Yildiz Aydin

T-cell-rich B-cell lymphoma: a clinicopathologic study of 21 cases and comparison with 43 cases of diffuse large B-cell lymphoma

Clinicopathologic features of 21 patients with T-cell-rich B-cell lymphoma (TCRBCL) were reviewed and compared to 43 patients with diffuse large B-cell lymphoma (DLBCL) to determine if there were distinguishing clinical characteristics and differences in response or survival to CHOP therapy. For the diagnosis of TCRBCL, the current WHO criteria was used. In all of our cases, the majority of cells are non-neoplastic T cells and <10% large neoplastic B cells are present. The initial pathologic diagnosis was nodular lymphocyte predominant Hodgkins lymphoma (NLPHL) in two cases. Patients with TCRBCL were significantly younger (median: 46 years) and had a significantly higher incidence of B symptoms (62%), hepatomegaly (33%) and marrow infiltration (33%) at presentation when compared to DLBCL (P<0.03). The CR rate after treatment was 48% for TCRBCL patients versus 79% for the DLBCL (P<0.003). Although the CR rates in between the two groups are significant, the difference in 3 years survival rates in each CR groups was insignificant (80% versus 77%). The overall survival time in the two groups was 17 months. Event-free survival time in TCRBCL was 12 months, compared with 17 months in the DLBCL (P>0.05). The frequency of patients with TCRBCL achieving CR was 52.6% whereas that of patients with DLBCL was 79% (P<0.003). The TCRBCL 3 years event-free survival 48% and overall survival 64% were 63 and 72% for DLBCL, respectively.

Effects of brassinosteroid on cotton regeneration via somatic embryogenesis

Brassinolide (BR), which is the most biologically active brassinosteroid, was used to examine the potential effect of hormone on cotton somatic embryogenesis. Ten-day-old cotton (Gossypium hirsutum L., cv. Cooker) seedlings were used for explant source and hypocotyls were removed and cultured on MS basal medium with B5 vitamins supplemented with 1 mg/L 6-benzylaminopurine + 0.5 mg/L kinetin for callus induction. After one month proliferating calli pieces were collected and cultured on MS basal medium containing various concentrations of BR (0.1, 0.5, 1.0 µM) with their controls. BR treatments were negatively effective on the fresh weight of calli when compared to control. Differential somatic embryogenesis maturation rates due to BR treatment were observed. Somatic embryogenesis was stimulated especially for transition to cotyledonary phase at 0.5 mg/L BR. Histological preparations from embryogenic calli and somatic embryos at different stages of development revealed the spontaneous polyploidisation during early somatic embryogenesis on BR-treated calli. Present results suggest that BR negatively effected calli growth, however, had a stimulating role in maturation of somatic embryos.

Chronic myeloid leukemia patients who develop grade I/II pleural effusion under second-line dasatinib have better responses and outcomes than patients without pleural effusion

Dasatinib is a potent second generation TKI, and it is widely used in patients with CML, both in the up-front setting and failure after imatinib. Lymphocytosis in cases receiving dasatinib therapy has been shown to be associated with pleural effusion (PE) and better outcome. Although patients who gather lymphocytosis during dasatinib have superior responses, there is only little data about the correlation between PE, response rates, and survival. In order to answer this question, the aim of our study was to determine the frequency of PE and lymphocytosis among our CML patients receiving second-line dasatinib, and to compare the responses and outcomes between patients with or without PE. There were 18 patients (44%) who developed PE, in a total of 41 patients, with a median time of 15 months. Lymphocytosis was observed in nine patients (9/41, 22%) with a median duration of 6.5 months of dasatinib treatment. There were fourteen patients with at least one comorbidity that may play a role in the generation of PE. The cumulative MMR and CCyR rates were greater in PE+ patients (p<0.05). The PFS was significantly higher in PE+ group than PE- patients (p=0.013), also the OS was higher among PE+ patients than PE- group (p=0.042). In patients with a grade I/II PE, and durable responses under dasatinib, performing the management strategies for the recovery of effusion, together with continuing dasatinib can be a reasonable choice mainly in countries where third generation TKIs are not available. But alternative treatment strategies such as nilotinib or third generation TKIs can be chosen in patients with grade III/IV PE especially if the quality of life is severely affected.

