A new generation computerised metacognitive cognitive remediation programme for schizophrenia (CIRCuiTS): a randomised controlled trial.

BACKGROUND: Cognitive remediation (CR) is a psychological therapy, which improves cognitive and social functioning in people with schizophrenia. It is now being implemented within routine clinical services and mechanisms of change are being explored. We designed a new generation computerised CR programme, CIRCuiTS (Computerised Interactive Remediation of Cognition - a Training for Schizophrenia), to enhance strategic and metacognitive processing, with an integrated focus on the transfer of cognitive skills to daily living. This large trial tested its feasibility to be delivered in therapist-led and independent sessions, and its efficacy for improved cognitive and social functioning. METHODS: A two arm single blind randomised superiority trial comparing CIRCuiTS plus treatment-as-usual (TAU) with TAU alone in 93 people with a diagnosis of schizophrenia. Cognitive, social functioning and symptom outcomes were assessed at pre- and post-therapy and 3 months later. RESULTS: 85% adhered to CIRCuiTS, completing a median of 28 sessions. There were significant improvements in visual memory at post-treatment (p = 0.009) and follow-up (p = 0.001), and a trend for improvements in executive function at post-treatment (p = 0.056) in favour of the CIRCuiTS group. Community function was also differentially and significantly improved in the CIRCuiTS group at post-treatment (p = 0.003) but not follow-up, and was specifically predicted by improved executive functions. CONCLUSIONS: CIRCuiTS was beneficial for improving memory and social functioning. Improved executive functioning emerges as a consistent predictor of functional gains and should be considered an important CR target to achieve functional change. A larger-scale effectiveness trial of CIRCuiTS is now indicated.

Metacognitive awareness of cognitive problems in schizophrenia: exploring the role of symptoms and self-esteem.

BACKGROUND: People with a diagnosis of schizophrenia have limited metacognitive awareness of their symptoms. This is also evident for cognitive difficulties when neuropsychological assessments and self-reports are compared. Unlike for delusions and hallucinations, little attention has been given to factors that may influence the mismatch between objective and subjectively reported cognitive problems. Symptom severity, and also self-esteem and social functioning, can have an impact on cognitive problem perception and help to explain the gap between objective and subjective cognitive assessments in psychosis. METHOD: One-hundred participants with a diagnosis of schizophrenia were recruited and assessed with a comprehensive neuropsychological battery, a measure of awareness of cognitive problems and measures of psychotic symptoms, social and behavioural functioning and self-esteem. Regression was used to investigate the influence of symptoms, social functioning and self-esteem, and patients with different levels of cognitive problem awareness were contrasted. RESULTS: Simple correlation analysis replicated the lack of association between objective cognitive measures and metacognitive awareness of cognitive problems. However, the results of the regression analyses highlight that self-esteem and negative symptoms predict metacognitive awareness. When significant predictors were controlled, individuals with better awareness had more impaired working memory but higher IQ. CONCLUSIONS: Poor self-esteem and high negative symptoms are negatively associated with metacognitive awareness in people with schizophrenia. Interventions that aim to improve cognition should consider that cognitive problem reporting in people with schizophrenia correlates poorly with objective measures and is biased not only by symptoms but also by self-esteem. Future studies should explore the causal pathways using longitudinal designs.

A naturalistic, randomized, controlled trial combining cognitive remediation with cognitive-behavioural therapy after first-episode non-affective psychosis.

BACKGROUND: Cognitive remediation (CR) preceding cognitive-behavioural therapy for psychosis (CBTp) was trialled within routine clinical services, with the hypothesis that following first-episode non-affective psychosis CR would enhance CBTp efficacy by improving neuropsychological performance. METHOD: A total of 61 patients with DSM-IV non-affective psychoses waiting for routine CBTp were randomized to computerized CR over 12 weeks, supported by a trained support worker, or time-matched social contact (SC). Primary outcome was the blind-rated Psychotic Symptoms Rating Scale (PSYRATS). Secondary outcomes included measures of CBTp progress, cognition, symptoms, insight and self-esteem: all at baseline, after CR (12 weeks) and after CBTp (42 weeks). PSYRATS and global neuropsychological efficacy were tested using mixed-effects models with a group × time interaction term. Measures of CBTp progress and some neuropsychological measures were modelled by regression. RESULTS: There was no significant difference between the CR and SC groups in PSYRATS (group × time coefficient 0.3, 95% confidence interval -0.4 to 1.1, p = 0.39). However, after CR CBTp was shorter [median 7 sessions, interquartile range (IQR) 2-12 after CR; median 13, IQR 4-18 after SC; model p = 0.011] and linked to better insight (p = 0.02). Global cognition did not improve significantly more after CR (p = 0.20) but executive function did (Wisconsin Card Sort, p = 0.012). CONCLUSIONS: CBTp courses preceded by CR were far shorter but achieved the same outcome as CBTp preceded by an active control, consistent with neuropsychological improvement enhancing CBTp. CR was delivered by staff with minimal training, offering the potential to reduce the costs of CBTp considerably.

