Course Of High-dose Dexamethasone Research Articles

ETMR-31. A UNIQUE CASE OF CNS DIFFUSE, NON-SYSTEMIC ALK+ HISTIOCYTOSIS IN A PEDIATRIC PATIENT

Abstract BACKGROUND Histiocytic disorders are a group of rare diseases with accumulation of of macrophages, monocytes, or dendritic cells in various parts of the body. ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 that is very rarely described in pediatrics. METHODS A 20 month old male presented to an adult hospital after a prolonged period of headaches, vomiting, and loss of developmental milestones. Imaging demonstrated severe hydrocephalus and extensive thickened leptomeningeal enhacement with mass effect. He underwent VP shunt placement and revision, a T7-T10 laminectomy, and tumor debulking. Extensive molecular testing, including DNA and RNA analysis by NGS was performed and a CLTC::ALK fusion was identified, along with Tier III DNA variants, yielding a diagnosis consistent with ALK-Positive Histiocytosis, with diffusivity in the CNS system. Full evaluation demonstrated no involvement of the peripheral nervous system or other systemic involvement. He initially demonstrated signs of neuro-irritation, altered tone, and lower extremity clonus. RESULTS After review of very little literature published on similar patients, although none with a clinical picture matching his, he was started on a treatment course of high dose dexamethasone, vinblastine, and lorlatinib targeting the ALK+, likely driver, mutation of his disease. On evaluation scans two months into treatment, he showed no change in his disease burden. He was transitioned to clofarabine cycles with daily lorlatinib for continued targetted therapy. After six total cycles, he demonstrated a high partial to complete remission (allowing for evidence of scarred tissue) and tremendous neurologic and developmental milestone gains. CONCLUSIONS This case demonstrates a unique presentation in which there is little described in the literature in way of clinical features or treatment standards, and further none exactly similar to this patient. After undergoing extensive evaluation and therapy modication, he responded remarkably well and continues to have optimal quality of life.

The clinical characteristics, putative drugs, and optimal management of 62 patients with stevens-johnson syndrome and/or toxic epidermal necrolysis: A retrospective observational study

Background:Case reviews of severe cutaneous adverse drug reactions (ADRs) such as SJS/TEN provide useful insights for clinical characteristics, putative drugs, and management protocols.Patients and Methods:Medical charts of 62 (m:f- 20:42) patients with SJS/TEN hospitalized between 2010 and 2019 were analyzed retrospectively for clinical attributes, putative drugs and their indications, extracutaneous complications, and therapeutic outcome. The diagnosis was clinical based on established criteria. WHO-UMC scale for reporting ADR and ALDEN algorithm score were used for causality assessment. Therapies were customized based on in-house resources and affordability.Results:Cases included were SJS (41.9%), SJS/TEN overlap (33.9%), and TEN (24.2%) aged 4–85 years. Complications included transaminitis (69.4%), lymphadenopathy (15.5%), septicemia (11.3%), and wound infections (4.8%). Aromatic anticonvulsants (37.1%), disease-modifying antirheumatic drugs (25.8%), antiretroviral drugs (12.9%), non-steroidal anti-inflammatory drugs (8.1%), antimicrobials (4.8%), and trihexyphenidyl (3.2%) were major putative drugs. The mean latent period was 16.6 days. The observed 8% mortality was because of primary comorbidities or multiorgan failure. Addition of fresh blood transfusion (BT, n = 11) or IVIg (n = 7) to systemic corticosteroids showed early relief in skin tenderness, improvement in general condition, and re-epithelialization. Only 16% of patients developed sequelae.Conclusion:Aromatic anticonvulsants, allopurinol, nevirapine, cotrimoxazole, paracetamol, and diclofenac remain the most implicated drugs. Sulfasalazine, leflunomide, ethambutol, and trihexyphenidyl were uncommon additions. A short course of high-dose dexamethasone in the early stage was useful. Addition of BT or IVIg provided rapid relief. Preexisting HIV disease, kidney disease, and sepsis remain important for in-hospital deaths. Retrospective study design and small number of cases remain major limitations.

A Phase II Study to Investigate the Efficacy and Safety of Eltrombopag in Combination with Dexamethasone As First-Line Treatment in Adults Patients with Newly Diagnosed Primary ITP (XPAG-ITP)

A Phase II Study to Investigate the Efficacy and Safety of Eltrombopag in Combination with Dexamethasone As First-Line Treatment in Adults Patients with Newly Diagnosed Primary ITP (XPAG-ITP)

A Phase II Study to Investigate the Efficacy and Safety of Eltrombopag in Combination with Dexamethasone As First-Line Treatment in Adult Patients with Newly Diagnosed Primary ITP (XPAG-ITP)

A Phase II Study to Investigate the Efficacy and Safety of Eltrombopag in Combination with Dexamethasone As First-Line Treatment in Adult Patients with Newly Diagnosed Primary ITP (XPAG-ITP)

