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Petra Jilma-Stohlawetz,
Friedrich W Kursten,
Michaela Horvath, Gerda Leitner,
Jana List,
Jana Marcek,
Peter Quehenberger,
Michael Schwameis,
Johann Bartko,
Ulla Derhaschnig,
Bernd Jilma
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ABSTRACT: BACKGROUND: Octaplas LG is a prion-depleted version of a previous generation product called Octaplas S/D. We compared the recovery, safety, and tolerability of these two pharmaceutical-grade plasmas. STUDY DESIGN AND METHODS: In this comparative, block-randomized, open-label, active-controlled, crossover Phase I trial, 60 healthy adult volunteers received single transfusions of 1200 mL of parent product (in Period 1) and of the LG plasma product (in Period 2) or vice versa. In both periods, plasmapheresis (600 mL) preceded the transfusion. Blood samples were drawn before and after apheresis and 15 minutes, 2 hours, 24 hours, and 7 days after end of plasma transfusion, to assess recovery, safety, and tolerability. The primary efficacy endpoints were the changes in coagulation factors and hemostatic variables compared to baseline; their relative recovery was computed in the per-protocol analysis (n = 43). Safety and tolerability were assessed (n = 60). RESULTS: Variations in coagulation factors and hemostatic variables over time were similar between the two treatments and within normal range; 90% confidence intervals for the derived recovery data were within predefined limits of equivalence. Both products were well tolerated. The advanced manufacturing process also significantly increased plasmin inhibitor concentrations after transfusion in vivo. CONCLUSION: The LG plasma product was bioequivalent to its predecessor with respect to recovery of clotting factors and demonstrated comparable safety and tolerability in healthy volunteers. Both products compensated well for the loss of clotting factors after apheresis (NCT01063595).
Transfusion 01/2013; · 3.22 Impact Factor
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ABSTRACT: Extracorporeal photopheresis (ECP) is a combination of leukapheresis and photodynamic therapy in which blood is treated with photoactivable drugs which are then activated with ultraviolet light and re-infused to the patient. It has been used successfully for more than 30 years in the treatment of erythrodermic cutaneous T-cell lymphoma (CTCL) and over 20 years for chronic graft-versus-host disease (GVHD). ECP has also shown promising results in the treatment of acute GVHD and other T-cell-mediated diseases, including systemic sclerosis, treatment and prevention of solid organ rejection, and more recently Crohn's disease. The use of ECP may allow a significant reduction or even discontinuation of corticosteroids and/or other immunosuppressants, thus leading to reduced long-term morbidity and mortality and improved overall survival. ECP is a well-tolerated therapy. No significant side effects have been reported during the last 30 years. It has been shown that ECP is not associated with an increased incidence of infections, malignancies, or recurrence of underlying malignant disease, neither during short-term nor during long-term therapy.
Transfusion Medicine and Hemotherapy 08/2012; 39(4):254-262. · 1.16 Impact Factor
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ABSTRACT: Due to the fact that the ABO and D system is inherited independently from the HLA system, approximately 40% of allogeneic hematopoietic stem cell transplants (HSCT) are performed across the blood group barrier. Reports on the development of de novo anti-D in patients undergoing reduced-intensity conditioning (RIC) followed by D-mismatched allogeneic HSCT are rare. The objective of this study was to evaluate the frequency of anti-D alloimmunization after D-mismatched HSCT following RIC and its prognostic impact on transplant outcome.
Forty patients with hematologic diseases who underwent D-mismatched HSCT were retrospectively analyzed: 19 D- patients with a D+ donor and 21 D+ patients with a D- donor. Routine serologic testing for blood group typing and antibody screening was performed by a column agglutination method every time when transfusion of red blood cell units was requested and in the posttransplantation course to demonstrate establishment of donor ABO type and to detect alloimmunization.
After a median serologic follow-up of 21 (range, 0 to 73) months after HSCT, anti-D was identified in 2 of 21 (10%) D+ patients receiving a D- transplant, 23 and 34 months after HSCT. None of the 19 D- patients with a D+ donor developed an anti-D.
We observed an infrequent de novo anti-D formation that is more likely in D+ recipients of D- grafts. However, the development of anti-D does not normally impair the transplant outcome and is not of clinical relevance in the posttransplant course.
Transfusion 12/2011; 52(6):1348-53. · 3.22 Impact Factor
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ABSTRACT: Universal plasma is intended to be transfused irrespective of the blood group. We compared the safety and tolerability of a novel, universal blood group-independent plasma with an ABO-matched plasma.
In this randomized, double-blind, active-controlled, crossover, Phase I trial, 30 healthy adult volunteers (blood group A, B, or AB) were randomly assigned to transfusion of 1200 mL of Uniplas LG and 1200 mL of Octaplas LG (both Octapharma AG) or vice versa. In both periods, plasmapheresis (PPh, 600 mL) preceded the infusion. Blood samples were drawn before and after PPh and 15 minutes, 2 hours, 24 hours, and 7 days after end of plasma transfusion, to assess safety and efficacy. The primary safety outcome was change in hemoglobin (Hb) concentration; secondary safety outcomes were direct antiglobulin test (DAT), complement activation, free Hb, haptoglobin, and indirect bilirubin. Efficacy was assessed by evaluation of coagulation variables.
