Sickle cell disease-related organ injuries cannot be prevented despite hydroxyurea use, infection prophylaxis and supportive therapies. As a consequence, disease-related mortality reaches 14% in adolescents and young adults. Hematopoietic stem cell transplantation is a unique curative therapeutic approach for sickle cell disease. Myeloablative allogeneic hematopoietic stem cell transplantation is curative for children with sickle cell disease. Current data indicate that long term disease-free survival is about 90% and overall survival about 95% after transplantation. However, it is toxic in adults due to organ injuries. In addition, this curative treatment approach has several limitations, such as difficulties finding donors, transplant-related mortality, graft loss, graft-versus-host disease (GVHD) and infertility. Engraftment effectivity and toxicity for transplantations performed with nonmyeloablative reduced-intensity regimens in adults are being investigated in phase I/II trials at many centers. Preliminary data indicate that GVHD could be prevented in transplantations performed using reduced-intensity regimens. It is necessary to develop novel regimens to prevent graft loss and reduce the risk of GVHD.

INTRODUCTION: We aimed to understand the molecular pathways affected by bortezomib and arsenic trioxide treatment on myelomonocytoid cell line P39.
METHODS: Oligonucleotide microarray platforms were used for gene expression and pathway analysis. Confirmation studies were performed using quantitative real time PCR.
RESULTS: Bortezomib treatment has shown upregulated DIABLO and NF-κBIB (a NF-κB inhibitor) and downregulated NF-κB1, NF-κB2, and BIRC1 gene expressions. Combination treatment of the two compounds showed gene expression deregulations in concordance by the results of single bortezomib treatment. Especially, P53 was a pathway more significantly modified and a gene network centralized around the beta estradiol gene. Beta estradiol, BRCA2, and FOXA1 genes were remarkable deregulations in our findings.
DISCUSSION AND CONCLUSION: Results support the suggestions about possible use of proteasome inhibitors in the treatment of high-risk myelodysplastic syndrome (MDS). NF-κB was observed as an important modulator in leukemic transformation of MDS.

INTRODUCTION: Positron emission tomography and computed tomography (PET/CT) has become an important part of staging and treatment evaluation algorithms of lymphoma. We aimed to compare the results of PET/CT with bone marrow biopsy (BMB) with respect to bone marrow involvement (BMI) in patients with Hodgkin’s lymphoma (HL) and aggressive non-Hodgkin’s lymphoma (aNHL).
METHODS: The medical files of a total of 297 patients diagnosed with HL or aNHL and followed at the hematology clinics of 3 major hospitals in İstanbul between 2008 and 2012 were screened retrospectively and 161 patients with classical HL and aNHL were included in the study. The patients were referred for PET/CT and BMB at the initial staging. BMB was performed as the reference standard for the evaluation of BMI.
RESULTS: There were 61 (38%) HL and 100 (62%) aNHL patients. Concordant results were revealed between PET/CT and BMB in 126 patients (78%) (52 HL, 74 aNHL), 20 with positive PET/CT and BMB results and 106 with negative PET/CT and BMB results. There were discordant results in 35 patients (9 HL, 26 aNHL), 16 of them with positive BMB and negative PET/ CT results and 19 of them with negative BMB and positive PET/CT results.
DISCUSSION AND CONCLUSION: We observed that PET/CT is effective to detect BMI, despite it alone not being sufficient to evaluate BMI in HL and aNHL. Bone marrow trephine biopsy and PET/CT should be considered as mutually complementary methods for detection of BMI in patients with lymphoma. In suspected focal involvement, combining biopsy and PET/CT might improve staging results.

INTRODUCTION: To investigate the relationship between CD4+CD25+CD127dim regulatory T cells (Tregs) and immune imbalance in acquired severe aplastic anemia (SAA).
METHODS: The quantity of CD4+CD25+CD127dim Tregs in 44 SAA patients and 23 normal controls were measured by flow cytometry. Correlations between Tregs and T cell subsets, dendritic cell (DC) subsets, granulocyte counts and percentage of reticulocytes (RET%) were analyzed.
RESULTS: The percentage of CD4+CD25+CD127dim Tregs in peripheral blood lymphocytes (PBL) of untreated patients was lower than in recovery patients and normal controls (0.83±0.44% vs 2.91±1.24% and 2.18±0.55%, respectively, p<0.05). The percentage of CD4+CD25+CD127dim Tregs in CD4+ T lymphocytes of recovery patients was higher than for untreated patients and normal controls (9.39±3.51% vs 7.61±5.3% and 6.83±1.4%, respectively, p<0.05). The percentage of CD4+ T lymphocytes in PBL of untreated patients was lower than for recovery patients and normal controls (13.55±7.37% vs 31.82±8.43% and 32.12±5.88%, respectively, p<0.05). T cell subset (CD4+/CD8+ ratio) was 0.41±0.24 in untreated patients, which was lower than recovery patients (1.2±0.4) and normal controls (1.11±0.23) (p<0.05). DC subset (myeloid DC/plasmacytoid DC ratio, DC1/DC2 ratio) was 3.08±0.72 in untreated patients, which was higher than recovery patients (1.61±0.49) and normal controls (1.39±0.36) (p<0.05). The percentage of CD4+CD25+CD127dim Tregs in PBL was positively associated with T cell subset (r=0.955, p<0.01), and negatively associated with DC subset (r=-0.765, p<0.01). There were significant positive correlations between CD4+CD25+CD127dim Tregs/PBL and granulocyte counts and RET% (r=0.739, 0.749 respectively, p<0.01).
DISCUSSION AND CONCLUSION: The decrease of CD4+CD25+CD127dim Tregs in SAA patients may cause excessive functions of T lymphocytes and thus lead to hematopoiesis failure in SAA.

