“Lymphomatous and Leukemic Meningitis – Patterns of Cytomorphology and Value of MRI and Protein Analysis”.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5011-5011
Author(s):  
Herwig Matthias Strik ◽  
Christina Perske ◽  
Peter Proemmel ◽  
Ingelore Nagel ◽  
Holger Nagel
Keyword(s):  
Cell Count ◽  
Total Protein ◽  
Research Funding ◽  
Protein Analysis ◽  
Irregular Shape ◽  
Aggressive Lymphoma ◽  
Oligoclonal Bands ◽  
Csf Cytology ◽  
Lymphomatous Meningitis ◽  
Leukemic Meningitis

Abstract Abstract 5011 Introduction Lymphomatous and leukemic meningitis (LM), although a well known and relatively frequent complication of aggressive lymphoma and leukemia, are still difficult to detect. With cytomorphology, neoplastic lyphocytes are difficult to distinguish from inflammatory lymphocytes. We evaluated here if specific morphological criteria can improve this differentiation. Moreover, we assessed the sensitivity of MRI and protein analysis for the detection of LM in comparison with CSF-cytology. Patients and Methods To establish cytomorphological criteria, 42 cytospin preparations of CSF from patients with confirmed CSF involvement by aggressive lymphoma or acute leukemia were compared with 26 samples of inflammatory diseases. CSF cytology was analyzed morphologically for pre-selected parameters of cell, cytoplasm and nucleic appearance and the presence of mitoses or apoptoses. For the comparison of cytology and MRI, 38 patients with leukemic or lymphomatous meningitis were evaluated retrospectively for MRI-signs of neoplastic meningitis and for CSF-protein abnormalities (total protein, oligoclonal bands, lactate, ferritine). Results as expected, none of the cytomorphological parameters sharply discerns neoplastic and inflammatory transformation. However, neoplastic cells were significantly larger than inflammatory lymphocytes with a mean of 3.0 as opposed to 1.8 times the size of normal small lymphocytes (p=0.0001). Moreover, irregular shape, pointed borders of the cytoplasm, and deep notches in the nucleus were significantly more often found with neoplastic than with inflammatory lymphocytes. The total cell count was elevated in 68% of cases of lymphomatous meningitis. While cytomorphology could achieve approx. 90% sensitivity for the detection of LM, spinal and/or cranial MRI only detected 71% of cases with normal and 52% with elevated cell counts. Total protein was elevated in 77% of cases, lactate in 55% and ferritine in 48%. Oligoclonal IgG was found in 11% isolated in the CSF and in 18% in CSF and serum identically. Only 3/38 patients (8%) had completely normal CSF cell count and proteins. Conclusions CSF cytology is more sensitive than MRI for the detection of LM, but application of both methods clearly enhances the sensitivity by approx. 10%. No single cytomorphological parameter is sufficient to detect neoplastic lymphocytes. Considering a combination of cell size and irregular shape of cell and nucleus may improve the diagnostic accuracy of CSF dissemination by aggressive hematological malignancies. Disclosures Strik: Mundipharma : Consultancy, Honoraria, Research Funding, Speakers Bureau; Essex/Shering-Plough/Merck: Consultancy, Honoraria, Speakers Bureau; Medac: Research Funding.

Distinguishing neurosarcoidosis from multiple sclerosis based on CSF analysis

Neurology ◽  
2020 ◽  
Vol 94 (24) ◽  
pp. e2545-e2554
Author(s):  
Tarunya Arun ◽  
Laura Pattison ◽  
Jacqueline Palace
Keyword(s):  
Multiple Sclerosis ◽  
Cell Count ◽  
Total Protein ◽  
White Cell Count ◽  
Binary Logistic Regression ◽  
White Cell ◽  
Oligoclonal Bands ◽  
Csf Analysis ◽  
Elevated Protein ◽  
Oligoclonal Igg