Variations of Hb concentration were similar between treatments and within normal range; 90% confidence interval was within predefined limits of equivalence. No subject exhibited a positive DAT. All other secondary variables which could reflect hemolytic transfusion reactions (HTRs) fell within normal range; this suggests that no HTRs occurred. Most adverse events were of mild intensity; two subjects experienced dyspnea, leading to the withdrawal from the study of one subject.
Universal plasma was equivalent to ABO-matched plasma with respect to safety and tolerability. Eliminating the risk of ABO incompatibility, this universal plasma represents an advance over blood group-specific plasma.
Transfusion 02/2011; 51(6):1228-40. · 3.22 Impact Factor
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ABSTRACT: The immune recovery of 66 patients undergoing allogeneic stem cell transplantation with either conventional or non-myeloablative conditioning regimen was studied. Infections post-transplant were enumerated and quantitative immunoglobuilins (IgG, IgA, IgM) and lymphocyte sub-sets 3, 6 and 12 months post-transplant were measured. A significant difference was found in the immunologic recovery of non-myeloablative and conventional ASCT in the patient population. The T-helper cell reconstitution was significantly faster after NMA than conventional transplantation and the recovery of B cells was faster after conventional transplantation. Regarding immunoglobulin levels, a faster recovery of IgM levels after NMA-ASCT and a delayed recovery of IgA levels was observed in both groups. These were accompanied by a significant difference in the frequency and severity of infectious episodes.
06/2009; 46(12):1755-1760.
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ABSTRACT: Granulocyte transfusions (GTs) may increase the absolute neutrophil count (ANC) before hematopoietic regeneration in neutropenic patients after chemotherapy or hematopoietic stem cell transplantation and support anti-infective immunity.
We assessed efficacy and tolerability of 778 GTs in 70 treatment episodes of 49 children and 10 young adults [median age 6.28 y (range: 0.13 to 17.7 y) and 21 y (18.0 to 28.0), respectively] suffering from bacterial (n=55) and/or fungal (n=31) infections during neutropenia owing to conventional chemotherapy (n=14), hematopoietic stem cell transplantation conditioning (n=44), or the underlying disease (n=1). We analyzed the impact of body weight, organ dysfunction, neutrophil dose on ANC increment, infection elimination, and survival.
The median day-5 ANC increment was 1460/microL, correlating to the administered dose. However, 28-day survival did not correlate to the neutrophil dose nor to the ANC increment, potentially owing to the high number of neutrophils transfused to all patients (median >6x10(9)/kg within 5 d). The 28-day survival probability of the total patient cohort was 0.72+/-0.06 and the 100-day survival was 0.52+/-0.07. Adverse reactions were rare including fever (< or =World Health Organization grade III, 14%), chills (3%), and mild pulmonary complications (1%).
These data corroborate the empirical evidence that GT with sufficient cell doses and rapid availability are a feasible, well-tolerated supplemental means to fight severe infections in neutropenic patients.
Journal of Pediatric Hematology/Oncology 03/2009; 31(3):166-72. · 1.16 Impact Factor
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ABSTRACT: Delayed severe immune hemolysis due to donor-derived passenger lymphocytes is observed in minor and/or bidirectional ABO-mismatched transplants, especially after reduced-intensity conditioning (RIC). The incidence is reported in up to 30 percent of patients and can result in multiorgan failure (MOF) and death.
A first group of 32 patients (historical control) underwent RIC followed by allogeneic hematopoietic peripheral blood progenitor cell transplantation at our institution. In 5 of 10 patients with a minor and/or bidirectional ABO-mismatched graft, severe immune hemolysis was observed, leading to death in 3 of them. Therefore, we initiated a protocol with prophylactic red blood cell (RBC) exchange in minor and/or bidirectional ABO mismatch of a second group of patients (study group) and investigated the incidence of hemolysis, transplant-related mortality (TRM), and overall survival (OS) and compared these data with the historical control group. Twenty-two of 80 patients in the study group had a minor and/or bidirectional ABO-mismatched donor.
In 20 patients, a prophylactic RBC exchange was performed. Three patients showed mild to moderate citrate reactions, and in 1 patient the procedure had to be stopped because of hypotension. Eighteen of 20 patients engrafted uneventfully, 1 patient rejected his graft, and another 1 showed signs of mild hemolysis. In the minor and/or bidirectional ABO-mismatched setting patients in the study group had a lower risk for TRM at 1 year compared to patients in the historical control group (16% vs. 53%, p < 0.05) and a better 1-year OS (65% vs. 40%, p < 0.05).
RBC exchange is a safe procedure, reducing the incidence of delayed severe immune hemolysis and thus the risk of TRM in minor and/or bidirectional ABO-mismatched cases.