INTRODUCTION: Venous thromboembolism (VTE) in children who undergo hematopoietic stem cell transplantation (HSCT) has high morbidity. The aim of this study is to assess the incidence of VTE in allogeneic pediatric HSCT recipients and the contribution of pretransplant prothrombotic risk factors to thrombosis. 

METHODS: We retrospectively evaluated 92 patients between April 2010 and November 2012 undergoing allogeneic HSCT who had completed 100 days post-HSCT. Before HSCT, coagulation profiles; acquired and inherited prothrombotic risk factors including factor V Leiden, prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T, and MTHFR A1298C mutations; and serum homocysteine and lipoprotein(a), plasma antithrombin III, protein C, and protein S levels were obtained from all patients.
RESULTS: In the screening of thrombophilia, 8 patients (9%) were heterozygous for factor V Leiden, 5 (6%) were homozygous for MTHFR 677TT, 12 (14%) were homozygous for MTHFR 1298CC, and 2 (2%) were heterozygous for prothrombin G20210A mutation. We observed VTE in 5 patients (5.4%); a prothrombotic risk factor was found in 3 out of these 5 patients, while 4 out of 5 patients had central venous catheters. It was determined there was no significant relationship between VTE and inherited prothrombotic risk factors.
DISCUSSION AND CONCLUSION: VTE after HSCT seems to be a low-frequency event that may be due to low-dose, low-molecular-weight heparin prophylaxis, and the role of inherited prothrombotic risk factors cannot be entirely excluded without a prospective study.

INTRODUCTION: Multiple myeloma is a common haematological malignancy and immune dysfunction is the hallmark of the disease. It leads to an increased infection risk, which is still a major cause of mortality. The infection spectrum and characteristics have evolved with the introduction of novel agents. An understanding of risk factors that increase susceptibility to infections is critical in fighting them. This retrospective investigation aimed to establish the incidence and main characteristics of infections in non-transplanted hospitalised myeloma patients in our department over a 3-year period, as well as factors associated with infections.
METHODS: A total of 240 hospitalised patients with multiple myeloma (120 males and 120 females; average age: 69 years, range: 41-89 years) who were diagnosed or treated in our department from January 2008 to December 2010 were included in this study and their data were retrospectively analysed.
RESULTS: Infections were identified in 17.9% of hospitalised patients. The most common pathogen found was Pseudomonas aeruginosa. The frequency of gram-positive and gram-negative pathogens was similar. In 37.2% of cases, the agent was not isolated. The most common sites of infections were the urinary system and the blood. The frequency of infection increased with duration of disease and the rate of reinfection was 41.9%. The patients treated with bortezomib had the highest infection occurrence. Fatal outcome occurred in 9.3% of cases.
DISCUSSION AND CONCLUSION: The factors associated with infections in this investigation were female sex, IIIB clinical stage of disease, increased serum creatinine and ferritin levels, neutropenia, poor general condition, and presence of catheters. Myeloma patients with one or more of these mentioned risk factors should be monitored with particular care in order to decrease the incidence and severity of infective complications.

INTRODUCTION: Febrile neutropenic episodes (FNEs) are among major causes of mortality in patients with hematological malignancies. Secondary infections develop either during the empirical antibiotic therapy or one week after cessation of therapy for a FNE. The aim of the study was to investigate the risk factors associated with secondary infections in febrile neutropenic patients.
METHODS: We retrospectively analyzed 750 FNEs in 473 patients between January 2000 and December 2006.
RESULTS: Secondary infections were diagnosed in 152 (20%) of 750 FNEs. The median time to develop secondary infection was 10 days (range 2-34 days). The duration of neutropenia over 10 days significantly increased the risk of secondary infections (p<0.001). The proportion of patients with microbiologically documented infections was found to be higher in primary infections (271/750, 36%) compared to secondary infections (43/152, 28%) (p=0.038). Age, sex, underlying disease, antibacterial, antifungal or antiviral prophylaxis, blood transfusion or bone marrow transplantation, central venous catheter or severity of neutropenia did not differ significantly between primary and secondary infections (p>0.05) While fever of unknown origin (FUO) (p=0.005) and catheter-related bacteremia (p<0.001) were less frequently observed in secondary infections, the frequency of microbiologically (p=0.003) and clinically (p<0.001) documented infections, fungal pneumonias (p<0.001), infections related with gram positive bacteria (p=0.04) and fungi (p<0.001) and 30-day mortality rate (p<0.001) were significantly higher in secondary infections (p<0.001).
DISCUSSION AND CONCLUSION: Secondary infections should be regarded as life-threatening complications of febrile neutropenia. Secondary infections represent a more severe and mortal complication and cannot be regarded just as another febrile neutropenic episode.

