Successful Treatment Response Research Articles

Risk Factors for Delayed Recurrence of Clostridium difficile Infection.

Clostridium difficile (C. difficile) is an anaerobic, gram-positive, spore-forming bacterium, and C. difficile infection (CDI) is a common cause of infectious diarrhea and pseudomembranous colitis. The incidence of CDI is increasing worldwide, most likely as a result of the increased use of antibiotics, and the subsequent emergence of hypervirulent strains.1 In Western countries, the incidence and severity of CDI are also increasing.2 Furthermore, recent reports suggest that in Asian countries, C. difficile is more prevalent than previously thought, and that the incidence of CDI is also increasing significantly in Korea.3,4 Recurrent CDI occurs either due to relapse (persistence of the same strain of C. difficile) or reinfection (acquisition of a new strain of C. difficile). The impact of recurrent CDI is significant because it influences the length of hospitalization and the cost of treatment.5 In a Canadian study of hospitalized patients, the independent predictors of recurrent CDI were found to be old age, acquisition of CDI during a hospital stay, and length of hospital stay.6 In a recent meta-analysis conducted by Garey et al., continued use of antibiotics after diagnosis, concomitant antacid medication, and old age were significant predictors of recurrent CDI.7 The risk factors associated with recurrent CDI have been investigated in some studies conducted in Korea.8,9,10 In a study by Kim et al., of 125 patients that developed C. difficile-associated diarrhea, 27 patients (21.6%) experienced one or more recurrence, and the risk factors for the CDI recurrence were identified as advanced age (over 65 years), a serum albumin level below 2.5 g/dL, and concurrent use of proton pump inhibitors.8 Jung et al. suggested that a history of surgery is a predictor of recurrence after metronidazole treatment of CDI.9 In a study by Ryu et al., patients who received tube feeding were at an increased risk of recurrent CDI.10 However, in these studies, the recurrence of CDI was evaluated only between weeks and 90 days only. In the present study,11 the authors investigated the long-term clinical outcomes of CDI in hospitalized patients in a single center. The authors evaluated delayed CDI recurrence after eight weeks of successful treatment response. The predictive factors associated with delayed CDI recurrence were tube feeding, and the use of anti-gastric acid medications. Tube feeding is a known risk factor for CDI because it can act as a transmission factor for C. difficile. Aseptic control of the feeding tube may aid in reducing contamination, and therefore preventing CDI. Another important result of this study is the mortality rate of patients with CDI. Although no deaths were attributed to CDI, the results of this study suggest that CDI may predict the poor prognosis of underlying diseases. As the authors mentioned, this study was limited in that it was retrospective, performed in a single center, and the hypervirulent strain was not evaluated appropriately. Another weak point of this study is that antacid medication history was not clearly defined. It would have been better if the authors had clarified the temporal relationship between antacid exposure and the development of diarrheal symptoms. In conclusion, risk factors for delayed recurrence of CDI were identified in the present paper. This study suggests that more sanitary manipulation of feeding tubes may prevent the recurrence of CDI. Further prospective studies with a large number of patients are needed to more accurately elucidate the factors associated with recurrent CDI.

Resting-State Cortico-Thalamic-Striatal Connectivity Predicts Response to Dorsomedial Prefrontal rTMS in Major Depressive Disorder

Despite its high toll on society, there has been little recent improvement in treatment efficacy for major depressive disorder (MDD). The identification of biological markers of successful treatment response may allow for more personalized and effective treatment. Here we investigate whether resting-state functional connectivity predicted response to treatment with repetitive transcranial magnetic stimulation (rTMS) to dorsomedial prefrontal cortex (dmPFC). Twenty-five individuals with treatment-refractory MDD underwent a 4-week course of dmPFC-rTMS. Before and after treatment, subjects received resting-state functional MRI scans and assessments of depressive symptoms using the Hamilton Depresssion Rating Scale (HAMD17). We found that higher baseline cortico-cortical connectivity (dmPFC-subgenual cingulate and subgenual cingulate to dorsolateral PFC) and lower cortico-thalamic, cortico-striatal, and cortico-limbic connectivity were associated with better treatment outcomes. We also investigated how changes in connectivity over the course of treatment related to improvements in HAMD17 scores. We found that successful treatment was associated with increased dmPFC-thalamic connectivity and decreased subgenual cingulate cortex-caudate connectivity, Our findings provide insight into which individuals might respond to rTMS treatment and the mechanisms through which these treatments work.

