Pulsed Dexamethasone Research Articles

G173 Development of the Evaluating Quality of Life in Acute Lymphoblastic Leukaemia (EQuALL) Questionnaire: A Treatment Specific Measure For the Effects of Corticosteroids on Quality of Life

AimsSurvival rates for childhood ALL now exceed 80%. The use of corticosteroids (particularly dexamethasone) has contributed greatly to this success. However this is not without cost – in addition to...

Polymorphisms of the IL-23R gene are associated with primary immune thrombocytopenia but not with the clinical outcome of pulsed high-dose dexamethasone therapy

Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder that is characterized by decreased platelet count. The interleukin-23 receptor (IL-23R) has been identified as a susceptibility gene for the development of multiple autoimmune diseases. To investigate the possible association of IL-23R gene single-nucleotide polymorphisms (SNPs) with ITP and the association with the clinical outcome of pulsed high-dose dexamethasone (HD-DXM) therapy, four SNPs in the IL-23R gene, rs10889677, rs1884444, rs7517847, and rs11209032, were tested in a cohort of 75 ITP subjects and 81 controls by direct sequencing. IL-23R rs1884444 GT/TT variant genotypes were observed to be associated with significantly increased risk of ITP as compared with controls (GT/TT vs. GG: odds ratio (OR) 2.776, 95% confidence intervals (CI) 1.086-7.090, p = 0.028). However, other three SNPs revealed no statistically significant differences between patients and controls (rs10889677 CA/AA vs. CC: OR 2.200, 95% CI 0.727-6.661, p = 0.155; rs11209032 GA/AA vs. GG: OR 0.747, 95% CI 0.379-1.472, p = 0.399; rs7517847 TG/GG vs. TT: OR 1.031, 95% CI 0.544-1.956, p = 0.925). Furthermore, IL-23R SNPs revealed no association with clinical outcome of HD-DXM therapy. This study suggests that polymorphism in the IL-23R gene, rs1884444, indicates a significant association with susceptibility to ITP in a recessive genetic model but does not have association with the clinical outcome of HD-DXM therapy.

Outcome of patients with acute lymphoblastic leukemia (ALL) following induction therapy with a modified (pulsed dexamethasone rather than continuous prednisone) UKALL XII/ECOG E2993 protocol at Tawam Hospital, United Arab Emirates (UAE)

This retrospective data analysis examined the outcome of 99 acute lymphoblastic leukemia (ALL) patients treated at Tawam Hospital between January 2000 and December 2009. Sixteen patients were treated before June 2002, and 83 patients were treated from June 2002. A modified form of UKALL XII/ECOG E2993 with pulsed dexamethasone in induction phase one (modified UKALL) was the main therapy from June 2002 (71/83). The median age was 28 years. Fifty-eight percent had pre-B ALL where 36 % of them were Philadelphia chromosome-positive (Ph+). Overall, complete remission (CR) rate was 86.7 % which was significantly inferior for patients with white blood cell count 30-100 × 10⁹/l (p = 0.009), therapy before June 2002 (p = 0.02), pregnancy (p = 0.005), CNS leukemia (p = 0.028), and unknown karyotype (p = 0.004). With a median follow-up of 11.8 months (0.49-126 months), the estimated overall survival (OS) and event-free survival (EFS) at 3 years were 50.6 and 28.7 %, respectively. OS and EFS were significantly inferior for patients not in CR after induction, age >20 years, Ph+, unknown karyotype and therapy before June 2002. In addition, CR, OS and EFS were significantly superior (p = 0.004, p < 0.001 and p = 0.001, respectively) for therapy with our modified UKALL protocol compared to Tawam protocol (main therapy before June 2002). In conclusion, the outcome of treatment for ALL at our institute is encouraging with significant improvement in the outcome of older adolescents and young adults when using high-intensity chemotherapy. This suggests that such an approach is feasible in developing countries in spite of some limitations including lack of stem cell transplantation service.

Pulse dexamethasone therapy versus pulse methylprednisolone therapy for treatment of Graves′s ophthalmopathy

Pulse methylprednisolone therapy is the recommended therapy for moderate to severe and active ophthalmopathy, but high dose pulse methylprednisolone therapy is marred by the chances of fulminant hepatic failure and the high cost of therapy. Dexamethasone pulse therapy can be considered as an alternative to pulse methylprednisolone therapy. A prospective randomized control trial was carried out in 21 patients comparing pulse dexamethasone therapy versus pulse methyprednisolone therapy in Graves's ophthalmopathy. This study proved that pulse dexamethasone therapy is a cheaper and equally effective therapy for Graves's ophthalmopathy and the cost of therapy is reduced to at least 1/8th s. Furthermore, dexa had a better effect on reduction of exophthalmos. The dreaded complication of fulminant hepatic failure, associated with high dose of methylprednisolone, is not seen with dexa therapy.

