P14.91 Study glycolytic metabolism in 1H-MRS monovoxel in the most aggressive part of 62 glioblastomas before and after 18 months of treatment

Abstract BACKGROUND To study the relationship between glycolytic metabolism, tumor proliferation, survival and treatment response in patients with glioblastoma (GBM). MATERIAL AND METHODS Patients: 62 patients with glioblastoma, all having a STUPP Protocol (radiotherapy and concomitant chemotherapy), were selected and separated into 2 groups: Biopsies (30) and resections (32). In total, 269 NMR spectra (PRESS at GE 1.5T and 3T; multi-TEs TE=35ms and TE=144ms) were acquired. Processing: MRS data were processed with jMRUI software and quantitated using HLSVD and QUEST algorithms. Statistical analysis of longitudinal MRS data (every 3 months) RESULTS 1H-MRS glucose (Glc/tCr) and lactate (Lac/tCr) measurements are highly correlated before the beginning of treatment. This correlation is less obvious after 3, 6, 9 and 12 months of treatment. Proliferation is also strongly correlated with Lactate and Glucose before the beginning of treatment in both groups, whereas these correlations decrease in resected patients.The variability of ratios follow-up is higher in biopsied patients. Tumoral proliferation (tCho/tCr) and Glucose ratio (Glc/tCr) levels decreased along the follow-up. Although, the Lac/tCr ratio progressively decreased, its level remains high until 6 months. After 15 months of treatment, glucose increased although the lactate decreased. CONCLUSION The study of glycolytic metabolism in GBM could be used to evaluate the response to treatment. Being able to have a treatment response biomarker at 3 months, especially for patients who could not be resected could help to monitor and adapt treatment. The increase of Glucose at the end of the follow-up shows the interest of spectral and metabolic follow-up of glioblastoma after 18 months of treatment.

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P14.92 Study of Glutaminergic and Glutamatergic Metabolism in 1H-MRS Monovoxel in the Most Aggressive Part of 62 Glioblastoma Before and After 18 months Treatment

Neuro-Oncology ◽

10.1093/neuonc/noz126.327 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii89-iii89

Author(s):

A Heintz ◽

J Chombar ◽

S Boussida ◽

Z Saidak ◽

M Lefranc ◽

...

Keyword(s):

Nmr Spectra ◽

Response To Treatment ◽

Tumor Proliferation ◽

Progressive Decrease ◽

Concomitant Chemotherapy ◽

1H Mrs ◽

Before And After ◽

Metabolic Activities ◽

Stupp Protocol

Abstract BACKGROUND To study the relationships between glutaminergic metabolism (Glx/tCr), tumor proliferation (tCho/tCr) and other metabolic activities in patients with glioblastoma (GBM). MATERIAL AND METHODS Patients: 62 patients with glioblastoma, all having a STUPP Protocol (radiotherapy and concomitant chemotherapy), were selected and separated into 2 groups: Biopsies (30) and resections (32). In total, 269 NMR spectra (PRESS at GE 1.5T and 3T; multi-TEs TE=35ms and TE=144ms) were acquired. Processing: MRS data were processed with jMRUI software and quantitated using HLSVD and QUEST algorithms. Statistical analysis of longitudinal MRS data (every 3 months) RESULTS Glx/tCr and Lac/tCr ratios are correlated with the tumoral proliferation (tCho/tCr) before the beginning of treatment. This correlations decreases over time in biopsied and resected patients. In biopsied patients, the evolution of lactate (Lac/tCr) and Glx (Glx/tCr) ratios is similar along the follow-up with a progressive decrease in tumor proliferation (tCho/tCr). However, in resected patients, the evolution of lactate (Lac/tCr) and Glx (Glx/tCr) ratios is similar until 6 months and differ above: a progressive decrease of Lac/tCr and Glx/tCr until 18 months with a higher level of Glx/tCr. CONCLUSION Despite the difficulties to separate glutamine from glutamate (post-processing improvement is ongoing), spectroscopic measurements of Glx changes before clinical deterioration. The increase of Glx is longer (in time) than the Lactate increase after 6 months of treatment in the resected patients could be predictive of the observed increase of tumor proliferation at 12 months of treatment.The study of glutaminergic metabolism in the GBM could be used to evaluate the response to treatment. Being able to predict the increase of tumor proliferation in resected patients could allow a faster treatment adaptation.

