Inotuzumab ozogamicin for the treatment of patients with acute lymphocytic leukemia.

Inotuzumab ozogamicin is an antibody-drug conjugate comprised of a humanized anti-CD22 monoclonal antibody conjugated to calicheamicin, a cytotoxic antibiotic agent. Inotuzumab ozogamicin binds to CD22-expressing tumor cells, resulting in apoptotic cell death. Based on the results of the pivotal, phase III INO-VATE trial in acute lymphoblastic leukemia (ALL), approval of inotuzumab ozogamicin was recently granted for the treatment of patients with relapsed or refractory ALL, a group that otherwise has a poor prognosis with standard chemotherapy. Several ongoing clinical trials are now testing whether outcomes can be further improved by combining inotuzumab ozogamicin with low-dose chemotherapy or by including inotuzumab ozogamicin in the front-line setting. In this article we discuss the preclinical, clinical and safety data of inotuzumab ozogamicin.

Outcomes for patients with chronic lymphocytic leukemia and acute leukemia or myelodysplastic syndrome.

Acute leukemia (AL) and myelodysplastic syndrome (MDS) are uncommon in chronic lymphocytic leukemia (CLL). We retrospectively identified 95 patients with CLL, also diagnosed with AL (n=38) or MDS (n=57), either concurrently (n=5) or subsequent (n=90) to CLL diagnosis and report their outcomes. Median number of CLL treatments prior to AL and MDS was 2 (0-9) and 1 (0-8), respectively; the most common regimen was purine analog combined with alkylating agent±CD20 monoclonal antibody. Twelve cases had no prior CLL treatment. Among 38 cases with AL, 33 had acute myelogenous leukemia (AML), 3 had acute lymphoid leukemia (ALL; 1 Philadelphia chromosome positive), 1 had biphenotypic and 1 had extramedullary (bladder) AML. Unfavorable AML karyotype was noted in 26, and intermediate risk in 7 patients. There was no association between survival from AL and number of prior CLL regimens or karyotype. Expression of CD7 on blasts was associated with shorter survival. Among MDS cases, all International Prognostic Scoring System (IPSS) were represented; karyotype was unfavorable in 36, intermediate in 6 and favorable in 12 patients; 10 experienced transformation to AML. Shorter survival from MDS correlated with higher risk IPSS, poor-risk karyotype and increased number of prior CLL treatments. Overall, outcomes for patients with CLL subsequently diagnosed with AL or MDS were very poor; AL/MDS occurred without prior CLL treatment. Effective therapies for these patients are desperately needed.

Soluble syndecan-1 (sCD138) as a prognostic factor independent of mutation status in patients with chronic lymphocytic leukemia.

Syndecan-1 (sCD138) is a transmembrane heparan sulfate-bearing proteoglycan expressed in epithelial cells as well as hematopoietic cells that demonstrate plasmacytoid differentiation. Higher levels of sCD138 correlate with poor outcome in myeloma. We examined the association of circulating sCD138 levels in plasma with clinical behavior in 104 patients with chronic lymphocytic leukemia. sCD138 levels were significantly higher in patients (median, 52.8 ng/ml; range, 13.4-252.7 ng/ml) than in healthy control subjects (median, 19.86; range, 14.49-33.14 ng/ml) (P < 0.01). Elevated sCD138 (>median, 52.8 ng/ml) was associated with significantly shorter survival (P = 0.0004); this association was independent of IgVH mutation status, beta2-microglobulin (beta2-M) level, and treatment history. Patients with mutated IgVH but high sCD138 levels (>52.8 ng/ml) had significantly shorter survival than those with mutated IgVH and lower levels of sCD138. Similarly, patients with unmutated IgVH but high sCD138 levels had significantly shorter survival than those with lower sCD138 levels and unmutated IgVH (P = 0.007). In a multivariate Cox regression model, only Rai stage, beta2-M, and sCD138 remained predictors of survival. These data suggest that sCD138 when combined with beta2-M and Rai stage, may replace the need for testing IgVH mutation status.

The role of prognostic factors in assessing 'high-risk' subgroups of patients with chronic lymphocytic leukemia.

