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ABSTRACT: We have designed a protocol for ABO-incompatible kidney transplantations based on antigen-specific immunoadsorption rather than plasmapheresis to remove anti-A or anti-B antibodies and with a Prograf/Cellcept/prednisolone protocol using rituximab rather than splenectomy to prevent rebound antibodies. Twelve patients have successfully received transplants with this protocol. The ABO-antibodies were readily removed by the antigen-specific immunoadsorption and maintained at a low-level posttransplantation. There were no side effects. All patients have normal renal transplant function with a follow-up of 1 to 34 months.
Transplantation Proceedings 11/2005; 37(8):3286-7. · 1.00 Impact Factor
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ABSTRACT: Acute rejection episodes still occur in spite of modern immunosuppressive protocols. We present seven patients with biopsy-proven acute rejections after kidney transplantation refractory to repeated pulses of high-dose steroids and antithymocyte globulin (ATG) or OKT-3, but responsive to photopheresis therapy.
Photopheresis is a nontoxic immunomodulatory, apheresis-based treatment with no general immunosuppressive action. Rather, it suppresses specific pathogenic T-cell clones. During photopheresis mononuclear leukocytes are collected from the patient using centrifugation technique, treated with a photosensitizing agent, irradiated, and subsequently retransfused.
All patients tolerated the treatment well, with no notable side effects. At the 12-month follow-up the median creatinine had decreased to 161 mumol/L compared to 282 mumol/L at the start of photopheresis and at the last follow-up 12 to 43 months after transplantation all patients still had functioning grafts. In five of the seven cases there had been a significant improvement in renal function, whereas in two of the patients the renal function remained stable but without a decrease in creatinine.
It is our experience that the prognosis for renal allografts with acute rejection unresponsive to conventional antirejection treatment (ie, repeated pulses of methylprednisolone and ATG or OKT-3) is very poor. Therefore, we conclude that the photopheresis treatment contributed to the favorable outcome in this small group of patients. We are presently designing a prospective randomized study to further evaluate the effect of photopheresis after renal transplantation.
Transplantation Proceedings 11/2005; 37(8):3288-9. · 1.00 Impact Factor
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M Remberger,
O Ringdén,
I W Blau,
H Ottinger,
B Kremens,
M G Kiehl,
J Aschan,
D W Beelen,
N Basara, G Kumlien,
A A Fauser,
V Runde
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ABSTRACT: The clinical results in 107 patients receiving a peripheral blood stem cell (PBSC) graft mobilized by granulocyte colony-stimulating factor (G-CSF) from HLA-A, -B, and -DR-compatible unrelated donors were compared to 107 matched controls receiving unrelated bone marrow (BM) transplants. Engraftment was achieved in 94% of the patients in both groups. The PBSC graft contained significantly more nucleated cells, CD34(+), CD3(+), and CD56(+) cells (P <.001), and resulted in a significantly shorter time-to-neutrophil (15 versus 19 days) and platelet engraftment (20 versus 27 days), compared to the BM control group (P <.001). Probabilities of acute graft-versus-host disease (GVHD) grades II to IV were 35% and 32% (not significant [NS]) and of chronic GVHD 61% and 76% (NS) in the PBSC and BM groups, respectively. There was no difference between the 2 groups in bacteremia, cytomegalovirus reactivation or disease, and fungal infection. The 3-year transplant-related mortality (TRM) rates were 42% in the PBSC group and 31% in the BM controls (P =.7) and the survival rates were 46% and 51%, respectively. The probability of relapse was 25% and 31% in both groups (NS), resulting in disease-free survival rates of 43% in the PBSC group and 46% in the BM controls (NS). In the multivariate analysis, early disease, acute GVHD grade 0 to I, and presence of chronic GVHD were independent factors associated with a better disease-free survival in this study. PBSC from HLA-compatible unrelated donors can be used safely as an alternative to BM for stem cell transplantation.