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T119. NO DIFFERENCE BETWEEN VOLITIVE AND EXPRESSIVE NEGATIVE SYMPTOMS FOR EARLY TREATMENT RESPONSE IN FIRST EPISODE OF PSYCHOSIS ANTIPSYCHOTIC NAïVE PATIENTS

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa029.679 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S276-S276

Author(s):

Bernardo Haguiara ◽

Gabriela Koga Tonsig ◽

Simão Kagan ◽

Daniel Cavalcante ◽

Cristiano Noto ◽

...

Keyword(s):

Treatment Response ◽

Negative Symptoms ◽

Real Life ◽

First Episode ◽

Antipsychotic Treatment ◽

Social Avoidance ◽

F Test ◽

The Social ◽

Highly Correlated

Abstract Background Negative symptoms are associated with a range of poor clinical and real-life functioning outcomes in people with schizophrenia. The division of negative symptoms into two separate factors, named “expressive deficits” and “social amotivation” could enable more accurate analysis and the development of new therapeutic tools. We aim to investigate whether the different symptoms that make up the negative dimension at baseline differently predict treatment response in first episode psychosis (FEP) antipsychotic naïve patients. Methods Patients with FEP (n=80), without previous use of antipsychotics, were recruited at an emergency service in São Paulo, Brazil, between 2014 and 2019. Individuals were assessed at admission and after 10 weeks of follow-up. Patients with schizophrenia, schizoaffective disorder and schizophreniform disorder were included. The diagnosis was confirmed using the Structured Clinical Interview for DSM-IV Disorders (SCID-I). Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) at the baseline and after 10 weeks of treatment. The “expressive deficits” factor was defined as the sum of the six following items of the PANSS: N1 (blunted affect), N3 (poor rapport), N6 (lack of spontaneity and flow of conversation), G5 (mannerisms and posturing), G7 (motor retardation), G13 (disturbance of volition). The “social amotivation” factor was defined as the sum of N2 (emotional withdrawal), N4 (passive/apathetic social withdrawal) and G16 (active social avoidance). To evaluate treatment response, we used the difference between the PANSS score at baseline and after ten weeks of follow-up (delta-PANSS). We performed three linear regressions, one using the “expressive deficits” factor, one using the “social amotivation” factor and another using the total negative symptom score at baseline. Results The mean age was 26.01 years old (SD ± 7.2), and the majority was male (58.75%). “Expressive deficits” (p=0.005, R-squared=0.084, F-test=8.28, β=8.24, df=78), “social amotivation” (p=0.009, R-squared=0,072, F-test=7.14, β=5.59, df=78); and negative symptoms (p=0.002, R-squared=0.105, F-test=10.23, β=9.08, df=78) at baseline behaved similarly in relation to delta-PANSS. All measures of negative symptoms are highly correlated to PANSS total at both time points. Discussion The results were different from our initial hypothesis of worse outcome for patients with higher expressive negative symptoms. We found that negative symptoms overall and both subdomains are highly correlated to PANSS total in acute phase in early stages, what can explain the association to better outcomes with antipsychotic treatment. Longer follow-up can help us to investigate whether differences between the subdomains of negative symptoms can be observed in more stable patients.

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Local Use of Dexamethasone in the Treatment of Ocular Myasthenia Gravis

10.21203/rs.3.rs-25812/v2 ◽

2020 ◽

Author(s):

Minghua Shi ◽

Yingjia Ye ◽

Junping Zhou ◽

Aijiao Qin ◽

Jing Cheng ◽

...

Keyword(s):

Myasthenia Gravis ◽

Extraocular Muscle ◽

Direct Injection ◽

Response To Treatment ◽

Ocular Myasthenia ◽

Ocular Myasthenia Gravis ◽

Before And After ◽

Local Use ◽

Symptom Recurrence

Abstract Background: At present, patients with ocular myasthenia gravis (OMG) are typically treated with systemic drugs. We investigated the use of dexamethasone injected in the peribulbar region or extraocular muscle to treat patients with OMG. Methods: Patients with OMG were given dexamethasone via peribulbar injection or direct injection into the main paralyzed extraocular muscles, once a week, for 4-6 weeks. The severity of diplopia, blepharoptosis, eye position, and eye movement were evaluated before and after treatment. The duration of follow-up time was ≥6 months. Results: Among the 14 patients with OMG who received this treatment, mean age was 38.7 ± 29.7 years. After treatment, symptoms were relieved in 12 patients (85.7%), 1 patient (7.1%) had partial response to treatment, and 1 patient (7.1%) had no response. Two patients (14.2%) experienced symptom recurrence during the follow-up period.Conclusions: Dexamethasone peribulbar or extraocular muscle injection is effective in the treatment of patients with OMG and may replace systemic drug therapy.

