Role of glutathione S-transferase P1 polymorphism in early transplant complications in patients undergoing allogeneic stem cell transplantation.

INTRODUCTION: Complications in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) cause serious morbidity and mortality. Predicting patients at risk in advance and changing the symptomatic care and/or preparation regimen according to this risk assessment have been emphasized recently. Several single-nucleotide polymorphisms have been studied, and some were found to be responsible for early complications. Glutathione S-transferase P1 (GSTP1) is an enzyme involved in the detoxification process that reduces oxidative stress by reducing the number of free oxygen radicals. AIM: This study aimed to investigate the relationship between GSTP1 polymorphism and early complications of allo-HSCT, iron parameters, overall survival (OS), and transplantation-related mortality (TRM). MATERIALS AND METHODS: A total of 50 patients diagnosed with acute myeloid leukemia (n = 23) or acute lymphoblastic leukemia (n = 27) who underwent allo-HSCT between May 2008 and February 2011 at Gazi University Faculty of Medicine, Stem Cell Transplantation Unit, were included. RESULTS: Of the 50 patients, 24 (48%) were women and 26 (52%) were men. The median age of the patients was 26 (16-74) years. GSTP1 polymorphism was detected in 23 (46%) patients, and 27 (54%) had no polymorphism (wild type). The two groups were compared in terms of early toxicity after transplantation, according to the preparation regimen. The group with GSTP1 polymorphism was found to have a high transferrin saturation index (P < 0.05). Patients with no GSTP1 polymorphism showed a high grade III-IV anemia ratio (P < 0.05). The presence of sinusoidal obstruction syndrome and graft-versus-host disease was similar in both groups (P > 0.05). OS and TRM were higher in the GSTP1 polymorphism group, but no statistical difference was found between the two groups (P > 0.05). CONCLUSIONS: TSI was higher in the GSTP1 polymorphism group. GSTP1 polymorphism had no effect on early transplantation complications. Although the OS and TRM ratios were higher in the GSTP1 polymorphism group, no statistically significant difference was found between the groups. Further studies with larger sample size are needed.

Impairments in dyspnea, exercise capacity, physical activity and quality of life of allogeneic hematopoietic stem cell transplantation survivors compared with healthy individuals: a cross sectional study.

Background: A limited number of studies have reported impairments in physical activity, exercise capacity and quality of life (QOL) in allogeneic hematopoietic stem cell transplantation (allogeneic-HSCT) recipients. We aimed to compare dyspnea, exercise capacity, physical activity and QOL in allogeneic-HSCT recipients with age-gender matched healthy individuals, since this has not been investigated hitherto. Methods: A total of 80 allogeneic-HSCT recipients (>100 days status post-transplantation) (38.88 ± 13.25 years) and 60 healthy individuals (35.92 ± 10.83 years) were compared. Exercise capacity [6-minute walk test (6-MWT)], physical activity level (total and active energy expenditure, moderate and severe physical activity duration, number of steps, average metabolic equivalent, lying down and sleeping duration) [metabolic holter], QOL [European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTCQOL)], dyspnea [Modified Medical Research Council Dyspnea scale] and pulmonary functions [spirometry] were evaluated. Clinical trials #NCT03606005. Results: Six-MWT distance, energy expenditure, physical activity duration, number of steps, average metabolic equivalent, global health status, functional and social function subscales of EORTCQOL were significantly lower in recipients compared with controls; dyspnea score, lying down, sleep durations, symptom and fatigue subscales of EORTCQOL were significantly higher in recipients compared with controls (p < 0.05). Conclusion: Dyspnea during daily living activities, exercise capacity, physical activity level and QOL are considerably impaired in allogeneic-HSCT recipients during post-engraftment period. To improve impaired outcomes, allogeneic-HSCT recipients should be oriented to cardiopulmonary rehabilitation programs.

Hemophagocytic lymphohistiocytosis: a review inspired by the COVID-19 pandemic.

