Second Course Of Therapy Research Articles

Ретроспективный сравнительный анализ эффективности хондропротективной терапии пациентов с хронической болью в нижней части спины

INTRODUCTION. The choice of optimal therapy for chronic lower back pain includes: influence on all links of the pain vicious circle, has analgesic and anti-inflammatory effects, chondroprotective effect. AIM. A retrospective comparative analysis of outpatient records of patients with chronic lower back pain with a course of therapy with drugs containing chondroitin sulfate – Chondroguard, and bioactive concentrate of small marine fish – Alflutop. MATERIAL AND METHODS. Outpatient records of patients who took Chondroguard and Alflutop in the period from January 2022 to April 2024 were included. Data from 60 patients (medium age 51.5±9.7 years). Patients were retrospectively divided into two groups depending on the strategy of pain management. The main group (n=30; medium age 51.0±9.8 years), who received Chondroguard intramuscularly (I/ m) every other day No. 25 according to the scheme: the first 3 injections (1st, 3rd, 5th day) - 1 ml (100 mg), with good tolerability from the 4th injection (7 day) – 2 ml (200 mg); and the Comparison group (n=30; medium age 49.3±9.9 years), received Alflutop 2 ml, 1 time a day, every other day, a short course of 10 days. The dynamics of the condition was assessed on days 10, 20, 50. RESULTS AND DISCUSSION. By day 50 in the Main group, there was a decrease in pain by an average of 86.6% according to the numerical rating scale and an improvement in the functional status according to the Oswestry scale of 95.5%, in the comparison group there was a decrease in pain by an average of 77.2%, an improvement in the functional status according to Oswestry scale of 86.7%. By day 50, the severity of pain syndrome in the Main group decreased by 91.2%, in the Comparison group – by 33.9%; indicators of the functional status of Oswestry scale in the Main group improved by 97.3%, in the Comparison group – by 84.8%. In the Main group, the need for multiple nonsteroidal anti-inflammatory drugs on the 10th day of therapy decreased to 1 tablet per day in 76.7%, in the Comparison group – in 16.7%. In the main group, after a course of therapy for 21.3±2.2 months. they did not consult a doctor in the comparison group after 5.3±1.1 months. A second course of therapy was conducted. CONCLUSION. In the Main group, the effects of therapy can be regarded as long-term, since the effects of highly purified chondroitin sulfate on the pathogenetic mechanisms of the formation of chronic lower back pain remain. KEYWORDS: pain syndrome, lower back pain, chondroitin sulfate, Chondroguard

Experience in the use of cladribine for the treatment of patients with highly active forms of multiple sclerosis in the Moscow region

To assess the efficacy and safety of cladribine in patients with highly active multiple sclerosis (MS) in the Moscow region. The analysis was based on data from 62 patients treated with cladribine between March 2021 and January 2024. The diagnosis of VAMS was confirmed in 51 patients, PPMS in 4 patients, and SPMS with exacerbations was diagnosed in 7 cases. Of these, 3 patients completely completed therapy more than a year ago, 20 people received 2 courses of the drug less than a year ago, 39 patients underwent 1 course of therapy. The effect of cladribine on reducing disease activity and progression, as well as the safety of therapy, was evaluated. After 1 course, the number of patients with activity decreased by 66.4%, after 2 years of therapy - by 72.7%. The mean annual frequency of exacerbations decreased from 1.32 to 0.2 after 12 months, and to 0.086 exacerbations per year after 24 months. The level of disability assessed by the EDSS scale remained virtually unchanged throughout the follow-up. The most common adverse events were haematological abnormalities in the form of lymphopenia and leukopenia. Most patients had mild grade 1-2 lymphopenia on the toxicity scale and recovered to the recommended values (>0.8·109/l) by the beginning of the second course of therapy. No cases of serious adverse events were reported. The results obtained indicate the high efficacy and favorable safety profile of cladribine and are consistent with the data of clinical trials of the drug.

The Occurrence of Infection and TP53 Mutation Are Risk Factors for Cardiovascular Toxicity of Acute Myeloid Leukemia Induction Therapy

