Idiopathic thrombocytopenic purpura is an autoimmune disease which involves opsonization of platelets by autoantibodies directed against different surface glycoproteins, leading to their premature destruction by the reticuloendothelial system. Management of patients with refractory ITP is difficult. Recent studies have shown that rituximab, a chimeric anti‐CD20 monoclonal antibody, is useful in the treatment of these patients, with overall response rates of about 50%. Most published reports have included a small number patients including case reports. The present study reports the results of a retrospective Danish multicenter study of rituximab in the treatment of adult patients with refractory ITP. Thirty‐five patients (median age 52 years, range 17–82 years, 17 males) were included. One patient had immune thrombocytopenia and neutropenia. All patients had received prednisolone (Pred). Next to Pred, 25 patients had been treated with high‐dose IgG, and in 16 patients a splenectomy had been performed. Sixteen patients had been treated with azathioprine. Other treatments included, e.g., cyclosporine, danazol, cyclophosphamide, vincristine, interferon, and dexamethasone. The patients were treated with a dose regimen of 375 mg/m2 i.v. approximately once weekly for 4 consecutive weeks. Six patients received a fixed dose of 500 mg disregarding their weight supplemented by 100 mg of methylprednisone i.v. or 50–100 mg of Pred given as premedication together with an antihistamine just before infusion of rituximab. The large majority of patients also received Pred and, in some cases, other concomitant immunosuppressive treatment during part of their rituximab treatment. A complete response (CR) was defined as a rise in the platelet count > 100 × 109/L, a partial response (PR) as a rise in the platelet count > 50 × 109/L, and a minor response (MR) as a rise in the platelet count < 50 × 109/L. No response (NR) was defined as no increase in the platelet count. Because 4 patients were treated twice, a total of 39 outcomes of rituximab treatment were evaluated. Rituximab proved to be effective in 17 of 39 treatments [overall response 44% with 7 CR (18%) (1 patient showed a CR twice), 6 PR (15%), and 4 MR (10%)]. In 9/13 cases of CR or PR, the response (platelet level > 50 × 109/L) was prompt, 1–2 weeks after the first infusion. The remaining patients responded 3–8 weeks later. Patients with CR and PR have been in remission for a median of 47 weeks. In general the side effects were few. In 2 cases, the treatment was stopped because of side effects either during or after the first infusion. Two fatal outcomes were recorded. A 71‐year‐old female with severe lung disease died 6 days after the first infusion of respiratory failure. The other patient, a 73‐year‐old man also with severe chronic obstructive lung disease, died of pneumonia approximately 13 weeks following the last rituximab treatment. It is concluded that rituximab may be a useful alternative therapy in patients with severe and symptomatic ITP refractory to conventional treatment. Am. J. Hematol. 78:275–280, 2005. © 2005 Wiley‐Liss, Inc.

Summary. During a 10-year period (1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001) in the region of Southern Denmark, 337 patients aged 15 years or older (range 16-93 years, median 67 years) were diagnosed with acute myeloid leukaemia (AML). Cytogenetic analysis was carried out in 90%, of whom 53% had clonal chromosome aberrations. Some 24% and 31% had only numerical or structural abnormalities respectively. The remaining patients showed both types of abnormalities. Ploidy levels in decreasing order were: pseudodiploidy, 41%; hyperdiploidy, 32%; and hypodiploidy, 27%. Pseudodiploidy characterizes type M3 (70%) and hypodiploidy M6 (56%). Recurrent cytogenetic abnormalities -t(8;21), t(15;17) and inv(16) -were found in 3AE3%, 3AE3% and 2AE0% of all patients respectively. Prognostically intermediate and adverse aberrations were found in 39% and 44%, respectively, of those with an abnormal karyotype. Rare recurrent aberrations were found in two patients in this material. A previously described non-recurrent abnormality was found to be recurrent in one patient [der(20)t(11;20)(q13.2;p13)]. New, previously undescribed abnormalities were found in 41 patients. Statistically significant correlations were found between t(15;17) and young age (P < 0AE001), inv(16) and young age (P < 0AE006), )17 and M6 (P ¼ 0AE007), and M6 and complex karyotype with five or more unrelated aberrations (P ¼ 0AE004). We conclude that this truely population-based cytogenetic study of adult AML showed distributions of chromosome abnormalities that differ from those described so far.Keywords: acute myeloid leukaemia, adults, cytogenetics, population based.Since 1976, when the first French-American-British (FAB) classification was published (Bennett et al, 1976), the subclassification of acute myeloid leukaemia (AML) has been based on cell morphology. In 1988, the Morphologic, Immunologic and Cytogenetic (MIC) classification was published (Second MIC Cooperative Study Group, 1988) and, since then, cytogenetic investigations have become more and more important in AML classification (Grimwade et al, 1998). The detection of recurrent non-random chromosomal abnormalities resulted in a new understanding of AML, subdividing the disease into true de novo (TDN)-AML including patients with t(8;21), t(15;17), inv(16), t(16;16), t(9;11), t(11;17), t(6;9), t(1;22) and t(8;16), and myelodysplastic syndrome related (MDR)-AML including patients with )5, 5q-, )7, 7q-, +8, 11q-, inv(3) and translocations involving 3q (Head, 1996). This model was incorporated in the latest World Health Organization (WHO) classification, which divides AML into four major categories: (1) AML with recurrent genetic abnormalities [t(8;21), t(15;17), inv(16) and 11q23 abnormalities]; (2) AML with multilineage dysplasia; (3) therapy-related AML; and (4) AML not otherwise categorized (including FAB subtypes M0-M7) (Jaffe et al, 2001).Many papers have been published describing the frequencies, correlations to FAB subtypes and prognostic significance of non-random chromosomal ab...