INTRODUCTION: To investigate the influence of chemotherapy (CT) on HBsAb titer in patients receiving CT due to hematological malignancy.
METHODS: The data of 75 patients who received CT with the diagnosis of various hematological malignancies and who had serum HBsAb levels measured prior to and after the cessation of CT were evaluated retrospectively.
RESULTS: The median age of the patients was 52 years (range: 16-78) with 49 (65%) males and 26 (35%) females. Median HBsAb titer decreased significantly after CT compared to the pre-CT median HBsAb titer [68 (range: 0-1000) vs. 100 (range: 6.2-1000)] (p=0.001). In subgroup analysis, median HBsAb titer decreased significantly after CT in acute leukemia patients [110 (range: 6.2-1000) vs. 67.8 (range: 0-1000)] (p=0.003) and in patients receiving intensive CT [97.2 (range: 6.2-1000) vs. 71 (range: 0-1000)] (p=0.036). The decrease in median HBsAb titer was significant in male patients (p<0.001). HBsAb became negative after CT in 9 patients who were HBcAb-negative and had lower pre-CT HBsAb levels.
DISCUSSION AND CONCLUSION: HBsAb decreased after CT, especially in acute leukemia and male patients, and in patients receiving intensive CT.

The patient, a 79-year-old Japanese man, was diagnosed with the chronic phase of chronic myeloid leukemia and begun on nilotinib therapy in April 2011. The therapeutic response was major molecular response in August. About 19 months after the start of nilotinib therapy at 400 mg/day (November 2012), an adenocarcinoma (24x20 mm) confined to the head of the pancreas developed. In February 2013, a pancreaticoduodenectomy was performed. The therapy regimen was switched to dasatinib at 100 mg/day, beginning in April. The response was still major molecular response with no recurrence of pancreatic carcinoma in July 2013. There have been 29 reported cases of secondary neoplasms associated with nilotinib therapy. These secondary neoplasms were characterized by relatively frequent occurrence of papilloma (6 cases), gastric cancer (3 cases), fibroma (3 cases), and thyroid neoplasms (2 cases). The present case, however, is the first to be reported as carcinoma of the pancreas. This report describes the case.

Experiences with new multikinase inhibitors are limited, especially in children. In this report we summarize our experience with 2 patients with relapsed acute myeloblastic leukemia (AML), one with FMS-like tyrosine kinase- 3-internal tandem duplication mutation and the other with a single base mutation (D835Y). Both patients received sorafenib, one for 19 days and the other for 42 days, with clofarabine-including chemotherapy. One additionally received sunitinib for a total of 20 days. Both patients developed severe pancytopenia, hypertension, life-threatening bleedings from the gastrointestinal system, and, finally, intrapulmonary hemorrhage. Although both reached severe aplasia of the bone marrow without blastic infiltration, death occurred with neutropenic sepsis.

Total anomalous pulmonary venous return (TAPVR) is a rare and frequently isolated defect identified in 1% to 3% of all congenital heart diseases. To the best of our knowledge, portal vein thrombosis (PVT) associated with TAPVR has not been reported in the literature. We report a successfully managed PVT in a newborn with infracardiac-type TAPVR and review the literature. Anticoagulation therapies were used during the neonatal period to prevent thrombus progression. PVT should be kept in mind in TAPVR patients who have open heart repair with total correction. The treatment in each neonate should be individualized with consideration of the risk/benefit ratio.

We present a 64-year-old man who was treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemoimmunotherapy for mantle cell lymphoma and developed purulent meningitis, probably caused by Leuconostoc sp. The patient had severe hypogammaglobulinemia, which is a possible complication of rituximab therapy. To our knowledge and after reviewing the available medical literature, this is the first described case of purulent meningitis caused by Leuconostoc sp. in a patient with mantle cell lymphoma that appeared after treatment with the R-CHOP protocol. The diagnosis of purulent meningitis was based on clinical, laboratory and cytological cerebrospinal fluid findings, in addition to blood culture results in which we isolated Leuconostoc sp. The patient was treated with meropenem with full recovery.