Introduction: For almost 50 years,induction therapy (IT) is the standard of care for acute myeloid leukemia (AML) patients. Nevertheless, little is known about cardiovascular (CV) toxicity during IT. We aimed to describe CV events (CVE)occurring during IT and to identify clinical, hematological and molecular risk factors of such events. Methods: Two hundred and twenty-four patients of 18 years or more (median age 61 (51;67) years, 58% males), treated with ITbetween 2014 and 2021 were enrolled in this study. Two hundred and one (90%) received an anthracycline-based IT, the others received gemtuzumab ozogamicin as part of a clinical protocol research. Survival from the time from initiation of IT until death or until the initiation of the second course of therapy (either salvage regimen in case of primary refractory or relapsed AML, or intensive consolidation therapy in case of response) was considered. The primary endpoint was the time to occurrence of the first CVE after IT initiation, with death as a competing event. Multivariate analysis included significant covariate, identified by univariate models among initial characteristics and occurrence of infection (coded as time dependent covariate). Results: Hematological characteristics were as follows: European LeukemiaNet (ELN) 2022 risk of myelodysplastic neoplasm (MDS)/AML was low, intermediate and adverse in 13%, 29% and 58% of patients respectively. Main mutations encounters were: DNMT3A, FLT3, NPM1, TET2, NRAS, RUNX1, ASXL1, IDH2, PTPN11, BCOR, SRSF2, WT1 and TP53. Main CV risk factors were tobacco (36%), arterial hypertension (35%), obesity (24%), hyperlipidemia (22%), diabetes mellitus (11%). Baseline left ventricular ejection fraction (assessed by transthoracic echocardiography) was >45% in all patients, >55% in 95% of patients. Seventy-five patients (33%) presented a CVE during IT. Eighty-six percent of CVE were severe (grade 3 or more). Patients presenting CVE during IT were significantly older (p=0.02) and presented more often a past history of dilated cardiomyopathy (p=0.04), arterial hypertension (p=0.005) or dyslipidemia (p=0.005). At baseline, CVE patients presented a greater left auricle volume (p=0.005), higher tricuspid regurgitation grade (p=0.01), and more often a right ventricular dilatation or a significative valvopathy (respectively p=0.01 and p=0.03). There was no difference in CVE occurrence between patients treated with and without anthracyclin (p=0.2). Competing risk models identified the following adverse characteristic for the risk of first CVE, namely the occurrence of the first infectious event (Hazard ratio [HR]= 2.43, p=0.005), TP53 mutation (HR=1.79, p=0.04). No other clinical characteristics nor mutation (including TET2 and DNMT3A) were identified. Multivariate analyses demonstrated that TP53 mutation (HR=1.78, p=0.04) and occurrence of infection (HR=2.29, p=0.008) retained independent prognostic value, see Table 1. In a response stratified model, only TP53 mutation was a risk factor of first CVE (HR=2.46, p=0.008). Conclusions: CVE occurred in 33% of patients during IT and were severe. The major adverse role of onset of infection for CVE occurrence after IT could overcome the prognostic value of mutations usually associated with CV risk in the healthy population (i.e. TET2, DNMT3A, ASXL1, ...). TP53 mutation was the only molecular abnormality associated with CVE, in agreement with the increased risk of doxorubicin-induced cardiac toxicity in a mouse model of TP53 clonal hematopoiesis developed by Sano et al. These results suggest that TP53 mutated patients could benefit from careful CV monitoring and optimization of primary prevention treatment.

Centralized MRD Assessment at Early Timepoints in Gimema AML1718 Trial, a Phase 2 Open-Label Study of Venetoclax, Fludarabine, Idarubicin and Cytarabine (V-FLAI) in the Induction Therapy of Non Low-Risk AML

Background: New therapeutic strategies are strongly needed to improve the prognosis of high risk Acute Myeloid Leukemia (AML) patients, such as combination of novel agents and conventional chemotherapy. The Italian GIMEMA AML1718 trial (NCT03455504) investigate the safety and efficacy of the BCL-2 inhibitor venetoclax (VEN) in combination with intensive fludarabine-based induction (FLAI) [fludarabine 30 mg/sqm from day 1 to day 5, cytarabine 2000 mg/sqm from day 1 to day 5, and idarubicin 8 mg/sqm on days 1, 3 and 5] as first-line therapy for newly diagnosed non low-risk ELN AML patients. Results from the Planned Interim Analysis of Safety Run-in and Part 1 (early expansion cohorts) were presented at the last 2022 ASH Meeting. Median overall survival (OS) was not reached; probability of 12-month OS was 76%. Median disease-free survival was not reached. With a median follow-up of 10.5 months, 28 patients (49%) received allogeneic stem cell transplantation (HSCT) in first complete remission (CR). Centralized multicolour flow cytometry minimal residual disease (MFC-MRD) assessment was planned during the phase 2, part 2 of the study (confirmatory cohort) where the lower effective dose of VEN (400 mg/day) was administered in association with FLAI. Here we report results from early time-points (TPs) MRD analysis with the aim of identify the most informative TPs for MRD assessment and prognostic correlations. Methods: Erythrocyte-lysed whole bone marrow (BM) samples obtained at diagnosis from patients enrolled in the confirmatory cohort were centralized and analysed with a broad panel of monoclonal antibodies to identify the leukemia-associated phenotype (LAIP) which was used to track residual leukemic cells during follow-up. Eight color flow cytometry analysis was performed at pre-defined TPs (TP1: post-induction I, TP2: post induction II/consolidation I, following TPs: post consolidation/pre-transplantation) (FACSCantoII; BD Facs Diva Software V6.1.3). A positive flow MRD was defined by the presence of no less than 10 clustered leukemic cells/10^4 total events. Enrollment closed on January 2023. Collection and analysis of later TPs is ongoing. Results: Sixty-seven patients from 11 centers were enrolled in the phase 2, part 2. Risk stratification according to ELN 2017 was intermediate in 46% of patients and high risk in 54%. Fifty-eight/67 patients (87%) obtained CR after induction I. In the centralized MRD analysis, 170 samples has been collected and analysed so far (60 baseline samples, 110 MRD samples). Seven patients lacking baseline sample for LAIP identification were excluded from the analysis. TP1 was available in 57/59 patient achieving CR (97%), and TP2 was available in 29 patients, so far. MFC-MRD negativity was obtained in 31/57 (54%) at TP1 (post V-FLAI, Fig. 1). An increase in MFC-MRD negativity rate was observed at TP2 (post Induction II or consolidation I) with 20 MFC-MRD negative patients/29 available samples (69%, Fig. 1). Thirteen/110 follow up samples (8%), albeit resulting MRD negative, were considered inadequate for the analysis due to haemodilution, 9 from TP1 and 4 from TP2 (Fig. 1). TP1 and TP2 MRD assessment were scheduled at day 28 of Induction I and Induction II/consolidation, respectively. However, in most cases, delayed haematological recovery was observed after V-FLAI, thus resulting in suboptimal samples for MRD evaluation. Conclusions: Preliminary results from centralized MRD analysis confirm that the combination therapy is able to induce high-quality remissions with a very high percentage of MFC-MRD negativity in a difficult cohort of patients, with a higher percentage of MFC-MRD-negative after the completion of the second course of therapy. Delayed haematological recovery may impact on reliability of MRD assessment due to hypocellular and regenerative marrow samples, suggesting that in those cases MRD analysis should be postponed. Correlation with survival will be performed as the data collection will be complete.