P 187. Tinnitus-related neuroplastic alterations in the motor cortex

Introduction Chronic tinnitus is a brain network disorder with involvement of auditory and non-auditory areas motivating the clinical use of repetitive transcranial magnetic stimulation (rTMS). Several small studies indicated that motor cortex excitability is altered in tinnitus. Furthermore, motor cortex excitability was changed according to treatment response of rTMS of auditory cortex. Objectives Here, we aimed to investigate motor cortex excitability before and after rTMS of auditory cortex. Materials and methods We investigated 231 patients with chronic tinnitus and 120 healthy controls in a retrospective manner pooling data from different studies. Variables of interest were resting motor threshold (RMT), short-interval intra-cortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). 118 patients were tested twice-at the first and last day of treatment with temporal oriented rTMS. Treatment response was defined as five-point change in tinnitus questionnaire. Results Tinnitus was associated with increased motor inhibition (SICI, CSP) and facilitation (ICF). Successful treatment response was associated with normalisation of increased SICI. Conclusion Our data suggest that altered SICI may reflect a state parameter, whereas CSP and ICF may rather mirror a trait-like predisposing factor of tinnitus.

An Adolescent With Nonsuicidal Self-Injury: A Case and Discussion of Neurobiological Research on Emotion Regulation

The management of nonsuicidal self-injurious behavior is a common focus of clinical care, particularly in the treatment of adolescents and young adults. Increased recognition of this problem has led to proposed criteria for future study in DSM-5, which may be beneficial in advancing the field. Clinical care may be fruitfully informed by an understanding of the neurodevelopmental underpinnings of this behavior. The authors discuss the current status of neurobiological research related to nonsuicidal self-injury with a focus on the key dimension of emotion regulation. A case is presented to illustrate the critical points. Preliminary empirical evidence suggests disturbances in neurobiological systems relevant to emotion regulation. Disturbances involve engagement of limbic brain regions and frontal regulatory brain regions that may evolve over time. Additionally, disturbances are observed in serotonin and physiological response systems relevant to emotion regulation. Treatment with serotonin reuptake inhibitors may be most beneficial in combination with dialectical behavioral therapy to address safety, build self-soothing strategies to enhance emotion regulation, and reduce interpersonal sensitivity. Delineation of the neurobiological markers that reflect successful treatment response will help in the identification of new avenues for research and the development of personalized treatments for adolescents with nonsuicidal self-injury.

The effects of statins on the clinical outcomes ofClostridium difficileinfection in hospitalised patients

An association between exposure to statin drugs and favourable treatment outcomes for various types of infections has been established.To determine the clinical characteristics and treatment outcomes of Clostridium difficile infection (CDI) among hospitalised patients taking statin drugs.The medical records were reviewed for consecutive in-patients with CDI confirmed by positive toxin assay (A or B), C. difficile culture, or the presence of pseudomembrane on endoscopy. Treatment success was defined as the resolution of diarrhoea within 6 days of therapy. The primary end points were assessed by average symptom recovery time and treatment response (success or failure).Among 949 patients, the overall response to metronidazole was 91.9%. The baseline characteristics showed some differences between statin users and statin non-users with respect to mean disease severity score. In the multivariate analysis, successful treatment response was significantly associated with the absence of exposure to proton pump inhibitors (PPIs) (OR = 0.690, 95% CI = 0.513-0.929, P = 0.014) and with exposure to statins (OR = 1.449, 95% CI = 1.015-2.070, P = 0.041). Contrary to the treatment response, univariate and multivariate analyses failed to show that exposure to PPIs or statins affected symptom recovery times. Sixty-day CDI recurrence rates for those patients with statin exposure were significantly lower compared with those patients without statin exposure (3% vs. 7.3%, respectively; RR = 0.393, 95% CI = 0.167-0.926, P = 0.033).Prior statin exposure in patients with C. difficile infection is associated with a successful response to treatment.

AB0458 Anti-tumor necrosis factor-alpha therapy in refractory behçet uveitis: a single center experience

ObjectivesTo evaluate the efficacy and safety of anti-tumor necrosis factor-alpha (anti-TNF-α) agents including infliximab (IFX) and adalimumab (ADA) in the treatment of refractory Behcet uveitis.MethodsThis retrospective study included 12 cases...

Clinical trial risk reduction in non-small cell lung cancer though the use of biomarkers and receptor-targeted therapies.

