An unusual presentation of a chronic lymphocytic leukemia patient with 17p deletion after reduced-intensity transplantation: Richter syndrome and concomitant graft-versus-host disease--case report.

Chronic lymphocytic leukemia (CLL) patients with 17p deletion comprise a challenging subgroup associated with poor overall survival. These patients should be treated with alternative strategies. Reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) can achieve long-term remission in this ultra-high-risk CLL group. Herein, we described a CLL patient with 17p deletion who developed Richter syndrome with extranodal involvement of the liver soon after RIC allo-SCT despite apparent acute graft-versus-host disease. The majority of chronic lymphocytic leukemia (CLL) patients respond well to chemoimmunotherapy. Patients who show ultra-high-risk genetics, such as 17p deletions, comprise a challenging subgroup of patients with poor response to chemoimmunotherapy and median life expectancy <2-3 years at the time of first-line treatment. Current treatment approaches for patients with 17p deletion include agents acting independently from the DNA damage pathway, such as alemtuzumab and high-dose corticosteroids. RIC allo-SCT for consolidation can achieve long-term remission in this ultra-high-risk CLL group.(1,2) Richter syndrome (RS) represents the clinicopathologic transformation of CLL to an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL).(3) RS appearing after allo-SCT can be managed by tapering of immunosuppression, followed by dose-escalated donor lymphocyte infusion titrated to the degree of leukemia response and graft-versus-host disease (GVHD) encountered.(4) Herein, we describe a CLL patient with 17p deletion who developed RS with extranodal involvement of the liver soon after RIC allo-SCT despite apparent acute GVHD (aGVHD).

Effects of imatinib mesylate on renin-angiotensin system (RAS) activity during the clinical course of chronic myeloid leukaemia.

The renin-angiotensin system (RAS) is involved in cell growth, proliferation and differentiation in bone marrow in an autocrine-paracrine manner, and it modulates normal and neoplastic haematopoietic cell proliferation. This study aimed to assess expressions of the RAS components, renin, angiotensinogen and angiotensin-converting enzyme (ACE), during imatinib mesylate treatment of patients with chronic myeloid leukaemia (CML). Expressions of RAS components were studied in patients with CML at the time of diagnosis (n = 83) and at 3, 6 and 12 months after diagnosis (n = 35) by quantitative real-time polymerase chain reaction. De novo CML patients had increased ACE, angiotensinogen and renin mRNA levels and these expression levels decreased following administration of imatinib. The RAS activities were significantly different among Sokal risk groups of CML, highlighting the altered biological activity of RAS in neoplastic disorders. The results of this study confirm that haematopoietic RAS affects neoplastic cell production, which may be altered via administration of tyrosine kinase inhibitors such as imatinib mesylate.

Fibrinolytic activity and d-dimer levels in Behçet's syndrome.

OBJECTIVE: Thrombophlebitis occurs in a third of patients with Behçet's syndrome (BS). The thrombotic tendency in BS has been studied with inconclusive results perhaps due to the inadequate numbers of patients studied during the acute phase of the thrombosis as well as the lack of appropriate diseased controls. We have studied tissue-type plasminogen activator (t-PA) and its inhibitor (PAI-1), and d-dimer levels in BS patients with and without thrombosis both in the acute and chronic phases along with suitable diseased and healthy controls. METHODS: t-PA and PAI-1 were studied by ELISA and d-dimer by semiquantitative latex agglutination slide test in 30 BS patients without deep vein thrombosis (DVT), 10 BS with acute DVT (ADVT), 25 BS with chronic DVT, 27 with ankylosing spondylitis, 26 diffuse systemic sclerosis, 15 patients with ADVT due to other causes, 10 patients with sepsis, and 23 healthy controls. RESULTS: The t-PA levels in BS with ADVT were significantly lower than those in patients with ADVT due to other causes (7.4 +/- 6.2 vs. 13.4 +/- 6.3, P = 0.027) while PAI-1 levels did not show significant differences between the groups (P = 0.60). The numbers of patients with d-dimer levels of > or = 0.5 microg/ml in BS with ADVT were similar to those found in patients with ADVT due to other causes (9/10 vs. 14/14). CONCLUSION: The relatively low t-PA levels point to a defect in fibrinolysis in BS. d-dimer levels are increased in the acute phase of thrombosis in BS.

Overview of 321 patients with idiopathic thrombocytopenic purpura. Retrospective analysis of the clinical features and response to therapy.

