Harish Gagneja

High Rate of Durable Remissions After Treatment of Newly Diagnosed Aggressive Mantle-Cell Lymphoma With Rituximab Plus Hyper-CVAD Alternating With Rituximab Plus High-Dose Methotrexate and Cytarabine

PURPOSE To determine the response, failure-free survival (FFS), and overall survival rates and toxicity of rituximab plus an intense chemotherapy regimen in patients with previously untreated aggressive mantle-cell lymphoma (MCL). PATIENTS AND METHODS This was a prospective phase II trial of rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD; considered one cycle) alternating every 21 days with rituximab plus high-dose methotrexate-cytarabine (considered one cycle) for a total of six to eight cycles. RESULTS Of 97 assessable patients, 97% responded, and 87% achieved a complete response (CR) or unconfirmed CR. With a median follow-up time of 40 months, the 3-year FFS and overall survival rates were 64% and 82%, respectively, without a plateau in the curves. For the subgroup of patients < or = 65 years of age, the 3-year FFS rate was 73%. The principal toxicity was hematologic. Five patients died from acute toxicity. Four patients developed treatment-related myelodysplasia/acute myelogenous leukemia, and three patients died while in remission from MCL. A total of eight treatment-related deaths (8%) occurred. CONCLUSION Rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine is effective in untreated aggressive MCL. Toxicity is significant but expected. Because of the shorter FFS concurrent with significant toxicity in patients more than 65 years of age, this regimen is not recommended as standard therapy for this age subgroup. Larger prospective randomized studies are needed to define the role of this regimen in the treatment of MCL patients compared with existing and new treatment modalities.

Clinical outcome of simultaneous self-expandable metal stents for palliation of malignant biliary and duodenal obstruction.

Background: Previous studies have shown that self-expanding metal stents are an effective method for palliation of malignant biliary or duodenal obstruction. We present our experience with the use of simultaneous self-expandable metal stents for palliation of malignant biliary and duodenal obstruction. Methods: We performed a retrospective review of all patients undergoing simultaneous biliary and duodenal self-expandable metal stent placement between November 98 and May 2001. All the patients had documented evidence of biliary obstruction and symptomatic duodenal obstruction. The patients received endoscopic biliary stenting with biliary Ultraflex or Wallstents, and endoscopic duodenal stenting using enteral Wallstents. They were followed until their death. Results: We identified 18 patients (11 men and 7 women) whose mean age was 65 years, (range, 46–85 years). Malignancies included pancreatic 14 (78%), biliary 2 (11%), lymphoma 1 (5%), and metastatic 1 (5%) disorders. Ten patients previously had plastic biliary stents placed for past malignant biliary obstruction (4 patients had recurrent biliary obstruction). All the patients had evidence of duodenal obstruction. Combined metal stenting was successful in 17 patients. One procedure failed due to a tortuous duodenal stricture. All the patients had effective palliation of biliary obstruction, as evidenced by a decrease in the level of total bilirubin and alkaline phosphatase. Of the 17 patients with successful duodenal stenting, 16 had a good clinical outcome, with relief of obstructive symptoms. No immediate stent-related complications were noted. During the follow-up period, 12 patients died of progression of the underlying malignancy. None of the deaths were stent related. Median survival time was 78 days. Two patients had recurrent biliary obstruction from tumor ingrowth at 45 and 68 days, respectively. Both underwent restenting: one by endoscopic retrograde cholangiopancreatography (ERCP) and the other by percutaneous transhepatic cholangiography (PTC). Two other patients had recurrent duodenal obstruction, respectively, 36 and 45 days after the initial stenting. One obstruction was secondary to tumor ingrowth, and the other was caused by distal stent migration. Both patients had successful duodenal restenting. Conclusion: Combined self-expandable metal stenting for simultaneous palliation of malignant biliary and duodenal obstruction may provide a safe and less invasive alternative to surgical palliation with an acceptable clinical outcome. Simultaneous self-expandable metal stents should be considered as a treatment option for patients who are poor candidates for surgery.

Role of self-expandable metal stents in the palliation of malignant duodenal obstruction

Background: Palliative surgical intervention for malignant duodenal obstruction is often associated with a significant morbidity. Endoscopic enteral stenting offers a suitable alternative, that is safe, effective, and less invasive. This study reports our experience with the use of self-expanding metal stents in the palliation of malignant gastric duodenal obstruction. Methods: A retrospective review of all patients who underwent duodenal stenting from November 1998 to February 2001 was performed. All the patients had symptomatic gastric outlet and duodenal obstruction with nausea, vomiting, and decreased oral intake. All of them underwent enteral stenting with self-expandable metal Wallstents 20 or 22 mm in diameter and 6 or 9 cm long. Results: For this study, 33 patients (19 men and 14 women) with a mean age of 62 years (range, 37–81 years) were identified, 32 of whom had successful duodenal stent placement (6 were performed as outpatient surgery). The malignancies were pancreatic 18 (54%), gastric 4 (12%), duodenal 3 (9%), metastatic 6 (18%), and cholangiocarcinoma 2 (6%) disorders. The site of obstruction was pyloric (n = 5; 15%), pyloroduodenal (n = 3; 9%), duodenal bulb (n = 11; 33%), second portion of duodenum (n = 9; 27%), second and third portion of duodenum (n = 3; 9%), C-loop (n = 1; 3%), and anastomotic (n = 1; 3%). A total of 29 patients (91%) had good clinical outcomes, with relief of obstructive symptoms, Two of three patients with no symptomatic relief underwent gastrojejunostomy. One patient refused further treatment. No immediate stent-related complications were noted. During the follow-up period, 20 patients died (none as a result stent-related causes) due to progression of cancer. Median survival was 102 days. Four patients had recurrent obstruction (2 tumor ingrowths, 1 overgrowth, and 1 distally migrated stent) at a mean interval of 82 days. All four had successful restenting without complications. Conclusion: Self-expandable metal stents placed endoscopically provide a safe, less invasive palliative treatment option with good clinical outcome in the management of malignant gastric outlet–duodenal obstruction.