Conventional Systemic Treatments Research Articles

Dr. Pagnoux, et al reply

To the Editor: We appreciate the comments by Drs. Garcia-Valladares and Espinoza1 regarding our study on granulomatosis with polyangiitis (Wegener’s, GPA) persistently localized to one organ2. As emphasized by their patient’s case, subglottic stenosis often evolves and can relapse as a limited process in GPA, in the absence of or with only a few other active systemic extra-respiratory tract vasculitis manifestation(s) and/or progress to fibrotic stenosis. Most of these patients with this potentially rapidly life-threatening manifestation represent a difficult therapeutic challenge3. Because the response of subglottic stenosis to conventional systemic treatments is, at best, partial and, if so, often only transient, local therapy, … Address correspondence to Dr. Pagnoux; E-mail: christian.pagnoux{at}cch.aphp.fr

Efficacy of adalimumab in the treatment of psoriasis: A retrospective study of 15 patients in daily practice

Background: Adalimumab is a fully human IgG1 monoclonal antibody that binds to tumor necrosis factor (TNF), a key proinflammatory cytokine involved in the pathogenesis of psoriasis. Objective: A single-center, retrospective study was conducted to assess the efficacy and safety of adalimumab in patients with moderate to severe psoriasis in daily practice. Methods: The medical records of 15 patients with moderate to severe psoriasis treated with adalimumab during a 1-year period were reviewed. Previous conventional systemic treatments or other biological agents were unsuccessful. All patients received subcutaneous injections of an initial dose of adalimumab (80 mg) at week 0 followed by adalimumab (40 mg) every other week. Results: A 75% improvement in the Psoriasis Area and Severity Index (PASI 75) score was achieved by 80% of patients at week 24 and by 73.3% of patients at week 48. Moreover, 13.3% of patients were almost completely cleared (PASI 90) at week 48. At 24 weeks, adalimumab therapy increased significantly a patient's quality of life as assessed by the Dermatology Life Quality Index (DLQI) (p = 0.001). The Nail Psoriasis Severity Index (NAPSI) decreased from a mean (SD) of 18.9 (12.2) to 8.2 (4.7) (p = 0.001) at week 24. Palmoplantar psoriasis decreased from a mean score of 1.1 (1.3) to 0.5 (0.9) (p = 0.026) and scalp involvement from a mean of 2.5 (1.2) to 1.1 (1.0) (p = 0.002) at week 24. Out of 11 patients with pruritus at the pre-treatment visit, this symptom had completely disappeared in nine of them after 24 weeks of treatment. Conclusions: Treatment with adalimumab proved to be effective for the management of chronic moderate to severe plaque-type psoriasis in patients whose disease had been refractory to systemic conventional therapies or other biologic agents.

Evaluation of serum vitamin C, β-carotene and α-tocopherol status in pneumonia of camels

Status of serum vitamin C, β-carotene and α-tocopherol concentrations was evaluated in 17 camels suffering from pneumonia. The grossly affected lungs were collected for histopathological examination from camels at slaughterhouses, and serum samples were processed for measuring β-carotene (micrograms per decilitre), vitamin C (milligrams per decilitre) and α-tocopherol (micrograms per decilitre) levels. Based on histopathological examinations, camels under investigation were classified as acute bronchopneumonia (N = 3), chronic bronchopneumonia (N = 4), chronic pleuropneumonia (N = 3), interstitial pneumonia (N = 3), embolic pneumonia (N = 3) and control group (N = 4). The results revealed significant decreases in serum vitamin C and α-tocopherol concentrations in all investigated types of pneumonia. However, serum β-carotene showed insignificant changes. Results of the present study clearly demonstrated the importance of supplementing camels suffering from pneumonia with sources of vitamins along with the conventional systemic treatment to overcome the oxidative stress and to avoid the possible complications of α-tocopherol and vitamin C deficiencies.

