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The treatment of patients with chronic lymphocytic leukemia (CLL) who fail purine analogues is sub optimal. CLL lymphocytes express two antigens, namely CD 20 and CD 52, for which monoclonal antibodies are readily available. Rituximab is a chimeric monoclonal antibody targeted against CD 20, which has some activity in refractory CLL, with primary effect on nodal disease. Alemtuzumab is a humanized anti-CD 52 antibody that is approved for the treatment of CLL in patients who fail alkylating agents and purine analogues. Alemtuzumab has better activity in the peripheral blood and the bone marrow compared to nodal disease. We investigated whether combining both antibodies is safe in refractory CLL. Both antibodies were given to a total of 12 patients divided into 3 cohorts with escalating alemtuzumab doses (3 mg, 10 mg, and 30 mg). The combination was proven to be safe, not toxic, feasible, and active. One patient attained PR by NCI criteria while all other patients had stable disease lasting a median of 101.5 days. All patients normalized their peripheral lymphocytosis within a median of 23.5 days. No treatment-related mortality was identified. No CMV reactivation occurred. Additional studies are needed to investigate the clinical significance of such a combination in this patient population, and whether this combination can be administered safely with systemic chemotherapy. These studies are currently underway.

Mycosis Fungoides and Sézary Syndrome are the most common types of cutaneous T-cell lymphomas. There is no current standard of care for Mycosis Fungoides/Sézary Syndrome, with a general tendency to rely on topical interventions for early disease delaying systemic, more toxic therapy until the development of extensive symptoms. Knowledge of the biological characteristics of this disease has allowed for the development of rational interventions and a significant advance in its treatment. Retinoids are active in Mycosis Fungoides/Sézary Syndrome with the newer rexinoids being available in topical and systemic forms. Interferon alpha remains one of the most active therapeutic agents for Mycosis Fungoides/Sézary Syndrome, especially in combination with other agents such as PUVA. The monoclonal antibody alemtuzumab leads to responses in at least half of patients with advanced disease with its side effect profile consisting mainly of immunosupression and infusion reactions. The recombinant IL2-diphteria toxin denileukin diftitox (Ontak) is active in this disease and appears to have a beneficial effect in symptoms relief and quality of life. Extracorporeal photochemotherapy as an immunostimulating intervention seems to be very effective in a subset of patients, but its availability is limited to less than a hundred centers worldwide. Experimental and less studied interventions include autologous and allogeneic peripheral stem cell transplantation, Interleukin-12, the histone-deacetylator depsipeptide and the synthetic deoxynucleotide CpG7909. Cutaneous T-cell lymphoma has served as a paradigm for the development of biological agents. Further knowledge of the signaling pathways in Mycosis Fungoides/Sézary Syndrome will allow for the development of more effective treatment strategies., (Copyright 2004 Taylor and Francis Ltd)

