Journal of Clinical Apheresis 30:61–133 (2015)
Special Issue Abstracts From the American Society for Apheresis 36th Annual Meeting, May 6–9, 2015 San Antonio, Texas P-01 TREATMENT OF THROMBOTIC THROMBOCYTOPENIC PURPURA PATIENTS REMAINS HETEROGENEOUS Yara A Park, MD,1 Jay S Raval, MD,1 Mark E Brecher, MD2 and Marshall Mazepa, MD1 1 Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina 2 Laboratory Corporation of America, Chapel Hill, North Carolina Purpose: Thrombotic thrombocytopenic purpura (TTP) is a lifethreatening thrombotic microangiopathy for which therapeutic plasma exchange (TPE) is the mainstay of therapy. In 1998, Bandarenko and Brecher conducted a survey of 20 apheresis centers which showed heterogeneity in the treatment of TTP. Despite many advances in the understanding TTP, there appears to be continued diversity in the care of these patients. The recent ASFA TTP Consensus Conference manuscript additionally noted a lack of consensus with regards to certain parts of therapy. We sought to characterize the current trends in the treatment of TTP by apheresis centers in the United States. Methods: Apheresis facilities were identified using the ASFA Facilities Directory and the Transfusion Medicine Fellowship List. A member of the research team emailed a physician at the facility to arrange a phone interview. Using an online survey tool, a research team member administered a 9 question survey. Our institutional review board approved this study. Results: A total of 32 apheresis centers from 22 states were surveyed between March and June of 2014. TTP patient volume varied between institutions: 11 centers treat 11–20 patients/year, 11 centers treat 5–10 patients/year, and 10 centers treat < 5 patients/year. At all centers, TPE is started as soon as TTP is the most likely diagnosis. ADAMTS13 testing is utilized to guide TPE in all but 1 center. 21 centers (66%) send the test to a reference lab and 10 (31%) perform testing in-house. 29 centers (91%) use plasma as the replacement fluid, 4 of the centers routinely utilize cryopoor plasma (CPP) as a replacement fluid (2 use it exclusively), and 2 centers reported routinely using albumin as part of the replacement fluid. 23 centers (72%) replace 1 plasma volume (PV), while 8 centers (25%) replace > 1 PV as some part of standard therapy; 1 center replaces volume on a mL/kg basis. Nearly all centers perform 1 TPE per day as their standard but 11 centers (34%) reported that they either have or would perform TPE twice in one day for extremely ill or refractory patients. In the medical care of patients with TTP, 26 centers (81%) reported the standard use of prednisone. Use of rituximab was highly heterogeneous: 4 centers (13%) do not use rituximab while 28 centers (88%) use it routinely. Of those that use rituximab
to treat TTP, 5 of 28 centers (18%) routinely use the drug during the first presentation of TTP while the remaining 23 centers (82%) use it in relapsed/refractory patients. 27 of the 28 centers (96%) administer rituximab concurrently with TPE, however, all wait until late in the TPE course to start therapy. However, even within centers, use of the drug varies from provider to provider. The decision to stop TPE is still primarily based on platelet count, however 2 centers reported using a ‘stable’ platelet count as a decision point, 1 center reported using platelet count > than LDH, and 1 center utilizes normalization of ADAMTS13 to stop daily TPE. 28 centers (88%) utilize a specific platelet count to stop TPE; 21 of these 28 centers (75%) use a platelet count of 150 3 109/L as their threshold. 22 centers (69%) taper TPE when criteria are met to stop daily TPE and 10 (31%) do not taper TPE. Conclusions: Despite increased understanding of TTP and the ASFA TTP Consensus Conference manuscript, there is not a universally-implemented standard of care for supporting the TTP patient. For TTP registries and studies to be successful, there must be standardization in the treatment of this patient population.