ObjectiveTo characterize a cohort of patients with neurosarcoidosis with particular focus on CSF analysis and to investigate whether CSF values could help in distinguishing it from multiple sclerosis (MS).MethodsThis retrospective cohort study enrolled 85 patients with a diagnosis of neurosarcoidosis (possible, probable, or definite). CSF total protein, white cell count, and angiotensin-converting enzyme levels were measured. CSF and serum oligoclonal immunoglobulin G (IgG) patterns were analyzed with the use of odds ratios and binary logistic regression.ResultsEighty patients had a probable (nonneural positive histology) or definite (neural positive histology) diagnosis of neurosarcoidosis. Most frequent findings on MRI were leptomeningeal enhancement (35%) and white matter and spinal cord involvement (30% and 23%). PET scan showed avid areas in 74% of cases. CSF analysis frequently showed lymphocytosis (63%) and elevated protein (62%), but CSF-selective oligoclonal bands were rare (3%). Serum ACE levels were elevated in 51% of patients but in only 14% of those with isolated neurosarcoidosis. Elevated CSF ACE was not found in any patient.ConclusionsLarge elevations in total protein, white cell count, and serum ACE occur in neurosarcoidosis but are rare in MS. The diagnostic use of these tests is, however, limited because minimal changes may occur in both. MS clinical mimics in neurosarcoidosis are not common, and intrathecal synthesis of oligoclonal IgG is a powerful discriminator because it is rare in neurosarcoidosis but occurs in 95% to 98% cases of MS. We suggest caution in making a diagnosis of neurosarcoidosis when intrathecal oligoclonal IgG synthesis is found.

scholarly journals A miniaturized optoelectronic biosensor for real-time point-of-care total protein analysis.

MethodsX ◽  
2021 ◽  
pp. 101414
Author(s):  
Ophir Vermesh ◽  
Fariah Mahzabeen ◽  
Jelena Levi ◽  
Marilyn Tan ◽  
Israt S. Alam ◽  
...  
Keyword(s):  
Real Time ◽  
Total Protein ◽  
Point Of Care ◽  
Protein Analysis ◽  
Time Point

scholarly journals Cerebrospinal Fluid Parameters in Antisense Oligonucleotide-Treated Adult 5q-Spinal Muscular Atrophy Patients

2021 ◽  
Vol 11 (3) ◽  
pp. 296
Author(s):  
Lars Hendrik Müschen ◽  
Alma Osmanovic ◽  
Camilla Binz ◽  
Konstantin F. Jendretzky ◽  
Gresa Ranxha ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Spinal Muscular Atrophy ◽  
Total Protein ◽  
Antisense Oligonucleotide ◽  
Muscular Atrophy ◽  
Neurological Diseases ◽  
Clinical Signs ◽  
Central Nervous System Disease ◽  
Oligoclonal Bands ◽  
System Disease

Approval of nusinersen, an intrathecally administered antisense oligonucleotide, for the treatment of 5q-spinal muscular atrophy (SMA) marked the beginning of a new therapeutic era in neurological diseases. Changes in routine cerebrospinal fluid (CSF) parameters under nusinersen have only recently been described in adult SMA patients. We aimed to explore these findings in a real-world setting and to identify clinical and procedure-associated features that might impact CSF parameters. Routinely collected CSF parameters (leukocyte count, lactate, total protein, CSF/serum albumin quotient (QAlbumin), oligoclonal bands) of 28 adult SMA patients were examined for up to 22 months of nusinersen treatment. Total protein and QAlbumin values significantly increased in the first 10 months, independent of the administration procedure. By month 14, no further increases were detected. Two patients developed transient pleocytosis. In two cases, positive oligoclonal bands were found in the beginning and in four patients throughout the whole observation period. No clinical signs of inflammatory central nervous system disease were apparent. Our data confirm elevated CSF total protein and QAlbumin during nusinersen treatment. These alterations may be caused by both repeated lumbar punctures and the interval between procedures rather than by the medication itself. Generally, there were no severe alterations of CSF routine parameters. These results further underline the safety of nusinersen therapy.