Transfusion 08/2007; 47(8):1494-502. · 3.22 Impact Factor
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ABSTRACT: Transplant-associated microangiopathy (TAM) is a severe complication following allogeneic hematopoietic stem cell transplantation (HSCT) even after reduced-intensity conditioning (RIC). Data on 112 patients following RIC were analyzed with respect to TAM according to the ASBMT and risk factors, response to well-defined therapy and outcome were determined. TAM occurred in 11 of 112 patients. Univariate analysis determined acute graft-versus-host disease and ABO-incompatibility as risk factors for TAM. Treatment consisted of withdrawal of calcineurin inhibitors and plasma exchange (PE). Response to PE was 64%. PE seems to be an effective therapeutic option that should be assessed in larger patient cohorts.
Transfusion and Apheresis Science 07/2007; 36(3):297-304. · 1.25 Impact Factor
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ABSTRACT: The immune recovery of 66 patients undergoing allogeneic stem cell transplantation with either conventional or non-myeloablative conditioning regimen was studied. Infections post-transplant were enumerated and quantitative immunoglobuilins (IgG, IgA, IgM) and lymphocyte sub-sets 3, 6 and 12 months post-transplant were measured. A significant difference was found in the immunologic recovery of non-myeloablative and conventional ASCT in the patient population. The T-helper cell reconstitution was significantly faster after NMA than conventional transplantation and the recovery of B cells was faster after conventional transplantation. Regarding immunoglobulin levels, a faster recovery of IgM levels after NMA-ASCT and a delayed recovery of IgA levels was observed in both groups. These were accompanied by a significant difference in the frequency and severity of infectious episodes.
Leukemia and Lymphoma 01/2006; 46(12):1755-60. · 2.58 Impact Factor
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Werner Rabitsch,
Erika Prinz,
Jutta Ackermann,
Stefan Wöhrer,
Hannes Kaufmann,
Sonja Seidl,
Felix Keil,
Peter Kalhs,
Hildegard Greinix,
Heinz Gisslinger, Gerda Leitner,
Johannes Drach
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ABSTRACT: Allogeneic transplantation may offer a curative approach to multiple myeloma (MM). We retrospectively analyzed the outcome of patients with multiple myeloma undergoing allogeneic stem cell transplantation in the context of beta(2) microglobulin and chromosome 13q.
All 13 patients with MM, who were referred to our center for allogeneic stem cell transplantation, were evaluated. Median age of patients was 38 yr, eight patients had chemo-sensitive disease, and median time between diagnosis of MM and transplantation was 15 months. Engraftment, acute and chronic graft vs. host disease, response to treatment, disease-free survival, and overall survival were evaluated according to standard criteria.
There was one transplant-related death. Among 12 evaluable patients, seven patients (58%) achieved a complete remission (CR), and four patients (33%) achieved a partial remission. Acute graft vs. host disease occurred in 46% of patients, and chronic graft vs. host disease in 42% of available patients. After a median follow-up of 69.5 months (range, 5-128) nine patients (70%) are still alive, and six of them have remained progression free. Among five patients with low beta(2) microglobulin and normal chromosome 13q, four patients achieved a CR, with CR duration >5 yr in three of them. Among seven patients with elevated ss(2) microglobulin and/or deletion of chromosome 13q, only three CR were observed, with two patients still in CR on days +920 and +161, respectively.
Allogeneic stem cell transplantation in patients with MM results in promising rates of CR, but durable remissions are predominantly seen in patients with favorable prognostic parameters.
European Journal Of Haematology 01/2004; 72(1):26-31. · 2.61 Impact Factor
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ABSTRACT: Plateletpheresis technologies differ among various cell separators. Differences in centrifugation force, centrifugation time, and platelet concentration in the platelet concentrate may affect platelet activation and function.
In a three-way crossover design, 12 donors were randomly assigned to three types of cell separators, two continuous flow systems (Amicus DN, Fenwall Division, Baxter and Spectra LRS, Gambro BCT) and one intermittent flow system (MCS+, Haemonetics). The response to vWF-coated beads was determined in the peripheral blood and fresh platelet concentrates to obtain information about the initiating step of platelet aggregation, that is, platelet adhesion. Levels of soluble p-selectin were measured as a marker of platelet activation.
Platelet yield and concentration of platelets were higher in platelet concentrates obtained with the Amicus DN than with the Spectra LRS or the MCS+. Maximal aggregation was significantly higher in platelets from the Amicus DN than in platelets from the Spectra LRS or the MCS+. Higher concentrations of soluble p-selectin were seen in platelet concentrates obtained with the Amicus DN than in concentrates from the Spectra LRS or the MCS+, but they did not differ after correction for the number of platelets per component.
Different plateletpheresis procedures induced distinct changes of platelet function. Platelets collected using the Amicus DN retained the strongest adhesion capacity irrespective of their activation.
Transfusion 04/2002; 42(3):375-9. · 3.22 Impact Factor