P-02 THERAPEUTIC APHERESIS WITH 5% ALBUMIN AS A NEW APPROACH FOR THE TREATMENT OF ALZHEIMER’S DISEASE Oscar Lopez, MD,1 Merce Boada, MD, PhD,2 Laura Nu~nez, BsSc,3 Pilar Ortiz,4 Fernando Anaya, MD,5 Isabel Hernandez, MD,6 Javier Olazaran, MD,7 Lluis Tarraga, MD,6 Mar Buendia, MD,6 Ramon P Pla, MD,4 Isidro Ferrer, MD,8 Thomas O Obisesan, MD,9 Joshua R Shua-Haim, MD10 and Antonio Paez, MD3 1 Alzheimer’s Disease Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 2 Fundacio ACE, Barcelona, ES 3 Clinical, Instituto Grifols, Barcelona, ES 4 Banc de Sang i Teixits, Blood and Tissue Bank, Barcelona, ES 5 Nephrology Service, Hospital General Universitario Gregorio Mara~non, Madrid, ES 6 Institut Catala de Neurociencies Aplicades, Fundacio ACE, Barcelona, ES 7 Neurology Service, Hospital General Universitario Gregorio Mara~non, Madrid, ES 8 Institut de Neuropatologia, Hospital Universitario Bellvitge, Barcelona, ES 9 Neurology, Howard University, Washington DC, District of Columbia 10 Neurology, Mid Atlantic Geriatric Association, Manchester, New Jersey
Published online in Wiley Online Library (wileyonlinelibrary.com) DOI 10.1002/jca.21385 C 2015 Wiley Periodicals, Inc. V
62
Journal of Clinical Apheresis 30 (2015)
Purpose: It has been postulated that there exists a dynamic equilibrium between Ab in the central nervous system (CNS) and plasma. Since most circulating Ab is bound to albumin, we investigated whether therapeutic apheresis in which plasma is removed and substituted by therapeutic albumin could modify the toxic Ab levels in Alzheimer’s disease (AD) patients which could be reflected in clinical benefits. Methods: In this multicenter, randomized, blind, phase II study, 42 patients with mild-moderate AD were enrolled and assigned (1:1) to therapeutic apheresis treatment (with plasma exchange using 5% Albutein,V; Grifols) and control (simulated apheresis: sham) groups. Patients received 2 therapeutic apheresis/week for three weeks, followed by one therapeutic apheresis/every week for 6 weeks, one therapeutic apheresis/2 weeks for 12 weeks plus 24 weeks follow-up. Ab-40 and Ab42 levels were determined by ELISA in plasma before and after each therapeutic apheresis, and in the cerebrospinal fluid (CSF) 4 times during the treatment period and 2 times during the follow-up. ADAS-Cog, MMSE, a battery of neuropsychological tests, activities of daily living (ADCS-ADLs scale) and psychiatric symptoms (NPI) were examined during the study. Results: Thirty seven patients completed the study (mean age: 6.767.9 years), 18 treated and 19 controls. CSF Ab-40 and Ab-42 levels between the end of the last therapeutic apheresis and the baseline levels were not significantly different between groups (values ranging 6000–7000 pg/mL for Ab-40 and 600– 1000 pg/mL for Ab-42), although there was a trend to have higher levels in the treated group (p ranging 0.07-0.09). Plasma Ab-42 was lower in the treated group. Ab-40 levels in plasma showed a saw-tooth pattern variation associated to the beforeafter sequence of the apheresis procedure (minimums and maximums around 150–200 pg/mL and 250–300 pg/mL, respectively). This pattern could not be clearly seen in Ab-42. ADAS-Cog scores showed no statistical differences between groups. MMSE scores tended to be higher in the treated group (P50.08). Treated patients performed in general better on language and memory function tests (BNT, RAVLT and SVF tests; P value ranging 0.001-0.05) and this persisted after the treatment discontinuation. Behavioral / functional tests scores were in general worse in the treated group (ADCS-ADLs and NPI; P value ranging 0.0001-0.05) although the difference subsided when therapeutic apheresis was discontinued. There were more adverse events related to study procedures in the treated group (94.7% underwent at least one adverse event throughout the study vs. 70.0% in controls), although the difference was not statistically significant. Conclusions: This novel approach of therapeutic apheresis plus plasma replacement with 5% albumin modified the Ab levels in CSF and plasma in AD patients. The treatment was associated with an improvement in language and memory abilities that persisted after the treatment was discontinued. Further studies are in progress. R