Antibody-Guided Therapy in Phospholipase A2 Receptor-Associated Membranous Nephropathy

A 6-month course of cyclophosphamide (CP) and steroids is effective in primary membranous nephropathy (MN), but unappealing because of long-term side effects. We evaluated efficacy of an "antibody-guided" treatment schedule. Patients with phospholipase A2 receptor (PLA2R)-related MN and high risk of progression were treated with CP 1.5 mg/kg/d and steroids in cycles of 8 weeks. Anti-PLA2R antibodies were measured by indirect immunofluorescence (IIFT) at 8, 16, and 24 weeks, and a negative test resulted in withdrawal of CP, and rapid tapering of prednisone. In patients with persistent anti-PLA2R antibodies at 24 weeks, CP was switched to mycophenolate mofetil. Treatment was repeated in patients with a relapse. Our analysis included 65 patients (48 males, 17 females), age 61 ± 12 years, estimated glomerular filtration rate (eGFR) 46 ml/min per 1.73 m2 (35-68), urine protein-to-creatinine ratio 7.7 grams/10 mmol creatinine (5.4-11.1) and serum albumin 20 g/l (16-26). Immunologic remission rate was 71% after 8 weeks, 86% after 16 weeks, 88% after 24 weeks, and 94% after 3 years. Twenty-seven patients (42%) had persistent clinical remission after only 8 weeks of therapy. Sixteen patients needed a second course of therapy because of immunologic or clinical relapse. Follow-up was 37 (26-58) months. Overall partial remission rate was 92%. One patient developed end-stage kidney disease. Antibody-guided therapy (ABG) was as effective as the standard 6-month course, whereas providing a lower cumulative dose of CP (11.1 [8.0-18.5] vs. 18.9 [14.2-23.6] grams). ABG is effective, and allows individualized therapy, with many patients responding to 8 weeks of CP-based therapy.

Palliative Split-Course pelvic radiotherapy for symptomatic cervical cancer

Objective: Palliative pelvic RT effectively relieves significant health issues such as bleeding from the tumor, pain, discharge, or mass effect on the rectum genitourinary tract vessels and nerves in cervical cancer patients. There is no exact conclusion about an ideal palliative radiation treatment dose regimen. Thus we share the results of a commonly used split-course palliative pelvic RT regimen in our hospital. Material and Methods: For a retrospective study, 9 patients records treated between 2015 and 2019 were reviewed. The dose of prescribed irradiation for the target was 20Gy in 5 daily fractions. An additional 20Gy in 5 fractions was delivered after a 2-week time for recovery. Symptomatic improvement and treatment-related toxicity during and after RT were assessed from handwritten clinician reports. Results: Vast majority of patients enduring, and rapid symptomatic improvement was observed. Grade 3 to 5 treatment toxicity was not examined. Maximum acute toxicity was grade 1 GI or GU toxicity in 4 patients and G2 in two patients. Three patients had no acute side effects. All patients had complete symptom remission after treatment, one patient did not complete the second course of therapy due to deteriorating performance status, but local symptom relief was achieved. Conclusion: Split course regimen effectively improved symptoms without significant toxicity. The integrated 2-week break allowed doctors to assess patients for increased dose palliative radiation and balanced therapeutic benefits with possible adverse effects. This regimen is a reasonable strategy for patients who do not tolerate definitive treatment.