scholarly journals Results of a Phase I Trial of Lenalidomide, Rituximab (R2) and Ixazomib for Frontline Treatment of High Risk Follicular and Indolent Non-Hodgkin Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-2
Author(s):  
Brian T. Hill ◽  
Deepa Jagadeesh ◽  
Alex V. Mejia Garcia ◽  
Robert M. Dean ◽  
Omer N. Koc ◽  
...  
Keyword(s):  
High Risk ◽  
Phase I ◽  
Board Of Directors ◽  
Research Funding ◽  
Marginal Zone ◽  
Proteasome Inhibitors ◽  
Marginal Zone Lymphoma ◽  
Aggressive Lymphoma ◽  
Advisory Committees ◽  
Frontline Treatment

INTRODUCTION: Lenalidomide and Rituximab (R2) is an effective frontline treatment regimen for patients (pts) with indolent B-cell lymphoma including follicular lymphoma (FL). Recent phase III data from the RELEVANCE trial comparing R2 to traditional chemoimmunotherapy showed that this regimen is generally well-tolerated and has favorable clinical efficacy [61% overall response, 53% CR rate, 77% 3-year progression free survival (PFS) (Morschhauser, et al)]. Proteasome inhibitors such as bortezomib disrupt NF-KB signaling and have shown clinical activity in indolent NHL. Although randomized trials have failed to demonstrate clinical benefit of adding bortezomib to standard chemoimmunotherapy regimen bendamustine + rituximab (BR) for frontline treatment of FL, the addition of proteasome inhibitors to lenalidomide is a mainstay of treatment for plasma cell neoplasms due to synergistic antitumor effect. The oral proteasome inhibitor ixazomib has less potential for dose-limiting neuropathy than bortezomib, making it an attractive option to incorporate into the R2 regimen. We sought to investigate the safety and efficacy of the addition of ixazomib to R2 for FL and indolent B-cell NHL through a phase I clinical trial of this combination for patients with high risk disease. METHODS: Adult (age ≥ 18) pts with untreated FL or other indolent lymphoma, adequate organ function and performance status were enrolled. To be enrolled, FL patients were required to have stage 2, 3 or 4 disease, with high tumor burden by GELF criteria and/or FLIPI score of 3-5. During 3 x 3 dose escalation, ixazomib was given at a dose of 2 mg (n=3), 3 mg (n=3) or 4 mg (n=12) PO on days 1, 8, and 15 with lenalidomide 20 mg PO on days 1-21 every 28 days. Rituximab was administered at standard dosing on days 1,8,15,21 for cycle 1, once every 28 days for cycles 2-6 and then once every 2 months for cycles 7-12. Treatment was continued for 12 cycles and no maintenance therapy was specified per protocol. All pts received low dose aspirin for venous thromboembolism prophylaxis and acyclovir for prevention of VZV reactivation. Response assessments by CT were performed after cycle 3 and 6 and by PET/CT