8040 Background: We analyzed the risk of clinical trial failure duringnon-small cell lung cancer (NSCLC) drug development between 1998 and 2012. Methods: NSCLC drug development was investigated using trial disclosures from publically available resources. Compounds were excluded from the analysis if they began phase I clinical testing before 1998 and if they did not use treatment relevant endpoints. Analysis was conducted in regards to treatment indication, compound classification and mechanism of action. Costs of clinical drug development for advanced NSCLC were calculated using industry data and assumptions, a 9% yearly discount rate and assuming a clinical trial length of 2.5 years for phase I trials, 4 years for phase II trials, 5 years for phase III trials and an average of 5 phase I trials, 7 phase II trials, and 4 phase III trials per approved drug. All funding costs are in US dollars (USD). Results: 2,407 clinical trials met search criteria. 676 trials and 199 unique compounds met our inclusion criteria. The likelihood, or cumulative clinical trial success rate, that a new drug would pass all phases of clinical testing and be approved was found to be 11%, which is less than the expected industry aggregate rates (16.5%). The success of phase III trials was found to be the biggest obstacle for drug approval with a success rate of only 28%. Biomarker-guided targeted therapies (with a success rate of 62%) and receptor targeted therapies (with a success rate of 31%) were found to have the highest likelihood of success in clinical trials. The risk-adjusted cost for NSCLC clinical drug development was calculated to be 1.89 billion US dollars. Use of biomarkers decreased drug development cost by 26% to 1.4 billion US dollars. Potential savings may be even higher if fewer clinical trials are required for successful development. Conclusions: Physicians that enroll patients in NSCLC trials should prioritize their participation in clinical trial programs that involve either a biomarker or receptor targeted therapy, which appear to carry the best chances for a successful treatment response. Given the high adjusted cost of clinical testing alone in NSCLC, efforts to mitigate the risk of trial failure need to explore these factors more fully.

The tryptophan hydroxylase 2 (Tph2) polymorphism C2432T mediates mRNA expression and responses to antidepressant treatment in a sex‐specific manner

The mechanisms behind successful treatment response in Major Depressive Disorder remain unclear. We examined whether a novel single nucleotide polymorphism (SNP) C2432T in the Tph2 gene mediates differences in response to SSRIs between two mouse strains: MRL/MpJ (MRL; SSRI‐responding, T/T) versus C57Bl/6J (C57; SSRI‐nonresponding, C/C) (Balu et al, 2009). We cross‐bred the MRL and C57 strains to isolate C2432T in the F2 generation and determined functionality using the response to SSRIs in the tail suspension test (TST). F2 T/T females showed an enhanced citalopram response (p<0.001, n=10), while males showed no genotype‐specific effects. The C2432T SNP also mediated Tph2 mRNA expression, with T/T animals showing increased expression in the midbrain (p<0.05, n=11–16). However, in response to chronic SSRI treatment, there was no difference by genotype in F2 generation animals in measures of hippocampal neurogenesis or novelty‐induced hypophagia behavior. The C2432T SNP may mediate serotonin involvement to acute antidepressant response in a sex‐specific manner, but did not mediate the effects of chronic antidepressant treatment.

Effectiveness of Coadministration of Varenicline, Bupropion, and Serotonin Reuptake Inhibitors in a Smoking Cessation Program in the Real-Life Setting

Varenicline has a significant impact on the ability to quit smoking. However, patients may have side effects similar to nicotine withdrawal symptoms. The aim of this study was to evaluate the effectiveness of varenicline in monotherapy or in combined therapy with bupropion and/or serotonin reuptake inhibitors (SRIs) in a specific cardiovascular smoking cessation service. It is an outcome research of 427 patients that received varenicline monotherapy or combined pharmacotherapy and were followed for 52 weeks. Patients were oriented to take varenicline until week 12. During each medical visit, the patients were evaluated and in the cases of mood changes after varenicline use, SRIs were prescribed. Bupropion was combined in patients that did not achieve complete tobacco abstinence in 2 or 3 weeks after starting varenicline use or if the patient presented uncomfortable abstinent symptoms. The success (continuous abstinence rate in 52 weeks) in different drug regimens were: varenicline monotherapy (32.1%), varenicline + bupropion (55.0%), varenicline + SRI (50.6%), and varenicline + bupropion + SRI (57.7%). In a multivariate analysis of successful treatment predictors, compared with varenicline monotherapy, patients who used bupropion + SRI adjuvant treatment had an odds ratio (OR) of 5.05 (1.99-12.80) for a successful treatment response after 1-year follow-up, while patients who used bupropion or SRI had OR of 3.21 (1.68-6.14) and 3.58 (1.98-6.48), respectively. Our results suggest that adjuvant treatment to varenicline therapy may be associated with improved success in smoking cessation, especially in patients with nicotine withdrawal symptoms. These results should be tested in randomized controlled trials.

