Microangiopathy in patients on cyclosporine prophylaxis who developed acute graft-versus-host disease after HLA-identical bone marrow transplantation

Holler, Ernst; Hj, Kolb; Hiller, Erhard; Mraz, W.; Lehmacher, Walter; Gleixner, B; Seeber, C; Jehn, U.; Gerhartz, HH; Brehm, G.

doi:10.1182/blood.v73.7.2018.bloodjournal7372018

Cited by 77 publications

(92 citation statements)

References 29 publications

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“…One patient had an elevated activated partial thromboplastin time (APTT), and we were unable to ascertain whether this corrected in vitro with protamine. Five patients had a reduced APTT ratio, which has been reported in this disease (Holler et al, 1989).…”

Section: Clinical Features At Diagnosis Of Ttpsupporting

confidence: 65%

“…A major question to be resolved is why our centre experiences a nearly 10 times higher incidence than that reported by the Italian multicentre group (Iacopino et al, 1999). The reasons are likely to be many.…”

Section: Discussionmentioning

confidence: 85%

“…Clinical risk factors found in some (but not all) studies include acute GvHD (Holler et al, 1989), cyclosporin prophylaxis for GvHD and female sex (Iacopino et al, 1999). Our relatively high incidence of cases (Iacopino et al, 1999) enabled us to do a detailed case±control analysis of the risk factors for post-transplant TTP. Female gender, similar to non-transplant-associated TTP (Rock, 2000), is an important factor, and our combined paediatric and adult population has enabled us to define age as a significant risk factor for the first time.…”

Section: Discussionmentioning

confidence: 99%

“…A recently reported Italian multicentre survey (Iacopino et al, 1999) reported a low incidence of TTP with a relatively high recovery rate and seemed to suggest that the problem is minor and a relatively uncommon cause of transplantassociated morbidity and mortality. There are a number of possible explanations for the variation in the reported incidence of TTP, including different definitions, underdiagnosis of milder TTP and variation in transplantconditioning protocols, types of donor and the underlying diseases treated.…”

mentioning

confidence: 98%

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The clinical features, risk factors and outcome of thrombotic thrombocytopenic purpura occurring after bone marrow transplantation

et al. 2001

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Summary. In this study, we retrospectively analysed the clinical features, risk factors and outcome of 22 patients with thrombotic thrombocytopenic purpura (TTP) occurring after allogeneic stem cell transplantation. All but two of these patients received stem cells from unrelated donors (UDs), two-thirds were female, three-quarters were adults and leukaemia was the major reason for transplant. The incidence of TTP was 20 out of 332 patients (6%) with UD transplants and two out of 104 recipients (2%) of matched sibling allografts (P 0´16). In order to ascertain basic demographic risk factors for the development of TTP, we compared the 22 patients with 434 patients who did not develop TTP. Compared with patients who did not develop TTP, patients with TTP were nearly three times older (P , 0´001) and were more than twice as likely to be female (P 0´001). Because . 90% of patients were recipients of UD marrow, we then compared the 20 UDbone marrow transplantation (BMT) patients with 60 randomly selected UD-BMT patients who did not develop TTP. On univariate analysis, age and female gender were again significant risk factors, as was grade II±IV acute graft-versus-host disease (GvHD) (P 0´002), and there was a trend towards an association with chronic GvHD (P 0´083). However, after logistic regression analysis, only age and sex remained significant (P , 0´001 and 0´009 respectively). We report an 86% mortality with only three survivors out of 22 patients, and one of these remains thrombocytopenic and red cell transfusion dependent, possibly in part because of graft hypoplasia. Six out of 17 patients responded to plasmapheresis, but the majority of them ultimately succumbed because of TTP, often in association with GvHD or fungal infection.

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Section: Clinical Features At Diagnosis Of Ttpsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

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The clinical features, risk factors and outcome of thrombotic thrombocytopenic purpura occurring after bone marrow transplantation

et al. 2001

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“…Discontinuation of CSA administration in cases of TTP does not usually clearly ameliorate the complication MUD, matched unrelated donor; VOD, veno-occlusive disease of the liver. (Holler et al, 1989;Sarode et al, 1995;Paquette et al, 1998). The role of CSA could not be analysed in a meaningful way in the present survey, as a large majority of patients had received CSA and only a small number of patients had not been given this drug.…”

