Clinical outcome of allogeneic hematopoietic stem cell transplantation with FLAG sequential busulfan/cyclophosphamide conditioning regimen for refractory/relapsed acute myeloid leukemia / 中华内科杂志

Objective@#To investigate the therapeutic effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with FLAG sequential busulfan/cyclophosphamide(Bu/Cy) conditioning regimen for refractory/relapsed acute myeloid leukemia.@*Methods@#From February 2012 to June 2017, 21 patients with refractory/relapsed acute myeloid leukemia underwent allo-HSCT with FLAG sequential Bu/Cy conditioning regimen. Transplantation-related complications and clinical outcome were retrospectively analyzed.@*Results@#After conditioning, no hepatic veno-occlusive disease (VOD) and grade Ⅲ hemorrhagic cystitis occurred. 76.2% (16/21) patients had fever with 4 septicemia. One patient died of septic shock before engraftment. Twenty patients achieved neutrophil engraftment with a median time of 13 days (range, 10 to 21 days). Seventeen patients achieved platelet engraftment with a median time of 18 days (range, 9 to 25 days). The cumulative incidence of acute graft-versus-host disease (aGVHD) was 39.5%, and 3 patients developed grade Ⅲ-Ⅳ aGVHD. Of 19 patients who survived more than 100 days after transplantation, 4 had local chronic graft-versus-host disease (cGVHD). Of 21 patients, the median survival time was 15 months (range, 0.5 to 67 months) post-transplantation. Transplantation-related mortality rate was 28.7%. Leukemia relapse occurred in 4 patients with a median time of 4 months (range, 3 to 8 months) after transplantation. The cumulative relapse rate at 1 year was 21.4%. The 1-year and 3-year overall survival (OS) rates were 60.7% and 54.9% respectively. Log-rank analysis revealed that bone marrow blasts ≥ 20% or extramedullary leukemia before transplantation, poor platelet engraftment and grade Ⅲ-Ⅳ aGVHD were significantly related to shortened OS (P<0.05).@*Conclusions@#Allo-HSCT with FLAG sequential Bu/Cy conditioning regimen in patients with refractory/relapsed myeloid leukemia has acceptable transplantation-related risk and relapse rate. The 1-year and 3-year OS rates are comparable with those in remission patients.

Combination of busulfan with increased-dose of fludarabine as conditioning regimen for MDS and MDS-AML patients with allo-HSCT / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS) and secondary acute myelogenous leukemia (MDS-AML) using conditioning regimen with busulfan (Bu) and increased-dose of fludarabine (ID-Flu).</p><p><b>METHODS</b>A total of 49 patients with MDS or MDS-AML were treated by allo-HSCT, the clinical data was analyzed retrospectively.</p><p><b>RESULTS</b>All patients achieved hematopoietic reconstitution. Neutrophil engraftment was at 10 - 22 days (median 13 days), and platelet engraftment was at 8 - 66 days (median 16 days). The cumulative incidences of Ⅱ-Ⅳ degree acute graft-versus-host disease (GVHD), hemorrhagic cystitis (HC), and hepatic venous occlusive disease (VOD) were 28.6%, 14.3% and 2.0%, respectively. The transplant-related mortality (TRM) was only 4.1% at 100d and 8.2% at 1-92 months of followed-up (median 14 months) period. Overall survival (OS) and disease free survival (DFS) was 75.5%, 73.5%, respectively. Kaplan-Meier curve showed that 3-year OS and 3-year DFS was (71.1 ± 7.8)%, (66.7 ± 8.3)%, respectively, with a relapse incidence (RI) 16.3%. OS for MDS and MDS-AML was 81.5% and 68.2%, and RI in two settings was 3.7%, 31.8%, respectively. OS for MDS-AML at complete remission (CR) and non-CR subgroup was 83.3% and 50.0%, respectively, while cumulative RR was 16.7% and 50.0%, respectively. OS and RI except for non-CR subgroup were 82.1% and 7.7%. Univariate analysis showed that pre-HSCT disease status had correlation with OS (P=0.031), but age, decitabine in conditioning regimen, stem cell source, HLA matching, patient-donor gender, dose of mononuclear cells and GVHD had no correlation with OS.</p><p><b>CONCLUSION</b>Bu/ID-Flu conditioning regimen for MDS and MDS-AML has high efficiency, fewer complications, lower toxicity and TRM. The OS and DFS were higher and RI was lower except for refractory MDS-AML patients. The regimen is valuable for clinical application.</p>