High-Dose Dexamethasone (HD-DXM) Plus Oseltamivir Versus High-Dose Dexamethasone for Treatment of Adult Primary Immune Thrombocytopenia: Interim Analysis of a Prospective, Multicenter, Randomized, Controlled Trial

Introduction: Primary immune thrombocytopenia (ITP) is an acquired hemorrhagic disorder caused by immune-mediated platelet destruction and insufficient platelet production. As the first-line treatment of ITP, corticosteroids enable the recovery of platelet count in 60% to 80% of cases. However, a large proportion of patients would relapse during steroid tapering or withdrawal. Recently, sporadic studies reported successful treatment of ITP with oseltamivir which decreased platelet destruction through inhibition of platelet desialylation, a possible mechanism leading to Fc-independent platelet phagocytosis by hepatocytes. We hypothesize that corticosteroids and oseltamivir might complement each other in terms of mechanisms and induce a better response in ITP. Therefore, a prospective randomized controlled trial was conducted to compare the efficacy and safety of high-dose dexamethasone (HD-DXM) plus oseltamivir with HD-DXM monotherapy in adult ITP. Here we report the interim analysis of this study. Methods: From February 2016 to May 2018, 80 newly diagnosed treatment-naïve ITP patients from 5 tertiary medical centers in China were screened in the trial (NCT01965626). Dexamethasone was administered orally at 40 mg daily to both arms for 4 days (days 1 - 4). If platelet counts remained < 30 × 109/L or there were bleeding symptoms by day 10, another course of HD-DXM was given (days 11 -14). For the combination arm, oral oseltamivir was given concomitantly at a dosage of 75 mg twice daily for the first 10 days (days 1 - 10). The primary endpoints were initial response and sustained response (SR). Platelet counts should be confirmed on two separate occasions at least 7 days apart when defining responses (CR: platelet count ≥ 100×109/L and absence of bleeding; R: platelet count ≥ 30 × 109/L but < 100 × 109/L and at least a doubling of baseline and absence of bleeding). Initial responses were assessed by day 14. Responders underwent follow-up for at least 12 months or until relapse. Response lasting for at least 6 consecutive months without additional ITP-specific intervention was regarded as SR. Secondary endpoints included time to response (TTR), bleeding scores, duration of response and adverse events (AEs). Platelet transfusion was permitted in patients with severe bleeding symptoms and recorded. Requirements for any additional ITP-specific intervention were considered as treatment failure. Results: Fifty-nine patients were enrolled, of whom 28 were randomly to receive HD-DXM plus oseltamivir and 31 to HD-DXM monotherapy. Demographics and baseline characteristics were balanced between the 2 arms (Table 1). Results showed that HD-DXM plus oseltamivir achieved a higher incidence of initial response than HD-DXM alone at day 14 (82.1% vs. 58.1%, P = 0.045). At the end of 6 months, SR rate in the HD-DXM plus oseltamivir arm was higher than that in the HD-DXM monotherapy arm even though it did not reach statistical significance (42.8% vs. 25.8%, P = 0.167). Relapse-free survival in the HD-DXM plus oseltamivir arm was significantly improved compared with the HD-DXM monotherapy arm during follow-up period (HR 1.96, Log Rank P =0.043), as estimated by the Kaplan-Meier analysis. There was no statistical difference in median TTR between the two arms (P > 0.05). Bleeding was well controlled in both arms, with comparable post-treatment bleeding events (7.1% vs.19.3%, P> 0.05) and lower bleeding scores in the HD-DXM plus oseltamivir arm (0 vs. 0, P = 0.036). Incidence of AEs was similar between the 2 arms (P > 0.05). A slight increase in gastrointestinal reactions was observed in the HD-DXM plus oseltamivir arm but it did not reach statistical significance. Most of the AEs were mild to moderate (grade 1 to 2) and usually resolved spontaneously after medication was completed. No previously undescribed AEs was observed. Conclusions: The combination of HD-DXM with oseltamivir significantly improved the initial response in newly diagnosed ITP patients. However, due to the limitation of sample size, the conclusion of SR superiority can hardly be drawn at the moment. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Oseltamivir, a sialidase inhibitor which is extensively used in the treatment of or prophylaxis against influenza virus A and B. It has been reported that the treatment of oseltamivir could concomitantly increase platelet counts, which was independent whether influenza was diagnosed. Along those lines, several studies showed successful treatment of ITP patients with oseltamivir. We hypothesize that HD-DXM and oseltamivir might complement each other in terms of the mechanisms and achieve better response rates in ITP patients.

