predicted PFS was 0.672 and 0.700 (P<0.001). It was suggested that the prognostic stratification ability of GELTAM0-IPI be superior to that of IPI, R-IPI, NCCN-IPI.@*CONCLUSION@#GELTAMO-IPI can make a clear distinction between DLBCL patients with different prognosis, especially for high-risk patients, and the prognostic stratification ability of GELTAMO-IPI is significantly better than that of IPI.

Diethylmorphine effect on action potential and calcium ion current of neonatal rat cardiomyocytes in vitro / 中国组织工程研究

BACKGROUND: Opioids can regulate the changes of membrane potential and Ca2+ current in cardiomyocytes, but whether diacetylmorphine can induce the changes of cardiac rhythm, cell action potential and Ca2+ current has not been reported. OBJECTIVE: To explore the effect of diacetylmorphine on action potential and calcium current of isolated cardiomyocytes from neonatal Sprague-Dawley rats. METHODS: Five concentrations of diacetylmorphine (0, 10-2, 10-3, 10-4, 10-5 mol/L) and 20 mol/L verapamil were used to treat the cardiomyocytes of neonatal Sprague-Dawley rats cultured in vitro. The cells were divided into control group, diacetylmorphine group, diacetylmorphine+verapamil group. The latter two groups were treated with diacetylmorphine and diacetylmorphine+verapamil (20 μmol/L), respectively, while the control group was treated with the same amount of PBS. The study protocol was approved by the Animal Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University on May 21, 2018 with approval No. IACUC201805-K1. RESULTS AND CONCLUSION: At 24 hours of culture with different concentrations of diacetylmorphine, the number of cardiomyocytes with abnormal morphology increased significantly in a dose-dependent manner. When the concentration of diacetylmorphine increased, the number of survived cells decreased, with a reduction in the size of cytoplasm and number of pseudopods, the cell membrane was shrunk and the nuclear structure was blurred. Compared with the control group, when diacetylmorphine was added to intervene with the cardiomyocytes, there was a significant difference in the spontaneous beating frequency and rhythm of cardiomyocytes. The negative value of resting membrane potential decreased, while the time course of action potential increased significantly, and the amplitude of action potential decreased significantly. Compared with the control group, the number of cells with changes in the membrane potential significantly increased in the diacetylmorphine group. The addition of verapamil reduced the number of cells with changes in the membrane potential. Compared with the control group, the number of cells with variation of membrane potential was increased to some extents. These findings suggest that diacetylmorphine can induce cardiomyocyte morphological abnormality, increase the spontaneous beating frequency and rhythm of cardiomyocytes, and change the membrane potential and action potential of cardiomyocytes. Verapamil acts as a calcium channel blocker that can improve the rhythm abnormality of cardiomyocytes induced by diacetylmorphine.

Effect of DSA on Vascular Endothelial Cell Injury in NK Cell -Mediated ADCC / 中国实验血液学杂志

OBJECTIVE@#To investigate the injury effect of anti-donor specific antibody (DSA) on human umbilical vein enolothelial cells (HUVEC) in NK-mediated antibody-dependent cell cytotoxity (ADCC).@*METHODS@#The peripheral blood of 10 healthy donors was colleced for allo-HSCT of AML patients diagnosed in Department of Hemology of the Tumor Hospital affiliated to Shanxi Medical University, then the peripheral blood NK cells were isolated and used as the effector cells; the HUVEC of passages 9-6 were selected and co-cultured with DSA, then the DSA-binding HUVEC were used as the target cells (CDH group), while the DSA-unbinding HUVEC were used as negative control (UDH group). After co-culture of effecor cells with target cells, the expression of IFN-γ was detected by flow cytometry and the HUVEC activity was detected by using MTT method, so as to indirectily reflect the injury effect of DSA-mediated ADCC on endothelial cells.@*RESULTS@#With the increase of effector-target (E:T) ratio, the activity of HUVEC decreased, the expression level of IFN-γ increased. Under the some effector-target ratio (1∶1, 10∶1, 20∶1), the activity of HUVEC in CDH group was significantly lower than that of UDH group, and the expression of IFN-γ was significantly higher than that of the UDH group (P<0.05).@*CONCLUSION@#DSA can damage vascular endothelial cells through the ADCC effect mediated by NK cells.