Urgent‐SQ implant in treatment of overactive bladder syndrome: 9‐year follow‐up study

Electrical stimulation of the posterior tibial nerve (PTN) is an established therapy for the treatment of refractory overactive bladder syndrome (OAB). The Urgent-SQ™ is an implant that is surgically placed near the PTN and activated by an external pulse generator, allowing for "on demand" PTN stimulation, without the need for needle insertion. The current study presents results of a 9-year, open-label, follow-up of eight patients to address the long term safety and efficacy of the implant. In 2003, eight patients with refractory OAB received a Urgent-SQ™ implant and were systematically followed up for 1 year. After that, the follow up continued as open-label study. The seven patients who still had the implant were contacted after 9 years and evaluated with an interview, physical exam, ankle X-ray, voiding diaries, and completed questionnaires about adverse events, performance, efficacy, safety, and quality of life (validated iQoL). Six of the seven patients still had sensory and loco-motor responses on stimulation at 9-year follow-up. Three of four patients who had a successful treatment response at 1 year, still use the device. The fourth patient restarted therapy. The implants are intact with no migration and/or displacement. All patients reported easy handling of the Urgent-SQ™. One patient reported sporadic spontaneous sensory responses. One patient reported occasional localized ankle discomfort. After 9 years of clinical experience, we demonstrated that implant driven PTNS with the Urgent-SQ™ is a safe therapy for OAB. The implant has a long lifespan and is well tolerated by patients.

Detectable Changes in The Blood Transcriptome Are Present after Two Weeks of Antituberculosis Therapy

RationaleGlobally there are approximately 9 million new active tuberculosis cases and 1.4 million deaths annually. Effective antituberculosis treatment monitoring is difficult as there are no existing biomarkers of poor adherence or inadequate treatment earlier than 2 months after treatment initiation. Inadequate treatment leads to worsening disease, disease transmission and drug resistance.ObjectivesTo determine if blood transcriptional signatures change in response to antituberculosis treatment and could act as early biomarkers of a successful response.MethodsBlood transcriptional profiles of untreated active tuberculosis patients in South Africa were analysed before, during (2 weeks and 2 months), at the end of (6 months) and after (12 months) antituberculosis treatment, and compared to individuals with latent tuberculosis. An active-tuberculosis transcriptional signature and a specific treatment-response transcriptional signature were derived. The specific treatment response transcriptional signature was tested in two independent cohorts. Two quantitative scoring algorithms were applied to measure the changes in the transcriptional response. The most significantly represented pathways were determined using Ingenuity Pathway Analysis.ResultsAn active tuberculosis 664-transcript signature and a treatment specific 320-transcript signature significantly diminished after 2 weeks of treatment in all cohorts, and continued to diminish until 6 months. The transcriptional response to treatment could be individually measured in each patient.ConclusionsSignificant changes in the transcriptional signatures measured by blood tests were readily detectable just 2 weeks after treatment initiation. These findings suggest that blood transcriptional signatures could be used as early surrogate biomarkers of successful treatment response.

Familial Mediterranean fever without cardinal symptoms and role of genetic screening

Familial Mediterranean fever is an autosomal recessive disorder characterized by paroxysmal episodes of fever and serosal inflammation. The classical presentation is fever and severe recurrent abdominal pain due to serositis that lasts for one to three days and the resolves spontaneously. Between the episodes patients are asymptomatic. Ninety-five percent of patients with familial mediterranean fever have painful episodes localized to the abdomen, which is usually the dominant manifestation of the disease. Herein, we present a case of 34-year-old man with incomplete abdominal pain episode of familial mediterranean fever limited to the epigastrum and had no cardinals symptoms of this disease. The diagnosis was made by genetic screening. Successful treatment response was achieved by colchicine.