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Local Use of Dexamethasone in the Treatment of Ocular Myasthenia Gravis

10.21203/rs.3.rs-25812/v3 ◽

2020 ◽

Author(s):

Minghua Shi ◽

Yingjia Ye ◽

Junping Zhou ◽

Aijiao Qin ◽

Jing Cheng ◽

...

Keyword(s):

Myasthenia Gravis ◽

Extraocular Muscle ◽

Direct Injection ◽

Response To Treatment ◽

Clinical Trial Registry ◽

Ocular Myasthenia ◽

Ocular Myasthenia Gravis ◽

Before And After ◽

Local Use

Abstract Background: At present, patients with ocular myasthenia gravis (OMG) are typically treated with systemic drugs. We investigated the use of dexamethasone injected in the peribulbar region or extraocular muscle to treat patients with OMG.Methods: Patients with OMG were given dexamethasone via peribulbar injection or direct injection into the main paralyzed extraocular muscles, once a week, for 4-6 weeks. The severity of diplopia, blepharoptosis, eye position, and eye movement were evaluated before and after treatment. The duration of follow-up time was ≥6 months.Results: Among the 14 patients with OMG who received this treatment, mean age was 38.7 ± 29.7 years. After treatment, symptoms were relieved in 12 patients (85.7%), 1 patient (7.1%) had partial response to treatment, and 1 patient (7.1%) had no response. Two patients (14.2%) experienced symptom recurrence during the follow-up period.Conclusions: Dexamethasone peribulbar or extraocular muscle injection is effective in the treatment of patients with OMG and may replace systemic drug therapy.Trial registration: Chinese Clinical Trial Registry, ChiCTR2000038863, October 7, 2020.Retrospectively registered.

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A prospective study tracking longitudinal changes in genome-wide cell-free DNA (cfDNA) methylation to identify early nonresponders to cancer treatment.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.3042 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 3042-3042

Author(s):

Andrew A. Davis ◽

Wade Thomas Iams ◽

David Chan ◽

Michael S Oh ◽

Robert William Lentz ◽

...

Keyword(s):

Predictive Value ◽

Epigenetic Modification ◽

Progression Free Survival ◽

Response To Treatment ◽

Treatment Regimens ◽

Cancer Pathogenesis ◽

Before And After ◽

The One ◽

A Prospective Study

3042 Background: Methylation is an epigenetic modification linked to cancer pathogenesis. The aim was to determine if changes in cfDNA methylation patterns before and after initiation of treatment could predict non-response to treatment prior to routine imaging and clinical follow-up. Methods: We prospectively collected clinical data and blood from 28 patients with metastatic malignancies (13 lung, 11 breast, 4 other). Blood was drawn prior to start of a new treatment, after first cycle (median 30 days), and/or second cycle (median 57 days). We performed whole-genome (WG) bisulfite sequencing (median depth 18X) on plasma cfDNA to determine methylation levels. By tracking how methylation levels deviate from unaffected individuals, from baseline to subsequent timepoints, we classified patients as either progressors (greater deviance) or non-progressors. Treatment response at first follow-up imaging (FUI) was determined by RECIST 1.1. Study endpoints were agreement with first FUI and progression-free survival (PFS) by cfDNA classification. Results: The cohort consisted of 68% females and the median age was 70. Main treatment regimens were chemo- (N = 12), immuno- (6), endocrine (5), or targeted-therapy (5). PFS was significantly shorter (log-rank p = 8 x 10-7) in patients classified as progressors by cfDNA (N = 8; median: 62 days) compared to non-progressors (N = 20, median: 263 days). For patients classified as progressors, the cfDNA assay preceded imaging and clinical evaluation by a median of 34 days. 7 out of 8 patients classified as cfDNA progressors were later confirmed to progress at first follow-up evaluation (88% positive predictive value). The one patient who was classified as progressor based on cfDNA was stable based on FUI (day 93 of treatment) but was later confirmed as progression on day 128 by FUI. For the remaining patients, 18 of 20 did not progress (90% negative predictive value). Thus, sensitivity for the assay for identifying progression was 78% and specificity was 95%. Conclusions: Our results show that WG cfDNA methylation change is a novel signature with potential to identify patients whose treatment regimen is ineffective prior to imaging.