The management of chronic lymphocytic leukemia (CLL) has historically relied on 'watchful waiting' and palliative approaches to therapy. However, the course of disease is highly variable and a substantial proportion of patients with early-stage CLL develop rapidly progressive disease requiring therapy. In recent decades, numerous clinical and biological prognostic markers that are predictive of decreased survival outcomes, disease progression and/or resistance to therapy, and that may play a role in defining the subgroups of patients with 'high-risk' CLL have been identified. At the same time, highly effective treatment modalities have become available with the advent of chemoimmunotherapy combinations and allogeneic stem cell transplantation. Thus, we are approaching an era when patients with CLL may potentially benefit from individualized risk assessments based on prognostic markers and when specific therapies may be offered to the subgroup of patients with high-risk disease. This review provides a brief overview of newer biological prognostic markers, discusses the challenges associated with identifying the subgroup of patients with high-risk CLL and further aims to provide recommendations on how prognostic markers may be used to assess high-risk subgroups in different clinical situations in CLL.

Having a higher blast percentage in circulation than bone marrow: clinical implications in myelodysplastic syndrome and acute lymphoid and myeloid leukemias.

Determining the percentage of peripheral blood (PB) and bone marrow (BM) blasts is important for diagnosing and classifying acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Although most patients with acute leukemia or MDS have a higher percentage of BM blasts than PB blasts, the relative proportion is reversed in some patients. We explored the clinical relevance of this phenomenon in MDS (n = 446), AML (n = 1314), and acute lymphoblastic leukemia (ALL) (n = 385). Among patients with MDS or ALL, but not AML, having a higher blast percentage in PB than in BM was associated with significantly shorter survival. In multivariate analyses, these associations were independent of other relevant predictors, including cytogenetic status. Our findings suggest that MDS and ALL patients who have a higher percentage of PB blasts than BM blasts have more aggressive disease. These data also suggest that MDS classification schemes should take into account the percentage of blasts in PB differently from the percentage of blasts in BM.

Homoharringtonine: history, current research, and future direction.

BACKGROUND: Cephalotoxine esters, including homoharringtonine (HHT), have shown encouraging activity in leukemia in initial studies in China and in later studies in the U.S. METHODS: The authors conducted a review of the literature to examine the studies pertinent to HHT in relation to preclinical studies and Phase I-II trials in patients with hematologic malignancies and solid tumors. RESULTS: HHT and analogues appear to induce differentiation and apoptosis. Studies from China reported high response rates in patients with leukemia. Trials in the U.S. using short HHT infusions (3-4 mg/m(2) daily for 5 days) resulted in a high incidence of cardiovascular complications that were reduced using continuous infusion schedules of 3-7 mg/m(2) daily for 5-7 days initially, and later lower dose schedules of 2.5 mg/m(2) daily for 7-14 days. Results in solid tumors were negative. However encouraging results were reported in patients with acute myeloid leukemia, myelodysplastic syndrome, acute promyelocytic leukemia, and, most important, chronic myeloid leukemia (CML). In CML patients, HHT has been investigated alone and in combination with interferon-alpha and low-dose cytarabine in late and early chronic phases, with positive results. Additional areas of interest include the potential use of HHT for the treatment of central nervous system leukemia, polycythemia vera, and other nonmalignant conditions such as malaria. New semisynthetic preparations and HHT derivatives that bypass multidrug resistance may improve the efficacy and toxicity profiles, and broaden the range of antitumor efficacy. CONCLUSIONS: HHT and its derivatives appear to have promising activity in hematologic malignancies, a finding that needs to be pursued.

Fractionated cyclophosphamide, vincristine, liposomal daunorubicin (daunoXome), and dexamethasone (hyperCVXD) regimen in Richter's syndrome.