Evidence‐based recommendations on conventional systemic treatments in psoriasis: systematic review and expert opinion of a panel of dermatologists

There is a high level of heterogeneity regarding the practical use of conventional systemic treatment in psoriasis. The aim of this study was to develop evidence-based recommendations for the use of traditional systemic treatments in psoriasis in daily clinical practice: methotrexate (MTX), cyclosporin and retinoids. A scientific committee selected clinically relevant questions concerning the use of MTX, cyclosporin and retinoids in psoriasis. This selection was made using the Delphi method. A systematic literature search was performed in Medline, Embase and the Cochrane Library. The articles selected for analysis were reviewed and the level of evidence was appraised according to the Oxford Levels of Evidence. An Expert consensus meeting took place in June 2010, including 66 dermatologists. Recommendations for daily use of psoriasis systemic treatments were made during interactive workshops where the evidence was reviewed. Agreement among participants and the impact of the recommendations on clinical practice were systematically assessed using voting procedure in a plenary session. A total of 2800 references were identified, among which 122 articles were included in the systematic reviews. Three key recommendations on the use of MTX in psoriasis were formulated, including optimal dosage and route, use of folic acid, risk factors for liver fibrosis and monitoring of hepatotoxicity. The recommendations for cyclosporin in psoriasis focused on the modalities of cyclosporin prescription: dosage, scheme of treatment, optimal duration of treatment, renal toxicity monitoring and evidence for use of cyclosporin in non-plaque psoriasis (erythrodermic, pustular and ungueal). Recommendations were also made concerning the efficacy and safety of retinoids (mainly acitretin) in plaque and non-plaque psoriasis. These recommendations for the use of traditional systemic therapies in psoriasis are evidence based and supported by a panel of dermatologists. The next step will be to disseminate these recommendations and assess the agreement of physicians who were not involved in generating the recommendations.

Use of conventional systemic treatments in psoriasis: systematic review and expert opinion of a panel of dermatologists

Use of conventional systemic treatments in psoriasis: systematic review and expert opinion of a panel of dermatologists

Treatment of refractory adult‐onset pityriasis rubra pilaris with TNF‐alpha antagonists: a case series

Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis with frequent clinical presentation as erythroderma. Conventional systemic treatment is often unsatisfactory and limited by long-term toxicity. The use of tumour necrosis factor (TNF) antagonists has been reported previously in single cases, but lacking long-term follow-up or comparison between different biological agents. To assess the long-term efficacy and safety of TNF-alpha antagonist, infliximab and etanercept, either in monotherapy or in combination therapy of severe, refractory adult-onset PRP. Seven patients of adult-onset PRP, six newly diagnosed type-I and 1 type-II, which were resistant or ineligible to conventional systemic treatment, received a single course of infliximab or etanercept therapy, alone or in combination with low-dose acitretin (>0.25 mg/kg/daily). After complete remission and treatment discontinuation, a follow-up period of 12 months was evaluated for relapses. Six patients obtained complete remission after a single course of anti-TNF-alpha therapy: mean therapy duration was 19.3 weeks (range 6-48 weeks). All patients obtained significant clearing (>75% of body surface area) of skin lesions at week 12. Two patients with marked keratoderma developed localized disease recurrence during treatment. During follow-up, only a single patient, affected by type II PRP, had disease relapse. Both TNF-alpha antagonists proved successful for the treatment of refractory, adult-onset PRP, yielding complete and persistent clinical responses in type-I PRP. Infliximab was associated with a more rapid onset of action, while treatment duration was comparable with etanercept. PRP type II warranted long-term therapy and showed relapse after drug discontinuation.

Molecular targeted therapies in head and neck cancer - An update of recent developements -

Targeted therapies have made their way into clinical practice during the past decade. They have caused a major impact on the survival of cancer patients in many areas of clinical oncology and hematology. Indeed, in some hematologic malignancies, such as chronic myelogenous leukemia or non-Hodgkin's lymphomas, biologicals and antibodies specifically designed to target tumour-specific proteins have revolutionized treatment standards. In solid tumours, new drugs targeting EGF- or VEGF- receptors are now approved and are entering clinical practise for treatment of colon, lung, kidney and other cancers, either alone or in combination with conventional treatment approaches.Recent data have now shown that molecular targeted therapy might display efficacy in patients with head and neck squamous cell carcinoma (HNSCC) as well. The evaluated biologicals are generally well tolerated from HNSCC patients, who usually have the burden of multiple co-morbidities that interfere with conventional systemic treatment options. Therefore, molecular targeted therapies offer new treatment options even for heavily pretreated and seriously ill patients usually unable to tolerate chemotherapy or radiation therapy.The two most promising and advanced strategies are the blockage of growth-factor based cellular signalling and interference with angiogenesis-related pathways. But inhibitors of alternative targets, such as Scr and proteasomes, have already been evaluated in early clinical trials with HNSCC patients.