Alopecia areata treated with phenolisation and intravenous dexamethasone pulses

Phenol is an aromatic hydrocarbon derived from coal tar or manufactured from monochlorobenzene. Alopecia areata is a common non scarring autoimmune condition characterised by patchy loss of hair without atrophy. Various treatment modalities have been proposed and used for the treatment of alopecia areata, which is indeed a difficult condition to treat. Variable results have been documented using intralesional corticosteroid injections, topical minoxidil, topical anthralin ointment, topical contact sensitizers like diphencyprone, dinitrochlorobenzene or squaric acid dibutyl ester, and oral mini pulse with betamethasone. The use of 88% phenol for the treatment of alopecia areata has been documented in literature, but it has failed to secure a place in the priority list. Herein we have reported a case of a young girl who was treated with short-time aggressive therapy using 88% phenol and dexamethasone pulse therapy and who responded well to the treatment with no recurrence in the last 6 months of follow-up.

Impact of the National Institutes of Health Focal Segmental Glomerulosclerosis (NIH FSGS) clinical trial on the treatment of steroid-resistant FSGS

Idiopathic focal segmental glomerulosclerosis (FSGS) is among the most common, morbid and treatment-resistant conditions faced by nephrologists. While glucocorticoids have traditionally been the mainstay of initial treatment, they induce remission in only a minority of patients. A variety of other immunosuppressants have been utilized against steroid-resistant FSGS, but few have been rigorously examined in well-controlled trials. Recently, the results were published from a National Institutes of Health (NIH)-sponsored multicenter randomized trial comparing cyclosporine (CSA) with a combination of mycophenolate mofetil (MMF) and pulse dexamethasone (DEX) for the treatment of steroid-resistant FSGS. No difference in treatment effectiveness was shown between the two groups, and adverse effects were comparable. This was the largest randomized trial ever undertaken in FSGS, but it was unfortunately underpowered to show clinically relevant differences in response rates. This shortcoming, along with particularities of the study population and outcome measures, makes it challenging to draw definitive conclusions from the trial results. Despite these limitations, the trial does provide valuable insights into treatment strategies for FSGS and offers important lessons for planning future research.

Endothelial stress products and coagulation markers in patients with multiple myeloma treated with lenalidomide plus dexamethasone: an observational study

In this prospective study of patients with relapsed or relapsed and refractory multiple myeloma (MM) treated with lenalidomide and dexamethasone, relationships between markers of endothelial stress and drug administration and incidence of venous thromboembolism (VTE) were assessed. Of 33 enrolled patients, laboratory and treatment data were available for 32 patients. Of these, 23 received pulsed dexamethasone (40mg/day on days 1-4, 9-12 and 17-21 of each 28-day cycle) and 9 received weekly dexamethasone (40mg/day on days 1, 8, 15 and 21 of each cycle). The overall incidence of VTE was 9%. A decreasing trend in markers values was observed with intercellular adhesion molecule (P=0·05), fibrinogen (P=0·008), plasminogen activator inhibitor-1 (P<0·001), homocysteine (P=0·002) and P-selectin (P<0·001) during therapy. Compared with weekly dexamethasone, pulsed dexamethasone was associated with significantly greater variation in mean adjusted relative values of fibrinogen, P-selectin and vascular endothelial growth factor (P<0·001 for all comparisons), although there was no apparent association with VTE incidence. Lenalidomide plus dexamethasone affects endothelial stress marker levels in patients with advanced MM. The higher variation seen with pulsed dexamethasone suggests greater endothelial stress with this approach.