Hemophagocytic syndrome (HPS) or hemophagocytic lymphohistiocytosis (HLH) is an acute and rapidly progressive systemic inflammatory disorder characterized by cytopenia, excessive cytokine production, and hyperferritinemia. Common clinical manifestations of HLH are acute unremitting fever, lymphadenopathy, hepatosplenomegaly, and multiorgan failure. Due to a massive cytokine release, this clinical condition is considered as a cytokine storm syndrome. HPS has primary and acquired (secondary, reactive) forms. Its primary form is mostly seen in childhood and caused by various mutations with genetic inheritance and, therefore, is called familial HLH. Secondary HLH may be caused in the presence of an underlying disorder, that is, secondary to a malignant, infectious, or autoimmune/autoinflammatory stimulus. This paper aims to review the pathogenesis and the clinical picture of HLH, and its severe complication, the cytokine storm, with a special emphasis on the developed classification criteria sets for rheumatologists, since COVID-19 infection has clinical symptoms resembling those of the common rheumatologic conditions and possibly triggers HLH. MED-LINE/Pubmed was searched from inception to April 2020, and the following terms were used for data searching: "hemophagocytic syndrome" OR "macrophage activation syndrome" OR "hemophagocytic lymphohistiocytosis", OR "cytokine storm". Finally, AND "COVID-19" was included in this algorithm. The selection is restricted to the past 5 years and limited numbers of earlier key references were manually selected. Only full-text manuscripts, published in an English language peer-reviewed journal were included. Manuscript selection procedure and numbers are given in Fig. 2. Briefly, the database search with the following terms of "Hemophagocytic syndrome" OR "Macrophage activation syndrome" OR "Hemophagocytic lymphohistiocytosis" OR "Cytokine storm" yielded 6744 results from inception to April 2020. The selection is restricted to the past 5 years and only limited numbers of earlier key references were selected, and this algorithm resulted in 3080 manuscripts. The addition of (AND "COVID-19") resulted in 115 publications of which 47 studies, together with four sections of an online book were used in the final review. No statistical method was used. HLH is triggered by genetic conditions, infections, malignancies, autoimmune-autoinflammatory diseases, and some drugs. In COVID-19 patients, secondary HLH and cytokine storm may be responsible for unexplained progressive fever, cytopenia, ARDS, neurological and renal impairment. Differentiation between the primary and secondary forms of HLH is utterly important, since primary form of HLH requires complicated treatments such as hematopoietic stem cell transplantation. Further studies addressing the performance of HScore and other recommendations in the classification of these patients is necessary.

The incidence of tuberculosis infection in hematopoietic stem cell transplantation recipients: A retrospective cohort study from a center in Turkey.

BACKGROUND: Immune-compromised patients with latent TB infection (LTBI) are at risk for TB reactivation and should receive prophylaxis. Whereas the tuberculin skin test (TST) has limitations particularly in immune-compromised patients. AIMS: This retrospective study was conducted to determine the incidence of TB infection in adult HSCT recipients whose preventive therapy for LTBI was determined according to the guidance of targeted TST. PATIENTS AND METHODS: Five hundred and fifty-eight consecutive HSCT recipients (287 autologous and 271 allogeneic) who survived ≥100 days post-transplantation were included in this analysis. RESULTS: Tuberculin skin test results were available in 493 of 558 transplants (88.3%). The incidence of negative TST was 54.5% (269 of 493 patients). One multiple myeloma patient with a history of TB and negative TST result and was not on INH prophylaxis developed reactivation of TB infection. None of the recipients under INH prophylaxis (151 of 558 transplants; 27.1%) and none of the 224 patients with TST ≥5 mm developed TB infection. DISCUSSION: Despite the limitations of being a retrospective analysis and variable prophylaxis thresholds of TST, there are some remarkable results of this analysis. We had no TB infection in the allogeneic HSCT recipients. The high incidence of negative TST results may be attributed to the underlying immune-deficiency. TST may not be a reliable guide for predicting TB reactivation risk in hematology patients. CONCLUSION: Tuberculin skin test may have a high rate of false-negative and false-positive results in HSCT recipients. The general guidelines for targeted TST to guide treatment of LTBI may not apply to all regions and situations. More reliable methods are required to predict and treat LTBI in these specific conditions.