Intra-articular morphine and bupivicaine for post-operative analgesia in anterior cruciate ligament reconstruction: a prospective randomised controlled trial

Anterior cruciate ligament reconstruction (ACLR) has the potential for significant post-operative pain. Conventional systemic opiate treatment may cause nausea and drowsiness, which may delay recovery. The use of intra-articular local anaesthesia has been shown to be effective. We wished to examine the additional effect of intra-articular morphine. This is a prospective, randomised, double-blind trial. Sixty patients were randomised to receive 20 ml 0.5% bupivicaine (group L, n = 30) or bupivicaine with 10 mg morphine (group M, n = 30) by intra-articular injection at the end of the operation. Visual analogue scores (VAS) were recorded before ACLR (expected pain) and repeated at 6 and 24 h after surgery. Time to first analgesic request and total systemic opiate and other analgesic use in the first 24 h was recorded. Pre-operative VAS measurements did not predict pain or analgesic use post-operatively. There were no significant differences between groups L and M with regard post-operative VAS or time to first analgesic request. Group M required less opiate analgesic post-operatively (oral morphine equivalent 50 mg for group L and 27 mg for group M, P < 0.007). There were no complications associated with the intra-articular analgesic. The simple addition of morphine to the intra-articular injection of bupivicaine gives a significant reduction in opiate analgesic requirement after ACLR.

Characterization of membranous and cytoplasmic EGFR expression in human normal renal cortex and renal cell carcinoma

Metastatic renal cell carcinoma (RCC) is highly resistant to conventional systemic treatments, including chemotherapy, radiotherapy and hormonal therapies. Previous studies have shown over-expression of EGFR is associated with high grade tumors and a worse prognosis. Recent studies suggest anticancer therapies targeting the EGFR pathway have shown promising results in clinical trials of RCC patients. Therefore, characterization of the level and localization of EGFR expression in RCC is important for target-dependent therapy. In this study, we investigated the clinical significance of cellular localization of EGFR in human normal renal cortex and RCC. RCC and adjacent normal kidney tissues of 63 patients were obtained for characterization of EGFR expression. EGFR protein expression was assessed by immunohistochemistry on a scale from 0 to 300 (percentage of positive cells × staining intensity) and Western blotting. EGFR membranous staining was significantly stronger in RCC tumors than in normal tissues (P < 0.001). In contrast, EGFR cytoplasmic staining was significantly higher in normal than in tumor tissues (P < 0.001). The levels of membranous or cytoplasmic EGFR expression in RCC tissues were not correlated with sex, tumor grade, TNM stage or overall survival (P > 0.05). These results showed abundant expression of membranous EGFR in RCC, and abundant expression of cytoplasmic EGFR in normal tissues. EGFR expression in RCC was mostly located in the cell membrane, whereas the EGFR expression in normal renal tissues was chiefly seen in cytoplasm. Our results suggest different locations of EGFR expression may be associated with human renal tumorigenesis.

Efficacy, safety, and cost of Goeckerman therapy compared with biologics in the treatment of moderate to severe psoriasis

Efficacy, safety, and cost of Goeckerman therapy compared with biologics in the treatment of moderate to severe psoriasis

Economic evaluation of systemic therapies for moderate to severe psoriasis

New biologics have dramatically changed therapeutic options for psoriasis, albeit at additional cost. To determine the cost-effectiveness and optimal treatment sequence for moderate to severe psoriasis. Psoriasis Area and Severity Index (PASI) response rates from 22 randomized controlled trials evaluating biologic (adalimumab, efalizumab, etanercept, infliximab) and nonbiologic systemic (methotrexate, ciclosporin) agents were considered. Short-term efficacy was based on relative probabilities of achieving PASI response (50/75/90) in a meta-analysis of trials. Published evidence and assumptions were used to predict long-term efficacy. Treatment benefits were determined by the relationship between PASI response and the EuroQOL 5D health utility measure. Costs included therapy, administration, monitoring and hospitalization. Incremental cost-effectiveness ratios (ICERs) were calculated and treatments ranked relative to supportive care. Infliximab provided the most incremental quality-adjusted life-years (QALYs) vs. supportive care (0.18 QALYs; 95% confidence interval, CI 0.13-0.24), followed by adalimumab (0.16 QALYs; 95% CI 0.11-0.22). Methotrexate and ciclosporin were less beneficial (0.13 and 0.08 QALYs, respectively) but were cost saving and considered the first two treatments in the optimal sequence. Comparing biologics, adalimumab was most cost effective (ICER pound30 000 per QALY), followed by etanercept ( pound37 000 per QALY), efalizumab ( pound40 000 per QALY) and infliximab ( pound42 000 per QALY). Methotrexate and ciclosporin are cost effective but require monitoring for toxicities. Of the biologics, adalimumab was most cost effective following conventional systemic treatment failure or inadequate response. Payers and policymakers will have to decide how to utilize their budgets effectively for treating patients with moderate to severe psoriasis.