Section: Discussionmentioning

confidence: 81%

Thrombotic thrombocytopenic purpura after allogeneic stem cell transplantation: a survey of the European Group for Blood and Marrow Transplantation (EBMT)

et al. 2002

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Summary.A survey was carried out among the European Group for Blood and Marrow Transplantation (EBMT) centres to determine the incidence, risk factors, treatment and outcome of thrombotic thrombocytopenic purpura (TTP) following allogeneic haematopoietic stem cell transplantation. TTP was defined as the simultaneous occurrence of red cell fragmentation, laboratory findings of haemolysis, red cell transfusion requirement and de novo or persistant thrombocytopenia caused by consumption, in the absence of disseminated intravascular coagulation. Forty-five centres reported all patients (n ¼ 406) transplanted between July and December 1996. Twenty-three patients developed TTP; the risk of developing TTP was 6AE7% at 2 years (95% CI: 4AE1% to 9AE3%). The median time of onset was 44 d (range 13-319) post transplantation. Significant risk factors for the development of TTP were female gender (P ¼ 0AE005) and an unrelated donor (P ¼ 0AE046). To treat TTP, cyclosporin administration was discontinued in 10 cases, plasma exchanges were performed in five cases and 12 patients received plasma infusions without plasma exchange. TTP resolved in 13 of the 23 patients (57%). The only factor predictive of resolution of TTP was the absence of nephropathy. Seven patients (30%) were alive at follow-up of 38-45 months from the onset of TTP. Sixteen patients died; the causes were multiple, only three patients had TTP as a central factor. The median time to death was 41 d (range 1-762 d) from the onset of TTP. TTP is a relatively frequent complication of allogeneic stem cell transplantation and it is associated with high mortality, though death is usually caused by multiple factors.

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Plasminogen activator inhibitor (PAI-1) antigen levels in primary TTP and secondary TTP post-bone marrow transplantation

et al. 1998

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Our objectives were to measure and compare plasminogen activator inhibitor levels (PAI-1) in primary adult thrombotic thrombocytopenic purpura (TTP) and in secondary TTP associated with bone marrow transplantation (BMT)-TTP. PAI-1 antigen levels were measured by an enzyme linked immunosorbent assay on platelet poor plasma samples obtained from patients at the time of diagnosis of the TTP disorder and from a group of normal volunteers. The samples were frozen at -70 degrees C. Patients with TTP secondary to bone marrow transplantation had their grade determined by percentage fragmented cells and lactate dehydrogenase levels. The primary TTP samples were contributed by investigators in the multi-institutional North American TTP Group, and the bone marrow transplant samples were obtained from an adult bone marrow transplant program. Nineteen patients with adult TTP, and 47 patients with bone marrow transplant-TTP were evaluated. Of the latter, 14 had Grade 2, 13 had Grade 3, and 20 had Grade 4 BMT-TTP. PAI-1 levels were elevated compared to control volunteers in both primary adult TTP and BMT-TTP, P < 0.001. Levels did not differ from normal in Grade 2 BMT-TTP (median = 16 ng/ml; quartiles = 9-20). PAI-1 levels were similar in primary TTP (median = 32 ng/ml; quartiles = 25-51) and Grade 3 BMT-TTP (median = 35 ng/ml; quartiles = 19-48 ng/ml), P = 0.7. However, PAI-1 levels were significantly higher in Grade 4 BMT-TTP (median = 83 ng/ml; quartiles = 60-143) than Grade 3 BMT-TTP, and primary TTP, P < 0.001. PAI-1 levels are high in primary TTP and secondary bone marrow transplant-TTP (Grades 3-4). In contrast, normal levels are seen in Grade 2 BMT-TTP, which is a self-limited disorder. Therefore, high PAI-1 levels may contribute to hypofibrinolysis in the pathogenesis of primary TTP and of moderate to severe TTP (Grades 3-4) following bone marrow transplantation.

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Microangiopathy in patients on cyclosporine prophylaxis who developed acute graft-versus-host disease after HLA-identical bone marrow transplantation

Cited by 77 publications

References 29 publications

The clinical features, risk factors and outcome of thrombotic thrombocytopenic purpura occurring after bone marrow transplantation

The clinical features, risk factors and outcome of thrombotic thrombocytopenic purpura occurring after bone marrow transplantation

Thrombotic thrombocytopenic purpura after allogeneic stem cell transplantation: a survey of the European Group for Blood and Marrow Transplantation (EBMT)

Plasminogen activator inhibitor (PAI-1) antigen levels in primary TTP and secondary TTP post-bone marrow transplantation

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