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.

Comparison of conditioning regimen toxicities among autologous stem cell transplantation eligible multiple myeloma patients: High-dose melphalan versus high-dose melphalan and bortezomib.

Background Autologous hematopoietic stem cell transplantation (AHSCT) remains the standard of care for younger patients with multiple myeloma (MM). Currently, high-dose melphalan (HDM) is recommended as conditioning regimen before AHSCT. Preclinical data suggest that combining bortezomib and melphalan has synergistic effect against multiple myeloma cells. Bortezomib and HDM (Bor-HDM) combination as conditioning regimen has been investigated by many other investigators. Objective In this retrospective study, we aimed to compare transplant-related toxicities and hematologic recovery of HDM and Bor-HDM conditioning regimens. Method We retrospectively evaluated hematologic recovery and toxicity profile in patients with MM who received AHSCT with either HDM ( n = 114) or Bor-HDM ( n = 53) conditioning regimen. Results Nonhematologic toxicities were comparable between HDM and Bor-HDM conditioning regimen, except mucositis and diarrhea being more frequent in the Bor-HDM group. Neutrophil and platelet engraftment time and duration of hospital stay were significantly shorter for HDM regimen. Conclusions In this retrospective analysis, we observed engraftment kinetics and duration of hospitalization were significantly worse in Bor-HDM conditioning regimen with manageable toxicities. Randomized studies are needed to further compare Bor- HDM regimen to HDM in terms of response rates, toxicities, and transplant-related mortality.

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.

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.

Factors associated with cytomegalovirus reactivation following allogeneic hematopoietic stem cell transplantation: human leukocyte antigens might be among the risk factors.

OBJECTIVE: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (AHSCT) recipients. Current practice includes prophylactic and preemptive treatment modalities, which have risks, side effects, and costs of their own. There is no established risk scoring system that applies to all patients. We aimed to investigate the risk factors for CMV reactivation in AHSCT recipients. MATERIALS AND METHODS: We retrospectively analyzed the risk factors for CMV reactivation in 185 consequent AHSCT recipients transplanted between September 2003 and December 2009 at the Stem Cell Transplantation Unit of Gazi University. Besides the standard transplant-related parameters, HLA antigens were also included among the variables analyzed. RESULTS: Despite the very high rate of donor (94.6%) and recipient (100%) seropositivity, which are the so-called major risk factors in previous reports, our reactivation rate was much lower, with a frequency of 24.9%. The underlying disease, sex, conditioning regimen, and presence of antithymocyte globulin or fludarabine in the conditioning regimen had no impact on reactivation rate. CMV reactivation was significantly more frequent in recipients with graft-versus-host disease (GVHD) compared to those without GVHD (p<0.0001). CMV reactivation was significantly more frequent (p<0.05) in patients with HLA-B14, HLA-DRB1*01, and HLA-DRB1*13 antigens and less frequent in recipients with HLA-A11 and HLA-DRB1*04 antigens (p<0.05). CONCLUSION: Universal risk factors/scores that apply to all transplant recipients are required for tailored prophylaxis and/or treatment strategies for CMV reactivation. Uncovering the role of genetic factors, including HLA antigens, as possible risk factors might lead the way to risk-adaptive strategies for adoptive cellular therapy and/or vaccination.

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.

The positive impact of regular exercise program on stem cell mobilization prior to autologous stem cell transplantation.