Real‐world experience of adalimumab therapy for patients with ulcerative colitis: A single tertiary medical center experience in Central Taiwan

AbstractThere are few studies on the treatment outcomes of adalimumab therapy in Taiwanese patients with ulcerative colitis (UC). A total of 102 patients with ulcerative colitis were identified from the electronic clinical database of the Changhua Christian Hospital. The demographic data and clinical features of the disease pattern of the UC patients receiving adalimumab therapy were retrospectively reviewed. Between January 2015 and June 2020, 18 patients with UC received adalimumab therapy. Due to the absence of a response, 5 of the 18 patients (27.7%) only received the induction therapy. Of the 13 patients who received maintenance adalimumab therapy, four discontinued the therapy: three (23.1%) stopped due to a loss of response, and one (7.7%) stopped due to a cutaneous reaction to adalimumab. Because of Taiwan's 1‐year limit on the use of adalimumab, seven patients relapsed and required a second course of therapy. The median period between course completion and relapse was 31 weeks. Two (20%) of the ten patients who finished the first course of therapy did not experience a relapse. The treatment response of patients with UC to adalimumab therapy appears to be comparable to those in previously published Western studies. The majority of patients who responded to adalimumab will relapse following a limited duration of adalimumab therapy in Taiwan.

Ingenol mebutate therapy in erythroplasia of Queyrat: a new approach.

Background Erythroplasia of Queyrat (EQ) is a rare squamous cell carcinoma in situ, usually occurring on the glans penis, the prepuce, or the urethral meatus. Therapy is mandatory because it can progress to invasive carcinoma in up to 30% of cases. Treatment options include 5-fluorouracil, curettage, cryotherapy, radiotherapy, laser, partial or total penectomy, and micro surgery, as also with imiquimod and photodynamic therapies. Methods Between 2015 to 2018 we treated five patients, with histologically confirmed EQ, with ingenol mebutate (IM) 0.015% gel applied for 3 days consecutively. Results Three patients showed complete response at one year follow up. Two patients showed partial response after two months so they received a second course of therapy with IM. At one year follow up, one of them showed complete response, the other partial response. Conclusions Our experience demonstrated that IM may be considered as an effective and safe treatment option in EQ. IM offers various advantages such as easy and fast application, rapid complete remission, better compliance, few side effects and excellent cosmetical results. The authors call for further exploitation in bigger trials.

Definitive-intent intensity-modulated radiation therapy provides similar outcomes to those previously published for definitive-intent three-dimensional conformal radiation therapy in dogs with primary brain tumors: A multi-institutional retrospective study.

Radiotherapy with or without surgery is a common choice for brain tumors in dogs. Although numerous studies have evaluated use of three-dimensional conformal radiotherapy, reports of definitive-intent, IMRT for canine intracranial tumors are lacking. Intensity-modulated radiation therapy has the benefit of decreasing dose to nearby organs at risk and may aid in reducing toxicity. However, increasing dose conformity with IMRT calls for accurate target delineation and daily patient positioning, in order to decrease the risk of a geographic miss. To determine survival outcome and toxicity, we performed a multi-institutional retrospective observational study evaluating dogs with brain tumors treated with IMRT. Fifty-two dogs treated with fractionated, definitive-intent IMRT at four academic radiotherapy facilities were included. All dogs presented with neurologic signs and were diagnosed via MRI. Presumed radiological diagnoses included 37 meningiomas, 12 gliomas, and one peripheral nerve sheath tumor. One dog had two presumed meningiomas and one dog had either a glioma or meningioma. All dogs were treated in the macroscopic disease setting and were prescribed a total dose of 45-50Gy (2.25-2.5Gy per fraction in 18-20 daily fractions). Median survival time for all patients, including seven cases treated with a second course of therapy was 18.1 months (95% confidence of interval 12.3-26.6 months). As previously described for brain tumors, increasing severity of neurologic signs at diagnosis was associated with a worse outcome. Intensity-modulated radiation therapy was well tolerated with few reported acute, acute delayed, or late side effects.

Ingenol mebutate therapy in erythroplasia of Queyrat: a new approach.

Erythroplasia of Queyrat (EQ) is a rare squamous cell carcinoma in situ, usually occurring on the glans penis, the prepuce, or the urethral meatus. Therapy is mandatory because it can progress to invasive carcinoma in up to 30% of cases. Treatment options include 5-fluorouracil, curettage, cryotherapy, radiotherapy, laser, partial or total penectomy, and microsurgery, as also with imiquimod and photodynamic therapies. Between 2015 to 2018 we treated five patients, with histologically confirmed EQ, with ingenol mebutate (IM) 0.015% gel applied for 3 days consecutively. Three patients showed complete response at one year follow up. Two patients showed partial response after two months, so they received a second course of therapy with IM. At one-year follow-up, one of them showed complete response, the other partial response. Our experience demonstrated that IM may be considered as an effective and safe treatment option in EQ. IM offers various advantages such as easy and fast application, rapid complete remission, better compliance, few side effects and excellent cosmetical results. The authors call for further exploitation in bigger trials.