Scleritis Therapy

To delineate factors associated with a successful response to treatment in patients with various manifestations of scleritis. Retrospective case series. A total of 392 patients with noninfectious anterior scleritis. We reviewed the electronic health records of 392 patients with noninfectious anterior scleritis seen at 2 tertiary referral centers and studied the factors associated with successful treatment. Patient characteristics (age, sex); ocular disease characteristics (laterality, type of scleritis, degree of scleral inflammation, ocular complications, delay in presentation, and follow-up period), systemic disease association (associated disease, potentially lethal associated disease); and anti-inflammatory and immunosuppressive medications were studied in patients with scleritis. Successful treatment response to nonsteroidal anti-inflammatory drugs (NSAIDs), steroidal anti-inflammatory drugs (SAIDs), immunosuppressive therapy drugs (immunomodulatory therapy [IMT]), or biologic response modifiers (BRMs) was assessed. Treatment of 392 patients with noninfectious anterior scleritis included NSAIDs in 144 (36.7%), SAIDs in 29 (7.4%), IMT in 149 (38.0%), BRMs in 56 (14.3%), and none (N = 14). Successful response to treatment with NSAIDs was associated with idiopathic diffuse or nodular scleritis with a low degree of scleral inflammation (≤ 2+) (odds ratio [OR] = 2.89, P < 0.001) and with idiopathic diffuse or nodular scleritis without ocular complications (OR = 3.13, P < 0.001). Successful treatment with SAIDs was associated with idiopathic diffuse or nodular scleritis with a high degree of scleral inflammation (>2+) (OR = 4.70, P = 0.001). Successful treatment with IMT was associated with diffuse or nodular scleritis with associated systemic disease (OR = 1.57, P = 0.047), mainly potentially lethal (OR = 17.41, P=0.007), and necrotizing scleritis (OR = 4.73, P = 0.026). Successful treatment with BRMs was associated with diffuse or nodular scleritis with associated systemic disease (OR = 3.15, P < 0.001). This study did not require institutional review board approval because the information does not contain any subject identifiers. Patients with idiopathic diffuse or nodular scleritis with a low degree of scleral inflammation or without ocular complications may respond to NSAIDs. Patients with idiopathic diffuse or nodular scleritis with a high degree of scleral inflammation may respond to SAIDs. Patients with diffuse or nodular scleritis with associated systemic disease may respond to IMT or BRMs. Patients with necrotizing scleritis may respond to IMT, mainly alkylating agents. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Continuing pursuit for ideal systemic anticancer radiotherapeutics

Cancer is one of the major causes of death for non-transmissible chronic diseases worldwide. Conventional treatments including surgery, chemotherapy and external beam radiotherapy are generally far from curative. Complementary therapies are attempted for achieving more successful treatment response. Systemic targeted radiotherapy (STR) is a radiotherapeutic modality based on systemic administration of radioactive agents for selectively delivering high doses of energy to destroy cancer cells. For this purpose, diverse tumour-target specific agents including monoclonal antibodies (MoAb), MoAb fragments and peptides have been tested and some of them have already got FDA approval for clinical use. However, MoAbs and their tailored analogues have shown non-homogeneous tumour distribution, limited diffusion, insufficient intratumoral accumulation and retention, unwanted uptake in normal tissues and scarcity of identified cancer antigens for generating new MoAbs. Similarly, peptides have also exhibited retention in normal organs, lacks of favourable membrane permeability or drug cell internalization and short-term residence in cancer cells. Recently, a new category of target-specific agent with strong affinity for necrosis has emerged as an excellent option for developing targeted radiotherapeutic agents to be used after necrosis-inducing treatments (NITs). The combination of their high, specific and long-term accumulation and retention at necrotic sites with the crossfire effect of ionizing particle-emitters allows irradiating adjacent residual viable tumour cells during a prolonged period of time. It may considerably enhance the therapeutic response and open a new horizon for improved cancer treatability or curability.

An observational efficacy and safety analysis of the treatment of acute invasive aspergillosis using voriconazole

The purpose of this study was to evaluate efficacy and safety of voriconazole in patients with acute invasive aspergillosis (IA) in a real-life, clinical setting. This was a multicenter observational study in adult patients treated with voriconazole for invasive mycosis. The study evaluated clinical response, mortality, use of other licensed antifungal therapy (OLAT), and treatment duration. This sub-analysis evaluated treatment and outcome data specifically from adult patients with proven/probable IA, while safety data were assessed in patients with proven/probable/possible IA. Of the 141 patients enrolled, 113 were adults with proven/probable IA and six had possible IA. Voriconazole treatment duration ranged from 1 to 183 days (median, 49.5 days). Voriconazole was used exclusively in 64% (72/113) of patients and in combination/sequentially with OLAT in 36%. Overall successful treatment response was 50% (57/113 patients). Twelve percent (14/113) of patients were switched to OLAT, either because of insufficient response (four patients) or for safety reasons (10 patients). Overall and attributable (entirely or partially due to fungal infection) mortality rates were 52% (59/113) and 17%, respectively. Treatment-related adverse events were reported for 18% (22/119) of patients. This observational study confirms the results of previous clinical trials demonstrating voriconazole as an effective and safe agent for treatment of confirmed acute IA.

