Ren Hy

[Clinical investigation of reduced-dose voriconazole on primary prevention in invasive fungal disease after allogeneic hematopoietic stem cell transplantation].

OBJECTIVE 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). METHODS 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. RESULTS 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. CONCLUSION Intravenous voriconazole on primary prevention for IFD after allo-HSCT is much better than oral fluconazole with well tolerability and satisfactory efficacy.

[Bortezomib-based chemotherapy for patients with multiple myeloma: a single center experience].

OBJECTIVE To evaluate the efficacy and safety of bortezomib-based chemotherapy for 80 patients with multiple myeloma (MM). METHODS 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). RESULTS 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. CONCLUSION MM patients could benefit from bortezomib-based chemotherapy with satisfactory efficacy and safety. HSCT could improve the OS for young MM patients.

[Long term follow-up and prognostic analysis of 85 cases with primary gastrointestinal diffuse large B cell lymphoma].

OBJECTIVE To analyze the clinical characteristics, prognostic factors in patients with primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL). METHODS 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. RESULTS 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). CONCLUSION IPI score was independent prognosis risk factor affecting OS of PGI-DLBCL patients.

[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].

目的 比较Ph染色体阳性（Ph+）急性淋巴细胞白血病（ALL）患者应用化疗联合酪氨酸激酶抑制剂（TKI）后行异基因造血干细胞移植（allo-HSCT）和Ph染色体阴性（Ph−）ALL患者化疗后进行allo-HSCT的疗效和安全性。 方法 2003年1月至2014年8月行allo-HSCT的55例B-ALL患者中配对选取19例Ph−ALL患者（Ph−ALL组）与19例TKI联合allo-HSCT的Ph+ALL患者进行回顾性分析。 结果 Ph+ALL组和Ph−ALL组在性别、中位年龄、发病时外周血WBC >30×109/L的例数、合并中枢神经系统白血病的例数、移植前疾病缓解状态、移植时间、干细胞来源、供受者HLA相合情况、预处理方案、输入单个核细胞数和CD34+细胞数等方面基本匹配。Ph+ALL组和Ph−ALL组白细胞和血小板植活时间相当（12 d和13 d，P=0.284; 14 d和17 d，P=0.246）。Ph+ALL组和Ph−ALL组3年总生存率和无病生存率分别为（67.5±12.4）％和（74.3±11.4）%（P=0.434）、（67.8±12.4）％和（74.3±11.4）%（P=0.456），差异均无统计学意义。Ph+ALL组和Ph−ALL组Ⅱ~Ⅳ度急性移植物抗宿主病（aGVHD）的累积发生率分别为（15.8±8.4）％和（21.1±9.4）%（P=0.665），其中Ⅲ~Ⅳ度aGVHD的累积发生率分别为（5.6±5.4）％和（11.5±7.6）%（P=0.541）。慢性移植物抗宿主病（cGVHD）的累积发生率分别为（44.1±14.0）％和（44.1±13.0）%（P=0.835），其中广泛型cGVHD的累积发生率分别为（13.1±8.7）％和（6.2±6.1）%（P=0.379）。Ph+ALL组和Ph−ALL组累积复发率和累积非复发死亡率差异亦无统计学意义[分别为（10.8±7.2）％对（20.0±10.7）%（P=0.957）和（23.9±12.4）％对（7.1±6.9）%（P=0.224）]。 结论 Ph+ALL患者化疗联合TKI后行allo-HSCT与Ph−ALL患者行allo-HSCT的疗效相当。OBJECTIVE 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. METHODS 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. RESULTS 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]. CONCLUSION 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.

[Combination of busulfan with increased-dose of fludarabine as conditioning regimen for MDS and MDS-AML patients with allo-HSCT].

目的 探讨白消安联合增加剂量氟达拉滨（Bu/ID-Flu）为主预处理方案进行异基因造血干细胞移植（allo-HSCT）治疗骨髓增生异常综合征（MDS）和MDS转化的急性髓系白血病（MDSAML）的疗效与安全性。 方法 回顾性分析Bu/ID-Flu预处理方案进行allo-HSCT治疗27例MDS和22例MDS-AML患者的临床资料。 结果 全部49例患者均达到造血重建。白细胞植活中位时间为13 (10~22) d，血小板植活中位时间为16 (8~66) d。Ⅱ~Ⅳ度急性移植物抗宿主病（GVHD）、出血性膀胱炎及肝静脉阻塞病的发生率分别为28.6%、14.3％和2.0%。移植后100 d和总体移植相关死亡率（TRM）分别为4.1 %（2/49）和8.2%（4/49）。中位随访14(1~92）个月，总生存（OS）率、无病生存（DFS）率分别为75.5%、73.5%。Kaplan-Meier分析示3年OS率、DFS率分别为（71.1±7.8）%、（66.7±8.3）%，复发率为16.3%。MDS、MDS-AML患者的OS率分别为81.5%（22/27）、68.2%（15/22），复发率分别为3.7%（1/27）、31.8%（7/22）。allo-HSCT前达完全缓解（CR）与未达CR的MDS-AML患者的OS率分别为83.3%（10/12）、50.0%（5/10），复发率分别为16.7%（2/12）、50.0%（5/10）。除化疗未达CR的MDS-AML患者（10例）外，其余39例患者的OS率及复发率分别为82.1 %（32/39）和7.7%（3/39）。单因素分析显示，移植前疾病状态是影响OS的高危因素（P=0.031），年龄、预处理中加入地西他滨、造血干细胞来源、HLA相合与否、供受者性别差异、输入CD34+细胞数和GVHD均不是影响OS的危险因素。 结论 应用Bu/ID-Flu为主的预处理方案对MDS和MDS-AML患者进行allo-HSCT，造血功能恢复迅速、植入稳定，并发症发生率和TRM较低。除MDS-AML化疗未达CR患者外，OS率较高且复发率较低。OBJECTIVE 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). METHODS A total of 49 patients with MDS or MDS-AML were treated by allo-HSCT, the clinical data was analyzed retrospectively. RESULTS 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. CONCLUSION 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.