Instability of Mitochondrial DNA D-loop Region Genes in Patients with Leukemia / 中国实验血液学杂志

OBJECTIVE@#To study the instability of mitochondrial DNA（mt DNA） D-loop region genes in patients with Leukemia.@*METHODS@#The HV-1 and HV-2 regions of D-loop region in 24 patients with leukemia were amplificated and sequenced, then their results were compared with revised Cambridge reference sequence (rCRS) and Databank mtDB. The mutation rate was detected by SPSS 22.0 statistics software.@*RESULTS@#The total mutation rate in patients was 95.83% (23/24), the detection showed 82 mutated genes, out of which 47 (57.32%) mutated genes located in HV-1 region, 35 (42.68%) mutated genes in HV-2 region. The comparison showed that the mutation rate in untreated (UT) group and treated (T) group of AML patients was (2.37±0.82)×10 and (4.76±2.45)×10 respectively(P＜0.01), the mutation rate in PR and CR groups of treated AML patients was (5.10±2.56)×10 and (4.51±2.51)×10 respectively (P＜0.05), the comparison among M3 group showed that the mutation rates in UT, PR and CR groups were (2.55±0.63)×10, (5.37±3.41)×10 and (3.71±1.65)×10 respectively (P＞0.05).@*CONCLUSION@#The more high mutation rate and many kinds of mutation types exist in D-loop region, suggesting that the genes in D-loop region display the more strong instability, the chemotherapy may aggravate the instability of genes in D-loop region.

Three-year Follow-up on the Safety and Effectiveness of Rituximab Plus Chemotherapy as First-Line Treatment of Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in Real-World Clinical Settings in China: A Prospective, Multicenter, Noninterventional Study / 中华医学杂志(英文版)

Background@#Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated.@*Methods@#A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation.@*Results@#In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively.@*Conclusions@#R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment.@*Trial Registration@#ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.

T-Lymphoblastic Lymphoma Combined with Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the diagnosis and treatment of patients with T-lymphoblastic lymphoma（T-LBL）combined with acute myeloid leukemia（AML）.</p><p><b>METHODS</b>The clinical features of 4 patients with T-LBL combined with AML were retrospectively analyzed, Among them the case 1 and 2 were synchronous occurrence，and case 3 and 4 were sequentially occurred. Especially for former 2 patients，the dliagnosis differentiated from the involved lymph node of AML is important.</p><p><b>RESULTS</b>The biopsies, immunohistochemical（IHC）test and T-cell receptor（TCR）gene rearrangement of the lymph node have been re-evaluated in our institulion. The diagnosis of T-LBL was confirmed. The diagnosis of AML was based on morphology，cytochemistry，immunophenotypy，karyotype and fusion gene of cells. The biphenotypic and bilineal types were found by flow cytometriy（FCM）. The diagnosis of mixed acute leukemin（MAL）was confirmed. All the patients received chemotherapy，all of which died from leukemia. The survivnl duration was 2 to 5 months from the diagnosis of AML.</p><p><b>CONCLUSION</b>T-LBL combined with AML is an aggressive disease with am unfarourable prognosis, The new therapies should be designed to treat these rare cases.</p>

Effect of CXCL12/CXCR4/MMP-2 signaling pathway on biological behavior in triple negative breast cancer / 临床与实验病理学杂志

Purpose To investigate the effect of CXCL12/CXCR4 and MMP-2 on the biological behavior of triple-negative breast cancer.Method CXCR4-siRNA and pcDNA3.1-CXCR4were transient transfected of in MDA-MB-231 cell line by liposome,RNA and protein were extracted.The mRNA and protein expressions of CXCR4,CXCL12 and MMP-2 were detected by RT-PCR and Western blot respectively.And the migration and proliferation of the transfected cells were detected by Wound-healing assay and MTF assay.Result The experiment of RT-PCR and Westen blot demonstrated that CXCR4 mRNA and protein level expression declines after the expression CXCR4 was down-regulated (P ＜ 0.01),CXCL12 mRNA and protein level expression increased and MMP-2 mRNA and protein level expression increased after the expression CXCR4 was down-regulated (P＜0.01),MTT assay and Wound-healing assay results showed that the proliferation ability of 72 h cells was decreased,and the wound healing was slow.The experiment of RT-PCR and Westen blot demonstrated that CXCR4 mRNA and protein level expression increased after the expression CXCR4 was up-regulated (P ＜0.01).The CXCL12 mRNA and protein level expression declined and MMP-2 mRNA and protein level expression increased after the expression CXCR4 was up-regulated (P ＜0.01),MTT assay and wound-healing assay results showed that the proliferation ability of 72 h cells was increased,and the wound healing was accelerated.Conclusion CXCL12/CXCR4/ MMP-2 signaling pathway is activated in the triple-negative breast cancer MDA-MB-231 cells,and the inhibition of CXCR4 can reverse the proliferation and migration of malignant biological process.