Approximately 3 to 5% of patients with chronic lymphocytic leukemia (CLL) develop an aggressive large cell non Hodgkin's lymphoma (NHL) known as Richter's syndrome (RS). RS has a poor prognosis and a response rate of < 10% with fludarabine-based or other cytotoxic combination regimens. The aim of this study was to evaluate the efficacy and toxicity of the hyperCVXD regimen in RS. Twenty-nine patients, median age 61 years (36-75) 23 males, were treated. Prior diagnosis was CLL in 26 patients, NHL in 2, and Prolymphocytic leukemia in 1. Treatment consisted of fractionated cyclophosphamide, vincristine, daunoXome and dexamethasone. Six patients (20%) died while receiving study therapy, 4 (14%) during the first cycle of whom 2 had started therapy with overt pneumonia. Grade 4 granulocytopenia occurred in all 95 cycles of therapy with a median time to recovery of 14 days. Twenty three (24%) cycles were complicated by fever, and 15 (15%) by pneumonia. Sepsis was documented in 8 (8%) cycles, and neuropathy in 5 (5%) of cycles. Twenty three patients had a platelet count < 100 x 10(9)/l prior to therapy: a greater than 50% decrease in platelet count over pre-therapy level occurred in 79% of first cycles, overt bleeding occurred in 4 (4%) of all cycles. Eleven of 29 (38%) patients achieved complete remission (CR), 4 of whom have relapsed after 5, 6, 9, and 12 months of remission. Two of 11 CR patients presented with RS without any prior CLL therapy. One patient had a partial remission. Thus the overall response rate was 12/29 (41%). Overall median survival was 10 months, 19 months in patients who achieved CR, 3 months in those who did not (p = 0.0008). A landmark analysis performed at 2 months from start of therapy comparing patients alive in CR versus patients alive but not in CR showed a median survival of 19 months versus 6 months, respectively (p 0.0017). In conclusion the hyper CVXD regimen has a relatively high response rate, significant toxicity and a moderate impact on survival in RS.

Can dietary treatment of non-anemic iron deficiency improve iron status?

OBJECTIVE: To investigate the efficacy of, first, a dietary regimen involving increased consumption of iron-rich foods and enhancers of iron absorption and decreased consumption of inhibitors of iron absorption and, second, a low dose iron chelate iron supplement, for increasing iron stores in young adult New Zealand women with mild iron deficiency (MID). METHODS: The study was a 16 week randomized placebo-controlled intervention. Seventy-five women aged 18 to 40 years with MID (serum ferritin < 20 microg/L and hemoglobin > or = 120 g/L) were assigned to one of three groups: Placebo, Supplement (50 mg iron/day as amino acid chelate) or Diet. Participants in the Diet Group were given individual dietary counseling to increase the intake and bioavailability of dietary iron. Dietary changes were monitored by a previously validated computer-administered iron food frequency questionnaire. RESULTS: Diet Group members significantly increased their intake of flesh foods, heme iron, vitamin C and foods cooked using cast-iron cookware and significantly decreased their phytate and calcium intakes. Serum ferritin increased in the Supplement and Diet Groups by 59% (p=0.001) and 26% (p=0.068), respectively, in comparison to the Placebo Group. The serum transferrin receptor:serum ferritin ratio decreased by 51% in the Supplement Group (p=0.001), and there was a non-significant decrease of 22% (p=0.1232) in the Diet Group. CONCLUSIONS: This study is the first, to our knowledge, to demonstrate that an intensive dietary program has the potential to improve the iron status of women with iron deficiency.

Blunt tracheobronchial injuries: treatment and outcomes.

BACKGROUND: Tracheobronchial injury is a recognized, yet uncommon, result of blunt trauma to the thorax. Often the diagnosis and treatment are delayed, resulting in attempted surgical repair months or even years after the injury. This report is an extensive review of the literature on tracheobronchial ruptures that examines outcomes and their association with the time from injury to diagnosis. METHODS: We reviewed all patients with blunt tracheobronchial injuries published in the literature to determine the anatomic location of the injury, mechanism of the injury, time until diagnosis and treatment, and outcome. Only patients with blunt intrathoracic tracheobronchial traumas were included. RESULTS: We identified 265 patients reported between 1873 and 1996. Motor vehicle accidents were the most frequent mechanism of injury (59%). The overall mortality among reported patients has declined from 36% before 1950 to 9% since 1970. The injury occurred within 2 cm of the carina in 76% of patients, and 43% occurred within the first 2 cm of the right main bronchus. The proximity of the injury to the carina had no detectable effect on mortality. Injuries on the right side were treated sooner but were associated with a higher mortality than left-sided injuries. No association was detected between delay in treatment and successful repair of the injury; ninety percent of patients undergoing treatment more than 1 year after injury were repaired successfully. CONCLUSIONS: This review of patients with blunt tracheobronchial injuries represents the largest cohort studied to date. These data suggest an ability to repair tracheobronchial injuries successfully many months after they occur. We are also able to assess the mortality associated with the location and side of injury, examine the time from injury until diagnosis and treatment, and evaluate treatment outcome.

Rituximab dose-escalation trial in chronic lymphocytic leukemia.