at the end-of-treatment (cycle 12). RESULTS: 20 pts were enrolled and 18 were eligible for treatment [15 FL (14 grade 1-2, 1 grade 3A), 2 splenic marginal zone lymphoma and 1 nodal marginal zone lymphoma].The median age of treated pts was 61 (range 40-83) years old. 55% of patients were female. Stage at diagnosis was II (n =2), III (n = 4) and IV (n = 12). For FL pts, FLIPI scores at enrollment were low (n=2), intermediate (n = 5) and high risk (n=8) and FLIPI-2 scores were low (n=3), intermediate (n = 2) and high risk (n=10). There were no dose limiting toxicities during 3 x 3 dose escalation. Grade (G) 1/2 and G3/4 treatment-related hematologic adverse events (AEs) included neutropenia (6%, 28%), thrombocytopenia (16.7%, 5.6%) and anemia (16.7%, 0%). The most common treatment-related AEs included nausea/vomiting (44% G1, 11% G2), diarrhea, (50% G1, 22% G2, 5% G3), rash (33% G1, 6% G2, 11%G3), peripheral neuropathy (22% G1, 6% G2), myalgia/arthralgia (17% G1, 17% G2), and infection (33% G2, 17% G3). There was one pulmonary embolism and no cases of febrile neutropenia. As of June, 2020, median follow-up among living pts was 21 months. 4 pts discontinued treatment due to disease progression; 2 with transformation to aggressive lymphoma. Of the transformed cases, one subject died on study due to progression disease and one developed CNS disease on study treatment but proceeded to autologous stem cell transplant. The best overall response rate was 61.2% [55.6% CR, 5.6% PR): 22.2% had stable disease and 16.7% had disease progression. 18-month Kaplan-Meier estimates of PFS and overall survival were 71% and 94%, respectively (Figure). CONCLUSION: R2 can safely be combined with at the target dose of 4 mg of ixazomib for treatment-naïve indolent NHL patients. Non-hematologic AEs were generally consistent with known toxicity of each component of therapy. CR rate and PFS were was similar to the outcomes reported in the RELEVANCE trial despite enrolling high risk patient. R2 may serve as backbone for future studies of novel treatment combinations for high risk FL after thorough evaluation for occult transformation to aggressive lymphoma. Disclosures Hill: Abbvie: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding. Jagadeesh:MEI Pharma: Research Funding; Regeneron: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Debiopharm Group: Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees. Caimi:Celgene Corp: Other: Incyte Corporation - Ownership - Pharmacyclics, Inc. - Ownership - Celgene Corp. - Other, Speakers Bureau; ADC Therapeutics: Research Funding; Genentech: Research Funding. Smith:Takeda: Research Funding; Celgene: Research Funding. OffLabel Disclosure: Ixazomib is off-label for treatment of NHL

