Randomized trial of 8-week versus 12-week VNCOP-B plus G-CSF regimens as front-line treatment in elderly aggressive non-Hodgkin's lymphoma patients.

BACKGROUND: Among the third-generation chemotherapy regimens specifically adapted in the last decade for elderly aggressive non-Hodgkin's lymphoma (NHL) patients, we designed an 8-week cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin and prednisone (VNCOP-B) plus granulocyte colony-stimulating factor (G-CSF) regimen which, in a national multicenter trial, induced good complete response (CR) and relapse-free survival rates with only moderate toxic effects. Here we report a prospective, multicenter, randomized trial comparing the efficacy and toxicity of 8- and 12-week regimens of VNCOP-B plus G-CSF. PATIENTS AND METHODS: From February 1996 to June 2001, 306 consecutive previously untreated stage II-IV aggressive NHL patients > or =60 years of age were enrolled from 12 Italian cooperative institutions. Of the 297 evaluable patients, 149 and 148 received 8- and 12-week regimens, respectively, of VNCOP-B. RESULTS: The CR rates were 63% and 56% in the 8- and 12-week groups; at a median of 32 months (range 3-62 months), relapse-free survival rates were 59% and 55%, respectively. Hematological and non-hematological toxicities were similar in both treatment groups. CONCLUSIONS: Our data show that extending induction treatment with the VNCOP-B plus G-CSF regimen from 8 to 12 weeks does not raise the CR rate or provide a more durable remission.     

Long-term effects of a high-dose methamphetamine regimen on subsequent methamphetamine-induced dopamine release in vivo

Rats were treated with a high-dose methamphetamine (METH) regimen (40 mg/kg/injection, four times at 2-h intervals) or a saline regimen (four injections at 2-h intervals). Temperature related measures taken during the high-dose METH treatment were maximum core temperature and minimum chamber temperature. Fourteen rats (METH N=7; Saline N=7) were implanted with in-vivo dialysis probes 4-7 weeks post-regimen (average=6 weeks). The next day, they received a challenge dose of METH (4.0 mg/kg) and dopamine release was measured. Results showed a significant decrease in challenge-induced dopamine release in rats previously treated with the high-dose METH regimen. These findings demonstrate a functional deficit in the dopamine system 6 weeks after high-dose METH treatment. Temperature-related measures taken during the high-dose regimen were not correlated with METH-induced dopamine release 6 weeks later. An additional group of rats were sacrificed 6 weeks after the high-dose regimen (METH N=12; Saline N=10), and their brains was analyzed for dopamine and serotonin concentrations. Tissue concentrations of dopamine were significantly depleted in striatum and nucleus accumbens/olfactory tubercle, but not septum, hypothalamus, or ventral mid-brain 6 weeks after the high-dose regimen. Tissue concentrations of serotonin were also significantly depleted in striatum, nucleus accumbens/olfactory tubercle, hippocampus, somatosensory cortex, but not septum, hypothalamus or ventral mid-brain. Significant correlations between the temperature-related measures and post-mortem neurotransmitter tissue concentrations were region and transmitter dependent.     

Effects of feeding regimen on ethanol intake by guinea pigs

During daily two-hr sessions, guinea pigs licked a drinking tube filled with either 0 (tap water), 2, 4 or 8% (v/v) ethanol solution under three feeding regimens. Consumption of each solution was highest when sufficient food to maintain subjects at 90% of free-feeding weight was provided during sessions, lower when the same food ration was provided after sessions, and lowest when ad lib access to food was provided within and between sessions. However, this decrease in consumption across feeding regimens was inversely related to ethanol concentration. Under all feeding regimens, volume of solution consumed decreased with increasing ethanol concentration while milligrams ethanol consumed increased with ethanol concentration. These results are similar in some respects to previous findings with rats and monkeys, suggesting that further studies of oral ethanol self-administration by guinea pigs may be merited.     

A Case of Severe Aplastic Anaemia Successfully Treated by Retransplantation from the Same Donor

A 16-year-old girl with severe aplastic anaemia was successfully treated with retransplantation of bone marrow from an HLA-identical sibling after rejection of the first transplantation from the same donor. Cyclophosphamide was used for the first transplantation and cyclophosphamide, 300 rad total-body irradiation and antilymphocyte globulin were used for the second transplantation. Permanent engraftment was achieved after the retransplantation with normalization of haemopoiesis, which has lasted for over 17 months. The patient is now in excellent clinical condition with minimal signs of chronic graft versus host disease.     

Relationship between HLA‐DPA1 mRNA expression and susceptibility to hepatitis B

Chronic hepatitis B virus (HBV) infection is influenced by both viral and host factors. In genome‐wide association studies, the human leucocyte antigen HLA‐DPA1 and related polymorphism rs3077 were found to be associated with susceptibility to and spontaneous clearance of HBV infection. Here, we evaluated the association between HLA‐DPA1 mRNA expression and the risk of HBV infection. HLA‐DPA1 and rs3077 polymorphisms were investigated in 169 patients with chronic HBV and 217 healthy controls (HCs) from Sichuan Han blood donors using sequence‐based typing and meta‐analysis for HLA‐DPA1 alleles. HLA‐DPA1 mRNA levels were measured by real‐time polymerase chain reaction. The results showed that HLA‐DPA1 and rs3077 were associated with HBV infection in the Sichuan population. Rs3077T and DPA1*01:03 played protective roles in HBV infection, and rs3077C and DPA1*02:02 increased susceptibility to HBV infection. We found that the HLA‐DPA1 mRNA expression was decreased in the CHB group; in particular, the 3077CT, 3077TT, DPA1*01:03 and DPA1*02:01 alleles showed a significant decrease. Our results demonstrated, for the first time, that expression of HLA‐DPA1 alleles and rs3077 affected the risk of HBV infection. Genotypes with lower HLA‐DPA1 expression had a greater susceptibility to HBV infection. Thus, further independent studies are needed to strengthen the associations of these polymorphisms with susceptibility to and clearance of HBV infection in Chinese populations.     