Long-term follow-up of lenalidomide in relapsed/refractory mantle cell lymphoma: subset analysis of the NHL-003 study.

BACKGROUND: Mantle cell lymphoma (MCL) is an uncommon type of non-Hodgkin lymphoma with poor overall prognosis, requiring the development of new therapies. Lenalidomide is an immunomodulatory agent demonstrating antitumor and antiproliferative effects in MCL. We report results from a long-term subset analysis of 57 patients with relapsed/refractory MCL from the NHL-003 phase II multicenter study of single-agent lenalidomide in patients with aggressive lymphoma DESIGN: Lenalidomide was administered orally 25 mg daily on days 1-21 every 28 days until progressive disease (PD) or intolerability. The primary end point was overall response rate (ORR). RESULTS: Fifty-seven patients with relapsed/refractory, advanced-stage MCL had a median of three prior therapies. The ORR was 35% [complete response (CR)/CR unconfirmed (CRu) 12%], with a median duration of response (DOR) of 16.3 months (not yet reached in patients with CR/CRu) by blinded independent central review. The median time to first response was 1.9 months. Median progression-free survival was 8.8 months, and overall survival had not yet been reached. The most common grade 3/4 adverse events (AEs) were neutropenia (46%), thrombocytopenia (30%), and anemia (13%). CONCLUSIONS: These results show the activity of lenalidomide in heavily pretreated, relapsed/refractory MCL. Responders had a durable response with manageable side-effects. Clinical trial number posted on www.clinicaltrials.gov NCT00413036.

Vaccination uptake for pertussis and influenza vaccines in pregnancy among different practices at a single institution.

OBJECTIVE: The authors investigated tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccination during pregnancy following Advisory Committee on Immunization Practices' (ACIP's) recommendation for antenatal pertussis vaccination. METHODS: A retrospective chart review was performed in 2019 of women receiving prenatal care at our institution between January 1, 2014 and December 31, 2018. Receipt of ACIP-recommended vaccines were examined using Current Procedural Terminology codes to identify initiation of prenatal care, then administration of Tdap and influenza vaccines. Data were examined by individual practice (university faculty, community physicians, obstetrics and gynecology (OBGYN) residents, and family medicine residents, practice staff composition, vaccination protocol use, and insurance status. Statistical analyses were performed using χ2 testing and χ2 testing of linear trend. RESULTS: Within our cohort (n = 17 973), highest vaccination uptake occurred in the university-based OBGYN faculty practice (Tdap = 58.2%, influenza = 56.5%) with lowest uptake in the OBGYN resident practice (Tdap = 28.6%, influenza = 18.5%). Higher uptake occurred in practices with standing orders, more advanced practice providers, lower provider to nursing ratios, and lower rates of Medicaid insurance. CONCLUSION: These data demonstrated higher vaccination uptake with standing orders, more advanced practice providers, and lower provider to nurse ratios. Future work optimizing practice staff composition and vaccination protocols may increase vaccine uptake.

An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma.

BACKGROUND: Lenalidomide is an immunomodulatory agent with antitumor activity in B-cell malignancies. This phase II trial aimed to demonstrate the safety and efficacy of lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular grade 3 lymphoma (FL-III), or transformed lymphoma (TL). METHODS: Patients received oral lenalidomide 25 mg on days 1-21 every 28 days as tolerated or until progression. The primary end point was overall response rate (ORR). RESULTS: Two hundred and seventeen patients enrolled and received lenalidomide. The ORR was 35% (77/217), with 13% (29/217) complete remission (CR), 22% (48/217) partial remission, and 21% (45/217) with stable disease. The ORR for DLBCL was 28% (30/108), 42% (24/57) for MCL, 42% (8/19) for FL-III, and 45% (15/33) for TL. Median progression-free survival for all 217 patients was 3.7 months [95% confidence interval (CI) 2.7-5.1]. For 77 responders, the median response duration lasted 10.6 months (95% CI 7.0-NR). Median response duration was not reached in 29 patients who achieved a CR and in responding patients with FL-III or MCL. The most common adverse event was myelosuppression with grade 4 neutropenia and thrombocytopenia in 17% and 6%, respectively. CONCLUSION: Lenalidomide is well tolerated and produces durable responses in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma.