The efficacy of generic formulations of imatinib mesylate in the treatment of chronic myeloid leukemia.

Th e treatment of chronic myeloid leukemia (CML) has changed greatly, and the outlook of patients with CML has improved dramatically, with the introduction of tyrosine kinase inhibitors (TKIs) [1]. Th e fi rst TKI developed for CML was imatinib mesylate (IM) (Glivec; Novartis, Basel, Switzerland) [2], and thereafter many other TKIs became available on the market [3]. Th e high cost of new cancer drugs including those developed for CML is a major concern for healthcare payers, especially in countries with restricted resources. Reimbursement policies worldwide, therefore, encourage generic drug use to lower the prices. It is true that generics lead to considerable cost savings, but they also give rise to questions associated with their effi cacy, safety and quality. In Turkey, there are three commercially available generics of IM (Imatis; Deva, Imatenil; Logus and Imavec; Ko c ak Farma), which have been licensed for the treatment of CML for more than a year. Th ere is a price diff erence between Glivec and the generics, and due to the reimbursement policy, patients who prefer to receive the original molecule must pay the price diff erence; the price diff erence was the only reason for switching from Glivec to any generic among our cohort. Th e fi rst issue that physicians caring for patients with CML encounter is whether the effi cacy of these generics is comparable to that of the original molecule; the second issue is what the potential adverse events (AEs) are, other than those with use of Glivec, if any. To answer these questions, we retrospectively reviewed our data.

Pleural and pericardial effusions in chronic myeloid leukemia patients receiving low-dose dasatinib therapy

They reported 4 patients who developed effusions with 50 or 100 mg daily dasatinib out of a total number of 13 patients. Pleural and pericardial effusions were grade III/IV in 2 of the patients. There were no reports of pre-existing cardiac or pul monary diseases for any of the 4 patients. In 3 cases, dasa tinib had to be discontinued because of the persistence of the pleural fluids despite treatment with diuretics and glu cocorticosteroids. In conclusion, Krauth et al. suggest that all patients should be examined for pre-existing comorbidities and risk factors before the initiation of dasatinib, and they should have repeated chest X-rays during the followup period because of the possibility of pleural or pericardial effusions even under low doses of dasatinib treatment. We report our experience of chronic myeloid leukemia patients receiving low-dose dasatinib who had developed pleural and pericardial effusion. In our institute, a total number of 23 chronic phase chronic myeloid leukemia patients receive dasatinib (50-100 mg daily) due to resist ance or intolerance to imatinib. Among these 23 patients, 10 of them (43%) had pleural and pericardial effusions (9 with pleural effusion and one with pericardial effusion). Eight patients were males and 2 were females. Median age was 61.5 (range 44-69). Nine patients out of 10 were in late chronic phase who were switched to dasatinib because of imatinib resistance. Only one patient was in early chronic phase since she started receiving dasatinib due to intolerance of imatinib. The median duration of dasatinib use was 26 months (range 13-33). All of the patients had grade I/II effusions. In 7 patients dasatinib therapy was interrupted and furosemide plus glucocorti costeroids were initiated; effusions were totally resolved in 4 of the 7. Dasatinib was restarted in those 4 patients and effusions did not reoccur. The remaining 3 patients had just started receiving furosemide and glucocorticosteroids and are under follow up so we were unable to make a comment on the success of the treatment. Dasatinib treatment was not stopped in one patient when he developed pleural effusion; we only added gluco corticosteroids and the effusion improved. No other inter vention was made in the other 2 patients other than inter rupting dasatinib treatment and the pleural effusions improved. After restarting dasatinib in those 2 patients, one of them developed pleural effusion which was then managed with furosemide and glucocorticosteroids, dasa tinib was discontinued and he then fully recovered. Pleural effusion is the most frequent non-hematologic adverse event in dasatinib-treated patients. 2 Although effu sion formation may require some time and the risk of effu sion formation is lower in patients treated with 100 mg dasatinib than patients receiving 140 mg dasatinib daily, patients treated with dasatinib at 100 mg daily dose may also develop pleural effusions.