Early Prognostic Value of Monitoring Serum Free Light Chain in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation.

We hypothesized the levels of free light chains obtained before and after autologous stem cell transplantation can be useful in predicting transplantation outcome. We analyzed 70 multiple myeloma patients. Abnormal free light chain ratios before stem cell transplantation were found to be associated early progression, although without any impact on overall survival. At day +30, the normalization of levels of involved free light chain related with early progression. According to these results almost one-third reduction of free light chain levels can predict favorable prognosis after autologous stem cell transplantation.

Inspiratory muscle training in allogeneic hematopoietic stem cell transplantation recipients: a randomized controlled trial.

PURPOSE: Respiratory muscles are known to be weakened and are a cause of reduced exercise capacity in both recipients and candidates of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Effects of inspiratory muscle training (IMT) in this patient population have not been comprehensively investigated so far. The current study was planned to investigate the effects of IMT during allo-HSCT on early transplantation-related outcomes. METHODS: This is a prospective, randomized controlled, double-blinded study. Thirty-eight allo-HSCT recipients, 20 of whom were allocated to the treatment group (40 % of maximal inspiratory pressure (MIP)) and 18 to the control group (5 % of MIP), received IMT for 6 weeks. Pulmonary functions, dyspnea, respiratory (MIP, maximal expiratory pressure (MEP)) and peripheral muscle strength, maximal exercise capacity using modified incremental shuttle walking test (MISWT) and submaximal exercise capacity using 6-min walking test (6-MWT), fatigue, depression, and quality of life were evaluated before and after IMT. RESULTS: The distance covered during MISWT (61.94 m) and 6-MWT (29.30 m), respiratory muscle strength (MIP 34.99 cmH2O, MEP 12.69 cmH2O), depression (-0.95), and modified Borg dyspnea scores (-0.11) showed a significant improvement in the treatment group compared to controls (p ≤ 0.05). CONCLUSIONS: Inspiratory muscle training is a safe and effective intervention which improves respiratory muscle strength and exercise capacity and decreases depression and dyspnea in allo-HSCT recipients. These positive changes might be further enhanced by prolonging the duration of training or inclusion of more recipients with inspiratory muscle weakness. CLINICAL TRIAL REGISTRATION NUMBER: NCT02270346.

Does low-molecular-weight heparin influence the antimyeloma effects of thalidomide? A retrospective analysis of data from the GIMEMA, Nordic and Turkish myeloma study groups.

BACKGROUND/AIM: Low-molecular-weight heparin (LMWH) has been shown to prolong survival among patients with solid tumors, but its role among myeloma patients is unknown. PATIENTS: Data from the GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto), Nordic and Turkish myeloma study groups comparing melphalan and prednisolone with (MPT, n: 404) or without thalidomide (MP, n: 393) are analyzed for effects of LMWH. Forty percent (159/394) of the patients on MPT and 7.4% (29/390) in the MP arm received LMWH. RESULTS: Thalidomide improved response and progression-free survival (PFS). Regardless of thalidomide treatment, response rate was higher among those receiving LMWH vs. none vs. other anticoagulants (58.1 vs. 44.9 vs. 50.4%, p = 0.01). PFS was significantly longer (median 32 vs. 21 and 17 vs. 17 months, p = 0.004) only among international scoring system (ISS) I patients receiving MPT ± LMWH vs. MP ± LMWH. The group of MPT patients who also received LMWH had a better OS compared to those who did not [45 months, 95% confidence interval (CI) 27.7-62.3, vs. 32 months, 95% CI 26.1-37.9; p = 0.034]. When multivariate analysis was repeated in subgroups, thalidomide was no longer a significant factor (response, PFS) among those receiving LMWH. CONCLUSION: Addition of LMWH to MPT, in particular in patients with low ISS, suggests additive effects, but the results are limited by the retrospective design of our study.