P-03 ANTI-MPO ANCA-ASSOCIATED DIFFUSE ALVEOLAR HEMORRHAGE IS ASSOCIATED WITH INCREASED MORTALITY COMPARED TO ANTI-PR3 DISEASE
Journal of Clinical Apheresis DOI 10.1002/jca
Grace M Lee, MD, Yara A Park, MD, Marshall Mazepa, MD and Jay Suman Raval, MD Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina Purpose: Therapeutic plasma exchange (TPE) is an ASFA Category I indication for the treatment of ANCA-associated diffuse alveolar hemorrhage (DAH). Despite emergent and aggressive intervention, some patients succumb to this disease. Nephrologists, pulmonologists, and pathologists have remarked on differences between anti-myeloperoxidase (MPO) vs. anti-proteinase 3 (PR3) ANCA vasculitis. However, little has been described regarding differences between these two variants of ANCAassociated DAH in the clinical setting. Our goal was to characterize patients with ANCA-associated DAH and determine if differences existed between those with anti-MPO vs. anti-PR3 disease. Methods: The apheresis and medical records were retrospectively analyzed at our institution for any patient with keywords “ANCA”, “Wegener’s granulomatosis”, “polyangiitis”, “diffuse alveolar hemorrhage”, “DAH”, or “pulmonary hemorrhage” between 1/2010 and 8/2014. Records that contained any of these keywords were reviewed and only those with a diagnosis of ANCA-associated DAH along with a detectable serologic antiMPO or anti-PR3 titer (measured by quantitative ELISA; normal
Special Issue Abstracts From the American Society for Apheresis 36th Annual Meeting, May 6–9, 2015 San Antonio, Texas P-01 TREATMENT OF THROMBOTIC THROMBOCYTOPENIC PURPURA PATIENTS REMAINS HETEROGENEOUS Yara A Park, MD,1 Jay S Raval, MD,1 Mark E Brecher, MD2 and Marshall Mazepa, MD1 1 Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina 2 Laboratory Corporation of America, Chapel Hill, North Carolina Purpose: Thrombotic thrombocytopenic purpura (TTP) is a lifethreatening thrombotic microangiopathy for which therapeutic plasma exchange (TPE) is the mainstay of therapy. In 1998, Bandarenko and Brecher conducted a survey of 20 apheresis centers which showed heterogeneity in the treatment of TTP. Despite many advances in the understanding TTP, there appears to be continued diversity in the care of these patients. The recent ASFA TTP Consensus Conference manuscript additionally noted a lack of consensus with regards to certain parts of therapy. We sought to characterize the current trends in the treatment of TTP by apheresis centers in the United States. Methods: Apheresis facilities were identified using the ASFA Facilities Directory and the Transfusion Medicine Fellowship List. A member of the research team emailed a physician at the facility to arrange a phone interview. Using an online survey tool, a research team member administered a 9 question survey. Our institutional review board approved this study. Results: A total of 32 apheresis centers from 22 states were surveyed between March and June of 2014. TTP patient volume varied between institutions: 11 centers treat 11–20 patients/year, 11 centers treat 5–10 patients/year, and 10 centers treat < 5 patients/year. At all centers, TPE is started as soon as TTP is the most likely diagnosis. ADAMTS13 testing is utilized to guide TPE in all but 1 center. 21 centers (66%) send the test to a reference lab and 10 (31%) perform testing in-house. 