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Imaging findings of patients undergoing SBRT for HCC after prior TACE.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.252 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 252-252

Author(s):

Aneliya Maleeva ◽

Tarita Thomas ◽

Joseph H Yacoub

Keyword(s):

Stereotactic Body Radiation Therapy ◽

Lesion Size ◽

The Other ◽

Response To Treatment ◽

Imaging Findings ◽

Inclusion Criteria ◽

Before And After ◽

Liver Sbrt ◽

Pre Treatment

252 Background: Our purpose is to assess the treatment response using follow up MRI or CT in lesions treated with stereotactic body radiation therapy (SBRT) after transarterial chemoembolization (TACE). Methods: Twenty-six patients treated with liver SBRT at our institution in the period between 2015 and 2017. Of these we included patients who had lesions diagnosed as HCC (LR-5) or probable HCC (LR-4), and who had prior TACE with a residual/recurrent enhancing component on the pre SBRT images with adequate post SBRT imaging. One radiologist (5 year experience) evaluated all pre and post SBRT imaging and measured the lesion size and the size of the largest enhancing component. Lesion decrease or increased in size was assessed based on the mRECIST criteria. Explant pathology results were collected for patients who received transplant. Necrosis > 90% on explant was considered full response to treatment. AFP (alpha-fetoprotien) values before and after SBRT were collected. Results: Eight patients with 9 lesions meet our inclusion criteria, 3 of which were LR-5 and 6 LR-4 prior to the TACE. At 3 month, 2 lesions had no residual enhancing component, 2 lesions decreased in size, 2 lesions increased in size, 3 lesions remain unchanged. After maximum available follow-up (ranging from 3 to 8 months), 3 lesions had no residual enhancing component, 2 decreased, 2 lesions increased in size, 2 lesions remain unchanged. Of the 3 lesions that were definitive HCC (LR-5): 1 lesion decreased in size, 2 lesions increased in size. 4 of 8 patients (4 lesions) underwent transplant, 3 of them showed only 50% necrosis on explant. 1 of 3 lesions showed no change in size by imaging, the other 2 lesions had no residual enhancing component. Only 1 lesion had full response on the transplant. This lesion was unchanged on 3 and 6 months follow up. The AFP was not helpful since the majority of the patient had low pre-treatment AFP. Conclusions: Patient with viable disease on imaging after TACE subsequently treated with SBRT demonstrated variable behavior on imaging. Close to half demonstrated resolution of the enhancing component, however, in the few that had explant follow up there was no correlation between imaging findings and pathology.

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Radiometric Quantitation of PAIgG Stratified Treatment Response in ITP Patients.

Blood ◽

10.1182/blood.v106.11.3986.3986 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3986-3986

Author(s):

Dexter Estrada ◽

Kenneth A. Schwartz2

Keyword(s):