Association between Plasma Endothelin-1, Transforming Growth Factor-ß, Fibroblast Growth Factor, and Nitric Oxide Levels and Liver Injury in Hematopoietic Stem Cell Transplantation Recipients with Persistent Iron Overload after Transplantation.

Graft-versus-host disease, iron overload, and infections are the major causes of liver dysfunction in allogeneic hematopoietic stem cell transplantation (AHSCT) recipients. We investigated the relationship between serum iron parameters and the levels of transforming growth factor-ß (TGF-ß), fibroblast growth factor (FGF), endothelin-1 (ET-1), and nitric oxide (NO) as predictors of chronic liver injury in 54 AHSCT recipients who survived at least a year after transplantation. Serum samples from patients were obtained for the evaluation of ET-1, TGF-ß, FGF, NO, and nontransferrin bound iron at the first year follow-up visit using commercially available ELISA kits. Patients were categorized depending on serum ferritin and transferrin saturation levels. The parameters were compared between the groups, and survival analysis was also performed. Most of the AHSCT recipients (81.5%) were in complete remission during the study. After a median follow-up time of 73 months (range, 13 to 109 months), 72.2% of the patients were alive. Mean serum levels of ET-1, NO, TGF-ß, and FGF were 81.54 ± 21.62 µmol/mL, 31.82 ± 26.42 µmol/mL, 2.56 ± 0.77 ng/mL, and 50.31 ± 32.69 pg/mL, respectively. Nineteen patients (35.2% of the cohort) had serum ferritin levels higher than 1000 ng/mL. Mean serum levels of ET-1, NO, TGF-ß, and FGF were similar in patients with serum ferritin levels below or above 1000 ng/mL (P > .05). Serum ferritin levels were positively correlated with serum alanine aminotransferase (r = .284, P = .042) and γ-glutamyl transferase (r = .271, P = .05) levels and were negatively correlated with serum albumin levels (r = .295, P = .034). There was a significant positive correlation between serum transferrin saturation and alanine aminotransferase levels (r = .305, P = .03). Serum ET-1 level was positively correlated with alkaline phosphatase levels (r = .304, P = .026). In univariate Cox regression analysis serum levels of iron parameters, ET-1, NO, TGF-ß, and FGF did not have an impact on overall survival (P > .05). The probability of progression-free survival was also similar in patients with ferritin levels above or below 1000 ng/mL (P = .275). The probability of survival was similar in patients with transferrin saturation ≥70% and <70% (P > .05). Serum iron parameters showed a positive correlation with liver injury. However, there was no correlation between fibrogenic cytokines and liver transaminases. Our results suggest that iron overload at least with the current levels of ferritin might have a relatively benign course. Prospective randomized trials will guide the actual role of iron chelation in the post-transplantation setting.

Inflammatory markers, oxidative stress, and antioxidant capacity in healthy allo-HSCT donors during hematopoietic stem cell mobilization.

The aim of this study is to investigate the impact of mobilization with granulocyte colony stimulating factor (G-CSF) and apheresis procedure on inflammatory and oxidative stress markers, and antioxidant capacity in healthy allo-HSCT donors. The study was conducted in the Stem Cell Transplantation Unit of Gazi University Hospital between October 2010 and March 2011, and 25 consecutive allo-HSCT donors were included. The alteration in the serum levels of iron, iron binding capacity, albumin, ferritin, IL-6, hs-CRP, TAC, MDA, and AOPP were determined at five different time points. (1) Prior to the first dose of G-CSF (T0), (2) preapheresis (on the fourth day of G-CSF before the apeheresis procedure) (T1), (3) immediately postapheresis (T2), (4) 24 h postapheresis (T3), and (5) a week after apheresis (T4). Serum ferritin levels increased steadily after administration of G-CSF and remained high up toT4. Both serum IL-6 and hs-CRP levels began to increase in the T1 sampling and reached to a maximum level at T3 and decreased even below the basal levels at T4. Serum AOPP levels decreased at preapheresis and postapheresis time points, while they increased at T3 and T4 samples. Serum MDA levels decreased at T1, T2, T3, and T4 samples. Serum TAC increased significantly and steadily at all time points post G-CSF. In conclusion; mobilization with G-CSF and apheresis caused a transient inflammatory reaction and a protein limited oxidative stress in healthy allo-HCT donors.