Thirteen patients with idiopathic myelofibrosis (5 osteomyelosclerosis) were treated with recombinant human erythropoietin (rHuEpo) for transfusion-dependent anemia. All but 7 patients were concomitantly treated with alpha interferon, and 5 patients also received a interferon before the start of erythropoietin (EPO) treatment. All but two patients became transfusion independent. The highly positive results of the present study of transfusiondependent patients with idiopathic myelofibrosis calls for further studies to delineate more precisely in larger series those patients who are likely to respond to rHuEpo. Am.

Imatinib mesylate targets the adenosine triphosphate (ATP)-binding sites of the protein tyrosine kinase domains associated with Bcr-abl, the platelet-derived growth factor (PDGF) and c-kit. In idiopathic myelofibrosis (IMF) PDGF is considered to be one of the growth factors responsible for the development of bone marrow fibrosis. Recently, it has been shown that imatinib has antifibrogenic effect on bone marrow fibrosis in chronic myelogenous leukemia. Treatment with imatinib alone in IMF has been associated with significant side effects. In this study, the safety and efficacy of imatinib therapy in IMF, either administered as a single agent or in combination with hydroxyurea (HU) and/or alpha-interferon (IFN-a) are evaluated. Eleven patients (median age, 63 years; range, 33-82 years) with IMF (n = 8) or postpolycythemic myelofibrosis (PPMF) (n = 3) were studied All patients had been treated with HU (n = 9) and/or IFN (n = 7) before study entry. In all but one patient, treatment with these agents was discontinued when imatinib therapy was instituted. One patient continued IFN when treatment with imatinib was started. Imatinib was given at a dose of 400 mg/day. Nine patients were in an advanced disease phase. The patients have been followed for a median period of 2 months (range, 0.5-12 months). Treatment with imatinib has been stopped in six patients (55%), because of overt side effects (n = 4), recurrence of transitory dizziness and visual defects owing to a rising platelet count (n = 1), or the occurrence of an acute subdural hemorrhage that was evacuated without neurological deficits (n = 1). In nine patients imatinib treatment was followed by a rise in leukocyte and platelet counts that required combination with HU or IFN. The combined treatment modalities were followed by a rapid decrease in cell counts and were well tolerated apart from IFN side effects. A beneficial effect of imatinib was documented in three patients. It is concluded that leukocytosis and thrombocytosis are seen in most patients with myelofibrosis during treatment with imatinib. Combination therapy with HU or IFN seems safe and well tolerated and followed by a decrease in disease activity. A subgroup of patients in an early disease phase might benefit from imatinib therapy alone. Am.

Two patients, one with B-cell chronic lymphocytic leukemia (CLL) and one with hairy-cell leukemia (HCL), were treated with immunosuppressive chemotherapy. The patient with CLL was a 54-year-old female, who had had a squamous cell carcinoma (SCC) excised from her forehead 5 months before receiving the ®rst course of¯udarabine. During thē udarabine treatment, the patient developed a local SCC relapse and metastases in the neck. The carcinoma was treated by excision and radiotherapy, and further¯udarabine treatment was withheld. Nevertheless, the SCC metastasized aggressively and the patient died 3 months after the start of¯udarabine treatment, primarily due to respiratory failure. The autopsy revealed heavy SCC in®ltrations involving the lungs, pleura, mediastinum, pericardium, and liver. The patient with HCL was a 69-year-old male. At the time of diagnosis of HCL, the patient had two solid tumors in the liver containing poorly differentiated epithelial carcinoma cells of unknown origin. During treatment with 2-chlorodeoxyadenosine (2CdA), the tumors in the liver rapidly spread in multiple intrahepatic metastases, followed by liver failure and death within 1 month. Fludarabine and 2CdA cause a substantial suppression of all lymphocyte subsets, in particular the T-cell line. T-lymphocytes are believed to be responsible for the usually slow growth and the low metastatic rate of the SCC skin lesions. It is therefore assumed that¯udarabine and 2CdA in these two cases triggered an exacerbation of both tumors due to the T-cell depletion.