Blood 09/2001; 98(6):1739-45. · 9.90 Impact Factor
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ABSTRACT: In caucasians, in about 15 percent of all pregnancies the mother has blood group O and the child blood group A or B which is the usual setting in cases of HDN due to ABO-incompatibility. We describe a case of HDN where the mother had blood group A2 and no irregular erythrocyte antibodies. The patient, who was born at full term, had blood group A2B and negative DAT (Direct Antiglobulin Test). At 36 hours of age exchange transfusion was performed due to a serum bilirubin level of 340 (< 150) mumol/l. The mother had high titres of anti-B antibodies of IgG type and elution indicated presence of anti-B antibodies on the child's erythrocytes.
Lakartidningen 09/2000; 97(38):4138-40.
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ABSTRACT: In a previous study, low adenine nucleotide levels and a reduced rate of glycolysis were found in platelet concentrates (PCs) prepared by apheresis and stored in a platelet additive solution (PAS). Our objective was to investigate whether the use of PAS with or without phosphate can influence platelet metabolism in a similar way.
The in vitro effects of storage in either plasma or a PAS (T-Sol or PAS-III, both containing citrate, acetate and sodium chloride, PAS-III containing also phosphate) of buffy-coat-derived pooled platelet concentrates (BC-PCs) and apheresis platelets were investigated. The use of PAS implies inclusion of some plasma (20 or 35%). Paired studies over 7 days included investigation of cell counts, pH, PO2, PCO2, bicarbonate, glucose, lactate, adenine nucleotides, and extracellular adenylate kinase activity as a marker for disintegration of platelets. The expected concentration of phosphate in T-Sol is 0.6-1.8 mmol/l (with CPD plasma) and 0.2-0.6 mmol/l (with ACD plasma), and in PAS-III, 15-25 mmol/l (calculated values).
BC-PCs were compared during storage in 35% CPD plasma and 65% PAS (T-Sol or PAS-III) (experiment 1), or alternatively 20% CPD plasma and 80% PAS (T-Sol or PAS-III) (experiment 3). In both studies, PAS-III shows similar and significantly higher rates of glycolysis in terms of consumption of glucose (0.06 vs. 0.04 mmol/day/10(11) platelets) and production of lactate (0.11 vs. 0.07 mmol/day/10(11) platelets) compared with T-Sol. Levels of pH and adenine nucleotides were similar when 35% plasma was used. With only 20% plasma, significantly higher levels of adenine nucleotides were found with PAS-III compared to T-Sol. The storage of apheresis platelets in 35% ACD plasma and 65% PAS (either T-Sol or PAS-III) (experiment 5) gave significantly higher values for PAS-III compared to T-Sol with regard to consumption of glucose (0.08 vs. 0.06 mmol/day/10(11) platelets), production of lactate (0.14 vs. 0.11 mmol/day/10(11) platelets) and adenine nucleotide levels.
With respect to apheresis PCs stored in media containing ACD plasma, our results suggest that the differences found are related to the concentration of phosphate. The results for BC-PCs stored in media containing CPD plasma suggest that PAS-III is preferable to T-Sol as the PAS at plasma concentrations below 35%. The mechanism behind the phenomena observed with BC-PCs is not known.
Vox Sanguinis 02/2000; 78(3):176-84. · 2.86 Impact Factor
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ABSTRACT: Six patients who were to undergo autologous PBSC transplantation with positively selected CD34+ cells were included in this study to compare the efficiency of two devices for clinical grade stem cell selection, the Isolex 300i (Baxter, Munich, Germany) and CEPRATE SC (CellPro, Bothell, WA). PBSC were mobilized by chemotherapy and G-CSF and were collected by leukapheresis on a CS3000 cell separator on 2 consecutive days. The two apheresis products were pooled for CD34 selection. The pooled apheresis products from each patient were divided into two equal portions to be separated on each of the two devices. Cell selection was performed according to the manufacturers' instructions. Enumeration of CD34+ cells was performed by flow cytometry using the HPCA-2 MAb. Purity and yield were significantly better with Isolex than with CEPRATE. Median purity was 93.0% (range 80%-98%) for Isolex and 61.5% (range 27%-72%) for CEPRATE (p = 0.03); median yields for Isolex and for CEPRATE were 48.0% (range 18%-73%) and 23.0% (range 17%-29%), respectively (p = 0.03). The number of CD34+ cells/kg body weight was also significantly higher with Isolex (median 3.8x10(6), range 1.7-5.2) compared with CEPRATE (median 2.35x10(6), range 0.7-4.3) (p = 0.03). Thus, the Isolex 300i device gave products of higher purity and recovered a higher proportion of the CD34+ cells in the harvest before separation. The yield was still poor with both devices, however, and further optimization of the technique for clinical grade stem cell selection is warranted.