Treatment of schizophrenia with electroconvulsive therapy

The treatment of schizophrenia, using convulsive therapy dates back several decades. The treatment was used extensively in the early years and then almost forgotten. In the past few decades it has a renaissance. Careful selection of the potential candidate is of importance in achieving a successful treatment response. The different indications for ECT treatment are discussed and the optimal ECT technique is described.

Generalized Morphea after Breast Cancer Radiation Therapy

We present a case of a 69-year-old woman who received external beam radiation for the treatment of breast cancer. Seven months later, she developed generalized morphea involving the area of irradiated skin of the breast as well as distant sites of the groin and distal lower extremity. Postirradiation morphea is an uncommon yet well-documented phenomenon, usually confined to the radiated site and the immediate surrounding tissue. To our knowledge, this is only the fourth reported case of morphea occurring distant from the radiation field. While most cases of postirradiation morphea have been shown to either resolve spontaneously or respond to topical corticosteroids, our patient required systemic therapy with methotrexate, which resulted in clinical improvement. With this paper, we hope to bring further awareness to this phenomenon and demonstrate a successful treatment response with the use of methotrexate in postirradiation generalized morphea.

Abstract CN01-02: Detecting tumor responses to treatment using magnetic resonance imaging and spectroscopy

Abstract CN01-02: Detecting tumor responses to treatment using magnetic resonance imaging and spectroscopy

Comparison of low-dose deferoxamine versus standard-dose deferoxamine for treatment of aluminium overload among haemodialysis patients

Patients on maintenance haemodialysis are at high risk of aluminium overload. While deferoxamine (DFO) has potential adverse effects, lower DFO dosages may afford good efficacy with fewer side effects. We evaluated the therapeutic response of low-dose (2.5 mg/kg/week) DFO among haemodialysis patients with aluminium overload. We recruited the participants via basal predialysis serum aluminium (Al) levels of >or=20 microg/L with clinical suspicion of aluminium toxicity or hyperparathyroidism indicating parathyroidectomy and positive DFO tests. Patients were randomly divided into standard-dose (5 mg/kg/week) and low-dose (2.5 mg/kg/week) groups. We compared the differences of mineral biochemical and haematological parameters before and after DFO treatment. Successful treatment was defined as a serum aluminium increase of <50 microg/L by DFO test. Adverse events during DFO therapy between the groups were also compared. In total, 42 haemodialysis patients completed treatment (standard-dose group, n = 21; low-dose group, n = 21). The demographic characteristics of the groups did not differ. Serum corrected calcium and ferritin decreased in both groups, while serum total alkaline phosphatase increased in both groups. Serum phosphorus increased in low-dose group (P = 0.029), while plasma intact parathyroid hormone increased in standard-dose group (P = 0.004). The successful treatment response rates did not differ between the two groups (standard-dose: 12/21, 57% vs low-dose: 13/21, 62%; P = 0.75). Low-dose DFO may offer similar therapeutic effects as standard-dose DFO therapy.

Quantitative monitoring of cyclin D1 expression: A molecular marker for minimal residual disease monitoring and a predictor of the disease outcome in patients with mantle cell lymphoma

In mantle cell lymphoma (MCL), minimal residual disease (MRD) is an indicator of the disease outcome. Quantitative methods used so far do not provide a suitable molecular marker in 30-70% patients with MCL (depending on the technique used). We tested cyclin D1 as a marker for quantitative MRD monitoring. The real-time PCR of cyclin D1 mRNA was performed in 144 bone marrow (BM) specimens including 95 BMs from MCL patients, 39 BMs from patients with other B-cell non-Hodgkin's lymphomas and 10 BMs from healthy volunteer donors. In 73 BMs obtained from 20 MCL patients we examined the cyclin D1 level during the treatment and follow-up period. We detected a cyclin D1 overexpression exclusively in BMs infiltrated with MCL, including minimal residual infiltration. Dynamics of cyclin D1 correlated with the patient's clinical status in 69/73 BMs. Individual monitoring of patients during the disease course showed cyclin D1 quantitative changes accompanying either the disease relapse or a successful treatment response or the disease-free survival (remission) and it showed a predictive significance. Cyclin D1 detection is a promising approach for the quantitative MRD monitoring in MCL patients, and the individual monitoring of the cyclin D1 dynamics represents a suitable indicator of the disease course.