Risk-adjusted manipulation of melphalan dose before stem cell transplantation in patients with amyloidosis is associated with a lower response rate

High-dose chemotherapy and autologous stem cell transplantation are used increasingly to treat patients with light-chain-related amyloidosis (AL). Treatment-related mortality is approximately 15%. To enable more patients to undergo stem cell transplantation, a risk-adapted strategy has been developed to treat with lower chemotherapy doses those patients who are at excessive risk. It is unclear whether reducing the chemotherapy dose in patients at excessive risk of treatment toxicity reduces the overall response. We retrospectively reviewed 171 AL patients who underwent conditioning chemotherapy with stem cell transplantation. The patients comprised two groups: those receiving standard high-dose melphalan and those receiving intermediate-dose melphalan. Responses were categorized as hematologic response, which used criteria for myeloma response. The two groups showed statistically significant differences; the overall response rates were 75% in the high-dose group and 53% in the intermediate-dose group although treatment-related mortality was the same in both groups. Reducing the melphalan dose appeared to render more AL patients eligible for stem cell transplantation but sacrificed an element of response. Methods are needed to reduce treatment-related toxicity so that more patients can receive full-dose conditioning chemotherapy.     

黏液瘤病毒对大鼠体内胶质瘤作用的研究

目的 探讨黏液瘤病毒对大鼠动物模型体内胶质瘤细胞的作用.方法 采用立体定向法向SD大鼠颅内注射C6细胞建立大鼠额叶胶质瘤模型,明确成瘤后,随机分组,以立体定向方法往瘤腔内注射黏液瘤病毒(MV),5-FU,MV+ 5-FU及灭活黏液瘤病毒(DV),观察不同组别间大鼠体重、肿瘤大小、GFAP表达、Akt表达情况.结果 SD大鼠注射C6细胞后,额叶可见胶质瘤生长.成瘤后瘤腔内注射MV、5-FU及MV+ 5-FU,肿瘤的生长较注射DV减慢,并有缩小趋势,GFAP表达较少.MV组及MV+ 5-FU组PI3k、Akt及mTOR表达较DV组及5-FU组下降.结论 立体定向法注射C6细胞可以建立稳定的胶质瘤模型.MV可以通过调节PI3K-Akt-mTOR通路相关基因的表达,从而增加化疗药物对动物模型体内肿瘤细胞的生物学活性.     

Gas exchange measurements within a magnetic environment: validation of a new system

Although simultaneous measurements of pulmonary oxygen uptake (VO2) and Phosphorus-31 magnetic resonance spectroscopy ((31)P MRS) is attractive to investigate muscular metabolism during exercise, the superconducting magnet requires the design of specific gas exchange analyser (GEA). Thus, this study aimed to assess the validity of a commercial GEA system (ZAN600) compatible with (31)P MRS measurements. Using nonmagnetic pneumotachograph and prolonged sampling line (from 2m, control condition, to 6.5m) did not alter the proper synchronisation between flow and gas concentration signals. Also, end-expiratory fraction of O2 (FETO2) and CO(2) (FETCO2), and finally the values of steady-state ventilation (V(E)), carbon dioxide production (VCO2) and VO2 kinetics during moderate knee-extension exercise were not significantly different between 2m and 6.5m conditions and between 6.5m condition inside and outside the magnet. These results showed that a prolonged sampling line used inside the superconducting magnet did not affect the accuracy of VO2 measurements of a commercial GEA system; the latter appears suitable for simultaneous measurements of VO2 and (31)P MRS.     

Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma

Approximately 60% of patients with diffuse large B-cell non-Hodgkin lymphoma (DLBCL) are curable with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemoimmunotherapy. Epratuzumab (E) is an unlabeled anti-CD22 monoclonal antibody with efficacy in relapsed DLBCL. This phase 2 trial tested the safety and efficacy of combining E with R-CHOP (ER-CHOP) in untreated DLBCL. A secondary aim was to assess the efficacy of interim positron emission tomography (PET) to predict outcome in DLBCL. Standard R-CHOP with the addition of E 360 mg/m(2) intravenously was administered for 6 cycles. A total of 107 patients were enrolled in the study. Toxicity was similar to standard R-CHOP. Overall response rate in the 81 eligible patients was 96% (74% CR/CRu) by computed tomography scan and 88% by PET. By intention to treat analysis, at a median follow-up of 43 months, the event-free survival (EFS) and overall survival (OS) at 3 years in all 107 patients were 70% and 80%, respectively. Interim PET was not associated with EFS or OS. Comparison with a cohort of 215 patients who were treated with R-CHOP showed an improved EFS in the ER-CHOP patients. ER-CHOP is well tolerated and results appear promising as a combination therapy. This study was registered at www.clinicaltrials.gov as #NCT00301821.     

Severe Distal Ischemic Syndrome after Buprenorphine Volunteer Intra-arterial Injection

High dosage buprenorphine (HDB) is a sublingual maintenance treatment of opioid dependence which have proved its substantial Public Health results, but it is also known to be frequently abused and diverted, in particular for intravenous injection, with deleterious consequences. Intra-arterial use is more rarely reported with this substance, just like its complications, mainly ischemic, potentially necrotic, phenomena. We report here such a case, with a 30 years-old man suffering from severe ischemia of the thumb, the forefinger and the middle finger few hours after direct injection of a suspension of buprenorphine crushed tablets in right radial arteria. A treatment combining surgery (video-thoracoscopic thoracic sympathectomy) and medicines (heparin, iloprost and piribedil mesilate), permitted a semi-complete digital rehabilitation (only forefinger pulp necrosis persisted and requiried a distal amputation), and the patient was discharged after 2 weeks.     

Hematopoietic stem cells from poor and good mobilizers are qualitatively equivalent

BACKGROUND: Marrow damage from chemo‐ and radiation therapies has been suggested to affect quality and quantity of hematopoietic stem cell (HSC) products. We tested the hypothesis that CD34+ cells (HSCs) from low mobilizers are qualitatively inferior to HSCs from high mobilizers. STUDY DESIGN AND METHODS: HSC quality was defined by proportion of primitive HSC subsets (CD34+CD38?, CD34+HLA‐DR?, and CD34+ in G0 stage of cell cycle), the proportion of HSCs that express CXCR4 and CD26 homing proteins, and days to neutrophil and platelet (PLT) engraftments after transplant. HSC content and CD34 subsets analyses were performed using flow cytometry following the ISHAGE protocol. We evaluated the HSC quantity and quality of 139 autologous filgrastim‐mobilized HSC products. Patients were categorized into low, moderate, and high mobilizers if their total HSC collection was less than 3 × 10⁶, 3 × 10⁶ or more and less than 5 × 10⁶, and 5 × 10⁶/kg or more, respectively. RESULTS: The median number of primitive CD34 subsets increases with increasing HSC numbers and this association was significant (p = 0.001). However, when the ratios of the primitive CD34 subsets to total HSC counts were compared among the mobilization groups, the ratios were not significantly different. Coexpression of neither CD26 nor CXCR4 with CD34 antigen correlated with HSC mobilization. Evaluation of days to neutrophil engraftment among the mobilization groups did not show a significant difference (p = 0.1). However, days to PLT engraftment among the mobilization groups was significantly different (p = 0.05). CONCLUSION: The quality of HSCs from low mobilizers was comparable to HSCs from high mobilizers.