Bone marrow transplantation for Behçet's disease: a case report and systematic review of the literature.

OBJECTIVES: Behçet's disease (BD) can be life threatening and may be refractory to corticosteroids and immunosuppressives. There has been some experience with haematopoietic stem cell transplantation (HSCT) in BD either for severe, refractory disease or for a haematological condition. The objectives of this study were to describe a BD patient undergoing HSCT and to evaluate the outcomes of BD patients who underwent HSCT. METHODS: We report a BD patient with refractory gastrointestinal (GI) involvement who had HSCT for concomitant myelodysplastic syndrome (MDS). We also performed a systematic literature search regarding HSCT for either refractory disease or concomitant haematological conditions in BD patients. RESULTS: A 30-year-old woman with refractory GI BD involvement with trisomy 8 MDS underwent a successful myeloablative allogeneic HSCT resulting in complete resolution of both BD and MDS. Additionally we identified 14 manuscripts providing data on 19 patients with BD who had HSCT. Among these 20 patients, including ours, refractory disease was the indication of transplantation in 9, while 11 patients were transplanted because of accompanying haematological conditions. Transplant indications for the nine patients (four male, five female) with refractory BD were neurological involvement in five, pulmonary artery aneurysm in two, GI disease in one and not reported in one patient. Three patients with neurological disease, both patients with pulmonary artery aneurysm and the patient with intestinal involvement achieved complete remission of their disease. Six patients transplanted for haematological conditions, including the presented case, also had GI involvement of BD. All of these patients achieved complete remission of GI findings after HSCT. CONCLUSION: When considering HSCT, the potential adverse events and complications, which can be fatal, need to be kept in mind.

Recommendations for the Treatment of Invasive Fungal Infections in Hematological Malignancies: A Critical Review of Evidence and Turkish Expert Opinion (TEO-1).

The introduction of novel antifungal agents for the treatment of invasive fungal disease in hematological malignancies and also changing treatment strategies have had a great impact in managing affected patients. The medical literature includes some important clinical studies that are being used as evidence for guidelines. The problem with these studies and the guidelines is that they are not very easy to interpret, they include controversial issues, and they are not easy to apply to every patient or country. This paper was designed to critically show the main problems associated with these approaches and provide important information that will help Turkish doctors to adopt them in daily clinical practice.

The Association Between JAK2V617F Mutation and Bone Marrow Fibrosis at Diagnosis in Patients with Philadelphia-Negative Chronic Myeloproliferative Neoplasms.

OBJECTIVE: Bone marrow fibrosis is the second most common complication that causes morbidity and mortality inpatients with Philadelphia-negative myeloproliferative neoplasms (MPNs). The aim of this study was to investigate theassociation between JAK2V617F mutation and bone marrow fibrosis at diagnosis in patients with MPNs. MATERIAL AND METHODS: In total, 149 patients with MPNs were retrospectively evaluated to determine if there was anassociation between the histological grade of bone marrow fibrosis and JAK2V617F mutation. RESULTS: In all, 67.7% of the patients carried the mutated JAK2 gene. The presence of JAK2V617F mutation was notassociated with the occurrence of bone marrow fibrosis (P=0.55) or its grade at diagnosis (P=0.65). CONCLUSION: Molecular mechanisms or genetic defects other than JAK2V617F may underlie the occurrence of bonemarrow fibrosis in patients with MPNs.

Imatinib reduces bone marrow fibrosis and overwhelms the adverse prognostic impact of reticulin formation in patients with chronic myeloid leukaemia.

AIMS: Before the era of tyrosine kinase inhibitors (TKIs), the presence of bone marrow fibrosis (MF) in patients with chronic myeloid leukaemia (CML) has been established as a poor prognostic factor. The aim of the present study was to evaluate the effects of imatinib treatment on MF and the prognostic significance of MF at this new era of CML therapy. METHODS: The study cohort consisted of 135 patients with CML who were exposed to imatinib. The grades of MF pre and post imatinib together with cytogenetic and molecular responses were evaluated. RESULTS: Severe MF (grade II-III) was observed in 44 (33%) patients prior to imatinib therapy, and in 8 (8%) after 12 months of imatinib treatment (p=0.001). The complete cytogenetic response (CCyR) rates at 12 months did not differ according to the pre-imatinib MF grades, and CCyR rates in patients with grades 0, I, II and III MF were 36/47 (76.5%), 26/33 (78.7%), 12/23 (52.1%) and 7/10 (70%), respectively (p=0.127). There was no significant difference between patients with or without CCyR at 12 months of imatinib regarding grades of MF (p=0.785). The distribution of the major molecular response rates at 18 months according to pre-treatment grades of MF were determined as grade 0 in 38/45 (84.4%), grade I in 21/28 (75%), grade II in 14/21 (66.6%) and grade III in 7/10 (70%) (p=0.112). There was no significant difference in overall survival rates between initial MF mild (grade 0-I) and severe (grade II-III) groups (p=0.278). CONCLUSIONS: According to our findings, MF regresses with imatinib therapy over time, and the MF grades at diagnosis do not have a negative impact on the responses to imatinib treatment. Therefore, the adverse prognostic impact of the MF among patients with CML seems to disappear in the era of the TKIs.

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.

Detailed analysis of diffuse large B cell lymphoma patients: a single-center, retrospective study.

The aim of this single-center, retrospective study was to investigate the impact of rituximab, reconsider the validity of International Prognostic Index (IPI), and evaluate the prognostic role of the cell of origin (CoO) in a relatively young cohort. Three hundred twelve diffuse large B cell lymphoma patients (median age: 52) were included. Rituximab significantly improved the 3- and 5-year progression free survival (PFS) (70% versus 65% and 41% versus 36%, resp.; P < 0.001) but led only to a slight, insignificant increase in 3- and 5-year overall survival (OS) (71% versus 77.3% and %67 versus 74.5%, resp.; P = 0.264). In the young, low risk patient subgroup (aaIPI = 0&1; n = 129), rituximab improved 3- and 5-year PFS and OS rates (P < 0.001 and P = 0.048, resp.). The efficacy of rituximab in young high risk patients was comparable to the literature. CoO data were available in 190 patients. The OS at 3 years was 79% for GC and 64% for non-GC subgroups (P = 0.014). To the best of our knowledge, this is the first study which investigated the impact of R-CHOP in the context of CoO and IPI in a relatively young cohort. CoO was not an independent risk factor for prognosis in the multivariate analysis although patients with GC showed a significant survival advantage in the univariate analysis. CoO was also found to be a significant determinant of response in refractory/relapsed patients. Our results confirm the efficacy of rituximab in low and high risk, young patients outside of a randomized clinical trial setting.