"Real-life" data of the efficacy and safety of belantamab mafodotin in relapsed multiple myeloma-the Mayo Clinic experience.

Belantamab mafodotin is a highly selective targeted therapy for multiple myeloma. It targets the B cell maturation antigen (BCMA) on plasma cells and showed promising results in several randomized clinical trials. We report the outcomes of 36 patients treated at Mayo Clinic. Our cohort received a median of eight prior lines of therapy. Six patients received belantamab in combination with other medications (pomalidomide, cyclophosphamide, thalidomide), 13 patients (36%) were 70 years or older, two patients had a creatinine of >2.5 mg/dL, and one patient was on dialysis. All three patients with renal failure received full dose belantamab. Chimeric antigen receptor (CAR-T) therapy was used prior to belantamab in seven patients and none of them responded to belantamab therapy. The overall response rate (ORR) was 33% (CR 6%, VGPR 8%, PR 19%), like the ORR reported in the DREAMM-2 trial. Keratopathy developed in 16 patients (43%), grade 1 in six patients, grade 2 in seven patients, and grade 3 in three patients. Eight percent discontinued therapy due to keratopathy. The median PFS and OS was 2 months and 6.5 months, respectively.

A practical guide to defining high-risk myeloma for clinical trials, patient counseling and choice of therapy.

Clinical outcomes for multiple myeloma (MM) are highly heterogeneous and it is now clear that pivotal genetic events are the primary harbingers of such variation. These findings have broad implications for counseling, choice of therapy and the design and interpretation of clinical investigation. Indeed, as in acute leukemias and non-hodgkins lymphoma, we believe it is no longer acceptable to consider MM a single disease entity. As such, the accurate diagnosis of MM subtypes and the adoption of common criteria for the identification and stratification of MM patients has become critical. Herein, we provide a consensus high-risk definition and offer practical guidelines for the adoption of routine diagnostic testing. Although acknowledging that more refined classifications will continue to be developed, we propose that the definition of high-risk disease (any of the t(4;14), t(14;16), t(14;20), deletion 17q13, aneuploidy or deletion chromosome 13 by metaphase cytogenetics, or plasma cell labeling index >3.0) be adopted. This classification will identify most of the 25% of MM patients for whom current therapies are inadequate and for whom investigational regimens should be vigorously pursued. Conversely, the 75% of patients remaining have more favorable outcomes using existing - albeit non-curative - therapeutic options.

Comparative adrenocortical suppression in dogs with otitis externa following topical otic administration of four different glucocorticoid-containing medications.

The safety of using otic formulations is often of concern for practitioners and pet owners alike, with "safe" in this context meaning no adrenocortical suppression. This study evaluated the effect of four glucocorticoid-containing otic formulations on plasma cortisol concentrations, measured by corticotropin stimulation testing (plasma cortisol concentrations before and after corticotropin injection), in dogs presented with otitis externa. Dexamethasone tended to have larger adrenocortical suppression compared with the other three formulations (betamethasone, triamcinolone, and mometasone), but the difference was not statistically significant. The largest difference among the four drugs was observed between dexamethasone and betamethasone (P=.09).

Lenalidomide plus R-CHOP21 in newly diagnosed diffuse large B-cell lymphoma (DLBCL): long-term follow-up results from a combined analysis from two phase 2 trials.