Pivotal Role of Rho-Associated Kinase 2 in Generating the Intrinsic Circadian Rhythm of Vascular Contractility

The circadian variation in the incidence of cardiovascular events may be attributable to the circadian changes in vascular contractility. The circadian rhythm of vascular contractility is determined by the interplay between the central and peripheral clocks. However, the molecular mechanism of the vascular intrinsic clock that generates the circadian rhythm of vascular contractility still remains largely unknown. The agonist-induced phosphorylation of myosin light chain in cultured smooth muscle cells synchronized by dexamethasone pulse treatment exhibited an apparent circadian oscillation, with a 25.4-hour cycle length. The pharmacological inhibition and knockdown of Rho-associated kinase 2 (ROCK2) abolished the circadian rhythm of myosin light chain phosphorylation. The expression and activity of ROCK2 exhibited a circadian rhythm in phase with that of myosin light chain phosphorylation. A clock gene, RORα, activated the promoter of the ROCK2 gene, whereas its knockdown abolished the rhythmic expression of ROCK2. In the mouse aorta, ROCK2 expression exhibited the circadian oscillation, with a peak at Zeitgeber time 0/24 and a nadir at Zeitgeber time 12. The myofilament Ca(2+) sensitization induced by GTPγS and U46619, a thromboxane A2 analog, at Zeitgeber time 0/24 was greater than that seen at Zeitgeber time 12. The circadian rhythm of ROCK2 expression and myofilament Ca(2+) sensitivity was abolished in staggerer mutant mice, which lack a functional RORα. ROCK2 plays a pivotal role in generating the intrinsic circadian rhythm of vascular contractility by receiving a cue from RORα. The ROCK2-mediated intrinsic rhythm of vascular contractility may underlie the diurnal variation of the incidence of cardiovascular diseases.

An Open-Label Phase 2 Study of Lenalidomide in Combination with Oral Dexamethasone in the Previously Untreated, Symptomatic Patients with Chronic Lymphocytic Leukemia (CLL).

AbstractAbstract 2895 Introduction:Lenalidomide is an immunomodulatory agent with promising anti-tumor activity in CLL. The use of lenalidomide in this disease, however, can be complicated by tumor lysis syndrome (TLS) and frequent tumor flare (TF). From our experience using low-dose lenalidomide (starting dose 2.5mg, titrating to a target of 10mg daily), TLS can be prevented but TF remains frequent (Chen et al. JCO 2010). In addition, when using low-dose single-agent lenalidomide, few complete responses (CR) are achieved. We therefore proposed the combination of lenalidomide and pulse dexamethasone, aiming to enhance anti-tumor activity through both synergy and mitigation of toxicities such as TF, enabling escalation to higher doses of lenalidomide. Our previous observation of “rebound” peripheral lymphocytosis when using intermittent dosing of lenalidomide led to the current use of continuous daily dosing. We present an interim analysis of the initial 18 of 31 planned pts in this ongoing trial of lenalidomide and dexamethasone as first-line CLL therapy. Methods:Eligible pts were previously untreated with symptomatic CLL (cytopenias, symptomatic adenopathy/organomegaly, constitutional symptoms, lymphocyte doubling count <12 mos). The starting dose for lenalidomide is 5mg daily continuously, with 5mg escalations every 28 days to a maximum of 25 mg, and dexamethasone 12 mg daily orally days 1–7, 14, 21 of each 28 day cycle, both to a maximum of 18 cycles. Supportive measures: allopurinol for TLS prophylaxis, DVT prophylaxis with low dose ASA, sulfatrim for PJP prophyaxis.Results: Demographics:To date, 18 pts have been enrolled: median age 61 yrs (range 40–84), male 13 pts (72%), Rai stage III-IV 13 pts (72%), baseline median Hb 98g/L (range 77–137), absolute lymphocytes 194.5 ×109/L (range 9.3–469.9), ß2M 319 nmol/L (range 253–813; normal <170), bulky nodes 15 pts (83%), organomegaly 9 pts (50%), del17p/del11q on FISH 3 pts (17%), ZAP70+ 12 pts (67%) and unmutated IgVH in 9 of 17 pts tested (53%). Seventeen pts have received at least 1 cycle and are evaluable for toxicity and response. The median number of cycles received is 8 (range 1–18). Hematologic toxicity:9 pts (53%) have developed Gr 3–4 neutropenia during at least 1 cycle; 4 pts (24%) febrile neutropenia; 6 pts (35%) have required GCSF support. Only 2 pts (12%) have developed Gr 3–4 thrombocytopenia, without bleeding. Nonhematologic toxicity:Non-desquamating rash (65%), fatigue (59%), diarrhea (53%), cough (53%), insomnia (47%), and constipation (47%), are common (most grade 1–2). Grade 3–4 toxicities include: atrial fibrillation with pulmonary embolism (1 pt), fatigue (2 pts), insomnia (1 pt), skin rash (1 pt), diarrhea (1 pt), muscle weakness (1 pt), infection (1 pt). Infections are frequent (all grades in 50% of pts, grade 3 in 6%), primarily affecting upper airway/lungs. One pt developed H1N1 influenzae, complicated by aspergillus pneumonia and multiorgan failure. In contrast to the high rate of TF from our previous single-agent lenalidomide trial (88%), TF is considerably less common in the current trial (5 pts; 29%). No TLS has been noted. Dose modifications/study withdrawals:The maximum 25mg dose has been achieved in 4 pts, with a median tolerated daily dose of 15 mg (range 2.5–25 mg). Grade 3–4 neutropenia is the most common cause of dose interruptions/reductions. Responses:All 17 pts have achieved stable disease (SD) or better with overall responses 59%: 9 PR (53%), 7 SD (41%), 1 CR (6%). Responses were reached at a median of 4 months (range 1.8–9.6). No patients have progressed to date. Correlatives:Recent studies have identified cereblon (CRBN) as a direct target of lenalidomide with expression required for anti-tumor activity. CRBN protein was detected by Western blot analysis in CD19-selected cells derived from screening blood samples of all 17 pts evaluated to date and correlation with response is ongoing. Conclusion:Preliminary results from this phase 2 study suggests that lenalidomide plus dexamethasone has significant activity in previously untreated CLL, is generally well-tolerated, and dramatically reduces the incidence of TF symptoms. This may facilitate dose escalation beyond the 10mg daily dose used in our previous single agent study and lead to higher quality responses. Rebound lymphocytosis has not been noted with continuous dosing. Response data are encouraging but whether this combination can achieve durable CR is forthcoming. Disclosures:Chen:Celgene: Honoraria, Research Funding; Lundbeck: Consultancy; GlaxoSmithKline: Research Funding; Janssen: Consultancy, Research Funding. Off Label Use: Lenalidomide is not approved for use in chronic lymphocytic leukemia. Johnston:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Trudel:Celgene: Honoraria, Research Funding, Speakers Bureau.