[Analysis of L-asparaginase induced elevation of blood ammonia and hepatic encephalopathy].

OBJECTIVE To summarize the incidence of various adverse reactions in the clinical application of L-asparaginase (L-Asp), and to analyze the cause of hepatic encephalopathy in three cases. METHODS The complete data of 23 patients in our department from December 2009 to December 2010 were collected. Their blood ammonia levels, transaminase, serum albumin and blood coagulation function before, during and after the L-Asp application were assayed. RESULTS (1) All patients had elevated blood ammonia level after the L- Asp application. This occurred 2 days after the beginning of treatment and the median time to reach peak level (ranged from 194 to 446 μmol/L, with a median value of 300 μmol/L) was 4 days. It returned to normal level after a median time of 5 days (ranged 3-7 days) with drug withdrawal. Of the 23 patients studied, 3 developed hepatic encephalopathy. (2) All patients appeared lower blood fibrinogen, 10 cases (43.5%) with lower fibrinogen only, while 13 cases (56.5%) with both prolonged APTT and lower fibrinogen. The lowest level of fibrinogen was detected at 1 week after drug application. Of the 23 patients, 14 (60.9%) had mild lower blood fibrinogen (1-2 g/L), and 9 (39.1%) had significantly lower fibrinogen (0-1 g/L). (3) Six cases (26.1%) had slightly elevated level of transaminase (<2 times the upper limits of normal), 8 (34.8%) appeared hypoalbuminemia. CONCLUSION As the incidence of elevated blood ammonia levels was high in the application of L-Asp, the level of blood ammonia should be closely monitored to avoid the occurrence of hepatic encephalopathy, especially in elderly patients and patients with previous liver disease or long-term heavy drinking. L-Asp can also lead to low fibrinogen level, hypoalbuminemia and abnormal transaminase. Monitoring the blood coagulation function and liver function is required and, if necessary, plasma infusion and liver protection therapy are required.

[Prognostic implications of hematopoietic cell transplantation-specific comorbidity index on non-relapse mortality and overall survival after allogeneic hematopoietic stem cell transplantation].

OBJECTIVE To study the prognostic implications of hematopoietic cell transplantation-specific comorbidity index (HCT-CI) on non-relapse mortality (NRM) and overall survival (OS) in patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS Clinical data of 161 cases received allo-HSCT from July 2003 to November 2010 were analyzed retrospectively. The prognostic significance of HCT-CI, age, sex, conditioning regimens, disease status before transplantation, graft source and the degree of HLA matches for NRM and OS was conducted by COX regression model. The prognostic impact of HCT-CI on NRM and OS was performed in all patients under different disease status before transplantation. RESULTS Of the 161 cases with allo-HSCT, 3-year NRM and OS were 26.4% and 61.4% respectively. NRM at 3 years in patients with HCT-CI score 0, 1-2 and ≥3 were 14.9%, 24.5% and 52.7% respectively. And OS at 3 years were 68.9%, 64.6% and 34.7% respectively. There were significant differences between HCT-CI score 0 and ≥3 groups for NRM and OS (P<0.01). High-risk disease status before transplantation (NRM: RR=3.35, P<0.01;OS: RR=3.53, P<0.01) and HCT-CI score≥3 (NRM: RR=6.85, P<0.01;OS: RR=3.77, P<0.01)were independent risk factors by COX regression model. In the subgroup analysis according to disease status, high score of HCT-CI was associated with poor OS (P<0.01) and high NRM (P<0.01) in patients with low-risk, but not in those with high-risk disease status. CONCLUSION HCT-CI score and disease status before transplantation are independent risk factors for patients received allo-HSCT. HCT-CI score have prognostic implication for NRM and OS in patients with low-risk disease status, but not in high-risk group.