Complete Hematologic and Cytogenetic Remission of Acute Myeloid Leukemia in an Elderly Patient Treated with Decitabine and Venetoclax: A Case Report

We present the case of a 77 year old woman, Caucasian, with medical history of diabetes mellitus, hyperthyroidism, hypertension and hyperlipidemia, that suddenly develops progressive articular pain, dyspnea at rest, easy bruising /ecchymosis in soft tissues, weakness and nose bleeding. At admission no visceromegaly was noted, gums and lymph nodes were normal. Initial lab workup showed severe anemia (Hb 7.7 g/dL), leukocytosis (19.1 x 10^3/uL) with monocytosis (51%) and left shift, severe thrombocytopenia (Plt 33 x 10^3/uL), hyperfibrinogenemia, hyperglycemia and hyperuricemia. Bone marrow morphology was conclusive of Acute Myeloid Leukemia with 45 % of blasts, hypercellular with progressive trilineage hematopoiesis and no ringed sideroblasts. Flow cytometry of peripheral blood detected only 0.8 % of blasts (CD34+) with positive myeloid markers. Flow cytometry of bone marrow detected 17 % of myeloid blasts expressing CD34+, HLA-DR, CD117, cytoplasmic (cy) MPO, CD13, partial CD11b, negative for cyTdT and cy CD79a. Genetically, 5q31/EGR1 deletion (86%) and gain of 20q12 (64%), with no other anomalies or mutations were found. Patient was treated with Decitabine 20mg/m2 IV daily x 10 d, followed by Venetoclax starting gradually from 100 mg escalating up to 300 mg oral as induction therapy. Complications during this phase were pleural effusion, C. difficile-associated diarrhea, urinary infection due to Enterococcus faecium, anemia, thrombocytopenia that required blood and platelet transfusions. After the first cycle of therapy a new bone marrow done showed morphologically < 2 % of blasts with moderate pancytopenia, but presence still of 10 % of CD34+ myeloblasts detected by flow cytometry. After a second course of therapy Decitabine/Venetoclax, peripheral blood leukocytes and platelets normalized, persisting only moderate anemia with no transfusion requirements. Bone marrow FISH report was normal, Del 5q disappeared, no detection of aberrations associated to myelodysplastic syndrome, and no detection of other abnormalities (results below the cut-off) were described, however a new pathogenic alteration in the DNMT3A gene not described before in other cases was detected with the New Generation System analysis. At the moment of presenting this case report there is a leukemia-free survival of 6 months, with impressing improvement in the general status. Conclusion: Therapy with the combination Decitabine/Venetoclax is a good alternative for treating elderly patients with AML, sparing the aggressiveness of regular induction chemotherapies and a tremendous impact in inducing cytogenetic remission. Disclosures No relevant conflicts of interest to declare.

Persistent Fever Can be Associated with Transient but Severe Hemophagocytic Lymphohistiocytosis (HLH) in Adult Recipients of Ventricular Assist Devices (VAD) for Treatment of Cardiomyopathy (CM)

Hemophagocytic lymphohistiocytosis (HLH) is an often fatal type of systemic inflammatory response (SIRS) which is characterized by T cell dysregulation and activation of macrophages, and which leads to multi-organ dysfunction. VAD insertion is often associated with transient SIRS (Galantier J et al, Arq Bras Cardiol 2008 91:301-08; Byrnes JW et al, Ann Thorac Surg 2015 99:1392-8), but VAD insertion has not previously been described to result in HLH.Through an IRB approved retrospective chart review of 123 VAD insertions between January 2014 and May, 2016, we describe the association of persistent fever and HLH following VAD insertions and the outcomes of subsequent orthotopic heart transplant (OHT). Four adults, with range of age 25-71 years, had non-ischemic CM, and developed persistent fevers following VAD insertion. One of the patients likely developed HLH prior to VAD insertion. This patient, one month following completion of chemotherapy for diffuse large B cell lymphoma, in remission, developed recurrent, idiopathic fevers and heart failure. This patient then underwent VAD insertion 7 weeks later and fevers persisted. The other three patients developed fever, 100.5o F or higher, within 48 hours of VAD insertion, and which persisted, often exceeding 103oF, for a median of 23 days (range 10- 135 days) before the diagnosis of HLH was made.All patients met at least 5 criteria as per HLH-2004 (Hentner J-E et al, Pediatr Blood Cancer 2007 48:124-131) All had extensive bone marrow hemophagocytosis. Median soluble IL-2 R at diagnosis was 2,771 U/ml (range: 2,286-14,600). Median ferritin was 2,570 mcg/L (range 643-12,351) Comprehensive investigation for diseases and predispositions associated with HLH was conducted in all. None had identifiable malignancy or persistent lymphoma, connective tissue disorder, family history of HLH, nor identifiable predisposing mutation on genetic testing. Viral testing of blood by pcr was negative except for EBV in one, HHV-6 in one.Therapy consisted of dexamethasone, etoposide in three patients for a median of 41 days (range 28-48), and dexamethasone alone for 6 weeks in one patient. No surviving patient required a second course of therapy. Despite receiving etoposide and dexamethasone for 31 days,one patient, age 71, died of HLH 41 days after VAD insertion. Three patients subsequently underwent successful OHT without relapse of HLH. Duration of their VAD implants prior to OHT were 4, 14, and 31 months. Survivorship from OHT is 3, 10, and 25 months. The progression free survivorship, free of HLH, from the time of initial therapy for HLH in the three OHT patients is 16, 28, and 38 months. The incidence of HLH is 2.4% for patients who did not have symptoms of HLH prior to VAD. We conclude that HLH is one cause of persistent fevers following VAD insertion. Prior HLH did not preclude successful OHT, and HLH has not recurred at a median of 28 months from HLH diagnosis. DisclosuresNo relevant conflicts of interest to declare.