Efficacy of 90 Y - Ibritumomab Tiuxetan in Relapsed or Refractory Primary Gastric Non Hodgkin Lymphoma

BACKGROUND: A prospective, single arm, open-label, phase II trial was performed to evaluate efficacy of 90Y-Ibritumomab Tiuxetan at conventional activity of 0,4 mCi/kg in Primary Gastric Non Hodgkin Lymphoma (NHL).PATIENTS AND METHODS: From May 2004 to May 2008, 13 patients affected by Primary Gastric NHL - either Mucosa Associated Lymphoid Tissue (MALT) or Diffuse Large B Cell (DLBC) NHL, relapsed/refractory disease - were enrolled to receive 90Y-Ibritumomab Tiuxetan at the activity of 0,4 mCi/kg. Median age was 57 ys (range 36–83), 6 female and 7 male. Nine out of 13 patients had gastric MALT NHL, the remaining 4 patients had DLBC NHL. At time of treatment 11 out of 13 patients had stage I/II, 2 patients had stage III/IV disease. Helicobacter Pylori was negative in all patients except one at time of treatment and positive at diagnosis in 5 of them. Median number of previous therapies received was 1 (1–4): all patients except 3 had received prior CT, 7 patients prior Rituximab, no one had received prior RT.RESULTS: Toxicities were primarily haematological and reversible. All patients had serial testing for HAMA and none developed antibodies to date. MALT-1 gene rearrangement was detected in 3 of the 9 cases analyzed, while none of the cases showed bcl-10 gene rearrangement. All patients are now evaluable for response: 10 out of 13 patients experienced a complete response (CR) (9 MALT, 1 DLBC); progressive disease (PD) was observed in 2 out of 13 patients, both DLBC NHL; finally another patient affected by DLBC NHL did not respond. After a median follow up of 24 months (range 3–50 months) 9 out of 10 CRs are disease free and 5 of them can be considered long term responders at 50, 43, 40, 32 and 31 months, respectively, following radioimmunotherapy (RIT). At the time of the analysis only 1 relapse occurred 17 months after RIT (MALT). Two patients - both DLBC - died due to disease progression. There was no statistically significant associations between response to RIT and the occurrence of the MALT-1 translocation.CONCLUSIONS: 90Y-Ibritumomab Tiuxetan seems to be very active in patients with primary gastric NHL relapsed or refractory to conventional systemic treatment, especially in gastric MALT NHL. Despite the relative short median follow-up (24 months), we observed durable long-term responses at least in 5 patients. High response rate and durable remissions could be related to the low tumor burden and consequently to higher absorbed doses to tumor, confirming the possible relationship between absorbed doses to tumor, efficacy and duration of response. If preliminary results can be confirmed in larger series, RIT could be offered as valid alternative approach in this setting because of its efficacy and low rate of side effects. These preliminary results warrant further studies.

Endocrine and Metabolic Manifestations of Invasive Fungal Infections and Systemic Antifungal Treatment

Systemic fungal infections are increasingly reported in immunocompromised patients with hematological malignancies, recipients of bone marrow and solid organ allografts, and patients with AIDS. Mycoses may infiltrate endocrine organs and adversely affect their function or produce metabolic complications, such as hypopituitarism, hyperthyroidism or hypothyroidism, pancreatitis, hypoadrenalism, hypogonadism, hypernatremia or hyponatremia, and hypercalcemia. Antifungal agents used for prophylaxis and/or treatment of mycoses also have adverse endocrine and metabolic effects, including hypoadrenalism, hypogonadism, hypoglycemia, dyslipidemia, hypernatremia, hypocalcemia, hyperphosphatemia, hyperkalemia or hypokalemia, and hypomagnesemia. Herein, we review how mycoses and conventional systemic antifungal treatment can affect the endocrine system and cause metabolic abnormalities. If clinicians are equipped with better knowledge of the endocrine and metabolic complications of fungal infections and antifungal therapy, they can more readily recognize them and favorably affect outcome.

