Management of chronic myeloid leukaemia in relapse following donor lymphocyte infusion induced remission: a retrospective study of the Clinical Trials Committee of the British Society of Blood & Marrow Transplantation (BSBMT)

Donor lymphocyte infusion (DLI) can restore remission in a high percentage of patients with chronic myeloid leukaemia (CML) who relapse after allogeneic stem cell transplant (SCT). Subsequent relapses after a DLI-induced remission do occur and the optimal management of these patients is not defined. A retrospective study of the practice of UK transplant centres was conducted. In all, 13 patients from seven centres were identified: all were treated for relapse post allogeneic SCT with DLI and achieved either a complete cytogenetic (n=5) or molecular (n=8) remission. All patients subsequently had a second relapse, at molecular (n=7), cytogenetic (n=4) and haematological (n=2) levels. Further DLI was used in the treatment of 11 patients, imatinib mesylate in three and chemotherapy in two. The two patients with haematological relapse died of blastic disease. The remaining 11 patients achieved either a complete cytogenetic (n=2) or molecular (n=9) remission. Nine patients remain in molecular remission at a median follow-up of 29 months, seven of whom had received DLI alone as treatment for second relapse, one DLI plus imatinib and one imatinib alone. Toxicity following DLI for second relapse was low. Longer follow-up will be required to see if these second DLI-induced remissions will be durable.     

Progress in allogenic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: a comparison between transplants performed 1983--93 and 1994--8 at European Group for Blood and Marrow Transplantation centres

Out of 690 allogeneic matched sibling donor transplants for multiple myeloma reported to the European Group for Blood and Marrow Transplantation (EBMT) registry, 334 were performed during the period 1983-93 (all with bone marrow) and 356 during 1994-98 [223 with bone marrow and 133 with peripheral blood stem cells (PBSCs)]. The median overall survival was 10 months for patients transplanted during the earlier time period and 50 months for patients transplanted with hone marrow during the later period. The use of PBSCs was associated with earlier engraftment but no significant survival benefit compared to bone marrow transplants during the same time period. The improvement in survival since 1994 with the result of a significant reduction in transplant-related mortality, which was 38%, 21% and 25% at 6 months and 46%, 30% and 37% at 2 years during the earlier period, and the later period with bone marrow and PBSCs respectively. Reasons for the reduced transplant-related mortality appeared to be fewer deaths owing to bacterial and fungal infections and interstitial pneumonitis, in turn a result of earlier transplantation and less prior chemotherapy. Better supportive treatment and more frequent use of cytokines may also play a role. The improvement in survival was not directly related to the increased use of PBSCs.     

Marrow versus peripheral blood for geno-identical allogeneic stem cell transplantation in acute myelocytic leukemia: influence of dose and stem cell source shows better outcome with rich marrow

Several studies have compared bone marrow (BM) and peripheral blood (PB) as stem cell sources in patients receiving allografts, but the cell doses infused have not been considered, especially for BM. Using the ALWP/EBMT registry, we retrospectively studied 881 adult patients with acute myelocytic leukemia (AML), who received a non-T-depleted allogeneic BM (n = 515) or mobilized PB (n = 366) standard transplant, in first remission (CR1), from an HLA-identical sibling, over a 5-year period from January 1994. The BM cell dose ranged from 0.17 to 29 x 10(8)/kg with a median of 2.7 x 10(8)/kg. The PB cell dose ranged from 0.02 to 77 x 10(8)/kg with a median of 9.3 x 10(8)/kg. The median dose for patients receiving BM (2.7 x 10(8)/kg) gave the greatest discrimination. In multivariate analyses, high-dose BM compared to PB was associated with lower transplant-related mortality (RR = 0.61; 95% CI, 0.39-0.98; P =.04), better leukemia-free survival (RR = 0.65; 95% CI, 0.46-0.91; P =.013), and better overall survival (RR = 0.64; 95% CI, 0.44-0.92; P =.016). The present study in patients with AML receiving allografts in first remission indicates a better outcome with BM as compared to PB, when the dose of BM infused is rich.     

Practical Guidelines for the Surgical Treatment of Gallbladder Cancer

At present, surgical treatment is the only curative option for gallbladder (GB) cancer. Many efforts therefore have been made to improve resectability and the survival rate. However, GB cancer has a low incidence, and no randomized, controlled trials have been conducted to establish the optimal treatment modalities. The present guidelines include recent recommendations based on current understanding and highlight controversial issues that require further research. For T1a GB cancer, the optimal treatment modality is simple cholecystectomy, which can be carried out as either a laparotomy or a laparoscopic surgery. For T1b GB cancer, either simple or an extended cholecystectomy is appropriate. An extended cholecystectomy is generally recommended for patients with GB cancer at stage T2 or above. In extended cholecystectomy, a wedge resection of the GB bed or a segmentectomy IVb/V can be performed and the optimal extent of lymph node dissection should include the cystic duct lymph node, the common bile duct lymph node, the lymph nodes around the hepatoduodenal ligament (the hepatic artery and portal vein lymph nodes), and the posterior superior pancreaticoduodenal lymph node. Depending on patient status and disease severity, surgeons may decide to perform palliative surgeries.