Platelet Count ◽

Treatment Response ◽

Conventional Treatment ◽

Retrospective Chart Review ◽

Response To Therapy ◽

Response To Treatment ◽

Platelet Surface ◽

Platelet Counts ◽

Cytotoxic Treatment

Abstract Because treatment response in ITP is variable, it would be useful to be able to assess which patients are likely to respond to conventional treatment. Toward this goal we correlated the number of platelet surface IgG molecules measured with a quantitative radiometric platelet antibody assay (PAIgG) with treatment related changes in platelet count. We tested the hypothesis that patients’ response to conventional treatment could be stratified based on quantitation of the patients’ PAIgG. Data was obtained via a retrospective chart review. Patients with a diagnosis of idiopathic thrombocytopenic purpura (ITP), age 18 or older with an initial platelet count of <150,000, and quantitation of antiplatelet IgG performed at the time of diagnosis were included in the study. Patients were treated using conventional approaches that included steroids, IVIgG, anti-D antibody, splenectomy, and or cytotoxic medications. Patient response to therapy was evaluated as the change in platelet count, computed as the difference in platelet count obtained at diagnosis and the latest stable platelet count available. There were 64 patients with at least 90 days between initial and follow-up platelet counts. Of the 31 patients whose PAIgG were ≤1,000 molecules/platelet (m/plt), only 1 had an initial platelet count of <50,000. Of the 33 patients who’s PAIgG were >1,000 m/plt 16 had platelet counts of <50,000 (p≤0.001. Patients with PAIgG levels >1000 m/plt exhibited a significantly greater increase in platelet count μ=73,000 ±92,000 as compared to those with PAIgG levels ≤1000 m/plt, μ=18,000 ±43,000 (p=0.03). Although a PAIgG level of 500 m/plt is 3 standard deviations above the mean of normals, a greater response to treatment was noted in patients if their PAIgG level was >1000 m/plt. Patients with PAIgG levels between 500 and 1000 m/plt respond in a similar fashion to those with PAIgG levels <499. In addition, more patients with PAIgG levels >1000 m/plt received conventional treatment (19/33 vs. 10/31; p<0.05). In particular, there were more patients who received cytotoxic treatment in this cohort, (11/33 vs. 3/31; p≤0.025). Similar results were observed in 74 patients with at least 30 days between initial and follow-up platelet counts. This study suggests that measuring the amount of antiplatelet IgG stratifies ITP patients into 2 groups: patients with PAIgG ≤1,000 m/plt with platelet counts over 50,000 and patients with PAIgG >1,000 m/plt platelet counts that are less than 50,000. Those patients whose PAIgG is >1,000 m/plt are more likely to receive treatment and have an increase in platelet count with conventional therapy. We conclude that radiometric quantitation of PAIgG is helpful for predicting a patient’s response to therapy.

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Anti-MAG Neuropathy: a Single Center Retrospective Study In 61 Patients

Blood ◽

10.1182/blood.v116.21.3951.3951 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3951-3951

Author(s):

Marie-Anne HOSPITAL ◽

Sonia Dragomir ◽

Vincent Levy ◽

Jean Neil ◽

Lucile Musset ◽

...

Keyword(s):

Retrospective Study ◽

Board Of Directors ◽

Response Rate ◽

Immunoglobulin M ◽

Response To Treatment ◽

First Line ◽

Advisory Committees ◽

Significant Difference ◽

Before And After

Abstract Abstract 3951 Background: Polyneuropathy is the most frequent neurological complication in Waldenstrom macroglobulinemia (WM). Most patients have an insidiously progressive distal symmetric sensorimotor and ataxic neuropathy due to a monoclonal immunoglobulin M anti-myelin-associated glycoprotein (MAG). There is still no treatment reference today. Recent studies underline the interest of Rituximab (RTX) but its efficacy is not yet proven. In order to identify the interest of immunotherapy, we performed a retrospective study in 61 patients with anti-MAG over a period of 12 years. Methods: All patients underwent neurological, biological (anti-MAG antibodies, IgM serum) and electrophysiological examination before and after each treatment. Clinically, patients were considered to be improved if they had a decrease of at least two points on the INCAT sensory sum score and/or a decrease of 20 mm on the visual analogue scale and/or motor strength improvement by at least two MRC points in the ankle dorsiflexor. Biologically, response anti-MAG antibodies and IgM serum were considered to be improved if their level was diminished by half. Electrophysiological studies were performed using standard procedures. Results: A total of 61 patients were analyzed. The median age at onset was 64 years (range 33–84), median serum IgM concentration 4.6 g/L (0-17), median anti-MAG antibodies 49900 BTU (23000>70000), RANKIN score 1 (35 patients), 2(20 patients), 3(6 patients). Twenty-five patients had WM with lymphoplasmacytic cells bone marrow infiltration. None of the patients had criteria for therapy initiation according to the 2th international workshop except symptomatic or evolving neuropathy. In first line, 45 patients were treated with Chlorambucil (CBL) (8 improved, 28 were stabilised, 9 worsened), 16 patients were treated with RTX alone (9) or in combination (7) (11 improved, 2 were stabilised, 3 worsened). RTX gave a significant higher response rate compared with CBL (p=2×10-4). With a median follow up of 96 months, 15 patients treated with CBL relapsed. Only one patient treated with RTX relapsed but the median follow up was not reached (60 months follow up). In the CBL group, 15 patients were treated at relapse with RTX and 11 improved, 3 were stabilised, 1 worsened. The average time follow up of the 2nd response was 48 months. Twelve patients in failure were treated with RTX: 8 improved, 1 was stabilised, 3 failed with an average follow up of 48 months. There was no significant difference between anti-MAG antibodies level before and after treatment (p=0.64) in patients in response but a low IgM level was associated with response to treatment (p<0.029). Conclusion: In first line, RTX alone or in combination is associated with a higher response rate than CBL. For patients who relapsed after CHL, patients favourably responded to RTX with an average time follow up of 48 months. IgM level is a prognosis factor (p<0.029) for clinical response to treatment. To better define the efficacy of RTX in this setting, results of a french randomized study comparing RTX to placebo are pending. Disclosures: Choquet: Roche: Consultancy. Leblond:ROCHE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MUNDIPHARMA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GENZYME: Membership on an entity's Board of Directors or advisory committees; CELGENE: Membership on an entity's Board of Directors or advisory committees; JANSSEN: Membership on an entity's Board of Directors or advisory committees.