Lenalidomide-RCHOP (R2-CHOP21) has been shown to be safe and effective in patients with untreated diffuse large B-cell lymphoma (DLBCL). The aim of this analysis is to report long-term outcome and toxicities in newly diagnosed DLBCL patients who received R2-CHOP21 in two independent phase 2 trials, conducted by Mayo Clinic (MC) and Fondazione Italiana Linfomi (FIL). All patients received R-CHOP21 plus lenalidomide. Long-term progression-free survival (PFS), time to progression (TTP), overall survival (OS) and late toxicities and second tumors were analyzed. Hundred and twelve patients (63 MC, 49 FIL) were included. Median age was 69 years, 88% were stage III-IV. At a median follow-up of 5.1 years, 5y-PFS was 63.5%, 5y-TTP 70.1% and 5y-OS 75.4%; according to cell of origin (COO): 5y-PFS 52.8% vs 64.5%, 5y-TTP 61.6% vs 69.6% and 5y-OS 68.6% vs 74.1% in germinal center (GCB) vs non-GCB respectively. Four patients experienced grade 4-5 late toxicities. Grade ≤ 3 toxicities were infections (N = 4), thrombosis (N = 1) and neuropathy (N = 3). Seven seconds tumors were observed. Long-term follow-up demonstrates that R2-CHOP21 efficacy was maintained with high rates of PFS, TTP, and OS. Lenalidomide appears to mitigate the negative prognosis of non-GCB phenotype. Incidence of therapy-related secondary malignancies and late toxicities were low.

Pomalidomide-dexamethasone in refractory multiple myeloma: long-term follow-up of a multi-cohort phase II clinical trial.

Despite therapeutic advances, multiple myeloma remains incurable, with limited options for patients with refractory disease. We conducted a large, multi-cohort clinical trial testing various doses and treatment schedules of pomalidomide and dexamethasone (Pom/dex) in patients with refractory multiple myeloma. Overall, 345 patients were enrolled to six cohorts based on number and type of prior lines of therapy, pomalidomide dose and schedule. Median prior lines of therapy were three with near universal prior exposure to proteasome inhibitors and/or immunomodulatory drugs. A confirmed response rate of 35% was noted for all cohorts (range 23-65%) with higher responses in cohorts with fewer prior lines of therapy. Median time to confirmed response was ⩽2 months and the longest progression-free survival and overall survival seen in any cohort were 13.1 and 47.9 months, respectively. Observed adverse reactions were as expected, with myelosuppression and fatigue being the most common hematologic and non-hematologic adverse events (AEs), respectively. Longer durations of treatment and response, higher response rates and fewer AEs were noted with the 2 mg pomalidomide dose. This is the longest follow-up data for Pom/dex in refractory multiple myeloma and will help shape the real-world utilization of this regimen.

Anemia in cancer and critical care patients: pharmacoeconomic considerations.

PURPOSE: The elements and limitations of pharmacoeconomic models, types of analytic methods used in pharmacoeconomic evaluations, outcomes used in studies of anemia treatments, and comparative efficacy and cost-effectiveness of the two available erythropoietic therapies in the treatment of anemia in cancer and critical care patients are discussed. SUMMARY: Clinical, humanistic, and economic outcomes should be taken into consideration in pharmacoeconomic models. The validity of such models may be compromised by a lack of outcome data, unreasonable assumptions, the heterogeneity of the patient population, patient selection bias in comparative studies, and inconsistent use of instruments to measure outcomes. The degree of anemia in patients with cancer correlates with health-related quality of life (QOL). Erythropoietic therapy increases hemoglobin concentrations and QOL, reduces the need for blood transfusions, and is cost-effective for treating anemia in cancer and critical care patients. Epoetin alfa may provide a more rapid hemoglobin response and improvement in QOL at a lower cost than darbepoetin alfa. Front loading with weekly doses of either erythropoietic agent followed by a three-week-long dosing interval for maintenance treatment may be used to quickly correct anemia, improve convenience, and reduce costs. CONCLUSION: Erythropoietic therapy for the treatment of anemia in cancer and critical care patients is cost-effective.

Multicenter phase 2 study of combination therapy with ruxolitinib and danazol in patients with myelofibrosis.

Myelofibrosis is a myeloproliferative neoplasm that is characterized by splenomegaly, profound symptom burden, and cytopenias. JAK inhibitor therapy offers improvements in splenomegaly, symptom burden, and potentially survival; however, cytopenias remain a significant challenge. Danazol has previously demonstrated improvements in myelofibrosis-associated anemia. We conducted a phase II clinical trial evaluating the efficacy and tolerability of combination therapy with ruxolitinib, an oral JAK inhibitor, and danazol. Fourteen intermediate or high-risk MF patients were enrolled at 2 institutions. Responses per IWG-MRT criteria were stable disease in 9 patients (64.2%) clinical improvement in 3 (21.4%) all of which were spleen responses, partial response in 1 (7.1%) and progressive disease in 1 (7.1%). Despite limited IWG-MRT response, stabilization of anemia and thrombocytopenia was demonstrated. In JAK inhibitor naïve patients, 4/5 (80%) had stable or increasing hemoglobin. Of the 9 patients on prior JAK inhibitor, 5 patients (55.5%) and 8 patients (88.9%) had stable or increasing hemoglobin or platelet levels, respectively. Adverse events possibly related included grade 3 or greater hematologic toxicity in ten patients (71.4%) and non-hematologic toxicity in two patients (14.3%). Although combination therapy did not lead to increased hematologic response per IWG-MRT criteria, hematologic stabilization was observed and may be clinically useful.