Etiological analysis of 67 cases of acute leukemia combined with fungal infection / 中国实验血液学杂志

In order to study the etiological distribution characteristics of fungal infection and improve the clinical therapeutic efficacy in acute leukemia (AL) patients, the fungal infection etiological distribution, infection site and cause were retrospectively analyzed in 67 cases of AL combined with fungal infection. The result indicated that 63 strains of pathogens were isolated from all detected samples. Infection sites involved oral cavity, low respiratory tract, gastrointestinal tract, blood and urethra; susceptible factors was correlated positively to the duration of administration of broad-spectral antibiotics, glucocorticoid and agranulocytosis. It is concluded that (1) Candida albicans accounts as the most of infection spectrum in AL; (2) main sites of invasive fungal infection are low respiratory tract (63.64%) and gastrointestinal tract (18.18%); (3) the susceptible factors to fungal infection are agranulocytosis and administration of broad-spectral antibiotics in acute leukemia patients; (4) there is interaction between the use of antibiotics and agranulocytosis for the same fungal infection, there is no relationship between long-term use of glucocorticoids and agranulocytosis, and also no relationship between long-term use of glucocorticoids and antibiotics.

Expression and significance of P-gp/mdr1 mRNA, MRP and LRP in non-Hodgkin's lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the expression and clinical significance of P-glycoprotein (P-gp)/mdr1mRNA, multidrug resistance-associated protein (MRP) and lung resistance protein (LRP) in newly diagnosed non-Hodgkin's lymphoma.</p><p><b>METHODS</b>mdr1 mRNA of in 41 patients with non-Hodgkin's lymphoma was assayed by semi-quantitative RT-PCR. The expressions of P-gp, MRP and LRP proteins in lymph node viable blasts were identified by flow cytometry. The results were compared with those obtained from control cases, and the correlation of the changes with clinical outcomes was analyzed.</p><p><b>RESULTS</b>(1) Among the 41 cases, the positive expression of P-gp protein was detected in 8 cases, MRP in 7 cases, LRP in 15 cases, and mdr 1 mRNA in 11 cases. (2) The P-gp and LRP levels in NHL were significantly higher than those in control group, but MRP wasn't. The P-gp over-expression was significantly associated with mdr1mRNA (r = 0.396, P = 0.01). No correlation was showed among the expressions of P-gp, MRP and LRP. (3) Patients with P-gp expression had a poorer outcome of chemotherapy than those with P-gp-negative (P = 0.005). P-gp expression was significantly associated with higher clinical stage (P = 0.046) and elevated serum lactate dehydrogenase level (P = 0.032), but not associated with malignant degree (P = 0.298). MRP had no impact on the outcome of chemotherapy (P = 0.212), and wasn't significantly associated with higher clinical stage (P = 0.369), elevated LDH (P = 0.762) and higher malignant degree (P = 0.451). Patients with LRP expression had a poorer outcome of chemotherapy than those LRP-negative (P = 0.012). LRP expression was significantly associated with higher clinical stage (P = 0.0019), elevated LDH (P = 0.02) and higher malignant degree (P = 0.01).</p><p><b>CONCLUSION</b>The data of this study indicate that P-gp and LRP expressions but not MRP expression are important in the mechanism of drug resistance associated with a poor clinical outcome in previously untreated NHL.</p>

Toll-like receptor and acute leukemia complicated with infection - review / 中国实验血液学杂志

Infection and antibiotic multidrug resistance have become the focal issue in clinical treatment of acute leukemia and will make anti-infection therapy facing to new challenge. Toll-like receptor (TLR) has been found a newly innate immunoreceptor. It is significant in immune response. Along with further investigation of TLR, infection and anti-infection immunity theory would gain a new breakthrough and play a guiding role in clinical treatment of acute leukemia complicated with infection. In this review, the progress in the research of TLR and its expression in acute leukemia complicated with infection were summarized.