Journal of Hematotherapy 03/1999; 8(1):75-80.
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ABSTRACT: In this retrospective study, 23 recipients of peripheral blood progenitor cells (PBPC) were compared to 23 recipients of bone marrow (BM). The donors were 12 HLA-A-B-DR identical siblings and 11 HLA-A-B-DR identical unrelated donors in the PBPC and BM groups, respectively. Diagnoses in the PBPC group were CML seven, AML, nine, ALL three, lymphoma one, myeloma two and aspartylglucosaminuria (AGU) one. The median age was 40 (5-55) years. The BM group was matched for diagnosis, age, conditioning therapy, GVHD prophylaxis and G-CSF treatment after BMT. A higher number of MNC (P<0.001), CD34+ (P = 0.05), CD3+ (P<0.001) and CD56+ (P<0.001) cells in the graft, a reduced number of platelet transfusions (P = 0.03) and a significant hastening of neutrophil and platelet recovery were seen in the PBPC group compared to the BM group. In logistic regression analysis, the following factors were important for engraftment of ANC >0.5 x 10(9)/l: peripheral blood progenitor cell transplantation (PBPCT) (P = 0.003) and mononuclear cells (MNC) > or =2.5 x 10(8)/kg recipient in the graft (above median) (P = 0.009) in univariate analysis. For recovery of platelets >30 x 10(9)/l: PBPCT (P = 0.03) and HLA-identical sibling donors (P = 0.05) were significant in multivariate analysis. A trend towards a lower incidence of bacteremia was seen in the PBPC group, ie 22 vs 48% (P = 0.06) in the BM group. GVHD, TRM and survival did not differ between the two groups.
Bone Marrow Transplantation 07/1998; 22(2):131-6. · 3.75 Impact Factor
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ABSTRACT: To determine the effects of the nitric oxide (NO) precursor L-arginine on the airway NO concentration in patients with preeclampsia.
NO was measured by a noninvasive chemiluminescence technique in air sampled directly from nasal and oral cavities during expiration before and during L-arginine infusion in 9 preeclamptic and 10 control pregnancies. Maternal blood pressure and heart rate were simultaneously recorded, and blood was sampled for analyses of cyclic guanosine monophosphate (cGMP) and nitrate.
Basal nasal and orally exhaled NO and the increment in nasal NO concentration during L-arginine infusion were similar in both groups. Basal plasma and platelet cGMP concentrations were similar in both groups. Following L-arginine infusion, plasma cGMP levels were significantly higher in preeclamptics (p < 0.01), while platelet cGMP was unaffected in both groups. Basal plasma nitrate was significantly higher in preeclamptics (p < 0.01), and this difference was not altered following infusion. Blood pressure and heart rate remained unaffected by the procedure in both groups.
Blood pressure did not decrease in the preeclamptics following L-arginine infusion, despite a significant increase in nasal NO sampled during breathhold and a concomitant increase in plasma cGMP, possibly reflecting an endogenous NO production. These results do not support the idea of a generalized decrease in NO production being a major cause of hypertension in preeclampsia.
Gynecologic and Obstetric Investigation 02/1998; 46(4):232-7. · 1.28 Impact Factor
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The Lancet 09/1996; 348(9023):346. · 38.28 Impact Factor