Drug and medical cost effects of a drug formulary change with therapeutic interchange for statin drugs in a multistate managed Medicaid organization.

OBJECTIVE: Therapeutic interchange (TI) interventions are commonly used to manage pharmacy benefit costs. While several studies have considered the effect that TI interventions have on drug costs, most have not considered the effect they have on medical management costs. The purpose of the present study was to assess drug cost and drug therapy management costs of a TI intervention following a change in the drug formulary for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) drugs, including the conversion of atorvastatin from formulary to nonformulary status. METHODS: A retrospective, quasi-experimental within-subjects design was used in this study. Administrative claims data were obtained from a select northeastern segment of a multistate Medicaid managed care organization (MCO). To be included in the study, patients had to meet the following criteria: (1) they must have had a minimum of 3 atorvastatin prescriptions during a 6-month enrollment phase, (2) they must have been continuously enrolled throughout the 900-day study period, and (3) they must have switched from atorvastatin to another statin between April 1, 2003, and July 31, 2003. The day of the switch from atorvastatin marked for each patient the end of the 12-month pre-TI period and the beginning of the 12-month post-TI period. Two separate dependent variables were developed: (1) statin drug costs (statin cost + dispensing fee) and (2) the costs paid by the MCO for the medical management of statin therapy, including office visit costs and the medical laboratory costs of measuring lipids and creatine kinase, and of checking liver functions. To estimate expenditures over 24 months, a panel analytic technique was used that allows each patient to serve as his or her own control. Multivariate models were used to assess the effects of the TI policy while controlling for age, gender, adjunctive dyslipidemia therapy, comorbidity, presence of a prior coronary artery event, statin compliance, cardiologist management, and disease severity. RESULTS: Of the 3,636 patients who met the study inclusion criteria and were converted from atorvastatin to an alternate statin drug, 129 patients (3.5%) switched back to atorvastatin following the TI. The average statin cost per claim in the 12-month post-TI period was Dollars 70.93, 9.5% less than the average cost in the 12-month pre-TI period (Dollars 78.40). The average cost per patient per year (PPPY) for statin laboratory tests (lipid panels, creatine kinase tests, and liver function tests) increased by 31.5% to Dollars 16.15 in the post-TI period compared with Dollars 12.28 PPPY in the pre-TI period, and medical office visit costs increased by 44.9% to Dollars 20.70 PPPY in the post-TI period compared with Dollars 14.29 PPPY in the preperiod. These increased costs related to the medical management of statin therapy were overwhelmed by an 11.7% reduction in statin drug costs, from Dollars 793.69 PPPY in the pre-TI period to Dollars 701.01 PPPY in the post-TI period, resulting in a net 10.0% reduction for combined statin costs and related medical costs, from Dollars 820.27 PPPY in the pre-TI period to Dollars 737.87 in the post-TI period. After limiting the analysis to patients who did not convert from atorvastatin to pravastatin (which cost more than atorvastatin before the rebate) and controlling for the influence of potential confounders, statin expenditure decreased by 33% (P < 0.001). Multivariate models indicated no statistically significant differences in the costs related to the medical management of statin therapy after the TI compared with before the TI.

Carfilzomib and the cardiorenal system in myeloma: an endothelial effect?

Carfilzomib (Cfz) has been associated with an ~5% incidence of unexplained and unpredictable cardiovascular toxicity in clinical trials. We therefore implemented a detailed, prospective, clinical cardiac and renal evaluation of 62 Cfz-treated myeloma patients, including serial blood pressure (BP), creatinine, troponin, NT-proBNP and pre- and post-treatment echocardiograms, including ejection fraction (EF), average global longitudinal strain and compliance. Pre-treatment elevations in NT-proBNP and BP, as well as abnormal cardiac strain were common. A rise in NT-proBNP occurred frequently post-treatment often without corresponding cardiopulmonary symptoms. A rise in creatinine was common, lessened with hydration and often reversible. All patients had a normal EF pre-treatment. Five patients experienced a significant cardiac event (four decline in EF and one myocardial infarction), of which 2 (3.2%) were considered probably attributable to Cfz. None were rechallenged with Cfz. The ideal strategy for identifying patients at risk for cardiac events, and parameters by which to monitor for early toxicity have not been established; however, it appears baseline echocardiographic testing is not consistently predictive of toxicity. The toxicities observed suggest an endothelial mechanism and further clinical trials are needed to determine whether or not this represents a class effect or is Cfz specific.