What's new in atopic dermatitis?

What's new in atopic dermatitis?

Es necesario el control de la psoriasis a largo plazo

Psoriasis is an immune mediated, inflammatory skin condition affecting approximately 1.43% of Spanish population. In clinical practice, physicians use PASI index to assess the severity. Psoriasis causes physical and mental disability comparable to other chronic diseases and affects seriously the patients quality of life. For treatment we have different options. Conventional systemic treatment such as methotrexate, cyclosporine and acitretin may be associated with relevant side effects, and organ toxicity that avoid long term therapy. Several psoriasis patients have other comorbid disorders like obesity, diabetes, dyslipemia, hypertension and an increased rate of cardiovascular disease and metabolic syndrome and these patients need safer treatments. The accumulating clinical experience with new therapies consistent on biological agents like efalizumab indicates that are effective therapies, with safety profile and no evidence of cumulative toxicity that allows a long term use. A better control of psoriasis improves patients quality of life.

Efficacy of 90Y-Ibritumomab Tiuxetan in Marginal-Zone Lymphoma (MZL).

Radio-immunotherapy (RIT) is an effective approach for patients with relapse-refractory NHL. RIT targets radiation to the tumor bulk while limiting exposure of normal tissues. Toxicity is prevalently hematologic, but transient and reversible. 90Y-Ibritumomab Tiuxetan in particular has demonstrated activity in follicular (FL) and Diffuse Large B-Cell (DLBC) NHL, but data are still lacking in MZL. 90Y-Ibritumomab Tiuxetan could offer an alternative option to those pts who relapse or do not respond to conventional treatment. We report efficacy results of a pilot study of 90Y-Ibritumomab Tiuxetan delivered at conventional activity (0,4 mCi/kg) in MZL patients. From May 2004 to July 2007, 15 patients were enrolled. Median age was 57 ys (range 36–83 ys); 9 female and 6 male. Six out of 15 pts had Helicobacter Pylori-negative gastric MALT (mucosa-associated lymphoid tissue) NHL. The remaining 9 pts had non gastric extranodal MZL. At time of treatment 6/15 pts had limited disease (stage I/II), 9/15 disseminated disease (stage III/IV; Ann-Arbor Staging System); bone marrow biopsy showed disease localization in 3/15 pts. Median number of previous therapies received was 2 (0–4): all pts except one had received prior CT, 7 prior Rituximab, 3 prior RT. Toxicities were primarily haematological, as expected, and reversible. Response evaluation was performed two months after 90Y-Ibritumomab Tiuxetan administration by upper gastrointestinal endoscopy with multiple biopsy and endoscopic ultrasonography in gastric NHL and by CT scan in the remaining pts. Ten out of 15 patients are now evaluable for response: 6 CR, 1 uCR, 3 SD. Response are durable: 5 CRs have been maintained for CR at 33, 26, 22, 15 and 14 months, respectively.CONCLUSIONS: 90Y-Ibritumomab Tiuxetan seems to be very active in pts with MZL resistant or refractory to conventional systemic treatment. Its mechanism of action mimics conventional RT already known as valid option in MZL with localized disease. If these preliminary results are confirmed in larger number of patients, one single administration of 90Y-Ibritumomab Tiuxetan delivered at conventional activity (0,4 mCi/kg) could be considered a possible alternative option in the treatment of such indolent disease.

Adalimumab for severe psoriasis and psoriatic arthritis: An open-label study in 30 patients previously treated with other biologics

Psoriasis is a chronic, genetically determined, immune-mediated, inflammatory skin disease affecting approximately 2% to 3% of the Caucasian population. Previously reported data demonstrated adalimumab to be an efficacious treatment of psoriatic arthritis and plaque-type psoriasis. Adalimumab is a fully human monoclonal antibody IgG1 against tumor necrosis factor alpha. To evaluate the efficacy and safety of adalimumab, in the treatment of psoriasis patients whose disease is refractory to treatment with other biologic agents. Thirty patients affected by plaque-type psoriasis with or without psoriatic arthritis, unresponsive to conventional and biologic systemic treatments were enrolled. Adalimumab was administered in monotherapy, at a dosage of 40 mg, subcutaneously, once a week. At week 12, 26 of 30 patients (87%) achieved Psoriasis Area and Severity Index (PASI) 75; at week 24, 25 of 30 patients (83%) achieved PASI 75. Concerning psoriatic arthritis, at week 24, the mean Health Assessment Questionnaire score improved from 0.99 to 0.2, Ritchie articular index from 10.15 to 2, and Pain Visual Assessment Score from 6.32 to 1.2. Furthermore, therapy with adalimumab considerably enhanced patients' quality of life as assessed by two measures (Dermatology Life Quality Index, Psoriasis Disability Index). Adalimumab was generally safe and well tolerated. This is not a randomized placebo-controlled study and is restricted to a small number of patients. In our experience, although preliminary, monotherapy with adalimumab 40 mg weekly proved to be an effective and safe treatment for the management of plaque-type psoriasis and psoriatic arthritis, with a rapid onset of action in patients whose disease had been refractory to both conventional and biologic agents.