High dose dexamethasone as an alternative rescue therapy for active bleeding in children with chronic ITP: clinical and immunological effects

High-dose dexamethasone (HD-DXM) is debated as a second-line therapy for chronic Immune thrombocytopenia (ITP) in children. The aim of this study is to evaluate the efficacy and safety of HD-DXM as an emergency therapy in uncontrolled bleeding in children with chronic ITP and to assess its immunological effect on dendritic cells (DCs) percentage and their co-stimulatory markers CD86 and CD83.Totally, 20 children previously diagnosed as chronic ITP were enrolled in this study and all admitted to hospital with uncontrolled bleeding. Patients received HD-DXM as a single daily dose for 4 days. Blood samples were withdrawn from patients just prior to HD-DXM therapy and on day 5 to evaluate the platelet count and for flowcytometric analysis of DCs. Daily assessment of bleeding severity was performed. The platelet counts significantly increased in patients after 5 days of initiation of therapy compared with platelet count before therapy (p-value = 0. 0002). Control of bleeding observed in (90%), complete response (CR) documented in (50%), response (R) documented in (40%), and no response (NR) documented in (10%) of patients. The time to respond was raging from 1 to 3 days and minor complication recorded in two patients. Both plasmacytoid DCs and myeloid DCs percentage and their expression of co-stimulatory markers, CD86 and CD83 decreased significantly after HD-DXM therapy. Conclusion: short course of HD-DXM as a rescue therapy seems to be an effective alternative emergency treatment for uncontrolled bleeding in chronic ITP children especially in nations with limited resources.

The effect of single course high dose dexamethasone on CD28/CTLA-4 balance in the treatment of patients with newly diagnosed primary immune thrombocytopenia

To evaluate the effect of a single course of high dose dexamethasone (HD-DXM) on CD28 and CTLA-4 expression in patients with newly-diagnosed primary immune thrombocytopenia (ITP). Twenty-8 ITP patients (18 females and 10 males, age range 18–65 years, median age 38.5 years) enrolled in this study and 26 healthy volunteers (19 women and 7 men, age range 16–66 years, median age 37 years) served as a control group. The patients were treated with HD-DXM (40 mg/day) for 4 consecutive days. CD28 and CTLA-4 expression was assessed by flow cytometry once-monthly for 6 months. Plasma levels of the cytokines IFN-γ and IL-10 were determined by enzyme-linked immunosorbent assay. One month after treatment, a platelet response was observed in 23 (82%) of the patients. The response rates over the next 5 months were 71%, 57%, 53%, 46%, and 39%, chronologically. We observed a significant decrease in CD28 expression after the first month (34.7 ± 4.8% vs. 44.5 ± 4.4% before treatment), after which the CD28 levels gradually increased. In contrast, CTLA-4 expression increased after the first month (3.2 ± 0.5% vs. 0.8 ± 0.4 before treatment), after which the CTLA-4 levels gradually decreased. Similar dynamic changes were seen in the levels of IFN-γ and IL-10. The dynamic changes of CD28 and CTLA-4 were consistent with those of IFN-γ and IL-10 and with the effectiveness of HD-DXM in the treatment of ITP. Our results suggest that a disturbed CD28/CTLA-4 balance may contribute to the immunopathogenesis of ITP.

Conventional Oral Prednisone Versus High-Dose Dexamethasone for Management of Adult Immune Thrombocytopenia: A Prospective Randomized Multicenter Clinical Trial

Introduction Oral prednisone (PDN) is conventional standard initial management for adult immune thrombocytopenia (ITP). In recent years single arm studies propose that high-dose dexamethasone (HD-DXM) improves response rate and remission duration and reduces adverse effects, though a randomized trial demonstrated no superiority of HD-DXM. It still lacks evidence-based conclusion on which one is better in efficacy and safety. We conducted a prospective randomized multicenter clinical trial to compare the efficacy and safety of HD-DXM and PDN as first-line strategy for adult newly diagnosed ITP.Methods We enrolled adult newly diagnosed ITP patients aging between 18 and 80 years, peripheral PLT count <30x109/L or with bleeding symptoms. Diagnosis of ITP and definition of newly diagnosed ITP followed international working group report and ASH evidence-based guideline. A 1:1 randomization was assigned between HD-DXM and PDN arm. In HD-DXM arm, dexamethasone was administered orally at 40mg/d for 4 consecutive days. If PLT count remained or dropped below 30x109/L by day 10, another four-day course of HD-DXM was given. Patients received prednisone orally at 1.0mg/kg/d for no more than 28 days in PDN arm, and then tapered rapidly to minimized maintenance dosage of <15mg/d in responders or stop in non-responders. Early response was evaluated according to criteria mentioned above. We defined sustained response as PLT count maintaining above 30x109/L for 6 months or more. Responders underwent follow-up for at least 6 months or until relapse. Adverse effects were recorded for analysis of safety. Informed consent was obtained from all enrolled patients in accordance with the Declaration of Helsinki. This study was approved by Ethics Committee of each participating site and registered at http://clinicaltrials.gov/ as NCT01356511.Results From Jan 2011 to May 2014, 182 newly diagnosed adult patients were enrolled from 9 sites over Shandong Province, China, with 92 randomized to HD-DXM arm (62 females and 30 males; age median 43, range 18~73 years) and 90 to PDN arm (68 females and 22 males; age median 44.5, range 18~76 years). Baseline PLT count were 8.93±8.19 (HD-DXM arm) and 10.60±8.67 (PDN arm) x109/L, respectively. Overall response rate in HD-DXM arm was 84.8% (78/92) with 52.2% (48/92) CR, while in PDN arm 74.4% (67/90) and 28.9% (26/90). HD-DXM arm showed similar overall response (P=0.099) but higher CR rate (P=0.002). HD-DXM arm also demonstrated shorter time to response (3.21±1.35 vs. 5.97±4.28 days, P=0.001). 149 patients were available for evaluation of sustained response, 76 in HD-DXM arm and 73 in PDN arm, with follow-up of a median of 10(1-40) and 12(1-39) months, respectively. There was no statistically significant difference between the two arms in sustained response rate (39.5% vs. 49.3%, P=0.251). Generally both treatments were well tolerated. Adverse effects were recorded (HD-DXM/PDN), including hyperglycemia (3/5), hypertension (3/3), peptic ulcer (1/3), gaining weight (0/4), and infection trend (0/2).Conclusion One or two courses of HD-DXM demonstrated higher CR rate and shorter time to response than PDN. HD-DXM could be a better first-line choice for adult ITP.Table 1Characteristics of patients in HD-DXM and PDN armParameterHD-DXMPDNNo. of patients9290Age, median (range)43 (18 - 73)44.5 (18 - 76)Gender, female/male62/3068/22Baseline platelet count, x109/L8.93±8.1910.60±8.67 DisclosuresNo relevant conflicts of interest to declare.