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predictors for failure of stent treatment for benign esophageal perforations- a single center 10-year experience

AIM:To investigate possible predictors for failed selfexpandable metallic stent(SEMS)therapy in consecutive patients with benign esophageal perforationrupture(EPR).METHODS:All patients between 2003-2013 treated for EPR at the Karolinska University Hospital,a tertiary referral center,were studied with regard to initial management with SEMS.Patients with malignancy as an underlying cause and those with anastomotic leakages were excluded.Sealing of the perforation with a covered SEMS was the primary strategy whenever feasible.Stent therapy failure was defined as a radical change of treatment strategy due to uncontrolled mediastinitis,which in this setting consisted of emergency esophagectomy with end-esophagostomy or death as a consequence of the perforation and subsequent uncontrolled sepsis.Patient and lesion characteristics were analyzed and are presented as median and interquartile range.Possible predictors for failed stent therapy were analyzed with uni-variate logistic regression,while variables with P<0.2 were further analyzed with multi-variate logistic regression.RESULTS:Of the total number of 48 patients presenting with EPR,40 patients(83.3%)were treated with SEMS at the time of admission,with an intention to heal the perforation.Twenty-three patients had Boerhaave’s syndrome(58%),16 had an iatrogenic perforation(40%)and 1 had external trauma to the esophagus(3%).The total in-hospital mortality,including the cases that had other initial treatments(n=8),was10.4%and 7.5%among those who were subjected to the SEMS-based strategy.In 33 of the 40 patients(82.5%)who were treated with stent,the EPR healed without further change in treatment strategy.Patients classified as treatment success received a SEMS at a median time of 1(1-1)d after the actual EPR,compared to 3(1-10)d among those where the initial treatment failed,P=0.039 in uni-variate analysis and P=0.052 in multi-variate analysis.No other significant factors emerged,indicating an increased risk for failure.Six of 7 patients,where stent treatment of the defect failed,underwent an emergency esophagectomy with end esophagostomy and one patient died.CONCLUSION:SEMS as an upfront therapeutic strategy seems to be a successful concept,when applied to an unselected group of patients with EPR.     

Role of endoscopy in the bariatric surgery of patients

Obesity is an increasingly serious health problem in nearly all Western countries.It represents an important risk factor for several gastrointestinal diseases,such as gastroesophageal reflux disease,erosive esophagitis,hiatal hernia,Barrett’s esophagus,esophageal adenocarcinoma,Helicobacter pylori infection,colorectal polyps and cancer,non-alcoholic fatty liver disease,cirrhosis,and hepatocellular carcinoma.Surgery is the most effective treatment to date,resulting in sustainable and significant weight loss,along with the resolution of metabolic comorbidities in up to 80%of cases.Many of these conditions can be clinically relevant and have a significant impact on patients undergoing bariatric surgery.There is evidence that the chosen procedure might be changed if specific pathological upper gastrointestinal findings,such as large hiatal hernia or Barrett’s esophagus,are detected preoperatively.The value of a routine endoscopy before bariatric surgery in asymptomatic patients(screening esophagogastroduodenoscopy)remains controversial.The common indications for endoscopy in the postoperative bariatric patient include the evaluation of symptoms,the management of complications,and the evaluation of weight loss failure.It is of critical importance for the endoscopist to be familiar with the postoperative anatomy and to work in close collaboration with bariatric surgery colleagues in order to maximize the outcome and safety of endoscopy in this setting.The purpose of this article is to review the role of the endoscopist in a multidisciplinary obesity center as it pertains to the preoperative and postoperative management of bariatric surgery patients.     

Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation

Because information on management and outcome of AML relapse after allogeneic hematopoietic stem cell transplantation (HSCT) with reduced intensity conditioning (RIC) is scarce, a retrospective registry study was performed by the Acute Leukemia Working Party of EBMT. Among 2815 RIC transplants performed for AML in complete remission (CR) between 1999 and 2008, cumulative incidence of relapse was 32% ± 1%. Relapsed patients (263) were included into a detailed analysis of risk factors for overall survival (OS) and building of a prognostic score. CR was reinduced in 32%; remission duration after transplantation was the only prognostic factor for response (P = .003). Estimated 2-year OS from relapse was 14%, thereby resembling results of AML relapse after standard conditioning. Among variables available at the time of relapse, remission after HSCT > 5 months (hazard ratio [HR] = 0.50, 95% confidence interval [CI], 0.37-0.67, P < .001), bone marrow blasts less than 27% (HR = 0.53, 95% CI, 0.40-0.72, P < .001), and absence of acute GVHD after HSCT (HR = 0.67, 95% CI, 0.49-0.93, P = .017) were associated with better OS. Based on these factors, 3 prognostic groups could be discriminated, showing OS of 32% ± 7%, 19% ± 4%, and 4% ± 2% at 2 years (P < .0001). Long-term survival was achieved almost exclusively after successful induction of CR by cytoreductive therapy, followed either by donor lymphocyte infusion or second HSCT for consolidation.     

Diagnosis and management of chronic graft-versus-host disease

A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Society for Bone Marrow Transplantation (BSBMT) has reviewed the available literature and made recommendations for the diagnosis and management of chronic graft-versus-host disease (GvHD). This guideline includes recommendations for the diagnosis and staging of chronic GvHD as well as primary treatment and options for patients with steroid-refractory disease. The goal of treatment should be the effective control of GvHD while minimizing the risk of toxicity and relapse.