Efficacy comparison between Ph⁺ ALL patients treated with chemotherapyplus tyrosine kinase inhibitors followed by allo-HSCT and Ph-ALL patients with allo-HSCT: a case control study from a single center / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the efficacy of the Ph⁺ acute lymphoblastic leukemia (ALL)patients treated with combination of tyrosine kinase inhibitors (TKI)and chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) and Ph⁻ ALL patients with allo-HSCT.</p><p><b>METHODS</b>A total of 19 Ph⁺ALL patients were matched with 19 Ph⁻ALL patients from 55 B-ALL patients receiving allo-HSCT in our hospital between January 2003 and August 2014 and were analyzed retrospectively.</p><p><b>RESULTS</b>Gender, median age, number of patients with blood white count more than 30 × 10⁹/L, number of patients with meningeal leukemia, disease status before allo-HSCT, period of allo-HSCT, the source of stem cell from donors, HLA disparities between donor and recipient, conditioning regimens and number of infused mononuclear cells and CD34⁺ cells were comparable between two groups of Ph⁺ and 19 Ph⁻ALL patients. The median time of engraftment of neutrophil cells was 12 days versus 13 days (P= 0.284) and that of platelet 14 days versus 17 days (P=0.246), which were comparable between two groups. The estimated 3-year overall survival (OS) in Ph⁺ and Ph⁻ALL groups was (67.5 ± 12.4)% versus (74.3 ± 11.4)% (P=0.434) and 3-year disease free survival (DFS)was (67.8 ± 12.4)% versus (74.3 ± 11.4)% (P= 0.456), respectively. The cumulative incidence of degree Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD)in Ph⁺ and Ph⁻ ALL group was (15.8±8.4)% versus (21.1 ± 9.4)% (P=0.665)and that of degree Ⅲ-Ⅳ aGVHD was (5.6 ± 5.4)% versus (11.5 ± 7.6)% (P=0.541), respectively. The cumulative incidence of cGVHD was (44.1 ± 14.0)% in Ph⁺ALL group versus (44.1 ± 13.0)% in Ph⁻ALL group (P=0.835) and that of extensive cGVHD was (13.1 ± 8.7)% versus (6.2 ± 6.1)% (P=0.379), respectively. The cumulative relapse rate and the cumulative non-relapse rate in both group also have no statistical difference [(10.8 ± 7.2)% versus (20.0 ± 10.7)% (P=0.957) and (23.9 ± 12.4)% versus (7.1±6.9)% (P=0.224), respectively].</p><p><b>CONCLUSION</b>The efficacy of Ph⁺ALL treated with combination of chemotherapy and TKIs and followed by allo-HSCT is comparable to that of Ph⁻ALL with allo-HSCT.</p>

Clinical investigation of reduced-dose voriconazole on primary prevention in invasive fungal disease after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and tolerability of intravenous voriconazole on primary prevention in invasive fungal disease (IFD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>At the time of conditioning regimen, patients without IFD was intravenously administered with voriconazole at a dose of 100 mg two times per day until neutrophils greater than 0.5×10⁹/L. Patients treated with oral fluconazole, 200 mg per day, were control group. The incidence and risk factors of IFD and side effects of medicines were evaluated.</p><p><b>RESULTS</b>Of the total 227 patients, 33 (14.54%) had IFD within 3 months after allo-HSCT. There was significant difference on overall survival between patients with or without IFD by Kaplan-Meier survival curve (P=0.029). Of the 83 cases with intravenous voriconazole, 7 cases occurred IFD (8.43%). In contrast, the incidence of IFD in control group was 18.06% (26 out of 144). There was remarkable difference between the two groups (P=0.048). But there was no significant difference on risk factors of IFD between the two groups. In addition, the incidence of liver function abnormalities between the two groups was no difference. The ratio of auditory hallucination and visual impairment induced by voriconazole was not high.</p><p><b>CONCLUSION</b>Intravenous voriconazole on primary prevention for IFD after allo-HSCT is much better than oral fluconazole with well tolerability and satisfactory efficacy.</p>