An EST-SSR marker linked with yellow rust resistance in wheat

Expressed sequenced tags containing simple sequence repeats (EST-SSRs) were used to identify molecular markers associated with yellow rust resistance in wheat (Triticum aestivum L.). A cross between yellow rust resistant (PI178383) and susceptible (Harmankaya99) wheat genotypes was performed and respective DNA pools from the resistant and susceptible F2 seedlings were constructed. 78 EST-SSR primers were used for bulked segregant analysis and one EST-SSR marker (Pk54), identified as 200 bp fragment, was present in the resistant parent and resistant F2 hybrids but not in the susceptible ones. 108 wheat genotypes differing in yellow rust resistance were screened with Pk54 and 68 % of the wheat genotypes, known to be yellow rust resistant, had the Pk54 marker, further suggesting that the presence of this marker correlates with yellow rust resistance.

First line treatment of chronic phase chronic myeloid leukaemia patients with the generic formulations of imatinib mesylate

in the prevalence of growth, endocrine and vitamin D abnormalities among the various thalassaemia syndromes in North America. British Journal of Haematology, 146, 546–556. Vogiatzi, M.G., Macklin, E.A., Fung, E.B., Cheung, A.M., Vichinsky, E., Olivieri, N., Kirby, M., Kwiatkowski, J.L., Cunningham, M., Holm, I.A., Lane, J., Schneider, R., Fleisher, M., Grady, R.W., Peterson, C.C., Giardina, P.J. & Thalassemia Clinical Research Network (2009b) Bone disease in thalassemia: a frequent and still unresolved problem. Journal of Bone and Mineral Research, 24, 543–557.

A Microsatellite Marker for Yellow Rust Resistance in Wheat

Bulk segregant analysis (BSA) was used to identify molecular markers associated with yellow rust disease resistance in wheat (Triticum aestivum L.). DNAs isolated from the selected yellow rust tolerant and susceptible F2 individuals derived from a cross between yellow rust resistant and susceptible wheat genotypes were used to established a “tolerant” and a “susceptible” DNA pool. The BSA was then performed on these DNA pools using 230 markers that were previously mapped onto the individual wheat chromosomes. One of the SSR markers (Xgwm382) located on chromosome group 2 (A, B, D genomes) was present in the resistant parent and the resistant bulk but not in the susceptible parent and the susceptible bulk, suggesting that this marker is linked to a yellow rust resistance gene. The presence of Xgwm382 was also tested in 108 additional wheat genotypes differing in yellow rust resistance. This analysis showed that 81% of the wheat genotypes known to be yellow rust resistant had the Xgwm382 marker, further suggesting that the presence of this marker correlates with yellow rust resistance in diverse wheat germplasm. Therefore, Xgwm382 could be useful for marker assisted selection of yellow rust resistances genotypes in wheat breeding programs.

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.

Essential Thrombocythemia and Multiple Myeloma: Two Rare Diseases in One Patient

Introduction Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN), characterized by the clonal proliferation of megakaryocytes in the bone marrow and high platelet count in the peripheral blood. ET has been associated with transformation to acute myeloid leukemia, myelodysplastic syndrome, chronic lymphoytic leukemia, and other MPNs, especially primary myelofibrosis. The association between multiple myeloma (MM) and ET is infrequent. Only a few cases in the medical literature have been demon-