In this retrospective study, we evaluated the clinical features and the effects of various treatment modalities on the clinical course in patients diagnosed with idiopathic thrombocytopenic purpura (ITP) at our center between 1984-2000. We retrospectively examined the medical records of 321 (229 females, 92 males) ITP patients. One hundred and seventy-one (53.3%) patients were lost to follow-up. When evaluating the clinical features, all 321 patients were included; however, when the response to treatment modalities was evaluated only 150 patients followed up regularly were considered. The median age of the patients on initial diagnosis was 34 years (range: 14-78). At initial diagnosis, 235 (73.2%) patients had signs of bleeding. Of patients diagnosed with ITP initially, six later turned out to have systemic lupus erythematosus (SLE) and two myelodysplastic syndrome (MDS). The median follow-up of 150 patients followed up regularly was 30 months (range: 4-396). One hundred and thirty-seven of these subjects had an indication for treatment and 94.2% of them were administered either standard or high-dose steroids as the first-line therapy. Complete remission (CR) was defined as any platelet count >100,000/mm(3) lasting for 3 months or longer without treatment. CR was achieved in 51.9% of the patients given steroids as the initial therapy. During a median follow-up of 33 months, relapse occurred in 58.2% of these patients, and after a median follow-up of 11 months the rest of them were still in remission. Ninety-eight patients followed up regularly were administered second-line therapies. CR was obtained in 44.4% of the patients who used steroids as second-line therapy. Within a median follow-up of 15 months, 20.8% of these patients relapsed. Splenectomy was performed in 76 patients and CR was obtained in 68.4% of the regularly followed up patients. Relapse occurred within a median of 96 months in 15.4% of the patients who had CR. Kaplan-Meier curves showed that the duration of CR obtained by splenectomy was significantly higher than that obtained by steroids (p<0.001). The 10-year disease-free survivals in patients who used steroids and who underwent splenectomy were, respectively, 13% and 58%. In our adult ITP patients, steroids induced nearly similar rates of CR both as first-and second-line therapies. Splenectomy seems to be effective in patients unresponsive to steroids. The duration of CR obtained by splenectomy is significantly longer when compared with the duration of CR obtained by steroid therapy.

The frequency of tuberculosis in adult allogeneic stem cell transplant recipients in Turkey.

In general, tuberculosis (Tb) is rarely seen in allogeneic stem cell transplant (alloSCT) recipients, but this observation has been challenged in developing countries such as Turkey, where Tb infection is more prevalent than in Europe and the US. In this retrospective study, we report on the incidence of Tb infections in 351 alloSCT recipients at 4 bone marrow transplantation units in Turkey over the last 10 years. The frequency of Tb in alloSCT recipients after allografting (5 of 351) was far greater than that in the general population (35.4 per 100,000). Of the 351 patients who underwent alloSCT, 77 who received isoniazid (INH) chemoprophylaxis for 6 months did not develop posttransplantation Tb. However, 5 of the remaining 274 patients who received no chemoprophylaxis developed Tb a median of 12 months (range, 10-47 months) after allografting. Antituberculosis therapy resulted in complete recovery in all cases. In 2 additional patients who were found to have active pulmonary Tb at the time of transplantation, alloSCT was delayed until the infections were treated. Infections of mycobacteria other than Mycobacterium tuberculosis were not observed. The number of patients who received and tolerated INH may not be sufficient for firm conclusions, but the data suggest that, in countries where Tb is prevalent, pre- and posttransplantation follow-up for Tb and the use of INH prophylaxis should be considered.

Congenital dyserythropoietic anemia type I with ringed sideroblasts.

A 25-year-old male with anemia, jaundice and liver dysfunction was admitted to our institution. Anisopoikilocytosis with tear-drop forms, polychromasia, basophilic stippling in peripheral blood smear, erythroid hyperplasia with megaloblastoid changes, binucleated cells and intranuclear bridging in bone marrow aspirate and spongy, unevenly condensed nuclear chromatin in electron microscopy studies indicated that he had congenital dyserythropoietic anemia (CDA) type I. As a rare finding in CDA, ringed sideroblasts were noted. It is proposed that this patient is an example for the designation 'variant congenital dyserythropoietic anemia with ringed sideroblasts'.

Evaluation of chimerism with DNA polymorphisms in bone marrow transplantation.

Evaluation of chimeric status following allogenic BMT is an important tool for monitoring the replacement of host cells with donor cells and for determining the risk of relapse. Polymorphic DNA sequences can be used as powerful markers in identification of donor/recipient genotype differences, even between close relatives. Polymerase chain reaction (PCR) amplification of three variable number of tandem repeat (VNTR) loci and five single-locus polymorphisms (SLP) was used to identify chimerism in 40 recipient-donor pairs. Mixed chimerism was present in 11 patients, and complete chimerism in 29. This PCR method is a rapid and sensitive assay to detect engraftment and evaluate relapse potential, and thus is very useful in the clinical management of BMT patients.

Successful outcome of aspergillus brain abscess in a patient who underwent bone marrow transplantation for aplastic anemia.

We report the course of an aspergillus brain abscess in an 18-year-old female patient who underwent bone marrow transplantation for aplastic anemia. The abscess was discovered on day 35 post-transplant, in a cranial computerized tomography (CT) scan performed for the evaluation of an unexplained headache. Meanwhile, she was receiving broad-spectrum antibacterials and liposomal amphotericin B for a right upper pulmonary lobe infiltrate. A percutaneous puncture of the cerebral lesion was performed; fungal elements were seen in the pus obtained and its culture yielded A. fumigatus. The dose of amphotericin B was increased, intraconazole was added and two more punctures were done. With these antifungals, the abscess regressed significantly; so, amphotericin B was discontinued after a cumulative dose of 6775 mg but intraconazole was maintained at 400 mg/day. At the last follow-up, seventeen months after detection of the abscess, the patient was well, without symptoms and the cerebral lesion diminished to a very small, thick-walled CT image.