Long term follow-up and prognostic analysis of 85 cases with primary gastrointestinal diffuse large B cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics, prognostic factors in patients with primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL).</p><p><b>METHODS</b>Long term follow-up of 85 patients with PGI-DLBCL was carried out and the patients clinical data were retrospectively evaluated. The risk factors for survival rate were analyzed by univariate and multivariate Cox regression analysis.</p><p><b>RESULTS</b>The median age of 85 patients was 61 years old (18-87), and male: female ratio was 1.83:1 (55/30). The stomach origin accounted for 63.5% (54/85), intestine origin for 35.3% (30/85) and multiple GI involvements for 1.2% (1/85). Bone marrow involvement accounted for 16.4% (11/64), Helicobacter pylori (HP) infection for 51.4% (19/37). The 5-year overall survival (OS) rates of all patients were 63.9%. The 5-year OS of patients in stomach and intestinal groups were 75.3% and 44.1%, respectively (P=0.005). The 5-year OS of germinal center B cell-like (GCB) group and non-GCB groups were 64.7% and 62.4%, respectively (P = 0.610). Univariated analysis revealed that the factors affecting OS of patients included age, lesion site, tumor size, gastrointestinal clinical Lugano staging system, IPI score (all P values < 0.05). Multivariate Cox regression analysis revealed that IPI score was independent prognosis risk factor affecting OS (RR = 3.609, 95 CI 2.034-6.404, P < 0.01).</p><p><b>CONCLUSION</b>IPI score was independent prognosis risk factor affecting OS of PGI-DLBCL patients.</p>

Bortezomib-based chemotherapy for patients with multiple myeloma: a single center experience / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of bortezomib-based chemotherapy for 80 patients with multiple myeloma (MM).</p><p><b>METHODS</b>A total of 80 cases with a median age of 57 (range: 25-78) years were enrolled in the study. Bortezomib-based regimens included VD (bortezomib and dexamethasone) and PAD (bortezomib, doxorubicin and dexamethasone). 16 of the 80 patients received autologous or allo-hematopoietic stem cell transplantation (HSCT).</p><p><b>RESULTS</b>The overall response (OR) rate was 80%, including a complete response (CR) of 46.3%. After a median follow-up of 25 months, the 1-year and 2-year overall survival (OS) was 81.4% and 72.9%, and the 2-year progression-free survival (PFS) was 76% and 62.5%, respectively. The 2-year OS and PFS were 100% and 73.9 % in patients with HSCT, while both were 66% (P=0.029) and 58.7% (P=0.447) in patients without HSCT. In univariate analysis, Durie-Salmon group, ISS stage, CR and very good partial response (VGPR), and HSCT were prognostic factors for OS. Gender and extramedullary plasmacytomas were important prognostic factors for PFS. Multivariate analysis by Cox regression revealed that CR and VGPR, Durie-Salmon group A, and HSCT were prognostic factors for better OS; while male and patients without extramedullary plasmacytomas were prognostic factors for longer PFS.</p><p><b>CONCLUSION</b>MM patients could benefit from bortezomib-based chemotherapy with satisfactory efficacy and safety. HSCT could improve the OS for young MM patients.</p>

Effect of CAG induction therapy in patients with acute myeloid leukemia / 中国综合临床

Objective To assess the effect of low-dose cytarabine and aclarubicin in combination with gran-ulocyte colony-stimulating factor (G-CSF) protocol (CAG) in patients with acute myeloid leukemia (AML),and to understand the potential factors affecting the outcome of CAG induction therapy, therefore to find the optimum pa-tients for CAG therapy. Methods Twenty-one AML patients were enrolled in the current study. All patients were treated with CAG regimen including cytarabine (10 mg/m~2, subcutaneously, every 12 h, days 1 - 14), lacinomycin (5～7 mg/m~2,intravenously,every day, days 1 -8) ,and G-CSF (200 μg/m~2,subcutaneously, every day,12 h be-fore Ara-C was given) priming. Results The overall complete remission (CR) rate of the 21 AML patients was 66.7% (14/21). The CR rates was 87.5% (7/8) in patients older than 60 yrs,60.0% (9/15) in the refractory or relapsed patients,83.3% (5/6) in the MDS transformed AML patients. The CR rates for patients with hyperprolif-erative BM and median to poor proliferative BM were 33.3% and 91.7% ,respectively(P =0.009). The median o-verall survival (OS) time of the 21 AML patients was 450 days. Two-year survival rate estimated by Kaplan-Meier Method was 30.6%. The overall median disease free survival (DFS) was 165 days. The median OS time for those refractory or relapsed was 435 days. The median OS time for those with poor cytogenetic state or standard or good cytogenetic state was 140 days and 620 days, respectively (P = 0.001). The median OS time for patients with hyperproliferative BM and median to poor proliferative BM was 321 days and 620 days, respectively (P = 0.05). The median recovery time of granulocytes above 1.0×10~9/L was 8 days. The median duration of fever was 3.5 days. The rate of infections exceeding WHO grade Ⅱ was 42.9%. No early death occurred. Conclusions The CAG induction therapy may have a higher CR rate in patients with refractory or relapsed AML, elderly AML and secondary AML from MDS transformation, and extend the median overall survival time in refractory or relapsed patients. CAG therapy can not improve the outcome of patients whose BM was in high grade proliferation state or whose cytogenetic state was poor. CAG therapy can shorten the duration of agranulocytosis and decrease the inci-dence of serious infection. Therefore, CAG therapy is worth recommending to patients who can not endure the rou-tine intensive chemotherapy.