Double times of autologous peripheral blood stem cell transplantation to treat multiple myeloma / 中国实验血液学杂志

In order to explore the security and feasibility of double autologous peripheral blood stem cell transplantation (APBSCT) for treatment of multiple myeloma, a 49 years old female patient with multiple myeloma was therapied with double APBSCT. The first peripheral blood stem cell (PBSC) mobilization regimen included CTX 2 g/m(2) x 1d and G-CSF [10 microg/(kgxd)] x 5 d. The conditioning regimen was given melphalan 200 mg/m(2). The transplanted number of mononuclear cells was 6.1 x 10(8)/kg and that of CD34(+) cells was 4.7 x 10(6)/kg. The second APBSCT was performed six months later. PBSC mobilization regimen was G-CSF [10 microg/(kgxd)] x 5 d. The conditioning regimen was melphalan 200 mg/m(2). The transplanted number of mononuclear cells was 10.2 x 10(8)/kg and that of CD34(+) cells was 5.9 x 10(6)/kg. The results showed that the absolute neutrophil count (ANC) rose to above 0.5 x 10(9)/L on day 17 and platelet count exceeded 20 x 10(9)/L on day 15 after first transplantation. After second transplantation ANC rose to above 0.5 x 10(9)/L on day 22 and platelet count exceeded 20 x 10(9)/L on day 13. There were neither obvious adverse reaction nor severe complication during the double transplantations. The patient's ostealgia and anemia were healed through above therapy. In the follow-up of 7 months, the patient's general status was good and she remained in complete remission phase. It is concluded that double APBSCT is safe, effective and feasible for the treatment of multiple myeloma.

Levels of intracellular IL-6 and IFN-gamma in children with acute lymphoblastic leukemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the changes of intracellular interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) expressions in children with acute lymphoblastic leukemia (ALL) at different stages, and to examine the correlation between IL-6 and IFN-gamma in ALL children.</p><p><b>METHODS</b>The levels of intracellular IL-6 and IFN-gamma in venous blood lymphocytes were detected by flow cytometry in 42 children with ALL at diagnosis and at remission stage. Twenty healthy children were used as the controls.</p><p><b>RESULTS</b>The intracellular IL-6 level in ALL children at diagnosis was 81.74+/-9.31, which was much higher than that in the Control group (5.67 +/- 0.96 ) (P < 0.01). The intracellular IFN-gamma level in ALL children (1.31 +/- 0.32) was significantly lower than that in the Control group (1.46 +/- 0.49) (P < 0.01). However, the intracellular IL-6 level (27.52 +/- 3.40) decreased remarkably in ALL patients at remission stage (P < 0.01), but was still higher than that in the Control group (P < 0.01). In contrast, the intracellular IFN-gamma level (1.97 +/- 0.72) increased noticeably in ALL patients at remission stage, which was higher than that at diagnosis and the Control group (P < 0.01). A negative correlation was found between the intracellular IL-6 and the IFN-gamma levels in ALL patients (r=-0.476, P < 0.05).</p><p><b>CONCLUSIONS</b>Intracellular IL-6 and IFN-gamma levels may be used as the markers for monitoring the response to treatment in ALL patients. There is a negative correlation between intracellular IL-6 and IFN-gamma levels in ALL children.</p>

Nonmyeloablative allogeneic hematopoietic stem cell transplantation in 26 cases of hematological malignancies / 中国实验血液学杂志

The purpose of this study was to investigate the efficacy of non-myeloablative allogeneic stem cell transplantation (allo-NST) and its related technologies in hematological malignancies. 26 patients with hematological malignancies (acute leukemia 10, chronic myeloid leukemia 14, multiple myeloma 2) received allo-NST following conditioning regimens with fludarabine/cyclophosphamide/ATG in 14 cases or busulfan or melphalan/cyclophosphamide/ATG in 12 cases prior to infusion of 2 or 3 collections of G-CSF (600 microg/d) or G-CSF (300 microg/d) plus GM-CSF (300 microg/d) mobilized blood stem cell on the fifth day. A combination of cyclosporine A (CsA) and methotrexate (MTX) was administered for GVHD prophylaxis. Patients were eligible for donor lymphocyte infusion (DLI) (or donor stem cell infusion (DSI)) given in graded increments according to the chimeric formation and clinical feature. Generally, the dose of the first infusion was 1 x 10(7)/kg in 4th week post-transplantation. The engraftment analyses included the detection of microsatellite short tandem repeats (STRs), bcr/abl fusion gene, Philadelphia chromosome, HLA-locus analysis, sex chromosome and ABO blood type or blood subtype. The results showed that out of 26 patients, 22 (84.62%) were engrafted, 18/22 were full donor chimerism (FDC) up to now. Acute GVHD occurred in 3/26 (11.54%), while chronic GVHD was diagnosed in 6 out of 26 (23.07%) patients. The incidence and degree of infection and hemorrhage were low and slight. It is concluded that NST is a safe and effective therapy for hematological malignancies, whereas related technologies such as adaptation selected, conditioning regimen and transplantation immunotherapy should be studied further.