SilTech: A New Approach to Treat Aerobic Vaginitis

Background: The aerobic vaginitis (AV) is characterized by increased levels of aerobic bacteria, vaginal inflammation and depressed levels of lactobacilli. Objective: The purpose of this study was to investigate the therapeutic efficacy of SilTechTM vaginal softgel capsules, containing new microcrystals of silver monovalent ions, for aerobic vaginitis (AV). Methods: This prospective study enrolled 32 women diagnosed with AV. All recruited women were treated with SilTechTM vaginal softgel capsules once daily for 7 days (one course). Therapeutic efficacy was evaluated based on clinical and microscopic criteria, and cure rates were calculated. Women who were improved (but not cured) received a second course of therapy. Patients classified with clinical and microscopic failure were treated using other strategies. Results: After one course of therapy, 59.2% (19/32) of women were cured, 19.0% (6/32) were improved (but not cured) and 21.8% (7/32) failed to respond to the therapy. After two courses of therapy, clinical improvement was achieved in additional two women. The therapy was very well tolerated, and during the entire study no drop out related to the SylTechTM vaginal capsules treatment was observed; only two patients (6.2%) experienced a mild transient burning after application. Conclusion: SylTechTM vaginal capsules is an effective therapeutic option for patients with AV, and most women with AV were cured with one course of therapy.

Meglumine antimoniate is more effective than sodium stibogluconate in the treatment of cutaneous leishmaniasis

Sodium stibogluconate (SSG, Pentostam) and meglumine antimoniate (MA, Glucantime) are two antimonials that are widely used to treat cutaneous leishmaniasis (CL), but the relative efficacies of these treatments are not clear. The aim of this study is to compare the efficacy of intralesional SSG with intralesional MA therapy in the treatment of CL. One month after completion of the therapy, 1431 of 1728 patients (82%) who received intralesional MA showed complete clinical cure compared to 1157 of 1728 patients (67%) in the SSG group. Patients who did not respond to the first round of therapy were re-administered the same treatment but with twice weekly injections. Following completion of the second course of therapy, 237 of 297 patients (80%) in the MA group and 407 of 561 patients (72%) in the SSG group healed their lesions by 1-month post-treatment. At both times, the differences in cure rates between MA and SSG groups were statistically significant (p < 0.05). Cure rates in the MA group were always significantly higher than SSG groups irrespective of other parameters including age, gender, lesion site and type of lesion. Intralesional MA is more effective than intralesional SSG in the treatment of CL.

A Phase I Dose-Finding Trial of Recombinant Interleukin-21 and Rituximab in Relapsed and Refractory Low Grade B-cell Lymphoproliferative Disorders

We conducted a phase I study to determine the safety, maximum-tolerated dose (MTD), and efficacy of weekly bolus recombinant human interleukin-21 (rIL-21) plus rituximab in patients with indolent B-cell malignancies. One week after a lead-in rituximab dose, cohorts of three patients were treated with 30, 100, or 150 μg/kg rIL-21 weekly for four weeks, concurrent with four weekly doses of rituximab. Patients with stable disease or better were eligible for a second course of therapy. Twenty-one patients with relapsed small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL, n = 11), follicular lymphoma (n = 9), or marginal zone lymphoma (n = 1) were enrolled, with 19 completing at least one course of therapy. The MTD for rIL-21 was 100 μg/kg, based on observed toxicities including nausea, vomiting, diarrhea, hypotension, edema, and hypophosphatemia. Clinical responses were seen in 8 of 19 evaluable patients (42%; 3 CR/CRu, 5 PR), with 4 of longer duration than the patient's previous response to rituximab-based treatment (median 9 months vs. 3 months). Outpatient therapy of indolent B-cell malignancies with rituximab and weekly rIL-21 was well tolerated and clinically active, with durable complete remissions in a small subset of patients. Additional studies of rIL-21 and anti-CD20 antibodies in lymphoma and SLL/CLL are warranted.