PURPOSE: To conduct a dose-escalation trial of rituximab in patients with chronic lymphocytic leukemia (CLL) to define the maximum-tolerated dose (MTD), to evaluate first-dose reactions in patients with high circulating lymphocyte counts, and to assess the efficacy at higher versus lower doses. PATIENTS AND METHODS: Fifty patients with CLL (n = 40) or other mature B-cell lymphoid leukemias (n = 10) were treated with four weekly infusions of rituximab. The first dose was 375 mg/m(2) for all patients; dose- escalation began with dose 2 but was held constant for each patient. Escalated doses were from 500 to 2,250 mg/m(2). RESULTS: Toxicity with the first dose (375 mg/m(2)) was noted in 94% of patients but was grade 1 or 2 in most, predominantly fever and chills. Six patients (12%) experienced severe toxicity with the first dose, including fever, chills, dyspnea, and hypoxia in all six patients, hypotension in five, and hypertension in one. Toxicity on subsequent doses was minimal until a dose of 2,250 mg/m(2) was achieved. Eight (67%) of 12 patients had grade 2 toxicity, including fever, chills, nausea, and malaise, although no patient had grade 3 or 4 toxicity. Severe toxicity with the first dose was significantly more common in patients with other B-cell leukemias, occurring in five (50%) of 10 patients versus one (2%) of 40 patients with CLL (P <.001). The overall response rate was 40%; all responses in patients with CLL were partial remissions. Response rates were 36% in CLL and 60% in other B-cell lymphoid leukemias. Response was correlated with dose: 22% for patients treated at 500 to 825 mg/m(2), 43% for those treated at 1,000 to 1,500 mg/m(2), and 75% for those treated at the highest dose of 2,250 mg/m(2) (P =.007). The median time to disease progression was 8 months. Myelosuppression and infections were uncommon. CONCLUSION: Rituximab has significant activity in patients with CLL at the higher dose levels. Severe first-dose reactions were uncommon in patients with CLL, even with high circulating lymphocyte counts, but were frequent in patients with other mature B-cell leukemias in which CD20 surface expression is increased. Efficacy of rituximab was also significant in this group of patients.

Results of the fludarabine and cyclophosphamide combination regimen in chronic lymphocytic leukemia.

PURPOSE: To assess the efficacy of combination therapy with fludarabine and cyclophosphamide in patients with chronic lymphocytic leukemia (CLL) based on data suggesting in vitro synergistic activity of the two agents. PATIENTS AND METHODS: A total of 128 patients with CLL were treated with fludarabine 30 mg/m(2) intravenously daily for 3 days and cyclophosphamide at either 500 mg/m(2) daily for 3 days (n = 11), 350 mg/m(2)/d for 3 days (n = 26), or 300 mg/m(2) daily for 3 days (n = 91). The cyclophosphamide dose was decreased because of myelosuppression in the early part of the study. Patients were divided into four groups based on the expectation for response to single-agent fludarabine, including previously untreated patients, patients previously treated with alkylating agents, patients successfully treated with alkylating agents and fludarabine but relapsing, and patients refractory to fludarabine with or without alkylating agents. RESULTS: Fludarabine and cyclophosphamide produced > or = 80% response rates in all patients not refractory to fludarabine at the start of therapy as well as a 38% response rate in patients who were refractory to fludarabine. The complete remission (CR) rate was 35% in previously untreated patients, which was not significantly different from the CR rate in historical control patients treated with single-agent fludarabine. However, residual disease assessed by flow cytometry occurred in only 8% of previously untreated patients achieving CR, and median time to progression has not been reached after a median follow-up of 41 months. The main complication of therapy was related to myelosuppression and infection. Neutropenia to less than 500 x 10(9)/L was noted in 48% of patients who received cyclophosphamide 300 mg/m(2). Pneumonia or sepsis occurred in 25% of patients, and fever of unknown origin occurred in another 25%. Pneumonia or sepsis were significantly more frequent in patients who were refractory to fludarabine at the start of combination chemotherapy. CONCLUSION: Fludarabine and cyclophosphamide seem to have a significant advantage over single-agent fludarabine in the salvage setting. Although the CR rate was not increased in previously untreated patients, residual disease detected by flow cytometry was rare and remission durations seemed to be prolonged in this subset. Myelosuppression and infection remain the most significant complications of therapy in CLL.

Utility of obtaining blood cultures in febrile neutropenic patients undergoing bone marrow transplantation.