29 centers (91%) use plasma as the replacement fluid, 4 of the centers routinely utilize cryopoor plasma (CPP) as a replacement fluid (2 use it exclusively), and 2 centers reported routinely using albumin as part of the replacement fluid. 23 centers (72%) replace 1 plasma volume (PV), while 8 centers (25%) replace > 1 PV as some part of standard therapy; 1 center replaces volume on a mL/kg basis. Nearly all centers perform 1 TPE per day as their standard but 11 centers (34%) reported that they either have or would perform TPE twice in one day for extremely ill or refractory patients. In the medical care of patients with TTP, 26 centers (81%) reported the standard use of prednisone. Use of rituximab was highly heterogeneous: 4 centers (13%) do not use rituximab while 28 centers (88%) use it routinely. Of those that use rituximab
to treat TTP, 5 of 28 centers (18%) routinely use the drug during the first presentation of TTP while the remaining 23 centers (82%) use it in relapsed/refractory patients. 27 of the 28 centers (96%) administer rituximab concurrently with TPE, however, all wait until late in the TPE course to start therapy. However, even within centers, use of the drug varies from provider to provider. The decision to stop TPE is still primarily based on platelet count, however 2 centers reported using a ‘stable’ platelet count as a decision point, 1 center reported using platelet count > than LDH, and 1 center utilizes normalization of ADAMTS13 to stop daily TPE. 28 centers (88%) utilize a specific platelet count to stop TPE; 21 of these 28 centers (75%) use a platelet count of 150 3 109/L as their threshold. 22 centers (69%) taper TPE when criteria are met to stop daily TPE and 10 (31%) do not taper TPE. Conclusions: Despite increased understanding of TTP and the ASFA TTP Consensus Conference manuscript, there is not a universally-implemented standard of care for supporting the TTP patient. For TTP registries and studies to be successful, there must be standardization in the treatment of this patient population.
P-02 THERAPEUTIC APHERESIS WITH 5% ALBUMIN AS A NEW APPROACH FOR THE TREATMENT OF ALZHEIMER’S DISEASE Oscar Lopez, MD,1 Merce Boada, MD, PhD,2 Laura Nu~nez, BsSc,3 Pilar Ortiz,4 Fernando Anaya, MD,5 Isabel Hernandez, MD,6 Javier Olazaran, MD,7 Lluis Tarraga, MD,6 Mar Buendia, MD,6 Ramon P Pla, MD,4 Isidro Ferrer, MD,8 Thomas O Obisesan, MD,9 Joshua R Shua-Haim, MD10 and Antonio Paez, MD3 1 Alzheimer’s Disease Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 2 Fundacio ACE, Barcelona, ES 3 Clinical, Instituto Grifols, Barcelona, ES 4 Banc de Sang i Teixits, Blood and Tissue Bank, Barcelona, ES 5 Nephrology Service, Hospital General Universitario Gregorio Mara~non, Madrid, ES 6 Institut Catala de Neurociencies Aplicades, Fundacio ACE, Barcelona, ES 7 Neurology Service, Hospital General Universitario Gregorio Mara~non, Madrid, ES 8 Institut de Neuropatologia, Hospital Universitario Bellvitge, Barcelona, ES 9 Neurology, Howard University, Washington DC, District of Columbia 10 Neurology, Mid Atlantic Geriatric Association, Manchester, New Jersey
Published online in Wiley Online Library (wileyonlinelibrary.com) DOI 10.1002/jca.21385 C 2015 Wiley Periodicals, Inc. V
62
Journal of Clinical Apheresis 30 (2015)
Purpose: It has been postulated that there exists a dynamic equilibrium between Ab in the central nervous system (CNS) and plasma. Since most circulating Ab is bound to albumin, we investigated whether therapeutic apheresis in which plasma is removed and substituted by therapeutic albumin could modify the toxic Ab levels in Alzheimer’s disease (AD) patients which could be reflected in clinical benefits. Methods: In this multicenter, randomized, blind, phase II study, 42 patients with mild-moderate AD were enrolled and assigned (1:1) to therapeutic apheresis treatment (with plasma exchange using 5% Albutein,V; Grifols) and control (simulated apheresis: sham) groups. Patients received 2 therapeutic apheresis/week for three weeks, followed by one therapeutic apheresis/every week for 6 weeks, one therapeutic apheresis/2 weeks for 12 weeks plus 24 weeks follow-up. Ab-40 and Ab42 levels were determined by ELISA in plasma before and after each therapeutic apheresis, and in the cerebrospinal fluid (CSF) 4 times during the treatment period and 2 times during the follow-up. ADAS-Cog, MMSE, a battery of neuropsychological tests, activities of daily living (ADCS-ADLs scale) and psychiatric symptoms (NPI) were examined during the study. Results: Thirty seven patients completed the study (mean age: 6.767.9 years), 18 treated and 19 controls. CSF Ab-40 and Ab-42 levels between the end of the last therapeutic apheresis and the baseline levels were not significantly different between groups (values ranging 6000–7000 pg/mL for Ab-40 and 600– 1000 pg/mL for Ab-42), although there was a trend to have higher levels in the treated group (p ranging 0.07-0.09). Plasma Ab-42 was lower in the treated group. Ab-40 levels in plasma showed a saw-tooth pattern variation associated to the beforeafter sequence of the apheresis procedure (minimums and maximums around 150–200 pg/mL and 250–300 pg/mL, respectively). This pattern could not be clearly seen in Ab-42. ADAS-Cog scores showed no statistical differences between groups. MMSE scores tended to be higher in the treated group (P50.08). Treated patients performed in general better on language and memory function tests (BNT, RAVLT and SVF tests; P value ranging 0.001-0.05) and this persisted after the treatment discontinuation. Behavioral / functional tests scores were in general worse in the treated group (ADCS-ADLs and NPI; P value ranging 0.0001-0.05) although the difference subsided when therapeutic apheresis was discontinued. There were more adverse events related to study procedures in the treated group (94.7% underwent at least one adverse event throughout the study vs. 70.0% in controls), although the difference was not statistically significant. Conclusions: This novel approach of therapeutic apheresis plus plasma replacement with 5% albumin modified the Ab levels in CSF and plasma in AD patients. The treatment was associated with an improvement in language and memory abilities that persisted after the treatment was discontinued. Further studies are in progress. R
P-03 ANTI-MPO ANCA-ASSOCIATED DIFFUSE ALVEOLAR HEMORRHAGE IS ASSOCIATED WITH INCREASED MORTALITY COMPARED TO ANTI-PR3 DISEASE
Journal of Clinical Apheresis DOI 10.1002/jca
Grace M Lee, MD, Yara A Park, MD, Marshall Mazepa, MD and Jay Suman Raval, MD Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina Purpose: Therapeutic plasma exchange (TPE) is an ASFA Category I indication for the treatment of ANCA-associated diffuse alveolar hemorrhage (DAH). Despite emergent and aggressive intervention, some patients succumb to this disease. Nephrologists, pulmonologists, and pathologists have remarked on differences between anti-myeloperoxidase (MPO) vs. anti-proteinase 3 (PR3) ANCA vasculitis. However, little has been described regarding differences between these two variants of ANCAassociated DAH in the clinical setting. Our goal was to characterize patients with ANCA-associated DAH and determine if differences existed between those with anti-MPO vs. anti-PR3 disease. Methods: The apheresis and medical records were retrospectively analyzed at our institution for any patient with keywords “ANCA”, “Wegener’s granulomatosis”, “polyangiitis”, “diffuse alveolar hemorrhage”, “DAH”, or “pulmonary hemorrhage” between 1/2010 and 8/2014. Records that contained any of these keywords were reviewed and only those with a diagnosis of ANCA-associated DAH along with a detectable serologic antiMPO or anti-PR3 titer (measured by quantitative ELISA; normal
