Antilymphocyte globulin for matched sibling donor transplantation in patients with myelofibrosis

The use of antihuman T-lymphocyte immunoglobulin in the setting of transplantation from an HLA-matched related donor is still much debated. Acute and chronic graft-versus-host disease are the main causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. The aim of this study was to evaluate the effect of antihuman T-lymphocyte immunoglobulin in a large cohort of patients with myelofibrosis (n= 287). The cumulative incidences of grade II-IV acute graft-versus-host disease among patients who were or were not given antihuman T-lymphocyte immunoglobulin were 26% and 41%, respectively. The corresponding incidences of chronic graft-versus-host disease were 52% and 55%, respectively. Non-adjusted overall survival, disease-free survival and non-relapse mortality rates were 55% versus 53%, 49% versus 45%, and 32% versus 31%, respectively, among the patients who were or were not given antihuman T-lymphocyte immunoglobulin. An adjusted model confirmed that the risk of acute graft-versus-host disease was lower following antihuman T-lymphocyte immunoglobulin (hazard ratio, 0.54; P= 0.010) while it did not decrease the risk of chronic graft-versus-host disease. The hazard ratios for overall survival and non-relapse mortality were 0.66 and 0.64, with P-values of 0.05 and 0.09, respectively. Antihuman T-lymphocyte immunoglobulin did not influence disease-free survival, graft-versus-host disease, relapse-free survival or relapse risk. In conclusion, in the setting of matched related transplantation in myelofibrosis patients, this study demonstrates that antihuman T-lymphocyte immunoglobulin decreases the risk of acute graft-versushost disease without increasing the risk of relapse.Peer reviewe

ECP versus ruxolitinib in steroid-refractory acute GVHD – a retrospective study by the EBMT transplant complications working party

IntroductionExtracorporal Photophoresis (ECP) is in clinical use for steroid-refractory and steroid-dependent acute GVHD (SR-aGVHD). Based on recent Phase-III study results, ruxolitinib has become the new standard of care for SR-aGVHD. Our aim was to collect comparative data between ruxolitinib and ECP in SR-aGVHD in order to improve the evidence base for clinical decision making. MethodsWe asked EBMT centers if they were willing to participate in this study by completing a data form (Med-C) with detailed information on GVHD grading, -therapy, -dosing, -response and complications for each included patient.Results31 centers responded positively (14%) and we included all patients receiving alloSCT between 1/2017-7/2019 and treated with ECP or ruxolitinib for SR-aGVHD grades II-IV from these centers. We identified 53 and 40 patients with grades II-IV SR-aGVHD who were treated with ECP and ruxolitinib, respectively. We performed multivariate analyses adjusted on grading and type of SR-aGVHD (steroid dependent vs. refractory). At day+90 after initiation of treatment for SR-aGVHD we found no statistically significant differences in overall response. The odds ratio in the ruxolitinib group to achieve overall response vs. the ECP group was 1.13 (95% CI = [0.41; 3.22], p = 0.81). In line, we detected no statistically significant differences in overall survival, progression-free survival, non-relapse mortality and relapse incidence.DiscussionThe clinical significance is limited by the retrospective study design and the current data can’t replace prospective studies on ECP in SR-aGVHD. However, the present results contribute to the accumulating evidence on ECP as an effective treatment option in SR-aGVHD

The relationship between serum adiponectin level and anthropometry, bone mass, osteoporotic fracture risk in postmenopausal women

WOS: 000269083500004PubMed: 19619110Objectives: The aim of the present study was to evaluate the possible correlation between bone mass and serum adiponectin levels, and the correlation between adiponectin levels and osteoporotic fracture risk in a prospective clinical trial. Patients and methods: Postmenopausal non-diabetic 105 women (mean age 63.4 +/- 8.1; range 52 to 64 years) with hip fracture were evaluated. Of these 105 patients, 46 had trochanteric fractures, 24 had subtrochanteric fractures and 35 had femoral neck fractures. Anthropometric measurements were performed. Serum adiponectin level was measured by means of ELISA. Total bone mineral density and bone mineral content of lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry (DEXA). Results: Lumbar bone mineral density and proximal femoral bone mineral density were not correlated with serum adiponectin levels. Serum adiponectin level was not found to have any significant effect on bone mass. Serum adiponectin levels were not significantly different between the patients with osteoporotic fractures and those with non-osteoporotic fractures. Conclusion: Our study showed that serum adiponectin level is not associated with bone mass and osteoporotic fracture risk. Investigation of local adiponectin levels in bony tissue is needed to clarify the possible relation between adiponectin and bone mass, and risk of fractures associated with osteoporosis

A Randomized Study Comparing the Efficacy of Three Hepatitis B Vaccine Induction Regimens in Adult Patients with Hematological Malignancies