Infection remains an important cause of morbidity and mortality after bone marrow or stem cell transplantation. To evaluate the role of obtaining blood cultures for intermittent or persistent fever in neutropenic patients on antibiotic therapy, we performed a retrospective chart review of 196 consecutive patients admitted to the Bone Marrow Transplant Unit at the University of North Carolina Hospitals from 1995 to 1998. From the cohort of 196 patients, 154 patients developed neutropenic fever. The initial blood culture was positive in 16 of 145 patients during the first fever episode giving a prevalence of 11%. From the total of 109 patients that had blood cultures drawn after day 1 of fever, five patients had blood cultures positive for a pathogen, a prevalence of 4.6%. In only one patient, did blood cultures drawn after day 1 identify an organism not present on day 1 (prevalence 0.9%). After reviewing the results in the first 105 patients, we changed our timing of collection of blood cultures. Forty-nine patients were treated in this manner and we found that the mean number of blood cultures decreased from 9.2 to 4.7 per patient without a change in the frequency of infectious complications or length of hospitalization.

Acute myeloid leukemia, inversion 16, occurring in a patient with chronic lymphocytic leukemia.

The occurrence of acute myeloid leukemia (AML) in patients previously diagnosed with chronic lymphocytic leukemia (CLL) is rare. In most cases, AML develops after treatment of CLL and is thought to be therapy related; unfavorable karyotypes are often evident. Herein, we report a patient with a long-standing history of CLL who developed AML with cytogenetic analysis revealing inversion 16. In keeping with the favorable prognosis of this abnormality, the patient has achieved a complete remission, which has been maintained for 13 months.

Informing patients of diagnostic mammography results: mammographer's opinions.

PURPOSE: The authors' purpose was to determine mammographers' practices and attitudes regarding disclosing results of diagnostic mammograms to patients. MATERIALS AND METHODS: In 1995, the authors mailed a questionnaire to 500 members of the Society of Breast Imaging; 399 (80%) responded to the survey. RESULTS: Three-quarters of respondents stated that mammographers should disclose results to their patients, and approximately half were already doing so (52% for normal results, 51% for abnormal results). A sizable minority (25%) said that not telling patients was the best practice and identified several barriers to direct disclosure, including lack of time. Although bivariate analysis showed direct disclosure to be more common among female mammographers, the sex difference did not persist in multivariate analysis. In both bivariate and multivariate analyses, reading more than 100 mammograms per week and having a radiology practice in a university or academic setting were each strongly associated with direct disclosure. CONCLUSION: Implementation of the Mammography Quality Standards Reauthorization Act of 1998 may not require a major change in mammographers' current practice. It remains critical to establish systems that help radiologists disclose results and communicate with referring physicians efficiently and effectively.

The ability of tumor volume to predict local control in surgically treated squamous cell carcinoma of the supraglottic larynx.

PURPOSE: Pretreatment CT volumetric measurement of the primary tumor has been shown to be a predictor of local control in patients with laryngeal carcinoma treated with radiation therapy (RT) alone. A direct association has been demonstrated between tumor volume of supraglottic squamous cell carcinoma (SGSCCA) and local control. However, the association between tumor volume of SGSCCA and local control has not been investigated in patients treated surgically. The purpose of this study was to determine the relationship between SGSCCA tumor volume and local control in patients treated surgically. MATERIALS AND METHODS: Primary site tumor volume was calculated from pretreatment CT studies in 37 laryngeal supraglottic carcinomas treated surgically. All patients had clinical follow-up for evidence of recurrent tumor along the surgical margins at the primary site for a minimum of 2 years after completion of treatment. Statistical analysis consisted of Mantel-Haenszel chi-square tests and Fisher's exact test. RESULTS: Overall local control rate was 92% (33 of 37). Tumor volume was significantly associated with local control (p <. 05). Local control rate for tumors with volumes <16 cc was 94% (32 of 34) (p <.05). CONCLUSIONS: Pretreatment CT volumetric analysis is useful for predicting local control in patients with SGSCCA carcinoma treated surgically.

Sequential cis-platinum and fludarabine with or without arabinosyl cytosine in patients failing prior fludarabine therapy for chronic lymphocytic leukemia: a phase II study.

