Background Mycosis fungoides and Sézary syndrome are a class of lymphomas of skin-trafficking T cells, and they are the most common forms of cutaneous T-cell lymphoma (CTCL). Mycosis fungoides and ...Sézary syndrome are chronic, frequently incurable diseases with limited therapeutic options. PF-3512676 (formerly CPG 7909) is a Toll-like receptor 9 agonist that is being investigated for treatment of patients with advanced cancer. Objective This study was conducted to determine the safety and tolerability of single-agent PF-3512676 in patients with CTCL. Methods In this phase I dose-escalation study, patients (N = 28) with treatment-refractory, stage IB to IVA CTCL were enrolled in 6 sequential cohorts and treated with PF-3512676 (0.08, 0.16, 0.24, 0.28, 0.32, or 0.36 mg/kg) administered as 24 weekly subcutaneous injections. Primary end points were safety and tolerability. Results Common adverse events (fatigue, rigors, injection-site reactions, myalgia, lymphopenia, leukopenia, neutropenia, and pyrexia) were mostly grade 1 or 2, and no patient developed specific symptoms associated with autoimmune disease. Clinical response rate to PF-3512676, as determined by both Composite Assessment of Index Lesion Severity and Physician Global Assessment, was 32% (3 complete clinical responses, 6 partial responses); the majority of responses (7/9; 78%) were ongoing at the end of study. Limitations This trial was not designed to rigorously assess efficacy. Conclusion Single-agent PF-3512676 was well tolerated and demonstrated antitumor activity in patients with refractory CTCL.
Background Standard-dose (36-Gy) total skin electron beam therapy (TSEBT) is a highly effective treatment in mycosis fungoides. However, the regimen is time-intensive and may be associated with ...significant toxicity. Objective We sought to evaluate the efficacy and tolerability associated with low-dose (12-Gy) TSEBT. Methods Data from 3 clinical trials using low-dose (12-Gy) TSEBT were pooled. In all trials, TSEBT-naïve patients with stage IB to IIIA mycosis fungoides were treated with TSEBT (12 Gy, 1 Gy per fraction over 3 weeks). The primary end point was clinical response rate. Secondary end points included time to response and duration of clinical benefit. Results In all, 33 patients enrolled. Eighteen were male; stages were 22 IB, 2 IIA, 7 IIB, and 2 IIIA. Overall response rate was 88% (29/33), including 9 patients with complete response. Median time to response was 7.6 weeks (3-12.4 weeks). Median duration of clinical benefit was 70.7 weeks (95% confidence interval 41.8-133.8 weeks). Toxicities from TSEBT were mild and reversible. Limitations Conclusions are limited because of the small number of patients. Conclusions Low-dose TSEBT provides reliable and rapid reduction of disease burden in patients with mycosis fungoides, which could be administered safely multiple times during the course of a patient's disease with acceptable toxicity profile.
Sézary syndrome (SS) has a poor prognosis and few guidelines for optimizing therapy. The US Cutaneous Lymphoma Consortium, to improve clinical care of patients with SS and encourage controlled ...clinical trials of promising treatments, undertook a review of the published literature on therapeutic options for SS. An overview of the immunopathogenesis and standardized review of potential current treatment options for SS including metabolism, mechanism of action, overall efficacy in mycosis fungoides and SS, and common or concerning adverse effects is first discussed. The specific efficacy of each treatment for SS, both as monotherapy and combination therapy, is then reported using standardized criteria for both SS and response to therapy with the type of study defined by a modification of the US Preventive Services guidelines for evidence-based medicine. Finally, guidelines for the treatment of SS and suggestions for adjuvant treatment are noted.
Summary Clinical management of cutaneous T-cell lymphoma (CTCL) and angioimmunoblastic T-cell lymphoma (AITL) differs markedly. Diagnostic distinction is critical. Herein, we describe a series of 4 ...patients with clinically, molecularly, and histopathologically annotated mycosis fungoides or Sézary syndrome whose nodal disease mimicked AITL. The patients otherwise exhibited classic clinical manifestations of mycosis fungoides/Sézary syndrome preceding the onset of lymphadenopathy by 1 to 5 years. Skin biopsies revealed epidermotropic infiltrates characteristic of CTCL. Lymph node biopsies revealed dense CD4+ T-cell infiltrates that coexpressed follicular helper T-cell markers and were accompanied by proliferations of high endothelial venules and arborizing CD21+ follicular dendritic cell networks. Two patients had T-cell receptor gene rearrangement studies performed on their skin, lymph node, and peripheral blood demonstrating identical polymerase chain reaction clones in all 3 tissues. A small secondary clonal B-cell population was present in 1 patient that mimicked the B-cell proliferations known to accompany AITL and persisted on successive nodal biopsies over several years. This latter phenomenon has not previously been described in CTCL. The potential for patients to be misdiagnosed with AITL for lack of consideration of advanced-stage CTCL with nodal involvement underscores the necessity of information sharing among the various pathologists and clinicians involved in the care of each patient.