Clinical studies on expressions of Fas and mdr-1 in acute leukemia and their correlations / 中国实验血液学杂志

To explore the Fas and mdr-1 expression and their correlation in multidrug resistance (MDR), Fas and mdr-1 expressions of bone marrow from 59 patients with newly diagnosed AL before therapy and after complete remission were detected by direct immunofluorescence with flow cytometry and semi-quantitative RT-PCR, respectively. The results showed that in newly diagnosed AL patients, Fas expression in AML was higher than in ALL (P < 0.05), mdr-1 expression in AML and ALL had no difference (P > 0.05), the expressions of Fas and mdr-1 had correlation (r = -0.282, P < 0.05) in AL; the results of simple-variable and multivariable COX survival factor model analysis suggested that Fas and mdr-1 expressions were prognostic factors for the effect of therapy and survival. Log rank test, comparing the groups of Fas(+) with Fas(-), mdr-1(+) with mdr-1(-), demonstrated that the CR rates and median remission time of every two groups had significant difference. It is concluded that in AL, Fas and mdr-1 expressions have high correlation with the effect of treatment, Fas expression probably is one of the favorable prognostic factors, mdr-1 is an unfavorable prognostic and less effective factor.

Non-myeloablative allogeneic stem cell transplantation in patients with hematologic malignancies / 中国实验血液学杂志

In order to investigate the clinical efficacy of non-myeloablative allogeneic stem cell transplantation (allo-NST) and related technology in patients with hematologic malignancies, twenty-six cases of hematological malignancies (10 AL, 14 CML, 2 MM patients) received NST following conditioning regimens with fludara + cyclophosphamide + ATG (14 cases) and busulfan or melphalan + cyclophosphamide + ATG (12 cases), G-CSF (600 micro g/d) or G-CSF (300 micro g/d) + GM-CSF (300 micro g/d) were used for mobilizing peripheral blood stem cell. A combination of cyclosporine A (CsA) and methotrexate (MTX) was administered for GVHD prophylaxis. Patients will be eligible for donor lymphocyte infusion (DLI) or donor stem cell infusion (DSI) given in graded increments according to the chimeric formation and clinical reaction. Generally the dose of the first infusion was 1 x 10(7)/kg at 4th week post-transplantation. The engraftment analysis included the detection of microsatellite short tandem repeats (STRs), Bcr/Abl fusion gene, Philadelphia chromosome, HLA-locus analysis, sex chromosome and ABO blood type or blood subtype. The results showed that 22 patients (84.62%) were engrafted, among which 18 patients were full donor chimerism (FDC) up to now. Acute GVHD occurred in 3/26 cases (11.54%). Chronic GVHD was diagnosed in 6 of 26 (23.07%) evaluable patients. The incidence of infection and hemorrhage was low and slight. It is concluded that allo-NST is a safe and effective therapeutic method for hematologic malignancies, but the related technology such as selection of indication, conditioning regimen and transplantation immunotherapy should be studied further.

Multidrug resistance mediated by membrane P-glycoprotein in acute myeloid leukemia / 中国实验血液学杂志

A key issue in the treatment of acute leukemia is the development of resistance to chemotherapeutic drugs. Several mechanisms may account for this phenomenon, including failure of the cell to undergo apoptosis in response to chemotherapy, or failure of the drug to reach and/or affect its intracellular target. This review focuses on the latter mechanisms, and on intracellular drug transport resistance mechanisms in particular. Expression of the ATP-binding cassette (ABC) transporter P-glycoprotein (P-gp) has generally been reported to correlate with prognosis in acute myeloid leukemia (AML). Additionally, of more controversial, expression of the ABC transporter multidrug resistance protein (MRP) and the vault-transporter lung resistance protein (LRP) have been correlated with the outcome in AML.