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Anti-Inflammatory Effect of Cross-Linked Hyaluronic Acids in Osteoarthritic Knee, Detected by Ultrasonography

10.21203/rs.3.rs-37185/v1 ◽

2020 ◽

Author(s):

Saradej Khuangsirikul ◽

Apiwat Yuwapan ◽

Danai Heebthamai ◽

Thanainit Chotanaphuti

Keyword(s):

Hyaluronic Acid ◽

Early Stage ◽

Joint Destruction ◽

Response To Treatment ◽

Knee Oa ◽

Before And After ◽

Practical Tool ◽

Hyaluronic Acids ◽

Anti Inflammation

Abstract Background: Synovial hypertrophy is one of the pathological characteristics of knee osteoarthritis (OA), which is associated with the inflammation process and disease severity. Ultrasonography (US) is a practical tool to monitor disease progression and the response to treatment. Intra-articular hyaluronic acid (IAHA) is one of the commonly-used alternative treatments for knee OA. In this study, we used US to assess the effects of cross-linked hyaluronic acid, in terms of minimizing inflammation, by comparing synovial thickness before and after IAHA.Methods: Seventy-nine OA patients (107 knees, KL II-III and KL IV with surgery refusal) were treated with cross-linked IAHA and underwent US before IAHA at 4-week and 3-month follow-up visits after injection. Comparisons of synovial thickness before and after injection were analyzed. Clinical outcomes were also evaluated by the recording of the visual analog scale for pain (pain VAS).Results: The overall synovial thickness was significantly decreased after IAHA at 4 weeks (p=0.01). The thickness was significantly reduced in KL II (p=0.01), but not significant in KL III and IV (p=0.096 and 0.083, respectively). In KL IV, the thickness was significantly increased at 3 months after IAHA (p=0.02).The pain VAS improved gradually at 4 weeks and 3 months after IAHA, significantly (p < 0.001) in all KL stages.Conclusion: Cross-linked hyaluronic acid injection provided pain relief in all KL stages at 4 weeks and lasted at least 3 months. However, its anti-inflammation action was temporary and predominated only in patients with early-stage OA knee. Concerning inflammation as a major risk factor for OA progression, adjunct intervention after IAHA should be added to enhance the therapeutic effect and prevent further joint destruction. IRBRTA: R074h/62

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The Effect of Plasma Exchange on Rituximab Levels and Response to Rituximab in Patients with Acute Idiopathic Thrombotic Thrombocytopenic Pupura (TTP).