Patients with chronic lymphocytic leukemia (CLL) who fail fludarabine (Fluda) therapy have a poor response to subsequent salvage regimens and a poor prognosis. This study was undertaken to determine the efficacy and toxicity of a cis-platinum, (cis-p)fluda and arabinosyl cytosine (ara-C) combination in patients who were refractory to fluda or had relapsed following prior fluda therapy for CLL. Forty-one patients who had progressive CLL were treated on study. Eleven patients (27%) were sensitive to fluda and thirty (73%) refractory prior to study entry. Therapy consisted of cis-p 100 mg/m2 continuous intravenous (i.v.) infusion over 4 days, fluda 30 mg/m2 i.v. over 15 minutes on Days 3 and 4 either given alone (PF) or with ara-C 500 mg/m2 i.v. over 1 hour on Day 4 (PFA). The median number of PF or PFA courses received was two. No patient achieved a complete response. Eight patients (19%) achieved a partial response (PR), 28 were taken off study with progressive or refractory disease and 5 had induction deaths. The overall median survival was 6 months, 15 months in responding patients, and 4 months in non-responding patients. Rai stage I-II patients had a median survival of 7 months and stage III-IV patients had a median survival of 3 months. Major toxicities (myelosuppression, sepsis, renal failure and tumor lysis syndrome) were frequent. In conclusion, it can be said that the PF and PFA regimens have equivalent modest activity in patients with progressive CLL following prior fluda therapy, predominantly among patients whose disease was sensitive to fluda at last prior exposure. Ara-C did not add to the activity of the cis-p/fluda combination in this study group.

Tumor volume: an independent predictor of outcome for laryngeal cancer.

PURPOSE: Other studies have shown a relationship between the volume of laryngeal tumors and local control when treated with radiation therapy. Our purpose was to determine the relationship between tumor volume, clinical staging, and several histologic abnormalities to local control in patients treated with initial surgery. METHOD: Tumor volume was calculated from pretreatment CT scans in 52 patients with squamous cell carcinoma treated surgically. The presence of perineural and lymphatic spread as well as cartilage and vessel invasion were obtained from histology. All cases had at least a 2 year clinical follow-up after initial surgery. Statistical analysis consisted of Mantel-Haneszel chi2-tests and Fisher exact test. RESULTS: Local control rate was 92%. Tumor volume and cartilage invasion were associated with local control (p < 0.05). Local control rate for tumors with volumes of < 16 cm3 was 98% compared with 40% for tumors with volumes of > 16 cm3 (p < 0.05). Evidence of cartilage invasion was associated with increased likelihood of local recurrence. There was no significant association between local control and perineural, vascular, or lymphatic tumor spread. We found a marginally significant association between clinical T-stage and local control (p = 0.05). CONCLUSION: Pretreatment CT volumes are useful in predicting local control in laryngeal carcinoma treated with surgery. Of the histologic features studied, only cartilage invasion was significant in predicting tumor control.

A 5-year follow-up of self-expanding metal stents in the endoscopic management of patients with benign bile duct strictures.

BACKGROUND: Metal stents offer superior biliary drainage in patients with malignant bile duct obstruction, with fewer episodes of stent occlusion compared with polyethylene stents. Metal stent patency has only been studied over limited time periods in such patients with malignant disease. OBJECTIVE: To assess the long-term patency of metal stents in a group of patients with benign bile duct strictures who are suitable for extended follow-up. METHODS: Between May 1989 and May 1992, eight patients (median age 59.0 years; range 26-88 years) with benign biliary strictures were selected at a tertiary referral centre for insertion of a metal stent. Strictures were secondary to bile duct trauma (n = 5), chronic pancreatitis (n = 2) or idiopathic (n = 1). A long metal stent was inserted in three patients and a short metal stent in five patients. RESULTS: After a median follow-up of 64.5 months (range 26-81 months, seven of the eight patients are alive. Baby scope examination at 1 year showed complete epithelialization of the metal stent in all subjects examined. Median stent patency was 35 months (range 7-72 months). Symptomatic episodes of metal stent occlusion have occurred on nine occasions in five patients (62.5%) secondary to mucosal hypertrophy (n = 3) or biliary calculi (n = 2). CONCLUSION: The long-term management of selected patients with benign bile duct strictures may be significantly improved by the use of metal stents avoiding the need for frequent polyethylene stent changes.

Clinical course and therapy of chronic myelogenous leukemia with interferon-alpha and chemotherapy.

This article begins with a review of the natural history of chronic myelogenous leukemia (CML), with an emphasis on prognostic features. Current standard therapy of CML with interferon-alpha based regimens, and interferon-alpha, in the context of allogenic stem cell transplantation is then discussed. Finally, some potentially effective novel agents including homoharringtonine, decitabine, ATRA, and topotecan are described.