Sequential High-Dose Dexamethasone and Response Adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) Chemotherapy Followed by High-Dose Therapy with ASCT for Newly Diagnosed Multiple Myeloma; Open-Labeled, Multicenter Phase 2 Study (KMM-94 Study)-Interim Analysis.

AbstractAbstract 3106 Background:Induction therapy followed by ASCT is the standard therapy for the newly diagnosed younger patients with MM. Recently, new drugs such as lenalidomide or bortezomib have shown the promising results as an induction treatment. However, these drugs are not available in many countries as a front line treatment and many different type of induction treatment regimens including old regimens are used. We evaluate the efficacy and safety of the brief course of high dose dexamethasone (HD) and the response adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) induction chemotherapy in the newly diagnosed younger patients with MM. Methods:One hundred fifty five newly diagnosed patients with MM from 23 institutions received 2 cycles of HD followed by PAD or VAD chemotherapy according to the response to the HD. PAD 4 cycles were given to nonresponsders and VAD 2 cycles were given to who achieved more than PR to HD. The primary endpoint was CR + nCR rate after ASCT. Among 155 patents enrolled this study from November 2009, 29 patients (19%) have been dropped out. This trial will be continued until total 210 patients will be enrolled. The trial is registered on National Cancer Institute website, number NCT01255514. Results:One hundred fifty five patients (88 male, 69 female) were enrolled (median age; 57). 34 (22%) patients had ISS stage I, 64 (41%) stage II and 55 (35%) stage III. Thirty six (26%) patients had abnormal cytogenetics. In FISH analysis, there were 25% del13, 9% del17, 21% t (4; 14), 13% t (14; 16) and 26% t (11; 14). Among the 115 evaluable patients, CR + PR rate was 53% (61/115) after 2 cycles of HD. 61 patients (53%) received subsequent VAD chemotherapy and 54 patients (47%) received PAD chemotherapy. Among the evaluable patients, CR + PR rate after induction therapy was 83% (79%, 48/61 in VAD group vs. 89%, 48/54 in PAD group). 95 patients finished ASCT. CR + nCR rate after ASCT were 74% (74% in VAD group vs 73% in PAD group). Mortality rate of this trial was 15% (17/115). The cause of death was disease progression (n=5), bleeding (n=1) and infections (n=11). Among 115 patients in whom VAD or PAD chemotherapy was actually performed, 1 year OS was 88.1%. (VAD arm 90.7% versus PAD arm 86.1% (P=0.105): median follow-up; 16.6 months). Conclusion:Risk adapted approach using initial HD response showed good response results after ASCT compared with previous trial (CR + nCR rate of IFM 2005-01 trial-Bortezomib+dexa induction & ASCT was 35%, J Clin Oncol. 2010;28:4621–9) The MM patients who showed poor response to HD also showed similar good response rate after ASCT compared with the patients who had good response to HD in this trial. PAD re-induction therapy after failure of initial steroid induction treatment might overcome the inferior results in the high risk MM patients. Our data shows that almost half of the patients who responded to HD can be saved of novel agents during induction treatment, and PAD can successfully rescue the other half who are not sensitive to HD. Therefore, initial steroid response adapted strategy might be the more cost-effective approach in the newly diagnosed ASCT eligible MM patients. [Display omitted] [Display omitted] 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.

Single course of high dose dexamethasone is more effective than conventional prednisolone therapy in the treatment of primary newly diagnosed immune thrombocytopenia.