scholarly journals Total Protein Analysis as a Reliable Loading Control for Quantitative Fluorescent Western Blotting

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e72457 ◽  
Author(s):  
Samantha L. Eaton ◽  
Sarah L. Roche ◽  
Maica Llavero Hurtado ◽  
Karla J. Oldknow ◽  
Colin Farquharson ◽  
...  
Keyword(s):  
Western Blotting ◽  
Total Protein ◽  
Protein Analysis

Machine Learning for Prediction of Cancer-Associated Venous Thromboembolism

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 37-37
Author(s):  
Simon Mantha ◽  
Andrew Dunbar ◽  
Kelly L. Bolton ◽  
Sean Devlin ◽  
Dmitriy Gorenshteyn ◽  
...  
Keyword(s):  
Machine Learning ◽  
Blood Cell ◽  
Cell Count ◽  
Cancer Diagnosis ◽  
Research Funding ◽  
Cross Validation ◽  
Genetic Data ◽  
Cancer Type ◽  
Cell Counts ◽  
Predicted Risk

Background: Several clinical prediction scores have been designed to assess the risk of cancer-associated thrombosis (CAT). The most commonly used in current clinical practice is the Khorana score, however it is applicable only to patients prior to initiation of chemotherapy. We now apply machine learning with clinical, demographic, and genomics parameters to predict CAT events. Methods: The random survival forest (RSF) ensemble learning method was selected to illustrate a machine approach to CAT prediction. The cohort consisted of 14,223 individuals with a solid tumor malignancy and MSK IMPACT somatic genomic data collected during the years 2014 to 2016. CAT was defined as the diagnosis of lower extremity deep vein thrombosis (proximal or distal) or pulmonary embolism, incidental or symptomatic. Covariates considered for inclusion in the model consisted of tumor type, metastatic status, age, exposure to cytotoxic chemotherapy in the month before cohort entry, time elapsed since cancer diagnosis, time elapsed since tumor sampling, normalized mean blood cell counts (white cell count, hemoglobin, platelet count) in the prior 3 months, normalized mean prothrombin time (PT) and activated partial thromboplastin time (aPTT) in the prior 3 months, body mass index (BMI), and presence or absence of a somatic genetic alteration for oncogenes/tumor suppressor genes with an alteration frequency ≥ 1.5% (n = 56). The primary endpoint consisted of time to CAT episode. The C-index for models including different covariates was derived from the test holdout sample using repeated 10-fold cross-validation. The C-index, measuring the relative agreement between the RSF predicted risk and the CAT times of patients, has values between 0.5 and 1.0 with the latter indicating perfect agreement. Results: 12,040 patients were included in the final analysis. There were 855 CAT events during the observation period. The most common tumor types were lung (17%), breast (15%) and colorectal cancer (9%). Blood cell count data and coagulation parameters were missing for 8% and 51% of patients respectively. Using cross-validation, the baseline model with cancer type and metastatic status had a C-index of 0.62 (95% CI = 0.61-0.64), which increased to 0.65 (95% CI = 0.63-0.66) with the addition of chemotherapy, age, time from tissue sampling, time from cancer diagnosis and BMI. Further adding genetic data increased the C-index to 0.68 (95% CI = 0.66-0.69). Replacing genetic data in this model with cell counts and coagulation parameters resulted in a C-index of 0.69 (95% CI = 0.68-0.70). The model with all available covariates had a C-index of 0.70 (95% CI = 0.69-0.71). The cumulative incidence of CAT at 6 months for 5 categories of predicted risk using the model with all available covariates is plotted in Figure A. Scaled Ishwaran-Kogalur Variable Importance (VIMP) values, presented in Figure B, indicate that cancer type and prior chemotherapy are the two top factors for model performance. Conclusions: Machine learning is a promising approach in the search of more accurate and generalizable models for prediction of CAT. In the application described here, the use of random survival forests performed well without information about future chemotherapy administration. Additional work is needed to identify the optimal algorithm and covariates, including better delineation of which cancer genomic information should be retained. Future models will have to be validated independently before being used for patient care. Disclosures Mantha: Physicians Education Resource: Honoraria; MJH Associates: Honoraria. Bolton:GRAIL: Research Funding. Soff:Bristol-Myers Squibb, Pfizer: Honoraria; Dova Pharmaceuticals: Honoraria; Janssen Scientific Affairs: Honoraria; Amgen: Research Funding; Janssen Scientific Affairs: Research Funding; Amgen: Honoraria; Dova Pharmaceuticals: Research Funding.

Outcome of Fungal Infection in Patients Undergoing Myelosuppressive Chemotherapy in a Tertiary Care Centre During 12 Years (1995-2006).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1384-1384
Author(s):  
Marie von Lilienfeld-Toal ◽  
Axel Glasmacher ◽  
Günter Marklein ◽  
Peter Brossart ◽  
Corinna Hahn-Ast
Keyword(s):  
Research Funding ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Tertiary Care ◽  
Underlying Disease ◽  
Aggressive Lymphoma ◽  
Tertiary Care Centre ◽  
Myelosuppressive Chemotherapy ◽  
Mortality And Morbidity ◽  
Related Mortality