AIM: The present study was planned to determine the effects of regular exercise program on hematopoietic stem cell (HSC) mobilization prior to autologous stem cell transplantation. METHOD: Twenty-two consecutive patients were enrolled in the study. A regular 20 min exercise program was administered to the patients. The hematopoietic stem cell mobilization outcome, number of Granulocyte Colony-Stimulating Factor (G-CSF) and aphaeresis application days were compared with 20 case-matched controls who did not receive exercise program during HSC mobilization. RESULTS: The median number of CD34(+) stem cells collected in the exercise and control groups were 8.15 × 10(6)/kg (range: 2.85-33.06 × 10(6)/kg) and 7.3 × 10(6)/kg (range: 1.78-25.9 × 10(6)/kg), respectively (p=0.696). G-CSF was administered for a median of 8 days (range, 5-10) in the exercise group and 8 days (range, 5-12) in the control group (p=0.848). The median apheresis duration was 1 day (range, 1-3) in both exercise and control groups (p=0.226). CONCLUSION: Exercise seems to have a positive impact on stem cell mobilization though without statistical significance.

The prognostic role of hemochromatosis H63D allele in allogeneic hematopoietic stem cell transplantation.

Iron overload is considered as a significant cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. The presence of hemochromatosis gene (HFE) mutations might exacerbate iron toxicity in the post-transplant setting. This prospective study was planned to evaluate the genetic spectrum of HFE mutations in Turkish patients undergoing HSCT and the impact of HFE genotype on transplant morbidity and mortality. HFE genotypes of 102 patients [median age, 27.5 years (16-64 years); male/female, 73:29], who underwent allogeneic HSCT, were analyzed. Twenty-two patients were heterozygous and 1 patient was homozygous for the H63D mutation, while the C282Y mutation was observed in none of our patients. The frequency of invasive fungal infections (IFI) was significantly higher in H63D-mutated patients (p=0.004). H63D mutation was identified as an independent risk factor for the development of IFI (p=0.006, OR=0.554, SE=0.208), without an impact on overall survival and transplant-related mortality. The multifactorial iron-overloaded state in HSCT recipients might affect the phenotypic expression of HFE mutations and alter the severity of clinical presentation. The impact of HFE genotype on iron parameters and transplant-related morbidity and mortality should be validated with further studies.

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.

Plerixafor use in patients with previous mobilization failure: A multicenter experience.

Plerixafor in conjunction with G-CSF (G-P) is an effective strategy for hematopoietic stem cell mobilization in patients with previously failed mobilization attempt. Here we report our results with G-P among patients with at least one mobilization failure with G-CSF alone (G) or G-CSF plus chemotherapy (G-C). The study included 20 consecutive patients with lymphoma and myeloma from five centers. In 14 (70%) patients, a minimum of 2×10(6)/kg CD34+ stem cells were collected and 16 out of 20 patients (80%) were able to proceed to ASCT. Our study indicates that plerixafor can safely rescue patients with a history of mobilization failure.

Gemcitabine and vinorelbine combination is effective in both as a salvage and mobilization regimen in relapsed or refractory Hodgkin lymphoma prior to ASCT.

We investigated the efficacy of gemcitabine and vinorelbine (Gem/Vin) combination chemotherapy as a salvage and mobilization regimen in relapsed or refractory Hodgkin lymphoma (HL) patients prior to autologous hematopoietic stem cell transplantation. We retrospectively reviewed the data of our relapsed or primary refractory HL patients treated with Gem/Vin regimen which consisted of gemcitabine 1,000 mg/m(2)/day and vinorelbine 30 mg/m(2)/day on days 1, 8, and 15 every 28 days. The overall response rate was 72.4%. Ten (34.5%) patients achieved complete remission, 11 (37.9%) partial remission, and eight (27.6%) patients had no response. Mobilization with Gem/Vin regimen was successful in 20/23 (87%) patients while mobilization failure was seen in three (13%) patients. Gemcitabine and vinorelbine is an effective salvage regimen with acceptable toxicity and high mobilization potential in relapsed or refractory HL patients.

Donor lymphocyte infusion for leukemia relapse after hematopoietic stem cell transplantation.

