Muhlis Cem Ar

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.

Methods for individualising factor VIII dosing in prophylaxis

Haemophilia A is a sex‐linked disorder characterised chiefly by recurrent, spontaneous joint and muscle bleedings resulting from deficiency of factor VIII (FVIII). Recurrent joint bleeds result in haemophilic arthropathy. Unless treated with factor replacement therapy, many patients with severe haemophilia become disabled. The first clinical evidence favouring prophylaxis originated from the studies in Sweden and the Netherlands in the 1960s. Later on, it was shown that prophylaxis could prevent arthropathy, if started early in life, or slow its progression in adults with established arthropathy. The optimal dosing of FVIII in long‐term prophylaxis has still not been determined, and there is growing evidence that the dose and frequency of FVIII should be individualised. We conducted a systematic search of PubMed to identify all relevant articles on FVIII prophylaxis in severe haemophilia A. We focused on articles with detailed information about individualisation of prophylaxis. Long‐term prophylaxis in haemophilia was introduced in Sweden in the late 1950s. However, standard prophylactic regimens may not be appropriate for all patients with severe haemophilia. Factors such as age, joint status, co‐morbidities and differences in pharmacokinetics lead to interindividual variation in factor requirement. Dose tailoring of FVIII by clinical outcome was first described in 1994. Since then, several dose‐finding studies questioned the necessity to maintain preinfusion levels of FVIII above 1%. Individualising prophylaxis by dose tailoring is now recommended. Each country should adopt policies for individualising prophylaxis in patients with severe haemophilia. This would lead to a better distribution of the available source of factor concentrates.

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.

Generics in chronic myeloid leukemia: current arguments for and against and the established evidence

Tyrosine kinase inhibitors became the mainstay of management in patients with chronic myeloid leukemia. The substantially high treatment cost has unfortunately been a major issue. Recent market entry of the imatinib generics are expected to lower the price and increase the availability of the drug worldwide. However, concerns about their efficacy and safety seem to slacken the approval of the generics in many countries. In this editorial, we discuss the current evidence on imatinib generics based mainly on Turkish experience and other limited data available.

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.

Intracranial extramedullary hematopoiesis in patients with thalassemia: a case report and review of the literature

BACKGROUND: Extramedullary hematopoiesis (EH) is a compensatory phenomenon that results in the production of blood cell precursors outside the marrow in patients with chronic hemolytic anemia and ineffective erythropoiesis. EH usually involves the liver, spleen, and lymph nodes. It can also be found at paravertebral, intrathoracic, or pelvic locations. Intracranial EH is a rare entity and often asymptomatic but can sometimes lead to symptomatic tumor‐like masses. Treatment options are controversial and include hypertransfusion, surgical excision, radiotherapy, and hydroxyurea (HU).

Is valganciclovir really effective in primary effusion lymphoma: case report of an HIV(−) EBV(−) HHV8(+) patient

Primary effusion lymphoma (PEL) is a human herpesvirus 8 (HHV8) associated lymphoproliferative disease characterized by effusions in body cavities, and lack of tumor mass. Valganciclovir is a treatment option in PEL, however, little is known about its clinical efficacy. Ganciclovir has been reported to be effective in HHV8(+) multicentric Castlemans disease (MCD) by decreasing the plasma HHV8 load, which is an important factor in the induction and persistence of MCD, Kaposis sarcoma (KS), and PEL. But there is no information about the efficacy of valganciclovir on HHV8 associated lymphoproliferative diseases. Here, we present the first EBV and HIV negative, HHV8 positive PEL case treated with valganciclovir; for whom it initially reduced the viral load leading to a transient partial improvement in the clinical status, but failed to induce a complete and durable remission.

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-

Acute colitis presenting with hematochezia in a patient with chronic myeloid leukemia during dasatinib therapy.

An 18-year-old male patient was diagnosed with a high Sokal risk chronic-phase CML in January 2000. He first received hydroxyurea (HU) for six years, and then he was admitted to our hematology department and imatinib mesylate (IM) 400 mg/daily was initiated in September 2006. He never achieved major molecular and complete cytogenetic responses with IM, and he did not have a donor for allogeneic hematopoietic stem cell transplantation. DAS 100 mg/day was started in September 2007, six weeks after the initiation of DAS, the patient presented with rectal bleeding and diarrhea. He never had such complaints prior to DAS. A colonoscopic examination was performed in November 2007, which revealed exudation, erosions and multiple ulcers with nodular hyperemic lesions in the entire colon. Histopathological examination showed nonspecific colitis. First glucocorticosteroid then oral 5-aminosalicylic acid (5-ASA) was started, and his complaints were diminished but never totally resolved. A BCR-ABL kinase domain mutation analysis was performed which lead to the identification of T315I, and dasatinib was stopped in June 2008. After the interruption of DAS, his rectal bleeding and diarrhea were completely resolved. HU was restarted, but during the follow-up, he was deceased due to myeloid blast crisis in September 2010.

Comparison of International Prognostic Index and NCCN-IPI in 324 patients with de novo diffuse large B-cell lymphoma: a multi-center retrospective analysis.

Erman Öztürk, Murat Özbalak, Selin Berk, Işıl Erdoğan, Emin Avşar, Anıl Dolgun, Mustafa Çetiner, Nil Molinas Mandel, Fevzi Fırat Yalnız, Tuğrul Elverdi, Ayşe Salihoğlu, Ahmet Emre Eşkazan Muhlis Cem Ar, Şeniz Öngören, Zafer Başlar, Yıldız Aydın, Teoman Soysal & Burhan Ferhanoğlu Division of Hematology, Department of Internal Medicine, Koç University, School of Medicine, Istanbul, Division of Hematology, Department of Internal Medicine, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Division of Oncology, V.K.V. American Hospital, Istanbul, Department of Biostatstics, Hacettepe University, Ankara, and Division of Oncology, Department of Internal Medicine, Koç University, School of Medicine, Istanbul, Turkey