Abstract Objective Hispanic parents in the United States are disproportionately affected by low health literacy and limited English proficiency (LEP). We examined associations between health ...literacy, LEP, and liquid medication dosing errors in Hispanic parents. Methods Cross-sectional analysis of data from a multisite randomized controlled experiment to identify best practices for the labeling/dosing of pediatric liquid medications (SAFE Rx for Kids study); 3 urban pediatric clinics. Analyses were limited to Hispanic parents of children aged ≤8 years with health literacy and LEP data (n = 1126). Parents were randomized to 1 of 5 groups that varied by pairing of units of measurement on the label/dosing tool. Each parent measured 9 doses (3 amounts 2.5, 5, 7.5 mL using 3 tools 2 syringes in 0.2 or 0.5 mL increments, and 1 cup) in random order. Dependent variable was a dosing error of >20% dose deviation. Predictor variables included health literacy (Newest Vital Sign) (limited = 0–3; adequate = 4–6) and LEP (speaks English less than “very well”). Results A total of 83.1% made dosing errors (mean SD errors per parent = 2.2 1.9). Parents with limited health literacy and LEP had the greatest odds of making a dosing error compared to parents with adequate health literacy who were English proficient (trials with errors per parent = 28.8 vs 12.9%; adjusted odds ratio = 2.2 95% confidence interval 1.7–2.8). Parents with limited health literacy who were English proficient were also more likely to make errors (trials with errors per parent = 18.8%; adjusted odds ratio = 1.4 95% confidence interval 1.1–1.9). Conclusions Dosing errors are common among Hispanic parents; those with both LEP and limited health literacy are at particular risk. Further study is needed to examine how the redesign of medication labels and dosing tools could reduce literacy- and language-associated disparities in dosing errors.
Background The diagnosis of mycosis fungoides (MF) is often difficult because of significant clinical and histopathologic overlap with inflammatory dermatoses. T-cell receptor (TCR)γ chain ...rearrangement by polymerase chain reaction (PCR) (TCR-PCR) is a helpful adjuvant tool in this setting, but several of the inflammatory dermatoses in the differential diagnosis of MF may contain a clonal T-cell proliferation. Objective We examined whether analysis for T-cell clonality and comparison of the clones with the standardized BIOMED-2 PCR multiplex primers for the TCRγ chain from two anatomically distinct skin sites improves diagnostic accuracy. Methods We examined two biopsy specimens each from 10 patients with unequivocal MF, from 18 patients with inflammatory dermatoses, and from 18 patients who could initially not be definitively given a diagnosis based on clinical and histopathologic criteria. Results Eight of 10 patients with unequivocal MF had an identical clone in both biopsy specimens. Two of 18 patients with inflammatory dermatoses were found to have a clone in one of the biopsy specimens. On further follow-up of the 18 patients with morphologically nondiagnostic biopsy specimens, 13 of 18 were later confirmed to have MF and 5 of 18 had inflammatory dermatoses. Eleven of 13 patients with MF had an identical clone in both biopsy specimens; two of 13 had a polyclonal amplification pattern in both biopsy specimens. Four of 5 patients with inflammatory dermatoses had no clone in either biopsy specimen. One patient with an inflammatory dermatosis had an identical clone in both specimens. The sensitivity of TCR-PCR analysis to evaluate for an identical clone at different anatomic skin sites (dual TCR-PCR) is 82.6% and the specificity is 95.7%. Limitations The number of patients in the study group was limited. Conclusion These data suggest that dual TCR-PCR is a very promising technique with high specificity in distinguishing MF from inflammatory dermatoses.
Woringer-Kolopp disease, also known as pagetoid reticulosis, is an exceedingly rare variant of mycosis fungoides. Accurate diagnosis and effective treatment is essential to prevent progression to ...debilitating disease. We identified 7 patients with Woringer-Kolopp disease treated at our institution. We review the major clinical and pathologic characteristics of this disease, focusing on treatment strategies and patient outcomes. All of our patients were successfully treated with skin-directed therapies including topical steroids, topical nitrogen mustard, psoralen plus ultraviolet A, narrow-band ultraviolet B, and radiation therapy. Our observations confirm that Woringer-Kolopp disease carries an excellent prognosis, and support that the most effective and appropriate treatment for recalcitrant or severe Woringer-Kolopp disease is localized radiation therapy.