Anti-Inflammatory, Immuno-Modulatory and Angiostatic Treatment As Third-Line Therapy for Multiple Myeloma (MM) – a Combined Treatment Setting of Lenalidomide with Pioglitazone, Dexamethasone and Low-Dose Treosulfan (phase I/II)

Abstract 5029 Introduction:Therapeutic options for patients (pts) with second progression of multiple myeloma (MM) are limited, as patients have already received novel targeted therapy approaches at this stage, i. e. bortezomib and lenalidomide. Acknowledging that continuous production of pro-inflammatory cytokines contributes to resistance towards the agents, we hypothesized, that a multi-targeted approach consisting of anti-angiogenic, anti-inflammatory, immuno-modulatory and anti-tumor components given continuously may have the potential to overcome resistance mechanisms. Methods:To clinically test this hypothesis we initiated a phase I/II trial combining daily lenalidomide (len, cohort 1: 10mg, cohort 2: 15 mg) with pioglitazone 60 mg and treosulfan 250 mg (twice daily), and dexamethasone 1 mg administered for one month (mo). Pulsed dexamethasone, 40 mg p. o. was given on day 1 to 4 and 14 to 17, then 20 mg every 14 days. In the absence of toxicity, pts were eligible to continue the same treatment regimen until progression. Key inclusion criteria were progressive/relapsing MM after at least two previous lines of therapy. Whereas the phase I of the study aimed to assess tolerance of this combination regimen, inclusion criteria in phase II also required previous treatment with len, since it aimed to test the hypothesis that this combination might overcome resistance towards len. We here report the results for phase I of the study. Results:Between November 2009 and February 2011 two cohorts of three patients have been included in the phase I part of the study. All six patients (4 males, 2 females) were heavily pretreated with tandem autologous transplantation using high-dose melphalan (n=5), bortezomib (n=4), thalidomide (n=1), interferon-alpha (n=2) as well as standard anti-myeloma chemotherapies (anthracycline, bendamustin, cyclophosphamide, n=6). Median number of previous lines of treatment were 3. 3 (range 3 to 5). Four pts suffered from progressive IgG MMs, 2 pts had light chain MMs. Median age was 64. 1 years (range 60 to 72 years). Noteworthy, neither the 3 pts included in cohort I receiving the combination regimen with 10mg, nor the 3 pts in cohort (15mg) experienced a dose limiting toxicity (defined as any toxicity with NCI-CTCAE grade 3 3 during the first treatment cycle). Therefore, all pts continued treatment in the extension phase. Serious adverse reactions observed during follow-up were infections (n= 6, Grade 2 NCI-CTCAE toxicity), depressed mood (n=1, Grade 2), osteonecrosis of the jaw and tooth extraction (n=1), and thrombosis during anticoagulation (n=1, Grade 2). Assessment of response demonstrated that 4 of the 6 pts increased serum hemoglobin levels by at least 1. 0 g/dl already during the first treatment cycle. During the extension phase (median observation time 23. 3 months), two patients achieved a partial response (duration: 24 mos, >19 mos), two a very good partial response (8 mos, respectively), and one pt the first complete response ever in his disease course, lasting for 14 mos. This pt had his longest progression-free interval (31 mo) since start of therapy for stage IIIA multiple myeloma. One pt achieved stable disease during 15 mos. Thus, none of the patients had progressive disease. Due to the high tolerance and the encouraging response data, this study proceeded to phase II including patients to be treated with 15 mg lenalidomide daily. All patients were treated in an outpatient setting. Hospitalization was necessary in 3 cases. Conclusions:We here provide evidence from a prospective phase I study that the combination of low-dose chemotherapy, dexamethasone and lenalidomide administered as long-term treatment on a daily basis exhibits a very favorable toxicity profile and is a feasible regimen applicable in an outpatient setting. In addition, we provide preliminary data that this combination treatment might have considerable clinical activity in heavily pretreated pts with relapsing/progressing MM. Disclosures:No relevant conflicts of interest to declare.