Abstract Abstract 1384 Poster Board I-406 Invasive fungal infections (IFI) contribute significantly to mortality and morbidity in patients receiving myelosuppressive chemotherapy for hematological malignancies. The present study evaluates the incidence of IFI, the overall survival (OS), the infection-related mortality and changes in treatment of IFI in our department from 1995 until 2006. Data of all consecutive chemotherapy courses were retrospectively collected with a standard questionnaire. EORTC/MSG criteria for IFI were applied with a modification: A positive PCR-result for Aspergillus spp. in bronchoalveolar lavage was also defined as probable IFI. In total, 1693 courses of 592 patients were evaluated. Sixty-three percent were given to treat acute myeloid leukemia, the rest for acute lymphoblastic leukemia or aggressive lymphoma. IFI were observed in 139/592 patients (23%, 95% confidence interval (CI) 20-27%), and in 149/1693 (8.8%, 95%CI 8-10%) courses. IFI-related mortality was 57% in 1995-2001 and 29% in 2002-2006, p<0.001. Accordingly, median OS in patients with IFI increased in the later years: 54 days (95%CI 26–82 days) in 1995-2001 versus 229 days (95% CI 35–423 days) in 2002-2006, p=0.001, figure 1. By multivariate analysis, factors predictive for better OS were controlled disease after chemotherapy (hazard ratio (HR) 0.226, p<0.001), possible IFI (in contrast to proven/probable IFI, HR 0.511, p=0.002), age < 60 years (HR 0.611, p=0.015), and use of novel antifungals (HR 0.493, p=0.002). In conclusion, IFI-related mortality decreased and OS in patients with IFI increased significantly in recent years compared to 1995-2001. In our cohort improved OS was associated with controlled underlying disease, certainty of IFI diagnosis (possible), younger age, and the use of novel antifungal agents. Figure 1 p=0.001 Figure 1. p=0.001 Time period ········ 2002-2006 —— 1995-2001 Number at risk 2002-2006 78 28 18 9 6 2 1995-2001 61 8 6 5 5 5 Disclosures: von Lilienfeld-Toal: MSD: Honoraria, Research Funding. Glasmacher: Celgene: Employment, Equity Ownership. Hahn-Ast: MSD: Research Funding.

A Randomized Comparison of Low-Dose Cyclophosphamide + G-CSF Versus G-CSF Alone Mobilization after Lenalidomide-Bortezomib-Dexamethasone (RVD) Induction in Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 847-847
Author(s):  
Raija Silvennoinen ◽  
Tuija Lundan ◽  
Pekka Anttila ◽  
Jouni Heiskanen ◽  
Marjaana Säily ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Cell Count ◽  
Primary Endpoint ◽  
Research Funding ◽  
Low Dose ◽  
Median Number ◽  
Cell Harvesting ◽  
Cd34 Cells ◽  
Neutrophil Engraftment