Objective: Non-responsiveness to hepatitis B virus (HBV) vaccines is not rare in hemato-oncological patients due to disease-associated or treatment-induced immune suppression. Although different strategies have been employed to improve the response rates, to date there is not an approved schedule for HBV immunization in patients with hematological malignancies. We designed a prospective randomized study to evaluate the efficacy of 3 different induction regimens for HBV vaccination. Materials and Methods: In the standard-dose (SD) group, total vaccine dose delivered was 40 mu g and patients were vaccinated with 20 mu g at weeks 0 and 4. In the high-dose dose-intensive (HDDI) group, total vaccine dose delivered was 80 mu g and patients were vaccinated with 40 mu g at weeks 0 and 4. In the high-dose time-intensive (HDTI) group, total vaccine dose delivered was 80 mu g and patients were vaccinated with 20 mu g at weeks 0, 2, 4, and 6. Results: In a cohort of 114 patients, 38.6\% responded to HBV vaccination. The response rate in the SD arm, HDDI arm, and HDTI arm was 26.2\%, 29.7\%, and 44.4\%, respectively (p>0.05). Age was the only variable identified as having a negative impact on response. Conclusion: Short of achieving statistical significance, a higher response rate was observed in the HDTI arm. Therefore, this study supports a high-dose, time-intensive HBV vaccine induction regimen in patients with hematological malignancies who are not on chemotherapy

Relationship of left ventricular mass to insulin sensitivity and body mass index in healthy individuals

Nur, Omer/0000-0002-9566-041XWOS: 000240232600002PubMed: 16970048Objective-The objective of this study was to investigate the contribution of insulin resistance, hyperinsulinaemia and obesity, independently of other major factors, to changes in left ventricular mass a cardiovascular risk indicator, in a healthy population without co-morbid states such as diabetes or hypertension. Methods and results-This cross-sectional relational study was perfomed in 153 healthy subjects, comprising 76 men and 77 women with ages ranging from 23 to 67 years. All of them were normotensive and had a normal oral glucose tolerance test, none had cardiovascular disease and none were taking any medication. Weight, height and waist circumference were measured and BMI was calculated.A blood sample was drawn in the fasting state: plasma glucose, insulin, serum total and high density lipoprotein (HDL), low density lipoprotein cholesterol and triglycerides were measured. Insulin resistance was determined by the 'Homeostasis Assessment Model' (HOMA-IR). Subjects were studied by echocardiography. The left ventricular mass was calculated by using the anatomically validated formula of Devereux et al. Results - Left ventricular mass significantly and positively correlated with BMI, age, systolic and diastolic blood pressure and fasting blood glucose. The correlation of left ventricular mass with fasting blood glucose was not maintained after controlling for BMI. BMI, fasting blood glucose, HOMAIR, systolic and diastolic blood pressure showed significant differences with higher values for people with left ventricular hypertrophy. The logistic regression analysis showed a strong association between left ventricular hypertrophy and BMI (p < 0.05). Conclusion - Insulin resistance and fasting insulin is not associated with left ventricular hypertrophy in healthy people, independent of obesity. Obesity appears to be an independent risk factor for left ventricular hypertrophy

Tuberculosis reactivation related with ruxolitinib in a patient with primary myelofibrosis

Primary myelofibrosis (PMF) is a clonal stein cell disease, characterized by bone marrow fibrosis. Ruxolitinib is a selective inhibitor of JAK-1 and JAK-2 used to treat PMF. Its mechanism of action is based on the reduction of signal transduction and cytokine levels; including IL-6 and tumor necrosis factor alpha. Increased infection risk related to Ruxolutinib is rarely reported. Here we describe a case of tuberculosis infection ractivation in a female patient treated with Ruxolitinib. During the treatment, she complained of night sweats, weight loss and enlarged mass in the neck. Excisional mass biopsy revealed a necrotizing granulomatous lymphadenitis. QuantiFERON-TB and PPD tests were not able to diagnose the tuberculosis infection. Therapy with Ruxolitinib was interrupted due to possible immunsuppressive effects and the patient was treated with the standard antituberculosis regimen. After six months, the patient's symptoms had resolved and there was no lymphoadenopathy. In conclusion, it is important to assess the risk of tuberculosis activation before Ruxolitinib treatment. In addition, the diagnosis of tuberculosis using QuantiFERON-TB and PPD may be misleading in patients treated with Ruxolutinib

An interim analysis of the Turkish Myeloma Registry among patients who have received up to two lines of therapy

[No Abstract Available

Prevalence of Monoclonal B Lymphocytosis in First-Degree Relatives of Chronic Lymphocytic Leukemia Patients in Turkey

Objective: Monoclonal B lymphocytosis (MBL) is considered to be a precursor state for chronic lymphocytic leukemia (CLL). This study was planned to evaluate the MBL prevalence in first-degree relatives of CLL patients in Turkey, which is considered to be an ethnic and geographic bridge between the Eastern and Western worlds. Materials and Methods: A total of 136 volunteers {[}median age: 40 (17-77) years; male/female: 60/76] from 61 families were included. Flow cytome try analysis by 4-colour staining was used for MBL diagnosis. Results: MBL was demonstrated in 17 cases (12.5\%). A total of 14 cases (10.3\%) were classified as CLL-like MBL, while 3 (2.2\%) exhibited a non-CLL-like phenotype. The prevalence of MBL was 12.72\% in subjects aged less than 40 years, 12.28\% in subjects between 40 and 60 years, and 40\% in subjects over 60 years, without statistical significance (p>0.05). A total of 115 cases were evaluated for intermarriage, which was observed in 19 cases (16.5\%). The prevalence of MBL did not differ based on intermarriage status (p>0.05). Conclusion: The current report is the first MBL prevalence study in a Eurasian population that demonstrates a similar distribution pattern of MBL in Anatolian CLL kindreds. Further efforts should be made to refine our understanding of the natural history and clinical outcomes of MBL