The only established treatment for patients with thrombotic thrombocytopenic purpura (TTP) is plasma exchange against fresh frozen plasma. For cases refractory to plasma exchange, no generally treatment schedule exists. One option is immunosuppressive therapy with corticosteroids and vincristine. Rituximab is a chimeric monoclonal antibody directed against the CD20 antigen, and it has been successfully used in B-cell malignancies and is being investigated in autoimmune diseases. Its efficacy in TTP has not yet been determined. We report two female patients with severe TTP refractory to multiple courses of plasmapheresis, high-dose steroid treatment, and vincristine who responded after adding rituximab while continuing plasmapheresis. Am. J. Hematol. 71: 105-108, 2002.

We performed a prospective pilot study on 12 patients to evaluate the efficacy of the anti-CD20 monoclonal antibody rituximab in relapsed idiopathic thrombocytopenic purpura (ITP). Inclusion criteria were relapse of ITP with a thrombocyte count <20 000 micro L-1 and unsuccessful corticosteroid treatment. Eleven patients had a previous splenectomy, five patients had unsuccessful cytotoxic treatment, and six patients were refractory to intravenous immunoglobulins before rituximab therapy. Response criteria were as follows. Complete remission (CR): normalization of thrombocyte count for at least 30 d. Partial remission (PR): an increase of thrombocytes to above 30 000 microL(-1) for at least 30 d. Minor response (MR): any increase above 30 000 microL(-1) for less than 30 d but more than 10 d. No response (NR): failure to achieve any of the above responses. Treatment plan: We administered 375 mg m(-2) of rituximab once weekly on up to four consecutive weeks, unless there was early CR. Five patients (41%) achieved CR, two patients (17%) PR, and two patients MR (overall response rate 75%, median follow-up of responders 320 d). Four CR patients are ongoing; one CR patient relapsed after 6 months. Adverse events included excessive thrombocytosis in one patient as well as minor infusion-related (grade I) toxicities in four patients. We conclude that rituximab is a promising agent in the treatment of relapsed ITP.

Antibodies against factor VIII occur in about 15-35% of hemophilia A patients and induce refractoriness to factor VIII substitution. In most cases, these antibodies are of the IgG class. Strategies to avoid or to treat such inhibitors are controversial. In very rare cases, factor VIII inhibitors also develop in nonhemophilic patients. Although there are anecdotal reports that these antibodies may disappear spontaneously without occurrence of bleeding tendencies, in the majority of patients the clinical course is characterized by severe hemorrhages. From 1980 to 1995, we observed ten nonhemophilic patients with acquired factor VIII inhibitors at our hospital. In most cases, a sudden bleeding tendency was observed shortly after an injury or surgery. Coagulation tests showed a prolonged aPTT and a decreased F VIII level. Other deficiencies of blood-clotting factors and acquired or hereditary von Willebrand's disease were excluded. Therapy with F VIII concentrates did not produce the expected increase. Measurement of F VIII inhibitor levels in Bethesda units/ml (BU/ml) revealed maximal values in the range of 2-128 BU/ml. Immunosuppressive therapy with azathioprine or cyclophosphamide in combination with methylprednisolone led to complete disappearance of the inhibitor, normalization of the coagulation tests, and complete remission of the bleeding tendency in seven treated patients within 6 weeks. Although the clinical course is not predictable and inhibitors may disappear spontaneously, combined therapy with methylprednisolone and azathioprine or cyclophosphamide is recommended for patients with bleeding tendency. In pregnancy, therapy should be started only with methylprednisolone; post-partum, azathioprine should be used additionally if methylprednisolone as a single drug does not lead to complete remission. In emergency situations, therapy with high doses of human factor VIII concentrate may be used. When bleeding does not cease, the additional use of activated prothrombin-complex concentrates or porcine factor VIII is indicated. Possible side effects may include hepatitis and short-lived intravascular thrombin production.

Summary:High-dose chemotherapy (HDCT) followed by autologous blood stem cell transplantation is considered the treatment of choice for patients with relapsed or resistant aggressive non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). However, several authors report failure of standard mobilization regimens in 29% to 56% of these patients making the completion of HDCT impossible and as a result, negatively influencing long-term outcome. High-dose chemotherapy (HDCT) followed by peripheral blood stem cell transplantation (PBSCT) is being increasingly used in patients with malignancies. However, there

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Summary:In humans, there are few reports dealing with cytokine production in chronic GVHD.

Summary:For autologous stem cell transplantation, it is common practice to infuse at least 2 ؋ 10 6 /kg CD34 ؉ cells to ensure rapid engraftment. However it was recently claimed that increasing the threshold to 5؋10 ؉ cells we found a significant reduction in the median number of days with fever (1 vs 3.5 days, P ‫؍‬ 0.0025), incidence of fever (78.8 vs 92.1%, P ‫؍‬ 0.032) as well as duration of antibiotic treatment (7 vs 10 days, P ‫؍‬ 0.038). This was paralleled by a faster neutrophil recovery to 0.5 ؋ 10 9 /l (9 vs 10 days, P ‫؍‬ 0.047). There was no significant difference in the number of platelet or red cell transfusions between the two groups. We conclude that transplantation with a stem cell dose of at least 5 ؋ 10 6 /kg CD34 ؉ cells reduces infectious complications and should thereby increase the safety of this type of therapy while reducing duration (and cost) of antibiotic therapy. The transplantation threshold should thus not remain at 2 ؋ 10 6 /kg particularly in patients with a good stem cell mobilisation capacity.

CNS involvement is one of the hallmarks underlying poor prognosis in SLE and for therapeutic strategies it is difficult to assess which patients are at risk. As detectability of cerebral microembolic signals (MES) using long-term transcranial Doppler ultrasonography (TCD) proved to be predictive of past and future thromboembolic events in patients with carotid artery stenosis, we investigated whether MES might be similarly useful in patients with antiphospholipid syndrome (APS). Our study population consisted of 46 SLE patients and five with primary APS (pAPS). Twelve of the 46 patients with SLE, 10 of them with secondary APS (sAPS), and four of five patients with pAPS had a history of cerebrovascular ischaemia (CVI). MES in the middle cerebral artery were detected in 14 of 16 patients with and in one of 35 without CVI (P < 0.001). Antiphospholipid antibodies (aPL) were positive in 12 of 15 patients with and 18 of 36 without MES, and the rate of MES correlated to the titre of aPL. MES from APS patients resembled in their energy distribution those from patients with symptomatic carotid disease and were significantly different from those associated with artificial heart valves. In conclusion, cerebral MES are detectable in APS patients and correlate with a history of CVI. Whether this innovative method may provide individual risk assessment in APS patients has to be addressed in prospective studies.