Application of light-cure resin-modified glass ionomer cement in orthodontic practice / 中国组织工程研究

BACKGROUND: Resin-modified glass ionomer (RMGI) cements have higher bond strength, especially can release fluoride. But there are fewer reports of the clinical application for the prevention of decalcification.OBJECTIVE: To test the benefit from using RMGI cement instead of a conventional composite resin in bracket bonding for patients with malocclusion, and observe bracket-failure rates and decalcification on enamel surfaces at pretreatment and at debonding.DESIGN: Observational and comparative trial.SETTING: The Second Hospital Affiliated to Hebei Medical University.PARTICIPANTS: Forty successive patients (358 teeth) with malocclusion admitted to the Department of Orthodontics in the Second Hospital Affiliated to Hebei Medical University, were selected for the study from July to August in 2002. All the patients (21 females and 19 males, mean age 16 years) had normal and complete anterior teeth, good oral hygiene. There were no obvious differences in bilateral teeth. Informed consents were obtained from all the subjects. The experiment was also approved by the ethical committee of the hospital. Experimental materials were RMGI adhesive (Fuji, GC, Japan, Lot 0005111) and composite resin cement (enamel adhesive of Beijing and Tianjin, Tianjin product, Lot 020402). Brackets produced from Hangzhou 3B and 37% phosphoric acid were used.METHODS: ①Bonding brackets: Subjects selected according to random procedure were divided into two groups, each with 20. GroupⅠ: The left buccal surfaces bonded with light-cure RMGI were etching for 30 seconds with 37% phosphoric acid, rinsed with water; the right buccal surfaces bonded with composite resin cement were etching for 60 seconds with 37% phosphoric acid, rinsed with water and dried; Group Ⅱ: After etching for 30 seconds with 37% phosphoric acid, the right buccal surfaces were rinsed with water and bonded brackets with light-cure RMGI. The left buccal surfaces were bonded brackets with composite resin cement after etching for 60 seconds with 37% phosphoric acid, rinsing with water and drying; Attachment of 0.036-cm NiTi wires with ligature to the brackets was conducted 10 minutes after light-curing. The information about differences in bilateral bonding materials was not told to patients. To ensure an equal bonding materials containing fluoride and minimize the error, all the patients were instructed to use toothpaste containing fluoride, a fluoride mouthwash was not prescribed. The treatment period was 9-26 months (mean 18 months).②Patients were rechecked at intervals of 4 weeks postoperatively. Each bonded tooth was checked for loose or missing brackets, and failures were recorded. A color transparency of anterior teeth area was taken using a standardized photographic technique. The enamel surface conditions were classified at a magnification of ×10. The condition of enamel surface recorded was made according to the scoring system by Geiger before treatment and at debonding.MAIN OUTCOME MEASURES: ①The number and site of bonding failures.②Enamel surface conditions at before treatment and debonding.RESULTS: Forty patients were all involved in the result analysis. Eliminating 4 teeth occurring bond failure and 4 teeth of opposite side at anterior teeth, a total of 232 teeth were evaluated.①The number and sit of bonding failures: There was no significant difference between the failure rates of RMGI adhesive and composite resin cement (P > 0.05). Significantly more premolar brackets failed than incisor brackets.②Decalcification of enamel surface: At debonding after treatment, the incidence rates of white spots in the surfaces bonded with the RMGI were significantly lower than that in the composite resin (25.9%, 38.8%, P < 0.05).CONCLUSION:The use of RMGI for brackets bonding results in a significant reduction in the incidence of white spot at debonding. Reducing etching time may obtain a similar survival rate with the routine etching time.

Research of nutritional support in COPD patients / 中国临床营养杂志

This stued examined the effects of nutritional support in 56 patients suffer from COPD. The influence of nutritional support on lung function and arteny blood gases after infusion of an amino acid solution (7% Fan Ming) were observed. The results suggested theft PaO2, FEV1. FVC levels were increased significantry compared to the control group. PaOz decreased significantly in Fan Ming infusion group compared 100 control group.