Low-Dose Rituximab and High-Dose Dexamethasone As Front-Line Therapy in Adult Patients with Primary Immune Thrombocytopenia

AbstractAbstract 3332 IntroductionCorticosteroids are the initial standard therapy for primary immune thrombocytopenia (ITP). A short course of high-dose dexamethasone as initial therapy is an alternative to prednisone with high initial responses, but about half of the patients relapse. Low dose rituximab has been used in the treatment of relapsed ITP, showing a similar activity to the standard dose. The aim of this prospective study was to evaluate the efficacy, safety and response duration of low-dose rituximab plus short pulses of high-dose dexamethasone as front-line therapy in newly diagnosed ITP adults. MethodsPatients ≥18 years old with newly diagnosed received dexamethasone, 40 mg/day/i.v. for 4 consecutive days (+1, +2, +3, +4), rituximab was administered at a fixed dose of 100 mg as an i.v. infusion weekly for 4 consecutive doses (days +1, +8+, +15 and +22). The use of rescue therapy was allowed, using the same schedule of dexamethasone, before day 30, but only if the platelet count was < 20×109/L.A complete blood cell count was performed at enrollment, weekly for the first 28 days, monthly until month 6 and then every 3 months. The degree of response was defined as follows: a complete response (CR) was a platelet count ≥ 100 × 109/L; a complete sustained response (CSR) was considered if it was maintained for six months. Partial response (PR) was defined as a platelet level between 50 and 100 × 109/L; an overall response (OR) was defined as partial or complete response. Patients with a platelet count <30 × 109/L were considered non-responders (NR). Time-to-response (TTR) and time-to-complete response (TCR) were also assessed, as well as the safety profile and side effects incidence according to the National Cancer Institute Common Toxicity Criteria version 3.0. ResultsTwenty-one consecutive patients were enrolled from December 2009 to December 2011 (17 women and 4 men); median age was 51 years (range, 18–82). The median platelet count at baseline was 5.19 × 109/L (range, 0.3–24.2 × 109/L). Patients were followed for a median of 12 months (range, 1–25). At day +28, sixteen patients (76.2%) had CR, three patients had PR (14.3%), with the OR being 90.5%. At month six, 16 of 21 patients (76.2%) had achieved CSR. Seven patients received a second course of dexamethasone (one at day +8 and six at day+15) (Table 1). The median duration of response was 12 months (range, 7–25 months). The median time to reach TTR and TCR was 8 days (range, 4–28). Partial response was achieved in two patients who were further treated with danazol and prednisone, being subsequently splenectomized. The relapse rate was 15.8%. The 6- and 12- month cumulative RFS were both 84%; the 6- and 12-month cumulative TFS probabilities were 94% and 87%, respectively (Fig. 1).Overall, combination therapy in our group was well tolerated with a lower incidence of adverse effects during infusion in this trial according to the data reported in previous studies. ConclusionsThe combination of low-dose rituximab and high-dose dexamethasone as front-line therapy for adults with ITP was effective and safe with a high OR rate and a low incidence of relapse. These data need to be confirmed in a prospective randomized clinical trial including a sample size with enough power to reach statistically significant conclusions.Table 1Salient features and response for 21 immune thrombocytopenic purpura (ITP) patients treated with high-dose dexamethasone and rituximab as front-line therapyPatient no.Age, y/SexBasal platelets × 109/LBest responseResponse at day 28Time to PR/CR, wkDuration of response, monthsCurrent statusFollow up, monthsAdditional