Abstract Introduction Autologous stem cell transplantation (ASCT) is the standard treatment in multiple myeloma (MM) for eligible patients below 70 years of age. The main mobilization treatment in Europe consists of combination of cyclophosphamide (CY) and G-CSF. It is questionable if CY is useful in mobilization. CY as an alkylating agent might also have some negative long-term effects. Bortezomib seems not to have negative impact on autologous stem cell harvesting, but prolonged use of lenalidomide might hamper mobilization. There are only a few studies regarding autologous stem cell mobilization after RVD induction. We designed this randomized study as a substudy of the Finnish Myeloma Group Study (NCT01790737) to compare the results of CY+G-CSF versus G-CSF mobilization in autologous stem cell harvesting. The primary endpoint is the percentage of patients reaching ≥ 3 x 106/kg CD34+ cells (or ≥ 6 x 106/kg for two transplants), with ≤ 2 apheresis after low-dose CY+G-CSF vs. G-CSF mobilization. Secondary endpoints are need for plerixafor, graft cellular composition and engraftment after ASCT. Patients and methods This phase 2 study will include 80 patients below 70 years of age with symptomatic MM and eligible for ASCT. At registration the patients are randomized equally to arm A) CY 2 g/m2 + G-CSF 5 μg/kg or arm B) G-CSF 10 μg/kg. Before mobilization three RVD induction cycles are given. Each 3-week RVD cycle includes lenalidomide 25 mg daily on days 1−14, bortezomib 1.3 mg/m2 subcutaneously on days 1, 4, 8, 11, and dexamethasone 160 mg/cycle. By this schedule the first harvest is estimated to be on day +10 in CY + G-CSF and on day +5 in G-CSF group. Apheresis will start with blood CD34+ level >10 x 106/l. The target cell yields for one and two grafts are ≥ 3 and ≥ 6 x 106 CD34+ cells/kg, respectively, and the minimum for one graft ≥ 2 x 106/kg. Plerixafor is given if B-CD34+ cell count is less than 10 x 106/l on days +10 or +5, respectively, or if the first apheresis product contains < 1 x 106/kg CD34+ cells. G-CSF support is used after ASCT if the number of CD34+ cells in the graft is less than 3 x 106/kg. Engraftment will be assessed by blood neutrophil count > 0.5 x 109/l, and unsupported platelets > 20 x 109/l. Results Fifty-six patients have been included, and the mobilization data for the first 37 patients are available for analysis. The primary endpoint was reached in 90% of the patients (18/20) in arm A and in 82% (14/17) in arm B (p=NS). The median number of apheresis to reach the goal in arms A and B is one (1-3) and two (1−3), respectively (p=0.03). The median number of harvested cells in the two arms is 6.2 (2.2−12.1) and 4.8 (2.9−7.6) x 106/kg, respectively (p<0.01). All patients achieved the minimum collection target of ≥ 2 x 106/kg CD34+ cells in both arms, and the target yield of ≥ 3 x 106/kg was reached in 95% (19/20) in arm A and in 94% (16/17) in arm B. Plerixafor was used in two (12%) patients in arm B. The median blood CD34+ cell count on the first apheresis day was 55.9 (13.0−118.6) and 35 (16.0−148.5) x 106/l for arms A and B, respectively (p=0.44). The median time from mobilization day 1 to the first apheresis day was 10 (10−13) days in arm A and 5 (5−6) in arm B. The median number of CD34+ cells transplanted, was 4.1 (2.2−7.3) and 3.2 (2.3−4.7) x 106/kg in arms A and B, respectively (p=0.01). In arm A the median neutrophil engraftment was on day +14 (9−28) (16 patients) and in arm B on day +15 (11−25) (15 patients) (p=0.68). The median platelet engraftment days were +13 (8−22) and +11 (8−21) in arms A and B, respectively (p=0.67). At ASCT the response rates in arm A were ≥ VGPR 65% (13/20), PR 25% (5/20), and 10% (2/20) were progressing, and the respective rates for arm B were 70% (12/17), 18% (3/17),and 12 % (2/17). Conclusions Preliminary results of this randomized mobilization substudy with a limited number of patients show no clinically significant differences between the number of harvested CD34+ autologous stem cells. However, in CY+G-CSF group the CD34+ cell target was reached by less aphereses. After short induction course of RVD it seems possible to harvest also for two autografts with G-CSF only mobilization. However, when compared to historical data the CD34+ cell counts in blood and grafts were lower than after bortezomib + dexamethasone induction, and also neutrophil engraftment seemed to be slower after lenalidomide-based induction therapy. We conclude that CY can be omitted in the mobilization regimen for MM patients who have responded to short course of RVD. Disclosures Silvennoinen: Janssen-Cilag: Research Funding; Celgene: Research Funding; Janssen-Cilag: Honoraria; Sanofi: Honoraria; Celgene: Honoraria. Porkka:BMS: Honoraria; BMS: Research Funding; Novartis: Honoraria; Novartis: Research Funding; Pfizer: Research Funding.

Impact of Erythrocytapheresis on Endogenous Anticoagulants in Sickle Cell Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4590-4590
Author(s):  
Ruchika Sharma ◽  
Gary Woods ◽  
Susan E Creary ◽  
Kan Hor ◽  
Cody Young ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Total Protein ◽  
Research Funding ◽  
Protein C ◽  
Protein S ◽  
Cell Disease ◽  
Educational Grant ◽  
Protein C Activity ◽  
D Dimer ◽  
Protein S Activity