Blood ◽

10.1182/blood.v112.11.2297.2297 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2297-2297 ◽

Cited By ~ 1

Author(s):

Vickie McDonald ◽

Marie Scully ◽

Ian J. Mackie ◽

Kate Manns ◽

Samuel J. Machin

Keyword(s):

Plasma Exchange ◽

Limit Of Detection ◽

Median Number ◽

Response To Treatment ◽

Adamts13 Activity ◽

Median Serum ◽

Significant Difference ◽

Before And After ◽

Anti Cd20

Abstract Most cases of acute idiopathic TTP have ADAMTS13 activity <5% and detectable anti-ADAMTS13 IgG. Rituximab, a monoclonal anti-CD20 antibody, is known to be an effective adjunct to eradicate the antibody. The initial doses of Rituximab are often given in the period that the patient is receiving plasma exchange (PEX). In order to ascertain whether Rituximab is removed by PEX and whether this affects response to treatment, we serially measured ADAMTS13 activity, anti-ADAMTS13 IgG level and serum Rituximab concentrations in patients who were treated with Rituximab within 3 days of admission for acute idiopathic TTP. Rituximab levels were measured before and after PEX, after each dose and then in remission. In addition we measured the above parameters in two patients who received Rituximab electively (not concurrently with plasma exchange). The ADAMTS13 activity (normal value >66%) was measured using a collagen binding assay while the anti-ADAMTS13 IgG (normal range <4%) and Rituximab levels (lower limit of detection 10mcg/ml) were measured using ELISA techniques. 16 patients (11 female, 5 male; median age 39y (range 13y – 75y)) with acute idiopathic TTP were treated with Rituximab. All patients had PEX from admission to remission, received Rituximab 375mg/m2 once weekly for 4 weeks and pulsed methylprednisolone 1g daily for three days. At presentation, all patients had ADAMTS13 activity <5% and anti-ADAMTS13 IgG (median 39.5%; range 12–85%). The median follow up was 6 months (m) (range 1–12 m). 14 patients received 4 doses of Rituximab, 2 received 6 doses. One patient died of TTP related complications before the third dose. The median number of PEX after the first dose of Rituximab was 15 (range 5–21). The median serum Rituximab concentration following each dose was: 1st dose 154 mcg/ml (range 108–467mcg/ml); 2nd dose 175 mcg/ml (range 116–436mcg/ml); 3rd dose 187.5 mcg/ml (157–301mcg/ml); 4th dose 216 mcg/ml (155–243mcg/ml); 5th 155 mcg/ml; 6th 211 mcg/ml. All PEX patients had Rituximab levels <10 mcg/ml immediately prior to the 2nd dose. Of those still being exchanged, 5/7 had levels <10 mcg/ml prior to 3rd dose and 5/6 patients had levels <10mcg/ml prior to the 4th dose. In contrast all the patients who had finished PEX had detectable Rituximab prior to their next dose. The median reduction in Rituximab per PEX expressed as a percentage of the pre-PEX level was 65 % (range 45–72%). The reduction was similar for 1.0 volume (65%) and 1.5 volume exchanges (70%). Rituximab was detected in the PEX fluid. Following completion of Rituximab therapy, the median concentration was 32mcg/ml (range 11–55mcg/ml) at 1m, 20 mcg/ml (range <10 – 42mcg/ml) at 2m and 16 mcg/ml (range <10– 20mcg/ml) at 3m. Seven patients reached 4 month follow up and had levels <10mcg/ml. Patients who had fewer than 10 PEX had higher median Rituximab levels (20mcg/ml) at 3m than those who had more than 10 PEX (Rituximab <10mcg/ml). There was no significant difference in ADAMTS13 activity or anti-ADAMTS IgG levels between these groups at 3m (patients receiving <10 PEX: mean activity 38% and IgG 6%; Patients receiving >10 PEX: mean activity 36% and IgG 15%). In 2 patients receiving elective Rituximab, the median concentrations before and after each dose were: 235mcg/ml after the 1st dose, 95mcg/ml before and 233mcg/ml after 2nd dose, 119mcg/ml before and 289mcg/ml after the 3rd dose, 167mcg/ml before and 373mcg/ml after 4th dose. Follow up is too short to correlate levels and ADAMTS13 activity/anti-ADAMTS13 IgG levels. There have been no relapses in any of the patients. In conclusion, Rituximab is removed by plasma exchange. The peak doses achieved are higher in those not receiving concurrent PEX. Higher Rituximab levels are associated with fewer PEX. Rituximab was still detectable at a low level in a third of patients 3 months after treatment but not at 4 months. Measurement of Rituximab levels will help to modify Rituximab doses and modification of the dosing schedule using higher initial doses or more frequent dosing may achieve higher levels earlier in treatment and a shorter time to remission. Longer term follow will also help to determine whether the peak Rituximab concentration achieved correlates with duration of remission.

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