PROSPECTIVE EVALUATION OF A 5 × 4 Gy PRESCRIPTION FOR PALLIATION OF CANINE NASAL TUMORS

We evaluated the efficacy of palliative radiation therapy using 5 × 4 Gy given daily in 18 dogs with nasal tumors. Dogs with malignant nasal tumors were evaluated for response rate, response duration, and survival. Seventy-eight percent of the dogs achieved complete resolution of clinical signs, and 16.5% had partial resolution of their signs. Overall median response duration for all dogs was 178 days after one course of radiation therapy. Six dogs received a second course of therapy when their disease progressed using the same daily 5 × 4 Gy scheme, and all six responded for a median time of 129.5 days for an overall median survival time in these six dogs of 309 days. Based on these results, a radiation prescription of 5 × 4 Gy appears to be useful palliatively in dogs with a malignant nasal tumor.

Flow Cytometric Assessment of Post Induction Response In Patients with Sub-Optimal Morphologic Response to Induction Chemotherapy- A Report From the Children's Oncology Group AML Protocol AAML0531

AbstractAbstract 2740Initial response to induction chemotherapy is a significant predictor of outcome in leukemias. Data from MRC10 AML trial demonstrated that patients (pts) with ≤15% blasts at the end of induction I (EOI1), as determined by morphologic analysis, had a similar outcome as those in morphologic complete remission (mCR, <5% blasts), whereas those with >15% blasts have a significantly diminished survival. The COG Phase III AML protocol AAML0531 has enrolled 968 eligible pts with de novo AML as of March 31, 2010. Those with >15% blasts by morphologic assessment (persistent disease, mPD) at EOI1 are considered a high-risk cohort; those with 5% to 15% blasts (partial remission, mPR) were included in the standard-risk group. As part of AAML0531, pts choose to enroll on a biology study to evaluate treatment response by multidimensional flow cytometry (MDF) after 2 courses of therapy (EOI1 and EOI2). Here we directly compared the morphologic bone marrow (BM) response at EOI1 in pts with mPR or mPD with that assessed by MDF and correlated the remission status at EOI1 to the mCR rate at EOI2. Of the 900 pts with evaluable response data at EOI1, 628 (70%) entered mCR; 104 (12%) had mPR; 126 (14%) had mPD; and 42 (5%) either died (n=19) or had refractory CNS AML (n=23). All pts, regardless of their blast %, were eligible to receive the second course of induction chemotherapy per protocol. Of those with mPD at EOI1 and evaluable data by EOI2, 65 (59%) entered mCR; 1 died; and 44 (40%) had mPD. At EOI1, 180 pts did not enter mCR (80 had mPR, and 100 had mPD). MDF evaluation of those 180 BM specimens showed that 74 (41%) had no evidence of disease by MDF at EOI1. Of those 74 pts, 69 (93%) entered mCR at EOI2. In contrast, mCR at EOI2 for those with any level of disease by MDF at EOI1 was 49% (p<0.001). When a blast threshold of 5% by MDF at EOI1 was used to correlate with EOI2 response, those with 0.5% to 4.9% blasts at EOI1 had an EOI2 mCR rate of 68% compared to 41% in those with >5% blasts by MDF (p=0.013). Because they are in different risk groups, pts with mPR and those with mPD were evaluated separately for the presence of disease by MDF. Median blast % in pts with mPR was 7% (range 5%-15%). Of the 76 pts with mPR at EOI1 with an evaluable EOI2 response, 19 (25%) did not enter mCR at EOI2. At EOI1, morphologic BM response was compared to that by MDF. Of the 80 pts in mPR at EOI1, 43 (54%) had no evidence of AML by MDF; 17 (21%) had <5% blasts; and 7 (9%) in mPR had >15%. In pts in mPR who did not have AML by MDF (n=43), 39 had remission status available by EOI2: 34 (87%) entered mCR, and 5 (13%) had refractory disease (>5% blasts). Of the latter 5 patients, 4 had no evidence of disease by MDF. We subsequently evaluated BM status of the pts with PD by MDF at EOI1 and EOI2. Of those with mPD at EOI1, 62% entered mCR at EOI2. Of the 100 pts with mPD at EOI1 and MDF data for response evaluation, 31 had no evidence of disease by MDF, and all 25 with evaluable response by EOI2 entered mCR. In the remaining 69 pts, the presence of AML by MDF ranged from 0.05% to 95% (median 22%). Patients with mPD at EOI1 with any level of disease by MDF had a mCR rate of 41% at EOI2. Of the 16 pts with mPD and 0.5% to 4.9% blasts by MDF at EOI1, 14 had an evaluable EOI2 response: 11 (79%) entered mCR; 2 (18%) experienced treatment failure at EOI1; and 1 suffered extramedullary relapse. When the EOI1 evaluation was limited to the 53 patients with '5% blasts by MDF, the mCR rate at EOI2 was 30%. This study demonstrates a substantial discrepancy between morphologic and MDF assessments of induction BM specimens and highlights the need to implement MDF for accurate evaluation of remission status. We further demonstrate that a blast threshold of 5% by MDF at EOI1 may be an accurate predictor of response to the second course of therapy. Disclosures:No relevant conflicts of interest to declare.