IntroductionImmune thrombocytopenia (ITP) is an immune disorder commonly presents as isolated thrombocytopenia. Generally corticosteroids are the main treatment of ITP. This study was designed to evaluate effectiveness of high dose dexamethasone comparing conventional corticosteroid therapy in the treatment of ITP.Materials and methodsIn a randomized prospective study, sixty adult patients with newly diagnosed primary symptomatic ITP (Platelet count < 20,000) were evaluated. Patients divided into two groups. In group A, thirty patients (mean age of 24.9 years) received Dexamethasone 40 mg/IV/daily for four days (10 mg/q6h); and then Prednisolone 1 mg/kg/day/PO with rapid tapering of prednisolone (10 mg/week). From the other hand, in group B, thirty patients (mean age of 27.2 years) were treated with Prednisolone 1 mg/kg/day/PO for four weeks, then the drug tapered weekly.ResultsAll the patients in group A showed favorable response within the first seven days, 27 cases presented complete response (CR) and three cases revealed response (R). In group B, 11 cases had CR, 13 cases showed R and six cases had No response (NR). After three months, rates of CR were 80% and 23.3% in group A and B; respectively. Responses were 16.7% and 33.3%, NRs were 6.6% and 43.3% in group A and B; respectively (P < 0.0001). After 6 months, CR was 73.3% vs.16.7%, and R was 16.7% vs.36.7% and NR was 10% vs. 46.7% in group A and B; respectively (P < 0.0001). After 12 months, there was no change in response rate in group A, but in group B 53% were non responsive, 40% showed R (chronic ITP) and complete response was observed only in 6.7% (P < 0.0001). Three cases in group A and 12 cases in group B had needed splenectomy (P < 0.00002).ConclusionWe showed that high dose dexamethasone is more effective than conventional steroid therapy in newly diagnosed ITP as initial treatment with less relapses and toxicities.

Sequential High-Dose Dexamethasone and Response Adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) Induction Chemotherapy Followed by High-Dose Chemotherapy with Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma; Open-Labelled, Multicenter Phase 2 Study (KMM-94 Study)-Interim Analysis

Abstract 2044 Background:Induction treatment followed by autologous stem cell transplantation (ASCT) is the standard therapy for the newly diagnosed younger patients with multiple myeloma (MM). Although new drugs such as lenalidomide or bortezomib have been shown the promising results as induction treatment, many different type of induction treatment regimens still have been used. We evaluate the efficacy and safety of the short course of high dose dexamethasone (HD dexa) and the response adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) induction chemotherapy in the newly diagnosed younger patients with MM. Methods:107 newly diagnosed patients with MM from 21 institutions received 2nd cycles of HD dexa followed by PAD or VAD chemotherapy according to the response to the initial high dose dexamethasone. The primary endpoint was complete response (CR) + near CR rate after ASCT. Among 107 patents enrolled this study from November 2009, 25 patients (23%) have been dropped out. This trial will be continued until total 210 patients will be enrolled. The trial is registered on National Cancer Institute website, number NCT01255514. Results:One hundred seven patients (58 male, 49 female) were enrolled (median age; 56). 26 (24%) light chain disease were included. 31 (29%) patients were D-S stage II and 67 (63%) were stage III. According to the ISS, 23 (22%) patients had stage I, 51 (48%) had stage II and 33 (31%) had stage III. 26 (24%) patients had abnormal cytogenetics. There were 31% del13, 7% del17, 19% t(4;14), 15% t(14;16) and 28% t(11;14) in FISH analysis. Among the 82 evaluable patients, CR + PR rate was 48% (39/82) after 2nd cycles of HD dexa therapy. 39 patients (48%) received subsequent VAD chemotherapy and 43 patients (52%) received PAD chemotherapy. Among the 64 patients finished VAD or PAD chemotherapy, CR + PR rate was 83% (79%, 26/33 in VAD group vs. 87%, 27/31 in PAD group). 56 patients were finished ASCT until now. CR + near CR rate after ASCT were 61% (58% in VAD group vs 63% in PAD group). Mortality rate of this trial was 13% (11/82). The cause of death was disease progression (n=3), bleeding (n=1) and infections (n=7). Among 82 patients in whom VAD or PAD chemotherapy was actually performed, 1 year overall survival (OS) rate was 84.7%. 1 year survival rate was 93.8% versus 77.2% (P=0.049) with VAD versus PAD (median follow-up; 9.1 months). Conclusion:Risk adapted approach using initial steroid response showed good response results after ASCT compared with previous trial (CR + near CR rate of IFM 2005-01trial-Bortezomib+dexa induction & ASCT was 35%, J Clin Oncol. 2010;28:4621–9) The MM patients who had poor response to HD dexa also showed similar good response rate after ASCT compared with the patients who had good response to HD dexa treatment in this trial. PAD re-induction therapy after failure of initial steroid induction treatment might overcome the inferior results in the high risk MM patients. Therefore, initial steroid response adapted strategy might be the more cost-effective approach in the newly diagnosed ASCT eligible MM patients. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Initial Therapy with High-Dose Dexamethasone for Patients with Idiopathic Thrombocytopenic Purpura