Treatment1F/495.7CRCR1/115CSR152M/5418.4CRCR1/123CSR233F/5415CRCR1/325CSR25Dex4F/328CRCR1/115CSR155F/562.5CRCR2/221CSR21Dex6F/6418PRPR1/−–PUR21P, D, S7F/1817.8PRPR1/1–PUR11P, D, S8F/734.9CRPR1/1–CUR18D9F/494CRCR1/120CSR2010M/190.9NRNR−/−–NR511M/588CRCR3/312CSR12Dex12F/517CRCR2/29CSR913F/583CRCR1/112CSR1214F/801.6CRCR3/312CSR12Dex15F/2924.2CRCR1/16CSR616F/625CRCR1/412CSR12Dex17F/820.3NRNR−/−–NR118M/410.4CRCR1/17CSR7Dex19F/405.38CRCR1/16CSR620F/213CRCR3/312CSR12Dex21F/332CRCR4/46CSR6PR, partial response; CR, complete response; CSR, complete sustained response; NR, no response; PUR partial unsustained response; CUR, complete unsustained response; P, prednisone; D, danazol; S, splenectomy; Dex, dexamethasone. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Continuous Glucose Monitoring: A Valuable Monitoring Tool for Management of Hypoglycemia During Chemotherapy for Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) maintenance therapy (MT) has been occasionally associated with symptomatic hypoglycemia (SH), attributed to purine analog (mercaptopurine [6-MP]). This hypoglycemia has been hypothesized to affect substrate utilization of gluconeogenic precursor alanine in the liver. An overweight 5-year-old boy with ALL was evaluated for SH (lethargy and vomiting) that occurred 8-10 h after fasting while receiving daily 6-MP. Hypoglycemic episodes (>20 episodes per month) occurred predominantly around midmorning but not during the 5-day dexamethasone pulse. The adrenocorticotropic hormone test yielded a normal cortisol response, which ruled out pituitary adrenal suppression. A 12-h overnight fasting glucose was 49 mg/dL, with suppressed insulin response <2 IU/mL, low C-peptide of 0.5 ng/mL, high insulin-like growth factor-binding protein >160 ng/mL, high free fatty acid of 2.64 mmol/L, and negative glucagon stimulation test (change in blood glucose [BG] <5 mg/dL). These results ruled out hyperinsulinism. The patient was placed on cornstarch therapy 5 h prior to dosing with 6-MP. This treatment reduced the SH events to fewer than two episodes per month. To study the efficacy of cornstarch, the patient was fitted with the iPro™ professional continuous glucose monitoring system (CGMS) (Medtronic MiniMed, Northridge, CA) with a preset low alarm at 70 mg/dL, which was worn for a period of 5 days while the patient was on cornstarch. With 1,000 sensor reading the BG range was 65-158 mg/dL, and the percentage mean absolute difference between sensor and finger-stick BG readings (the parent monitored his BG four times a day) was 9.4%. There were no hypoglycemic episodes detected by the CGMS while the patient was on cornstarch. After the cessation of chemotherapy, a 15-h fasting study was performed, and the CGMS was placed. Results showed resolution of hypoglycemia. The CGMS helped us devise an effective management plan for our patient. CGMS proved useful as an adjunct to characterize the pattern of hypoglycemia and to validate the benefit of cornstarch in hypoglycemia associated with 6-MP treatment of ALL.

Seizures as a Presentation of a Pelvic Neuroblastoma in a 5-Month-Old Infant

Epilepsy is a very uncommon first manifestation of a neuroblastoma. A 5-month-old healthy infant presented with acute onset seizures and developmental regression. Extensive investigation was remarkable for urinary vanillylmandelic acid and homovanillic acid peaks. Abdominopelvic magnetic resonance imaging (MRI) disclosed a presacral unresectable pelvic neuroblastoma. Chemotherapy and monthly dexamethasone pulses were administrated. Seizures stopped 3 days after the first pulse of dexamethasone. At 3-year follow-up, the patient is asymptomatic and has normal neurologic and developmental examinations. This case illustrates an impressive clinical and electroencephalographic (EEG) improvement on corticosteroid therapy, raising several hypotheses, including the possibility of a nonclassic paraneoplastic neurologic syndrome.