Persistence Patterns with Oral Antidiabetes Drug Treatment in Newly Treated Patients—A Population-Based Study

Objective We assessed persistence patterns with oral antidiabetes drug (OAD) in patients newly dispensed with different OAD classes. Methods We conducted a population-based cohort study using Quebec Health Insurance Board data. Patients aged 18 years or more newly dispensed an OAD between January 1, 1998 and December 31, 2003 were included in the study (n = 98,940). Persistence was defined as consistently refilling a prescription for the initial OAD within three times the days' supply of the preceding claim. For nonpersistent patients, a second course of therapy was defined as treatment initiation with any OAD after a first discontinuation. Patients were followed from treatment initiation up to December 31, 2004, ineligibility for the drug plan or death, whichever came first, and treatment discontinuation or second course of treatment. Cox regression models were used to compute adjusted hazards ratios (AHR) of persistence and initiation of second courses of therapy. Results The probability of persisting with the initial OAD over a 12-month period was 65% and 56% for patients initiated on metformin and sylfonylurea, respectively. Compared to metformin, the likelihood of discontinuing the initial OAD over the study period was significantly higher for patients on sulphonylureas (AHR: 1.32; 95% CI 1.29–1.34). Patients started on sulphonylureas were also less likely to start a second course of therapy after a first treatment discontinuation (AHR: 0.91; 95% CI 0.89–0.93). Conclusions Compared to diabetic patients initiated on metformin, those initiated on sulphonylureas displayed poorer persistence patterns.

P100 Primary cutaneous peripheral T-cell lymphoma, unspecified: a case report

Introduction Primary cutaneous T-cell lymphomas (PCTCLs) represent 76,9% of all primary cutaneous lymphomas. MF/Sezary and CD30+ T cell lymphoproliferative disorders are the most common, while the histological entity of PTCL unspecified (NOS) represents<10% of all CTCLs [1–4]. Case history A 44-year-old male patient presented to our department with several (up to 10) asymptomatic, isolated, sharply demarcated violet red nodules on trunk, extremities, as well as, on his face, and neck. The lesions were generally oval and ranged size from 1 to 4 cm in diameter. According to the patient, the skin lesions appeared on his face 9 months ago, and become multiple and more generalized. Initial skin biopsy was consistent with the diagnosis of pseudo-T-cell lymphoma. Three months later, a new skin biopsy was performed due to progression of the disease, and the diagnosis of peripheral T cell lymphoma unspecified was reached. Histological examination revealed diffuse infiltration of dermis with medium and large size lymphoid cells. Immunophenotypic analysis showed expression of the following markers: CD3+, CD4+, CD43+, while there was no expression of CD30. Ki67 was expressed on 60–70% at large lymphoid cells. Tissue clonality studied by PCR detected positive TCR rearrangement. Physical examination, complete blood cell counts, computed tomography of chest and abdomen and bone marrow aspirate failed to demonstrate extracutaneous disease. After all the adequate staging procedures the diagnosis of a primary cutaneous peripheral T cell lymphoma unspecified was established. The patient was treated with combined chemotherapy (cycloposphamide, Mitoxantron, Vincristine, and Prednisolone). Complete remission of skin lesions was achieved after the second course of therapy. Discussion Most patients with unspecified PTL presented with nodular or tumorous skin lesions, solitary, localized or multifocal [1]. The duration of skin lesions prior to diagnosis varied between 1 and 100 months (median 6 months) [1] Therapy consists in most cases of Doxorubicin-based chemotherapy (CHOP or CHOP-like), radiotherapy, or a combination of both. Complete remission can be achieved but are generally short-lived, requiring additional multiagent chemotherapy soon afterward. Prognosis is poor, with a 5-year survival rate of<20%. Conclusion PTCLs unspecified, presenting in the skin are rare and have an unfavorable prognosis. It is fair to conclude that it is as yet unknown how such patients with a PTL unspecified, can best be treated. Because of the inefficacy of current standard regimens, new therapies should be investigated.

Comparison of different biologic agents in patients with rheumatoid arthritis after failure of the first biologic therapy

Switching between different biologic agents for the treatment of rheumatoid arthritis has become a common practice even within similar substance groups. This longitudinal observational study was performed to follow the therapeutic management of patients with rheumatoid arthritis who were switched from one biologic therapy to another. We found no differences between the different biologic agents in regard to drug survival respectively efficacy, neither in the first nor in the second course of therapy. The reason to switch (side effect, lack of efficacy or loss of efficacy) did not influence the following treatment, although a lack of efficacy showed the shortest drug survival in the subsequent therapy. In conclusion, while switching between different biologic substances in rheumatoid arthritis is feasible and reasonable, the choice of substance has to be made on an individual basis.