A rare case of acute leukemia relapsing with a granulocytic sarcoma causing ectopic pregnancy.

A 33 year old female was admitted to department of obstetric and gynaecology with profuse vaginal bleeding. She was diagnosed with acute myeloid leukemia 3 months ago. Pelvic ultrasound was unremarkable. Since vaginal bleeding persisted despite normal platelet counts low dose methotrexate was administered with the presumptive diagnosis of ectopic pregnancy. A laparoscopic investigation was performed as she did not respond to this treatment which revealed an intraluminal ectopic pregnancy in her right fallopian tube. A pathological specimen was obtained. Granulocytic sarcoma is an infiltrate of immature granulocytic precursor cells in an extramedullary site. To best of our knowledge, this case is the third patient with GS in the fallopian tube and the first case causing ectopic pregnancy.

The intensive care management process in patients with hematopoietic stem cell transplantation and factors affecting their prognosis.

OBJECTIVES: Hematopoietic stem cell transplantation (HSCT) recipients may require further management in intensive care unit (ICU). The ICU outcome of the HSCT recipients is claimed to have improved significantly over the last two decades. Our aim was to investigate the ICU outcome of the HSCT recipients who required management in ICU, together with the factors that are likely to affect the results. MATERIALS AND METHODS: We retrospectively investigated the ICU outcome of 48 adults (≥18 years of age) who received HSCT in the bone marrow transplant unit of our hospital and required admission to ICU between 01 January 2007 and 31 December 2010. The data were retrieved from the databases of the adult bone marrow transplantation unit and the ICU. RESULTS: Sixty-one percent of the patients were male with a median age of 39 years (28-46.75) in the study cohort. Leukemia (54%) and lymphoma (27%) were the leading underlying disorders. The type of HSCT was autologous in 14.6% and allogeneic in 85.4% of the patients. The reason for admission to ICU was acute respiratory failure in 85.5% of the HSCT recipients and 75% had sepsis/septic shock. The mean duration of ICU stay was 104.5 (48-168) hours. Sixty-nine percent of the patients died during their ICU stay while 31% survived. Besides the several statistically significant differences between the patients who survived or died in ICU in univariate analysis, baseline Acute Physiology and Chronic Health Evaluation (APACHE II) score (odds ratio 1.38, 95% confidence interval: 1.06-1.79) and requirement of vasopressors in the ICU (odds ratio 72.29, 95% confidence interval:4.47-1169.91) were found to be independent risk factors for mortality in multivariate analysis. CONCLUSION: Baseline APACHE II score and requirement of vasopressors during ICU stay were the most significant independent risk factors for mortality in HSCT recipients who required ICU management in our center.

Brain abscess caused by Nocardia cyriacigeorgica in two patients with multiple myeloma: novel agents, new spectrum of infections.

OBJECTIVE AND IMPORTANCE: Introduction of high-dose chemotherapy and the novel agents including bortezomib, Lenalidomide, and Thalidomide has provided a significant progress in the treatment of multiple myeloma (MM) with an increase in median overall survival up to 6-8 years. However, the advances in myeloma treatment comes at a price with new spectrum of treatment-related infectious complications which should be taken into consideration while treating these patients. CLINICAL PRESENTATION: We report here two patients with Ig G λ MM presenting with intracerebral mass lesions in the abscence of constitutional symptoms that would suggest an infectious etiology. Both patients had severe hypogammaglobulinemia and lymphopenia, which was attributed to treatment regimens including bortezomib. Intervention The surgical intervention-revealed abscess in both cases caused by Nocardia cyriacigeorgica, a relatively new pathogen which rarely causes infections in humans and also an unexpected pathogen in myeloma patients. CONCLUSION: Although every aspect of immune system is known to be affected in MM, humoral immune deficiency is the hallmark of the inherent immune defect in this disease. Introduction of the novel agents, bortezomib in particular seems to have changed the characteristics of the immune dysfunction and the spectrum of the opportunistic infections by causing qualitative and quantitative changes in cellular immunity. The new spectrum of infectious agents might not be limited to hepatitis B and herpes zoster. Monitoring lymphopenia and administration of prophylactic antimicrobial agents accordingly could be considered in patients treated with bortezomib.

