HaemophiliaVolume 16, Issue 4 p. 706-707 Treatment of mantle cell lymphoma with autologous stem-cell transplantation in a patient with severe congenital haemophilia-A and chronic (B and C virus) hepatitis L. REJTO, L. REJTO Division of HaematologySearch for more papers by this authorA. SCHLAMMADINGER, A. SCHLAMMADINGER Division of HaemostasisSearch for more papers by this authorP. ILONCZAI, P. ILONCZAI Division of HaemostasisSearch for more papers by this authorI. TORNAI, I. TORNAI Division of Gastroenterology, 2nd Department of Internal Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, HungarySearch for more papers by this authorP. BATAR, P. BATAR Division of HaematologySearch for more papers by this authorGY. REMENYI, GY. REMENYI Division of HaematologySearch for more papers by this authorA. KISS, A. KISS Division of HaematologySearch for more papers by this authorM. UDVARDY, M. UDVARDY Division of HaematologySearch for more papers by this author L. REJTO, L. REJTO Division of HaematologySearch for more papers by this authorA. SCHLAMMADINGER, A. SCHLAMMADINGER Division of HaemostasisSearch for more papers by this authorP. ILONCZAI, P. ILONCZAI Division of HaemostasisSearch for more papers by this authorI. TORNAI, I. TORNAI Division of Gastroenterology, 2nd Department of Internal Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, HungarySearch for more papers by this authorP. BATAR, P. BATAR Division of HaematologySearch for more papers by this authorGY. REMENYI, GY. REMENYI Division of HaematologySearch for more papers by this authorA. KISS, A. KISS Division of HaematologySearch for more papers by this authorM. UDVARDY, M. UDVARDY Division of HaematologySearch for more papers by this author First published: 21 June 2010 https://doi.org/10.1111/j.1365-2516.2010.02243.xCitations: 1 Laszlo Rejto, 2nd Dept. of Medicine, Health Sciences Center, University of Debrecen, Nagyerdei 98, Debrecen 4012, Hungary.Tel.: +36 52 314 410; fax: +36 52 255 152;e-mail: lrejto@dote.hu Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume16, Issue4July 2010Pages 706-707 RelatedInformation

The chronic myeloproliferative disorders (CMPD) are a group of clinically related diseases characterized by clonal hematopoiesis with increased proliferation of one or more myeloid cell lineages. The identification of JAK2 mutations (JAK2V617F and JAK2 exon 12) in patients with CMPD is of great significance in the understanding of the molecular mechanisms underlined the pathogenesis of the disease contributing also to clinical management of patients. However, the precise pathogenetic contribution of JAK2 mutation is far from being fully elucidated and it is currently under intense investigation. Testing of JAK2 mutations has made the diagnosis of CMPD more precise than ever before, while genotype–phenotype associations have been identified. Furthermore, the discovery of JAK2 mutations facilitated the development of new targeted therapies and clinical trials are currently ongoing.

To evaluate whether children with acute myeloblastic leukemia (AML) presenting with extramedullary infiltration (EMI) have different clinical, morphologic features and prognosis from children without EMI, a 127 consecutive previously untreated children with AML were entered in this study. Fifty-one children (40%) had EMI at diagnosis and 27% of these showed multiple site involvement. Twenty-seven of 127 children (21%) presented myeloid tumors. No age related differences in the incidence of EMI was noted. However, analysis of clinical and biological features at diagnosis showed that WBC count ≥50×109 l−1, hepatosplenomegaly >5 cm, FAB AML-M4 and AML-M5 subtypes and CD13, CD14 expression of bone marrow (BM) leukemic cells (>20%) were more frequent in children with EMI. Two consecutive treatment protocols were used. In both protocols remission was achieved with combined high-dose methylprednisolone (HDMP) as a differentiating and apoptosis inducing agent with mild cytotoxic chemotherapy (low-dose cytosine arabinoside (LD Ara-C), weekly mitoxantrone and Ara-C or 6-thioguanine). Administration of short-course (4–7 days) HDMP (20–30 mg/kg per day) alone resulted in a remarkable decrease in peripheral blood, BM blasts and in the size of EMI in responding patients. In both protocols, remission rate in patients with EMI was 71 and 80%, which was lower than that of the patients without EMI (87 and 89%). This may be attributed to the higher frequency of unfavorable features in children with EMI. However, in patients who presented with myeloblastoma and treated with a more intensive post-remission therapy (AML-94), the 4-year disease-free survival (DFS) and event-free survival (EFS) rates were not found to be significantly different from children who had no EMI (P>0.05). Whereas, the outcome of children who presented with gingival infiltration did not improve. In further studies, the prognostic significance of different localisation of EMI and the effect of addition of HDMP to cytotoxic chemotherapy should be explored in larger series.