Abstract Objective Some experts recommend eliminating “teaspoon” and “tablespoon” terms from pediatric medication dosing instructions, because these terms could inadvertently encourage use of ...nonstandard tools (ie, kitchen spoons), which are associated with dosing errors. We examined whether use of “teaspoon” or “tsp” on prescription labels affects parents' choice of dosing tools, and the role of health literacy and language. Methods Analysis of data collected as part of a controlled experiment (SAFE Rx for Kids Safe Administration For Every Prescription for Kids study), which randomized English- and Spanish-speaking parents (n = 2110) of children 8 years of age and younger to 1 of 5 groups, which varied in unit of measurement pairings on medication labels and dosing tools. Outcome assessed was parent self-reported choice of dosing tool. Parent health literacy was measured using the Newest Vital Sign. Results Seventy-seven percent had limited health literacy (36.0% low, 41.0% marginal); 35.0% completed assessments in Spanish. Overall, 27.7% who viewed labels containing either “tsp” or “teaspoon” units (alone or with “mL”) chose nonstandard dosing tools (ie, kitchen teaspoon, kitchen tablespoon), compared with 8.3% who viewed “mL”-only labels (adjusted odds ratio AOR = 4.4 95% confidence interval (CI), 3.3–5.8). Odds varied based on whether “teaspoon” was spelled out or abbreviated (“teaspoon”-alone: AOR = 5.3 95% CI, 3.8–7.3); “teaspoon” with mL: AOR = 4.7 95% CI, 3.3–6.5; “tsp” with mL: AOR = 3.3 95% CI, 2.4–4.7; P < .001). Similar findings were noted across health literacy and language groups. Conclusions Use of teaspoon units (“teaspoon” or “tsp”) on prescription labels is associated with increased likelihood of parent choice of nonstandard dosing tools. Future studies might be helpful to examine the real-world effect of eliminating teaspoon units from medication labels, and identify additional strategies to promote the safe use of pediatric liquid medications.
Abstract Background and Objectives A recent American Academy of Pediatrics policy statement recommends milliliter-exclusive dosing for pediatric liquid medications. Little is known about parent ...preferences regarding units, perceptions about moving to milliliters only, and the role of health literacy and prior milliliter-dosing experience. Methods Cross-sectional analysis of data collected as part of a randomized controlled study in 3 urban pediatric clinics (SAFE Rx for Kids study). English- and Spanish-speaking parents (n = 493) of children aged ≤8 years were randomized to 1 of 4 study arms and given labels and dosing tools which varied in label instruction format (text plus pictogram, text only) and units (milliliter only “mL”, milliliter/teaspoon “mL”/“tsp”). Outcomes included teaspoon preference in dosing instructions and perceived difficulty with milliliter-only dosing. The predictor variable was health literacy (Newest Vital Sign; low 0–1, marginal 2–3, adequate 4–6). The mediating variable was prior milliliter-dosing experience. Results Over two-thirds of parents had low or marginal health literacy. The majority (>70%) preferred to use milliliters, perceived milliliter-only dosing to be easy, and had prior milliliter-dosing experience; 11.5% had a teaspoon preference, 18.1% perceived milliliter-only dosing will be difficult, and 17.7% had no prior milliliter-dosing experience. Parents with lower health literacy had a higher odds of having a teaspoon preference (low vs adequate: adjusted odds ratio AOR = 2.9 95% confidence interval CI 1.3–6.2), and greater odds of perceiving difficulty with milliliter-only dosing (low vs adequate: AOR = 13.9 95% CI 4.8–40.6, marginal vs adequate: AOR = 7.1 95% CI 2.5–20.4). Lack of experience with milliliter dosing partially mediated the impact of health literacy. Conclusions Most parents were comfortable with milliliter-only dosing. Parents with low health literacy were more likely to perceive milliliter-only dosing to be difficult; educational efforts will need to target this group to ensure safe medication use.
Background Optimal treatment of indolent primary cutaneous B-cell lymphoma (CBCL), marginal zone lymphoma, and follicle center lymphoma, presenting as multiple lesions, has yet to be established. ...Rituximab is a chimeric monoclonal IgG1 antibody directed against the CD20 antigen of B cells. Clinical efficacy of systemic rituximab in CBCL has yet to be established. Objective We sought to assess the efficacy of systemic rituximab in the treatment of CBCL. Methods This was a retrospective study of 15 patients with indolent CBCL treated with intravenous rituximab (375 mg/m2 ) as a single agent. Variable maintenance regimen was used in a subset of patients. Responses were categorized as complete response, partial response, stable disease, or progressive disease. The efficacy end points included were objective response rate, time to response, time to progression, and duration of response. Results Ten patients with follicle center lymphoma and 5 with marginal zone lymphoma were included. The objective response rate was 87% (60% complete response, 27% partial response). All patients with follicle center lymphoma had a response with 80% achieving complete response. Of the patients with marginal zone lymphoma, 3 had a response, one stable disease, and one progressive disease. Median follow-up was 36 months. Median time to response, duration of response, and time to progression was 30 days, 24 months, and 24 months, respectively. Limitations The study was limited by the small sample size and retrospective design. Conclusions This study, although small, suggests that rituximab is a reasonable first-line treatment option for indolent CBCL with multiple lesions where local treatment is not effective or desirable.
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