Hyper-CVAD regimen in routine management of adult acute lymphoblastic leukemia: a retrospective multicenter study.

Treatment of acute lymphoblastic leukemia is unsatisfactory in adults due to disease and patient-related factors and probably because adult chemotherapy regimens are weaker than pediatric protocols. Worries about inadequacy of adult regimens urged many hematologists, including us, to reconsider their routine treatment practices. In this retrospective multicenter study, we aimed to evaluate results of hyper-CVAD treatment in comparison to other intensive protocols. All patients aged ≤65 years who were commenced on intensive induction chemotherapy between 1999 and 2011 were included in the study. Sixty-eight of 166 patients received hyper-CVAD, 65 were treated with CALGB-8811 regimen and 33 with multiple other protocols. Limited number of patients who were treated with other intensive protocols and mature B-acute lymphoblastic leukemia cases who were mostly given hyper-CVAD were eliminated from the statistical analyses. In spite of a favorable complete remission rate (84.2%), overall (26.3 vs. 44.2% at 5 years, p = 0.05) and disease-free (24.9 vs. 48.2%, p = 0.001) survival rates were inferior with hyper-CVAD compared to CALGB-8811 due to higher cumulative nonrelapse mortality risk (29.7 vs. 5.9%, p = 0.003) and no superiority in cumulative relapse incidence comparison (45% for both arms, p = 0.44). Hyper-CVAD, in its original form, was a less favorable regimen in our practice.

Outcome of autologous stem-cell transplantation in relapsed or refractory Hodgkin lymphoma patients in a centre from Turkey.

PURPOSE: The aim of this study is to assess the predictors of outcome in patients with relapsed or refractory Hodgkin's lymphoma (HL) receiving autologous stem-cell transplantation (ASCT) MATERIALS AND METHODS: Fifty-two consecutive patients who received ASCT at the Stem Cell Transplantation Unit of Gazi University Hospital from February 2005 through June 2011 for relapsed or refractory HL were analysed retrospectively RESULTS: Fifty-one patients could be evaluated after transplantation, as one of the patients died in the early post-transplantation period. Complete remission was obtained in 36 (71%), partial remission in 9 (18%), stable disease in 4 (8%), and progressive disease in 2 (3%) patients. After a median follow-up of 22 (range, 0.5-75) months, 46 (88%) patients were alive. The probability of overall survival (OS), progression free survival (PFS) and transplantation related mortality at 5 years were 87, 53, and 2%, respectively. Chemosensitive relapse had a positive impact on both OS and PFS CONCLUSION: ASCT remains to be the standard treatment of relapsed or refractory HL patients. Chemosensitive relapse is the most important prognostic factor determining the outcome of the ASCT.

TCTP/HRF pathway and angiogenesis: a feasible intercourse in chronic lymphocytic leukemia.

This prospective study was planned to determine the intercourse between translationally controlled tumor protein (TCTP)/histamine releasing factor (HRF)/histamine pathway and angiogenesis in chronic lymphocytic leukemia (CLL). A total of 153 CLL patients were included. Serum histamine levels were higher in CLL patients. A positive correlation was found between microvessel density (MVD)-mast cell (MC) count; MVD-TCTP/HRF and MC count-TCTP/HRF. Microvessel density, MC and ZAP 70 were significantly higher in TCTP/HRF-positive group. Time to first treatment was shorter in patients with increased MVD and TCTP/HRF. Further data is essential to ascertain the role of TCTP/HRF pathway in tumor angiogenesis and CLL prognosis.

Tumor-associated macrophages as a prognostic parameter in multiple myeloma.