A phase II study of sequential combination chemotherapy with cyclophosphamide, prednisone, and 2-chlorodeoxyadenosine in previously untreated patients with chronic lymphocytic leukemia.

In an earlier study of previously untreated patients with chronic lymphocytic leukemia (CLL), we used a concomitant combination of chlorambucil and 2-chlorodeoxyadenosine and reported overall (OR) and complete (CR) remission rates of 80% and 20%, respectively. After a median follow-up of 5 years, more than 80% of the responders have had a relapse. In the current phase II study of 27 previously untreated patients with CLL, we used a sequential combination of six cycles of intravenous cyclophosphamide (1 g/m2) plus oral prednisone (100 mg/m2 per day for 5 days) followed by two to six cycles of 2-chlorodeoxyadenosine (5 mg/m2 per day for 5 days). The OR and CR rates were 96% and 33%, respectively. After a median follow-up of 29 months, 35% of the responders have had a relapse. Progression-free survival was significantly better in CR patients than in those with partial remission. However, minimal residual disease was phenotypically detected in four of the nine CR patients. Despite the fact that the current OR and CR rates are superior to those seen in a historical cohort treated with a concomitant schedule, a longer follow-up period is needed to assess the durability of these remissions, and a controlled trial is necessary to estimate the impact on overall survival and toxicity.

Leadership versus management: translating pharmacists' abilities into quality performance.

OBJECTIVE: To describe the quality gap in health care as it was referred to in the Institute of Medicine's reports, to try to harness pharmacy's potential to improve the quality of drug therapy, and to provide insight into the elusive leadership, management, and dynamics of change. SUMMARY: Current health care is nowhere near ideal. Successful quality initiatives have included establishing a "culture of quality" (promoting a learning organization), having good leadership, and developing strong management. Ideally, all of these concepts must be applied concurrently for the best results because using only one will not spirit medicine across the gap. To close the gap, pharmacists need to understand various types of change and select a change mechanism that will continuously improve care. CONCLUSION: Optimizing drug therapy is both a great challenge and a great opportunity for pharmacy. AMCP's Framework for Quality Drug Therapy is a continuous quality improvement model that gives us the tools to plan, implement, and evaluate strategies to improve the quality of patient care and cross the "quality chasm."

Phase 2 trial of ixazomib in patients with relapsed multiple myeloma not refractory to bortezomib.

This phase 2 trial was designed to evaluate ixazomib, an orally bioavailable proteasome inhibitor, in patients with myeloma who have limited prior exposure to bortezomib. Thirty-three patients with relapsed multiple myeloma were enrolled. Ixazomib was given at 5.5 mg weekly for 3 of 4 weeks. Dexamethasone was added for lack of a minor response (MR) by end of cycle 2 or lack of a partial response (PR) by end of cycle 4 or for disease progression at any time. Median age was 69 years; patients had a median of two prior therapies (range 1-7). A grade 3 or 4 adverse event considered at least possibly related to drug was seen in 19 (59%) and 6 (19%) patients, respectively. The most common adverse events were thrombocytopenia, fatigue, nausea and diarrhea. Dexamethasone was initiated in 22 (67%) patients, 17 for not reaching the desired response and 5 for progression. Response (⩾PR) to single agent was seen in five patients within four cycles of therapy including three patients with PR, one patient with complete response (CR) and one patient with stringent CR. Six additional patients with either an MR (2) or SD (4) achieved a PR after addition of dexamethasone, translating to an overall response rate of 34%.

The evolution of Hodgkin's disease and necrobiotic xanthogranuloma syndrome.

We describe a woman in whom hypogammaglobulinemia and severe granulomatous cutaneous lesions had developed during childhood; subsequently, Hodgkin's disease and necrobiotic xanthogranuloma were diagnosed. This case illustrates an apparent association with disease activity and raises the question of a direct relationship of necrobiotic xanthogranuloma with lymphoproliferative disease.