have been reported on. We assessed the effectiveness of a single course of high dose dexamethasone as first-line treatment for adult patients with ITP. Methods: The subjects of the study were previously untreated adult patients with newly diagnosed ITP and who had a platelet count of less than 20,000/ μL or a platelet count less than 50,000/μL. High-dose dexamethasone at a dose of 40mg/day for four consecutive days was given orally. A response was defined as an increase in the platelet count of at least 30,000/μL and a platelet count of more than 50,000/μL by day 10 after the initial treatment. A sustained response was defined as a platelet count of more than 50,000/μL that was maintained for six months after the initial treatment. Results: Twenty two patients were eligible. The median platelet count before treatment was 19,000/μL. Seventeen patients (77%) among the 22 patients achieved an initial response by day 10: the mean platelet count 10 days after the initial treatment was 144,000/μL (range: 51,000 to 428,000/μL). Among the patients with a response, 4 (23.5%) had a sustained response, and the other 13 (76.5%) relapsed within six months. All the patients well tolerated the high-dose dexamethasone treatment. Conclusion: A single course of high-dose dexamethasone is effective as an initial treatment for adults ITP patients, although the response duration is short. To maintain the response, repeated high-dose dex- amethasone treatment may be needed or other alternative therapies can be considered. (Korean J Hematol 2009;44:22-27.)

Prompt and sustained response of a steroid-refractory autoimmune hemolytic anemia to a rituximab-based therapy in a chronic lymphocytic leukemia patient

Autoimmune hemolytic anemia (AIHA) is a rare and potentially life-threatening event which may complicate the course of chronic lymphocytic leukemia (CLL) at any time and steroid-refractory AIHA of CLL poses a therapeutic challenge for physicians. Here, we report the safety and efficacy of a rituximab-containing regimen in a CLL patient with steroid- and IVIg-refractory AIHA. A 57-year- old man affected by CLL, presented with fatigue, dyspnoea, tachycardia and jaundice. His physical examination revealed overt jaundice, hepato- and splenomegaly, and enlargement of lymph nodes in all superficial sites. The blood chemistry showed severe anemia (Hb value 3.9 g/dL), high white blood cell count (89 x 10(9)/L), altered hemolysis markers and direct antiglobulin test (DAT) was positive for both complement and IgG. The patient failed to respond to both a 4-day course of high-dose dexamethasone IV (40 mg/day) and intravenous immunoglobulin (IVIg) (1 g/kg/day x 2 days). Thus, a schedule containing rituximab (375 mg/m(2) day +1), cyclophosphamide (750 mg/m(2) day +2) and prednisone (60 mg/m(2) from day +1 to day +7) (R-CP) were administered. Four cycles, repeated every 4 weeks, were administered. After 4 days from the infusion of this schedule, the patient showed a marked reduction of the lymphocytosis, and the hemoglobin level started to increase. No rituximab-related side effects were recorded. At the end of treatment DAT became negative and patient achieved a nodular Partial Remission (nPR). Our data showed the safety and efficacy of a rituximab-containing regimen in a life-threatening CLL-related AIHA, refractory to steroid and IVIg therapy. This schedule has allowed the patient to obtain a prompt and dramatic rise in hemoglobin level and a response to both AIHA and CLL.

Expansile, enhancing cervical cord lesion with an associated syrinx secondary to demyelination

The authors describe the case of a patient with an enhancing, intramedullary cervical spinal cord lesion and associated syrinx. Biopsy sampling of the cervical lesion was performed, and the histological findings were consistent with a demyelinating process supporting the diagnosis of multiple sclerosis (MS). Syrinx formation associated with demyelinating disease has only been described in isolated cases, almost exclusively in Japanese patients with MS. A 22-year-old woman of Caribbean descent presented with a subacute, progressive myelopathy including symptoms of pain and weakness in all extremities, bladder incontinence, and the inability to ambulate. Magnetic resonance imaging of the brain and spinal cord demonstrated an enlarged cervical cord with enhancement and central cavitation consistent with a syrinx. The patient underwent a C3-7 laminoplasty and placement of a dural graft for cord decompression as well as fenestration of the central syrinx. Biopsy sampling of the lesion was performed, and the histopathological analysis, in conjunction with subsequent laboratory and diagnostic testing, supported the diagnosis of demyelinating disease. After treatment with a course of high-dose dexamethasone and inpatient rehabilitation therapy, the patient demonstrated significant clinical improvement. Spinal cord involvement is not uncommon in patients with demyelinating disease; however, enhancing lesions associated with extensive tissue loss and syrinx formation have rarely been reported. For the consulting neurological surgeon, demyelinating disease should be included in the differential diagnosis of such lesions given the level of complexity and risk to the patient associated with open biopsy of the spinal cord.