The interaction between multiple myeloma (MM) cells and the bone marrow stroma constitutes the basis of myeloma pathogenesis and has led the way for the corresponding therapeutic strategies. The aim of this study is to evaluate tumor-associated macrophages (TAMs) which is an important element of bone marrow stroma and its prognostic relevance in newly diagnosed MM patients. We also wanted to determine the association between TAMs and microvessel density (MVD). Sixty-eight patients, who were diagnosed with MM at the Department of Hematology, Gazi University Hospital, between January 2000 and January 2011, were reviewed retrospectively. Tumor-associated macrophages were evaluated by staining with anti-CD68 and anti-CD163 monoclonal antibodies, and MVD was evaluated by factor VIII staining. Median age was 60 (range, 40-84) years with 36 males and 32 females. The number of both CD 68+ and CD 163+ cells had a negative impact on OS at 6 years (p = 0.013 vs. 0.036; p = 0.015 vs. 0.039) in univariate and multivariate analysis in which age, sex, ISS, the induction treatment, and response to induction treatment are included as variables. High-grade MVD was found to be associated with increased CD163+ cell count. In conclusion, TAMs seems to be a promising prognostic histopathological marker in newly diagnosed MM patients.

HBV-related events after allogeneic hematopoetic stem cell transplantation in a center from Turkey.

To investigate the frequency of hepatitis B virus (HBV)-related events after allogeneic HCT in a moderate endemic area for HBV infection. The data of 197 patients who underwent allogeneic hematopoetic stem cell transplatation (HCT) from September 2003 through December 2010 were reviewed retrospectively with respect to HBV-related events. Resolved HBV infection was described as negative HBsAg, positive HBcAb, and positive HBsAb. Latent HBV infection was defined in patients with HBcAb positivity in the abscence of HBV DNA and HBsAb. Hepatitis B naive patients are defined as the patiens with no serological or molecular marker related to HBV. Seropositive patients were the patients with positive HBsAg and HBV-DNA. Median age was 28 (range, 15-64) years, with 128 male and 69 female patients. Median follow-up of the cohort was 8 (range, 0.5-78) months. We detected HBV-related events in 7 (3.6 %) recipients after allogeneic HCT. Five (71.4 %) of these events were HBV reactivation, while two cases (28.6 %) had acute hepatitis B infection. Four of the five reactivations were in the seropositive group (80 %), while one ocurred in a patient with resolved hepatitis. Two patients who developed acute hepatitis B were HBV naive and previously immunized patients, respectively. Hepatitis B virus reactivation remains a problem in seropositive patients and might require more effective treatment strategies.

Prognostic role of pre-transplantation serum C-reactive protein levels in patients with acute leukemia undergoing myeloablative allogeneic stem cell transplantation.

The aim of this study was to identify indicators of outcome prior to transplantation in allogeneic hematopoietic stem cell transplantation (HCT). Clinical data of 106 patients with acute leukemia were retrospectively analyzed. We examined the role of pre-conditioning serum C-reactive protein (CRP) and ferritin levels, HCT-CI and European Group for Blood and Marrow Transplantation (EBMT) scores on transplant toxicities, transplant-related mortality (TRM), progression-free survival (PFS), and overall survival (OS). High pre-conditioning serum CRP levels showed a positive correlation with higher EBMT scores (p < 0.001), HCT-CI (p = 0.004), and ferritin levels (p < 0.001). In univariate Cox regression analysis, serum CRP ≥10 mg/L, serum ferritin ≥1500 ng/mL, and HCT-CI ≥3 had a significant adverse effect on OS. Serum CRP ≥10 mg/L and HCT-CI ≥3 predicted increased risk of TRM in univariate analysis. Multivariate Cox regression analysis showed that HCT-CI score ≥3 independently predicted increased risk of TRM and CRP ≥10 mg/L predicted increased risk of disease progression. Although CRP lost its significance on TRM in multivariate analysis, as an inexpensive and readily available serum biomarker of inflammation, the prognostic role of pre-transplant CRP levels should be analyzed in selected diseases and increased number of patient groups.