Bortezomib (Velcade) proved to be the standard element of refractory myeloma 2nd and 3rd line treatment, while many studies are suggesting excellent results in 1st line. Proteasome inhibition, the block of angiogenesis, modification of the NF-kappa-B system seems to be a challenging target in other malignant diseases, including refractory acute myeloid leukemia (AML), as well. In vitro data clearly support, that bortezomib exerts antiproliferative and pro-apoptotic effects in different AML cell-lines, along with human AML cell cultures, and moreover bortezomib was able to restore, or at least improve anthracyclin and possibly ARA-C sensitivity in different cell-lines (including AML). More recently, a Phase I trial showed bortezomib monotherapy efficient (only in few percents) in childhood refractory acute leukemia. Some case reports were shown at ASH 2007. We have tried bortezomib containing first or second line combinations in 27 (14 female, 13 male, mean age 57.6 years) patients with refractory or poor risk AML, in a small retrospective survey. The combinations were as follows: HAM or Flag-Ida, combined with bortezomib 1,3 mg pro sqm, day O and seven). The following groups were considered as refractory or poor risk AML: De novo AML, 2nd line: No response/remission to first line standard treatment (“3+7”), n=2 (Velcade- Flag-Ida treatment) De novo AML 1st line: bilineal or biphenotypic (flow-cytometry) n=2 (Velcade-Flag- Ida treatment) De novo AML with complex (numerical or more than 3 abnormalities) karyotype or normal karyotype with flt-3 TKD mutation, n=9, 1st line (Velcade-Flag-Ida n=6, Velcade- HAM protocol, n=3) Secondary AML or AML with evidence of previous more than 6 mo duration high grade MDS, n=14, 1st line: (Velcade-Flag-Ida n=9, Velcade-HAM n=5) RESULTS: Complete remission (CR) 12/27, partial remission (PR) 9/27, no remission 5/27, progression during treatment: 1/27.Best responses were seen in de novo cases. CR had been achieved in all patients of group 1 (two standard risk patients not responding to 3+7 protocol), and group 2 (biphenotypic, bilineal). The CR rate was quite appreciable in group 3, i.e. 6/9 (complex karyotype or normal karyotype with FLt-3 mutation – the response rate was excellent with flt-3 mutated cases). In group 4. (MDS, secondary AML) the results were less impressive. There were no major differences according to protocol (Flag-Ida or HAM) Allogeneous stem cell transplantation could have been performed in 1st CR in two patients (one from group 1. and another from group 2.). One of them died due to relapse, the other one is in CR since then. The combinations seem to be relatively safe. Induction related death rate was low (1 elderly patient acute thrombocytopenic bleeding with refractory MDS-AML). 5 other patients had severe neutropenic sepsis (2 with fatal outcome). Pulmonary syndrome, which may follow Velcade+ARA-C had not been documented. Other adverse events did not differ from the pattern observed with standard induction therapies.

Severe, life-threatening acute upper gastrointestinal bleeding may occasionally occur in patients receiving coumarol prophylaxis for prosthetic heart valves. These patients are exposed to two potential, serious risks: bleeding due to the severe blood loss induced by excessive anticoagulant effect or as a consequence of the cessation of anticoagulation subsequent thrombotic occlusion of the valve and loss of patency. Herein a short case report is presented. The elderly male patient had a prosthetic valve in the aortic position and also suffered from two malignant diseases: chronic lymphocytic leukaemia and a more recently developed lung cancer with metastatic spread into both lungs. The patient had a major gastrointestinal bleed, leading to a sudden fall of haematocrit (0.09), and to a collapse of peripheral circulation due to too excessive a coumarol effect (International Normalized Ratio > 8). An acute left ventricular failure developed during the early period of the emergency blood transfusion, so the correction of prothrombin time by fresh-frozen plasma (due to the large volume requirement) was not feasible. The patient received 50 microg/kg intravenous bolus of NovoSeven (recombinant active factor VII) in an almost desperate situation. The International Normalized Ratio changed to 2.1 in 30 min; bleeding had stopped immediately. There was neither evidence of disseminated intravascular coagulation (in spite of the age and underlying diseases) nor loss of valve patency or infective endocarditis during follow-up. This modest report may call attention to the potential use of recombinant active factor VII in the coumarol-induced severe bleeding episodes of prosthetic heart valve patients.

Collagen and thrombin-activated (COAT) platelets represent a unique subset of activated platelets that exhibit high levels of several adhesive and procoagulant α-granule proteins on their surface. In this report we demonstrate that a similar subpopulation of platelets can also be generated by the combined stimulation of FcγRIIA and thrombin receptors. Platelets activated in this manner are referred to as Fc receptor and thrombin-activated (FcRT) platelets, and they share many of the characteristics of the formerly observed COAT platelets, including aminophospholipid exposure, adhesive and procoagulant protein enrichment, increased frequency among young platelets, and sensitivity to transglutaminase inhibitors. Although FcγRIIA receptor activation can be achieved either with anti-CD9 monoclonal antibodies (ALB-6 and ML-13) or with direct Fc receptor cross-linking, FcRT platelet generation occurs only with concurrent or slightly delayed thrombin stimulation. In fact, when thrombin was the second agonist, time delays of up to 120 seconds after FcγRIIA receptor stimulation had little effect on the generation of FcRT platelets; however, a similar delay for convulxin plus thrombin activation results in a 90% diminution in COAT platelet production. FcRT platelet formation in platelet-poor plasma and whole blood was also investigated, and results were similar to those observed with gel-filtered platelets. Previous experiments with COAT platelet formation used physiologic agonists (collagen and thrombin) that might be encountered under either physiologic or pathologic conditions; however, the current experiments with Fc receptor stimulation offer the first example in which these highly prohemostatic platelets are likely to be strictly pathogenic. (J Lab Clin Med 2001;138:393-402)

Hairy cell leukaemia (HCL) is a rare, clinically and haematologically well characterised entity. The prognosis of patients with hairy cell leukaemia has significantly improved due to the new therapeutic approaches. Development of diagnostic and therapeutic methods, together with the analysis of their own hairy cell leukaemia patients, is reviewed by the authors. Between 1977 and 1998 twenty five patients (16 male, 9 female) were treated. The malignant cells were usually analysed by morphological and cytochemical methods and recently flow cytometric analysis could be performed in eight patients. Splenectomy with lethal outcome in six patients was performed in 21 cases. Approximately one third of patients received interferon, while 2-chlorodeoxyadenosine was given only to three patients. Favourable experiences obtained by splenectomy and efficacy of interferon treatment are emphasised, but according to the literature and their own results administration of purine analogues can be highly recommended in the future.