Clomiphene Citrate and Dexamethasone in Treatment of Clomiphene Citrate-Resistant Polycystic Ovary Syndrome: A Prospective Placebo-Controlled Study

Traditionally, clomiphene citrate (CC) is the first-line treatment for the chronic anovulation that is part of polycystic ovary syndrome (PCOS). As many as one fourth of affected women, however, fail to ovulate in response to incremental doses of CC, and conception rates are far lower than ovulation rates. Many women resistant to CC lack overt signs of a treatable disorder. This study evaluated a short course of high-dose dexamethasone (DEX) when added to CC in 80 infertile women with CC-resistant PCOS. All participants had been infertile for at least 2 years and had normal levels of dehydroepiandrosterone sulfate (DHEAS). CC resistance was defined as failure of ovulation after 3 treatment cycles reaching 150 mg daily. CC was given in a dose of 100 mg daily from cycle day 3 to day 7. In addition, patients received either 2 mg daily of DEX orally from day 3 to day 12 of the cycle or folic acid placebo tablets. Transvaginal ultrasonography was used to detect ovarian follicles more than 18 mm in size. Human chorionic gonadotropin (hCG) was given in a dose of 10,000 U when at least one follicle of this size was detected, and women were advised to have timed intercourse. The actively treated and placebo patients did not differ significantly at the outset with regard to age, duration of infertility, body mass index (BMI), menstrual pattern, hirsutism, serum DHEAS, or day of hCG treatment. Steroid-treated women had more large follicles and significantly greater endometrial thickness than did placebo recipients. They also had significantly higher rates of ovulation and pregnancy. Three fourths of women given DEX and 15% of placebo recipients ovulated, and 40% and 5%, respectively, became pregnant. No patient described side effects from DMX. Women responding to DEX did not differ from nonresponders in age, time of infertility, or BMI. Responders did, however, have significantly higher rates of oligomenorrhea/amenorrhea and hirsutism. The investigators conclude that a significant number of CC-resistant infertile women with PCOS will benefit from adding a brief, high-dose course of DEX and that such treatment does not have adverse antiestrogenic effects. A trial of DEX would be appropriate before resorting to gonadotropin therapy or laparoscopic ovarian drilling.

The Feasibility of High-Dose Dexamethasone (HD-DEX) in Idiopathic Thrombocytopenic Purpura (ITP) in Adults; a Multi-Center Study in Korea.

Short term use of HD-DEX has shown less adverse effects (AEs) than PDS maintenance but its success rates reported differently by several studies. The objective of this study was to determine HD-DEX effectiveness in adult ITP with newly diagnosed (group 1) and relapsed after other treatments(Tx) (group 2). 71 (median age; 45, 20~82) with ITP with a platelet counts (PC) 20,000/uL or less than 50,000/uL and clinically significant bleeding were enrolled. DEX a dose of 40 mg/day for 4 consecutive days was tried. A response was defined as an increase in the PC of at least 30,000/uL, PC of more than 50,000/uL by day 10 (D10) after DEX. A maintenance was defined as a PC of more than 50,000/uL 6 ms after Tx. The number of group 1 and 2 were 54, 17, retrospectively. In group 2, previous regimens included;oral PDS and/or IVIG (16)and splenectomy (4). Median PC before Tx were 8,500(1,000~45,000/uL) and 9,000(100~33,000/uL) in group 1 and 2, retrospectively (p=0.80). 27(50%) and 6(35.3%) in group 1, 2 showed good initial response to 1st course of DEX, retrospectively (p=0.40). After 1st course of DEX, 11(20.3%) in group 1 and 1(5.9%) in group 2 could maintain response for 3 ms (p=0.27). By 6 ms, 8 (14.8%) in group 1 and 1 (5.9%) in group 2 kept first response (p=0.68). Among 33 patients bearing initial response, 12 (44.4%)and 2 (33.3%) in group 1, 2 relapsed (p=1.0). Good correlation revealed between PC (D10) and response rate (RR) (p<0.05). Of 21 with PC (D10) above 100,000/uL, 6(28.6%) experienced relapse. On the other hand, nine of 11 patients (81.8%) in whom PC (D10) were less than 100,000/uL relapsed after all. There was no significant difference in relapse-free survival (RFS) after 1st DEX between 2 groups (p=0.9). 13 of 14 relapsed received 2nd DEX and then maintained PDS without interruption. After several weeks of maintenance, PDS tapered according to the PC. 9(75.0%) in group 1 and 2(100%) in group 2 showed response in 2nd DEX. Of these 11 patients, 2 in group 1 relapsed 10 ms after receiving 2nd DEX. After 1st DEX, 12 (16.9%), 5(7%) and 6 (8.5%) temporarily suffered from vague generalized sx., facial edema, and mild liver function abnormality, retrospectively. During the 2nd DEX and consecutive oral PDS, 4(30.7%), 3(23.1%) and 1(7.7%) experienced same AEs, retrospectively. Additionally, of these 13, overt DM requiring hypoglycemic agents appeared in 2(15.4%) and 1(7.7%) experienced duodenal ulcer bleeding. In conclusion, 1 course of HD-DEX revealed good initial response in group 1 but in group 2, the RR was lower than in historical results of oral PDS. However, it has an advantage for the patients to have a good compliance to the Tx because of few AEs and no need to maintain long-term daily medication. Furthermore, although the 2nd DEX and PDS maintenance showed good response, it revealed no benefit compared as a previously established oral PDS regimen because of frequently occurrence of AEs and poor compliance. Therefore, the proper DEX schedule remained to be determined according to the early achieved platelet counts (eg. D10) with 1st course DEX or to the presence of previous Tx.