Patient Recruitment into a Multicenter Randomized Clinical Trial for Kidney Disease: Report of the Focal Segmental Glomerulosclerosis Clinical Trial (FSGS CT)

We describe the experience of the focal segmental glomerulosclerosis clinical trial (FSGS CT) in the identification and recruitment of participants into the study. This National Institutes of Health funded study, a multicenter, open-label, randomized comparison of cyclosporine versus oral dexamethasone pulses plus mycophenolate mofetil, experienced difficulty and delays meeting enrollment goals. These problems occurred despite the support of patient advocacy groups and aggressive recruitment strategies. Multiple barriers were identified including: (1) inaccurate estimates of the number of potential incident FSGS patients at participating centers; (2) delays in securing one of the test agents; (3) prolonged time between IRB approval and execution of a subcontract (mean 7.5 ± 0.8 months); (4) prolonged time between IRB approval and enrollment of the first patient at participating sites (mean 19.6 ± 1.4 months); and (5) reorganization of clinical coordinating core infrastructure to align resources with enrollment. A Web-based anonymous survey of site investigators revealed site-related barriers to patient recruitment. The value of a variety of recruitment tools was of marginal utility in facilitating patient enrollment. We conclude that improvements in the logistics of study approval and regulatory start-up and testing of promising novel agents are important factors in promoting enrollment into randomized clinical trials in nephrology.

Guidelines on the diagnosis, investigation and management of chronic lymphocytic leukaemia

Royal Bournemouth Hospital, Bournemouth, 2 Royal Marsden Hospital, London, 3 Southampton General Hospital, Southampton, Cardiff and Vale NHS Trust, Cardiff Cambridge University Hospitals NHS Foundation Trust, Cambridge UK; St. James's Institute of Oncology, Leeds, Christie Hospital NHS Trust, Manchester Royal Marsden Hospital London; Heart of England NHS Foundataion Trust, Birmingham; 10 Royal Liverpool University Hospital, Liverpool; Churchill Hospital, Headington, Oxford, Norfolk and Norwich University Hospital, Norwich

Immunoglobulin G4–related sclerosing disease of the paranasal sinus

Immunoglobulin G4 (IgG4)-related sclerosing disease is a systemic disease characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration of various organs. We present a case of a 69-year-old man with maxillary sinus IgG4 sclerosing disease, with orbital invasion treated with rituximab and dexamethasone pulse therapy. Surgery was used as well to debulk the disease and to obtain tissue for diagnosis. A PubMed search using the key phrase "IgG4-related Sclerosing Disease" was performed. There were 304 different articles regarding the disease for a multitude of different organ sites. Of the 304 articles, there were 3 articles that reported this disease in the paranasal sinuses. IgG4-related sclerosing disease is a rare entity in the head and neck. There are documented reports of steroid therapy for this disease, but the patient presented here demonstrated clinical progression of disease with steroids alone. The use of combination therapy of surgery, dexamethasone, and rituximab provided clinical improvement and stable disease determined by radiographic means.

Cytomegalovirus retinitis as an adverse immunological effect of pulses of vincristine and dexamethasone in maintenance therapy for childhood acute lymphoblastic leukemia

We describe a 5-year-old female with acute lymphoblastic leukemia (ALL) who suffered from cytomegalovirus (CMV) retinitis during maintenance therapy consisting of 6-mercaptopurine (6-MP) and methotrexate (MTX) with pulses of vincristine (VCR) and dexamethasone (DEX). Administration of anticytomegaloviral drugs led to a complete regression of active retinitis. Her low CD4 positive T cells and serum immunoglobulin G (IgG) recovered when maintenance therapy was resumed without VCR and DEX. The patient has been in complete remission (CR) for more than 5 months after completion of maintenance therapy without recurrence of CMV retinitis.

An update on the management of chronic inflammatory demyelinating polyneuropathy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune mediated disorder of the peripheral nervous system with clinical features that include weakness, sensory loss, imbalance, pain and impaired ambulation which may lead to substantial disability. This review highlights current treatment strategies for CIDP, how best to utilize proven therapies such as intravenous immunoglobulin, oral prednisone, pulse dexamethasone, and plasma exchange, and when and how to use alternative immunosuppressive agents when first-line therapies are ineffective or poorly tolerated.

Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis

Idiopathic inflammatory myopathies are chronic diseases with significant mortality and morbidity. Whilst immunosuppressive and immunomodulatory therapies are frequently used, the optimal therapeutic regimen remains unclear. This is an update of a review first published in 2005. To assess the effects of immunosuppressants and immunomodulatory treatments for dermatomyositis and polymyositis. We searched the Cochrane Neuromuscular Disease Group Specialized Register (August 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3 2011), MEDLINE (January 1966 to August 2011), EMBASE (January 1980 to August 2011) and clinicaltrials.gov (August 2011). We checked the bibliographies of identified trials and wrote to disease experts. We included all randomised controlled trials (RCTs) or quasi-RCTs involving participants with probable or definite dermatomyositis and polymyositis as defined by the criteria of Bohan and Peter, or definite, probable or mild/early by the criteria of Dalakas. In participants without a classical rash of dermatomyositis, inclusion body myositis should have been excluded by muscle biopsy. We considered any immunosuppressant or immunomodulatory treatment. The two primary outcomes were the change in a function or disability scale measured as the proportion of participants improving one grade, two grades etc, predefined based on the scales used in the studies after at least six months, and a 15% or greater improvement in muscle strength compared with baseline after at least six months. Other outcomes were: the International Myositis Assessment and Clinical Studies Group (IMACS) definition of improvement, number of relapses and time to relapse, remission and time-to-remission, cumulative corticosteroid dose and serious adverse effects. Two authors independently selected papers, extracted data and assessed risk of bias in included studies. They collected adverse event data from the included studies. The review authors identified fourteen 14 relevant RCTs. They excluded four trials.The 10 included studies, four of which have been added in this update, included a total of 258 participants. Six studies compared an immunosuppressant or immunomodulator with placebo control, and four studies compared two immunosuppressant regimes with each other. Most of the studies were small (the largest had 62 participants) and many of the reports contained insufficient information to assess risk of bias.Amongst the six studies comparing immunosuppressant with placebo, one study, investigating intravenous immunoglobulin (IVIg), showed statistically significant improvement in scores of muscle strength in the IVIg group over three months. Another study investigating etanercept showed some evidence of a steroid sparing effect, a secondary outcome in this review, but no improvement in other assessed outcomes. The other four randomised placebo-controlled trials assessed either plasma exchange and leukapheresis, eculizumab, infliximab or azathioprine against placebo and all produced negative results.Three of the four studies comparing two immunosuppressant regimes (azathioprine with methotrexate, ciclosporin with methotrexate, and intramuscular methotrexate with oral methotrexate plus azathioprine) showed no statistically significant difference in efficacy between the treatment regimes. The fourth study comparing pulsed oral dexamethasone with daily oral prednisolone and found that the dexamethasone regime had a shorter median time to relapse but fewer side effects.Immunosuppressants were associated with significant side effects. This systematic review highlights the lack of high quality RCTs that assess the efficacy and toxicity of immunosuppressants in inflammatory myositis.

Pulsed High-dose Dexamethasone Improves Interleukin 10 Secretion by CD5+ B Cells in Patients with Primary Immune Thrombocytopenia

B cells expressing CD5 are potentially capable of producing interleukin 10 (IL-10) which contributes to the regulatory function of B cells. This study was aimed at exploring the alteration of numbers of CD5(+) B cells and their ability of producing IL-10 in patients with immune thrombocytopenia (ITP), and the effects of pulsed high-dose dexamethasone (HD-DXM) therapy on CD5(+) B cells. Peripheral blood mononuclear cells from 25 adult ITP patients were stained with PE-CD5/FITC-CD19 antibodies for flow cytometry analyses before and after HD-DXM therapy. The expression of IL-10 mRNA was measured by RT-PCR. After 24h culture with or without dexamethasone in the presence of PMA, ionomycin and Brefeldin A, cells were permeabilized and stained with APC-IL-10 antibody to investigate intracellular IL-10 expression. Supernatant IL-10 concentration was detected by ELISA. The number of CD5(+) B cells was elevated in patients with ITP. Expression of IL-10 mRNA, percentage of IL-10(+) cells and intracellular IL-10 in CD5(+) B cells from untreated patients were significantly higher than that in controls. In contrast, ITP patients showed lower IL-10 concentration in supernatants than controls. After HD-DXM therapy, the number of CD5(+) B cells decreased to normal level, while intracellular IL-10 expression in CD5(+) B cells was further enhanced and IL-10 concentration in supernatants was also increased. Similar results were observed when dexamethasone was administrated in vitro. Increased number of CD5(+) B cells in which IL-10 is accumulated with decreased IL-10 concentration in supernatants suggests that the ability of CD5(+) B cells to secret IL-10 is impaired in ITP patients. Both the aberrant number and ability of IL-10 secretion of CD5(+) B cells could be corrected by HD-DXM.