Quality of life (QOL) considerations are important in the treatment decision making process for prostate cancer patients. Although patient involvement in the treatment decision process has been encouraged, low health literacy can limit patient understanding of the complex information about treatments and their probable QOL outcomes and is a barrier to patient participation in the decision-making process. The objectives of the study were to evaluate (i) knowledge, level of satisfaction, and treatment preferences and intentions of men newly diagnosed with prostate cancer after participation in a CD-ROM shared decision making program; and (ii) the relationship between prostate cancer knowledge and health literacy. Thirty newly diagnosed prostate cancer patients from two Veteran's Administration (VA) hospitals in Chicago completed a demographic questionnaire and participated in an interactive CD-ROM shared decision making program. Subsequently, knowledge of prostate cancer, satisfaction with the information in the computer CD-ROM program, treatment preferences, and likelihood of following treatment preferences were assessed using interviewer-administered questionnaires. Health literacy was assessed using the Rapid Estimate of Adult Literacy in Medicine (REALM). The Pearson correlation test was used to assess the relationship between health literacy and prostate cancer knowledge. The chi2 test and the Fischer exact test were used to evaluate relationships between patient demographics and other variables. More than three-quarters of the patients rated the information in the CD-ROM as "very satisfactory" (highest possible rating). Two-thirds of the patients (21 of 30) selected a treatment after participation in the CD-ROM program and 90.5% of these patients stated that they were very or somewhat likely to adhere to their selection. However, prostate cancer knowledge was variable, with one-third of the patients scoring 69.9% or lower. Participants' health literacy was equivalent to a 7th-8th grade reading level (mean = 57.1+/-10.9), and more than one-third of participants (36.7%) had lower than 9th grade literacy levels. Participants' prostate cancer knowledge was correlated with health literacy (Pearson correlation rhor = 0.65, rhop = 0.0001). Patients were satisfied with the interactive shared decision making CD-ROM program, and two-thirds of patients were able to select a preferred treatment based on the information presented in the program that they intended to follow. However, prostate cancer knowledge scores varied among participants after participation in the CD-ROM program, raising doubts that patients were adequately informed to make appropriate choices regarding their treatment. Lower prostate cancer knowledge scores corresponded to lower literacy scores, indicating that low literacy may have hindered patient understanding of the shared decision making program. The development of shared decision making tools should include collaborative efforts with the target population to improve the success of shared decision making programs among patients with low health literacy.

The efficacy and toxicity of 2-chlorodeoxyadenosine (2-CdA) in cutaneous T-cell lymphoproliferative disorders was examined. Between February 1991 and April 1996, 25 patients with relapsed or refractory cutaneous T-cell lymphoproliferative disorders (24 mycosis fungoides or Sezary syndrome, one Ki-1+ anaplastic large cell lymphoma) were treated with 2-CdA initially administered by continuous intravenous infusion at a dose of 0.1 mg/kg/d for 7 days (13 patients). The infusion duration was subsequently reduced to 5 days (9 patients) because of prohibitive hematologic toxicity. Three patients were treated at the same daily dose by bolus injection over two hours for 5 days. Cycles were administered at 28 day intervals. Seventeen patients received more than one cycle. An overall response rate of 24% was achieved. Three patients (12%) had a complete response with a median duration of 4.5 months (range, 2.5 to 16). Three (12%) had a partial response with a median duration of 2 months (range, 2 to 4). Nineteen patients (76%) had no response. The most significant toxicities encountered were myelosuppression (64%) and infectious complications (64%). 2-CdA has activity as a single agent in patients with previously treated relapsed T-cell lymphoproliferative disorders.

The purpose of this study was to investigate the biologic activity of DAB486IL-2 when administered three times daily, in terms of toxicity, pharmacokinetics, and anti-tumor effects in patients with IL-2R expressing hematologic malignancies, especially mycosis fungoides. 20 patients were enrolled in this dose escalation phase I trial. Patient cohorts were treated at levels of 0.03 mg/kg, 0.05 mg/kg, 0.07 mg/kg and 0.09 mg/kg every 8 hours for a total of 12 doses, every 21 days as toxicity and response warranted. Eight patients experienced transient fevers associated with DAB486IL-2 administration. One patient experienced grade 3 hypotension, and a second developed fluid retention manifested as weight gain/pedal edema. Dose limiting toxicity consisted of one episode of transient grade 4 hepatic transaminase elevation, and 8 episodes of transient asymptomatic grade 3 hepatic transaminase elevation. At the maximum tolerated dose DAB486IL-2 exhibited biphasic clearance kinetics; transient receptor saturation may be one mechanism for this observation. Initial serum concentration and apparent steady state level (plateau) directly correlated with the dose administered, but no difference in area under the concentration curve with greater dose was observed. Biologic activity was noted in patients with mycosis fungoides with skin lesion clearing and relief of pruritus. One patient with mycosis fungoides, and one patient with a relapsed intermediate grade non-Hodgkin's lymphoma achieved partial responses. The novel mechanism of action, toxicity profile, and evidence of biologic activity in refractory cancer patients, support development of more active constructs of this agent; such trials are underway.