CALENDAR OF EVENTS

OBJECTIVE AND IMPORTANCE: This is the second report of a Citrobacter-associated brain abscess in an adult and the first report of its association with an intradural tumor. Excluding those associated with trauma, neurosurgical procedures, and proximity to the skull base, only seven other cases of abscesses associated with intracranial tumors have been published. Five of seven tumor-associated abscesses with a microbiological diagnosis involved gram-negative bacteria, a finding that may indicate a predilection of these microorganisms for intracranial tumors. CLINICAL PRESENTATION: A 78-year-old female patient presented with a 6-month history of confusion and personality changes. Her medical history included paroxysmal atrial fibrillation and a 10-day course of high-dose dexamethasone but no other predisposing conditions for sepsis. She was afebrile, had no focal neurological deficits, and had no systemic abnormalities on examination. Computed tomographic imaging revealed a noncalcified, homogeneously enhancing, 3-cm-diameter, extra-axial tumor associated with the right anterior falx cerebri. The tumor did not extend to the skull base. INTERVENTION: At craniotomy, 10 to 20 ml of thick pus was found around the posteroinferior surface of the tumor. On extended culture, this material demonstrated Citrobacter koseri growth, which was effectively treated with ceftriaxone followed by meropenem and one repeated abscess aspiration. No systemic source of the infection was found. CONCLUSION: The characteristic endothelial invasiveness of Citrobacter and related gram-negative bacteria may predispose to the formation of abscesses in association with intracranial tumors.

Peritumoral Citrobacter koseri Abscess Associated with Parasagittal Meningioma

This is the second report of a Citrobacter-associated brain abscess in an adult and the first report of its association with an intradural tumor. Excluding those associated with trauma, neurosurgical procedures, and proximity to the skull base, only seven other cases of abscesses associated with intracranial tumors have been published. Five of seven tumor-associated abscesses with a microbiological diagnosis involved gram-negative bacteria, a finding that may indicate a predilection of these microorganisms for intracranial tumors. A 78-year-old female patient presented with a 6-month history of confusion and personality changes. Her medical history included paroxysmal atrial fibrillation and a 10-day course of high-dose dexamethasone but no other predisposing conditions for sepsis. She was afebrile, had no focal neurological deficits, and had no systemic abnormalities on examination. Computed tomographic imaging revealed a noncalcified, homogeneously enhancing, 3-cm-diameter, extra-axial tumor associated with the right anterior falx cerebri. The tumor did not extend to the skull base. At craniotomy, 10 to 20 ml of thick pus was found around the posteroinferior surface of the tumor. On extended culture, this material demonstrated Citrobacter koseri growth, which was effectively treated with ceftriaxone followed by meropenem and one repeated abscess aspiration. No systemic source of the infection was found. The characteristic endothelial invasiveness of Citrobacter and related gram-negative bacteria may predispose to the formation of abscesses in association with intracranial tumors.

Peritumoral Citrobacter koseri Abscess Associated with Parasagittal Meningioma

OBJECTIVE AND IMPORTANCE: This is the second report of a Citrobacter-associated brain abscess in an adult and the first report of its association with an intradural tumor. Excluding those associated with trauma, neurosurgical procedures, and proximity to the skull base, only seven other cases of abscesses associated with intracranial tumors have been published. Five of seven tumor-associated abscesses with a microbiological diagnosis involved gram-negative bacteria, a finding that may indicate a predilection of these microorganisms for intracranial tumors. CLINICAL PRESENTATION: A 78-year-old female patient presented with a 6-month history of confusion and personality changes. Her medical history included paroxysmal atrial fibrillation and a 10-day course of high-dose dexamethasone but no other predisposing conditions for sepsis. She was afebrile, had no focal neurological deficits, and had no systemic abnormalities on examination. Computed tomographic imaging revealed a noncalcified, homogeneously enhancing, 3-cm-diameter, extra-axial tumor associated with the right anterior falx cerebri. The tumor did not extend to the skull base. INTERVENTION: At craniotomy, 10 to 20 ml of thick pus was found around the posteroinferior surface of the tumor. On extended culture, this material demonstrated Citrobacter koseri growth, which was effectively treated with ceftriaxone followed by meropenem and one repeated abscess aspiration. No systemic source of the infection was found. CONCLUSION: The characteristic endothelial invasiveness of Citrobacter and related gram-negative bacteria may predispose to the formation of abscesses in association with intracranial tumors.