Abstract Introduction The rate of venous thrombo-embolism (VTE) in patients with sickle cell disease (SCD) is estimated to be 4 - 8%; the incidence of catheter-associated VTE in this cohort is 0.16-0.99 per 1000 catheter days. Possible mechanisms for VTE in patients with SCD include hyperviscosity, ischemia reperfusion injury and chronic vascular inflammation. Additionally, patients with SCD exhibit decreased plasma levels of natural anticoagulants such as proteins C and S compared to healthy adults. A retrospective review at our institution found that the incidence of central venous line (CVL)-associated VTE in children with SCD was 0.12/1000 catheter days. On multivariate analysis, CVLs were identified as the only independent risk factor for VTE. Among patients with CVL, we found an association between bilateral CVLs and VTE (Odds Ratio [95% CI] = 10.3 [1.1-92.2]). Children with SCD frequently require CVLs for intravenous access or chronic erythrocytapharesis to reduce SCD-related complications. It is unknown, however, if erythrocytapharesis may also disrupt their natural anticoagulants levels and further increase their risk for subsequent VTE. We hypothesized that erythrocytapheresis may contribute to the pro-coagulant phenotype by altering patients' natural anticoagulants levels. Methods As part of a quality improvement initiative we measured antithrombin (AT), protein C antigen and activity, protein S antigen (total and free) and activity prior to being placed on the apheresis circuit and after completion of exchange in patients with SCD (0-21 years of age) undergoing chronic erythrocytapheresis who had a CVL (between January 1, 2009 and January 31, 2015). D-Dimer levels were obtained pre exchange only. Protein C and S levels were measured using ELISA based assays; protein C and S activities were measured using a clotting based assay and AT was measured using a chromogenic assay. The resulting levels, pre and post-erythrocytapheresis were analyzed using a paired nonparametric Wilcoxon rank test. Results Eleven patients were eligible for this study (8 females, 3 males). Median age at the time of erythrocytapheresis was 14 years (±3.65 SD) years. Indications for erythrocytapheresis included primary/ secondary stroke prevention or recurrent acute chest syndrome. All patients had bilateral CVLs in place. Four of the included patients had a history of VTE; 2 patients were on anticoagulation with low molecular weight heparin at the time of the study. The mean value for total protein S antigen (65u/dL; normal >72u/dL), free protein S antigen (53u/dL; normal >70u/dL), and protein S activity (51IU/mL; normal 65-138IU/ml) were all abnormal pre- erythrocytapheresis and decreased significantly following erythrocytapheresis (52u/dL, 44u/dL, and 44IU/mL respectively). Mean protein C antigen (71u/dL; normal >55u/dL), protein C activity (71%; normal 55-111%), and AT activity (104%; normal 77-132%) were within the normal range pre-erythrocytapheresis and decreased significantly post-erythrocytapheresis. We demonstrated significantly lower levels of protein C antigen (p=0.01), protein C activity (p=0.01), total protein S antigen (p=0.005), free protein S antigen (p=0.036), protein S activity (p=.04), and AT activity (p=.004) following erythrocytapheresis (Figure). D-Dimer levels were elevated in 6/11 patients (54.5%). Conclusions Pre- and post-erythrocytapheresis levels of natural endogenous anticoagulants investigated in a cohort of patients with SCD undergoing chronic erythrocytapheresis demonstrated that levels of all investigated proteins were significantly lower in patients following erythrocytapheresis. D-dimer levels were elevated in the majority of patients pre exchange but the importance of this finding is unclear. Given the relatively short half-life of the natural anticoagulants (2-3 hours for protein C and 36-60 hours for AT and protein S), it is unclear if this acute decrease of natural anticoagulants is clinically relevant. Further investigation is needed to determine if this acute decrease may contribute to an increased VTE risk in children with SCD undergoing apheresis. Figure 1. Figure 1. Disclosures Woods: Biogen: Other: Educational Grant. Dunn:Novo Nordisk: Consultancy, Other: Educational Grant; CSL Behring: Consultancy, Other: Data Safety Monitoring Board; Bayer: Consultancy, Other: educational grant; Biogen: Consultancy, Other: Educational grant, Research Funding; Baxalta: Consultancy, Other: educational grant, Research Funding; Ohio State University: Employment; Pfizer: Other: Grant Review Board.

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