Addition of bortezomib to high-dose cyclophosphamide therapy as a conditioning regimen for autologous peripheral blood stem cell harvest leads to an increased yield of hematopoietic stem cells

Peripheral blood stem cell harvest (PBSCH) is a crucial procedure for autologous stem cell transplantation in patients with multiple myeloma. We herein report a retrospective study to verify the usefulness of bortezomib and high-dose cyclophosphamide therapy (Bor-HDCY) as a conditioning regimen for PBSCH. Thirty-three patients were evaluated. The median age at the first apheresis was 61 (interquartile range, 53–64) years old, and 18 (54.5%) patients were male. Bor-HDCY was performed in 15 patients, and HDCY was performed in 18. In the patients who underwent Bor-HDCY, the CD34⁺ cell count at the first apheresis was significantly higher than in the others (P<0.01), and the total CD34⁺ cell count also tended to be high (P=0.0933). In terms of apheresis days, two-thirds of the patients who underwent HDCY had two-day apheresis, whereas most who underwent Bor-HDCY had one-day apheresis. According to univariate analysis, Bor-HDCY (P<0.01), VRd (Bor, lenalidomide, and dexamethasone) as induction therapy (P=0.0529), and ≥VGPR before PBSCH (P=0.0767) were factors associated with a higher CD34⁺ cell count at first apheresis. Although multivariate analysis showed that there were no independently significant factors influencing the CD34⁺ cell count at the first apheresis, the stepwise selection method revealed that only the Bor-HDCY regimen remained in the final model (P<0.005). Bor-HDCY may be a useful conditioning regimen for increasing the CD34⁺ cell yield.     

复方阿胶浆联合XELOX方案治疗晚期胃癌的临床观察

目的 观察复方阿胶浆联合奥沙利铂与希罗达（XELOX方案）治疗晚期胃癌的临床疗效及对化疗的增效减毒作用.方法 将60例晚期胃癌患者分为治疗组与对照组,治疗组接受复方阿胶浆联合XELOX方案化疗,对照组仅接受XELOX方案化疗,观察2组临床疗效及不良反应情况.结果 治疗后2组患者症状均改善,治疗组较对照组改善更明显;治疗组与对照组卡氏评分总有效率分别为100%,83%,2组比较有显著性差异（P〈0.05）.治疗组与对照组总有效率分别为17%,10%,2组比较无显著性差异;治疗组的化疗不良反应（白细胞减少、贫血、消化道反应及手足综合征）发生率明显低于对照组（P〈0.05）;治疗组治疗后CD3＋、CD4＋、CD4＋/CD8＋较治疗前及对照组均升高（P均〈0.05）.结论 复方阿胶浆联合XELOX方案化疗治疗晚期胃癌,可提高机体免疫力,减轻化疗不良反应,改善生活质量.     

ProMACE—cytaBOM方案治疗非霍奇金淋巴瘤的临床疗效观察

目的观察ProMACE-cytaBOM方案一线治疗中高度恶性非霍奇金淋巴瘤(NHL)的近期和远期疗效.方法采用ProMACE-cytaBOM方案一线治疗30例中高度恶性非霍奇金淋巴瘤,并进行疗效分析.结果全组总有效率(CR+PR)为86.7%,完全缓解(CR)率为66.7%,中位缓解期为9(3～58)个月.中位生存时间为35(1.5～68)个月,全组1、3、5年生存率分别为56.7%、45.3%、45.3%.Ⅱ～Ⅲ期、中度恶性、来源于B细胞、无巨大肿块、LDH正常、化疗≥4个周期者的生存率高于Ⅳ期、高度恶性、来源于T细胞、有巨大肿块、LDH不正常、化疗＜4个周期者,但无显著性差异(P＞0.05).治疗后疗效达到CR者的长期生存率明显高于无效者(P＜0.05).主要的不良反应为骨髓抑制和胃肠道反应,患者均可耐受.结论ProMACE-cytaBOM方案是治疗中高度NHL的1个安全有效的化疗方案.     

Leukaemic variants of cutaneous T-cell lymphoma: Erythrodermic mycosis fungoides and Sézary syndrome

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of cutaneous lymphoma, accounting for approximately 60% of cutaneous T-cell lymphomas. Diagnosis requires correlation of clinical, histologic, and molecular features. A multitude of factors have been linked to the aetiopathogenesis, however, none have been definitively proven. Erythrodermic MF (E-MF) and SS share overlapping clinical features, such as erythroderma, but are differentiated on the degree of malignant blood involvement. While related, they are considered to be two distinct entities originating from different memory T cell subsets. Differential expression of PD-1 and KIR3DL2 may represent a tool for distinguishing MF and SS, as well as a means of monitoring treatment response. Treatment of E-MF/SS is guided by disease burden, patients’ ages and comorbidities, and effect on quality of life. Current treatment options include biologic, targeted, immunologic, and investigational therapies that can provide long term response with minimal side effects. Currently, allogeneic stem cell transplantation is the only potential curative treatment.