Combining immunotherapy and radiation therapy for small cell lung cancer and thymic tumors.

Recent work with immunotherapy has shown promising results with treatment of several solid malignancies, and there are several reports of good systemic responses with the combination of immunotherapy and radiation therapy (RT), most notably in advanced melanoma. Given the rapid increase in the use of checkpoint blockade as well as anti-tumor vaccines, we review here the preclinical rationale and ongoing clinical work in combining immunotherapy with RT for small cell lung cancer (SCLC) and thymic tumors. While there are several reports of promising results with the combination of immunotherapy and conventional systemic treatment, we focus here on the ongoing clinical studies that combine immunotherapy with RT, and highlight the emerging data for this multimodality approach as well as key preclinical and clinical issues that remain to be addressed. With regards to SCLC, trials exploring to the combination of immunotherapy and RT are already ongoing, but clinical studies for this combination in thymoma are lacking.

Efficacy of 90Y-Ibritumomab Tiuxetan (Zevalin) in Refractory or Relapsed MALT Gastric Non Hodgkin's Lymphoma.

Radio-immunotherapy (RIT) is an effective approach for patients with relapse-refractory NHL. The aim of RIT is to use the monoclonal antibody to target radiation to the tumor bulk while limiting exposure of normal tissues. Toxicity is prevalently hematologic, but transient and reversible. Zevalin in particular has demonstrated activity in follicular (FL) and diffuse large B-cell (DLBC) NHL, but data are still lacking in MALT NHL. In this setting of pts Zevalin could offer an alternative option to those pts who relapse or do not respond to conventional treatment. We report efficacy results of a pilot study of Zevalin delivered at conventional activity (0,4 mCi/kg) in gastric NHL pts resistant or refractory to conventional systemic treatment. From May 2004 to January 2006, 7 patients were enrolled. They all had gastric resistant-refractory CD-20 positive B-cell NHL: 2 DLBC and 5 MALT. Median age was 57 ys (range 36–64), 3 female and 4 male. At time of treatment 5 out of 7 patients had stage I/IIA (MALT), while 2 out of 7 pts had stage III/IV (DLBCL) of disease. Helicobacter Pylori was negative in all pts at time of treatment, positive at diagnosis in 3 out of 5 pts affected by MALT gastric NHL. Median number of previous therapies received was 2 (1–4): all of them had received prior CT, 3 prior Rituximab, no one had received prior RT. Toxicities were primarily haematological, as expected, and reversible. Response evaluation was performed two months after Zevalin administration by upper gastrointestinal endoscopy with multiple biopsy and endoscopic ultrasonography. All patients are now evaluable for response: 5 CR (all MALT), 2 PD (both DLBC NHL). All responders still maintain a CR at 27, 20, 16, 9 and 8 months after treatment.Conclusions: Zevalin seems to be very active in pts with MALT gastric NHL resistant or refractory to conventional systemic treatment. Its mechanism of action mimics conventional RT already known as valid option in MALT gastric NHL. If these preliminary results are confirmed in larger number of pts, one single administration of Zevalin delivered at conventional activity (0,4 mCi/kg) could be considered a possible alternative option in the treatment of such indolent disease.

Acanthamoeba Species Keratitis in a Soft Contact Lens Wearer Molecularly Linked to Well Water

Acanthamoeba species keratitis has been associated with soft contact lens wear. In the present report, an epidemiological link was established between the patient's isolate and well water from the home using molecular methods. To the authors' knowledge, this is the first case in Canada where such a link has been established. Primary care practitioners and specialists, including ophthalmologists and infectious diseases specialists, must maintain a high degree of clinical suspicion in soft contact lens wearers with keratitis unresponsive to conventional topical and systemic treatment.