Leukemia relapse is a serious therapeutic challenge following hematopoietic stem cell transplantation (HSCT). In this retrospective study, 23 patients [15 (65.2%) AML, 8 (34.8%) ALL] who received DLI+/-reinduction chemotherapy for post-transplant relapse were reviewed. The overall response rate of DLI was 66.7% for AML and 50% for ALL. A total of 15 patients (65.2%) developed acute graft versus host disease (GVHD). Response rates were higher in patients with GVHD (80% versus 25%; p=0.01; OR: 12.0). The probability of OS was better in patients who respond to DLI (p=0.04). Further strategies are required to improve the anti-tumor properties of alloreactive donor lymphocytes and to obtain durable responses with DLI in patients with relapsed acute leukemia after allogeneic HSCT.

Factors affecting stem cell mobilization for autologous hematopoietic stem cell transplantation.

High-dose chemotherapy with autologous stem cell transplantation (ASCT) is curative treatment in various hematologic malignancies. Mobilization and collection of peripheral blood stem cell is the essential part of ASCT. The aim of this study was to evaluate the effectiveness of various mobilization regimens, determine the risk factors associated with mobilization failure (MF). We also investigated whether iron overload, which has an adverse impact on various aspects of HSCT including overall survival had any impact on mobilization kinetics. A total of 118 consecutive patients were included in this study. The rate of MF was 11.8 % with the first mobilization regimen. Frequency of MF was higher in lymphoma (P < 0.001) patients and in those receiving G-CSF alone (P= 0.01). Peripheral CD34+ cell count (P < 0.001), bone marrow cellularity (P < 0.001), reticulin fibrosis (P < 0.05) were significantly lower whereas serum ferritin levels (P = 0.06) tended to be higher in patients with MF. CD34+ cell count of the first apheresis product was positively correlated with the white blood cell count (P < 0.05; r = 0.232), platelet count (P = 0.01; r = 0.233), peripheral CD34+ cell count (P < 0.001; r = 0.704) and the grade of bone marrow reticulin fibrosis (P < 0.001; r = 0.366). Serum ferritin levels were negatively correlated with maximum peripheral CD34+ cell count (P = 0.02; r = -0.216) and the CD34+ cell count in the first product (P = 0.05; r = -0.183). Platelet count (P = 0.03; ß = 0.262), peripheral CD34+ cell count (P = 0.02; ß=0.279) were the two variables which remained to be significant in multivariate analysis. Predicting the poor mobilizers with the platelet count for instance may reduce the risk of MF by using more effective regimens in advance.

Autonomic nervous system dysfunction and serum levels of neurotoxic and neurotrophic cytokines in patients with cobalamin deficiency.

OBJECTIVE: The imbalance between neurotoxic cytokine tumor necrosis factor-α (TNF-α) and neurotrophic cytokines epidermal growth factor (EGF) and interleukin-6 (IL-6) plays a role in the pathogenesis of cobalamin (Cbl) deficiency-induced neuropathy. The aim of this study was to evaluate autonomic nervous system dysfunction and to look for any relationship between autonomic nervous system disturbances and serum cytokine levels (TNF-α, EGF, IL-6) in patients with Cbl deficiency. METHODS: Serum levels of TNF-α, EGF and IL-6 were studied in patients with Cbl deficiency (n=41) and a healthy control group (n=17) and after 3 months in patients who underwent Cbl replacement therapy (n=22). All patients with Cbl deficiency underwent electrophysiological studies (EPS) for the diagnosis of neuropathy. Statistical analysis was performed using SPSS for Windows 11.5 software. RESULTS: With EPS, 29 of 41 Cbl-deficient patients (70.73%) demonstrated neurological dysfunction [3 (7.32%), 19 (46.34%) and 7 (17.07%) patients with sensorimotor peripheral neuropathy, parasympathetic, and sympathetic autonomic dysfunction, respectively]. Although there was no significant difference in serum levels of EGF and IL-6 between patients with versus without autonomic dysfunction, levels were significantly lower in Cbl- deficient patients than healthy controls. CONCLUSION: Presence of autonomic dysfunction seems to be a frequent neurological finding in patients with Cbl deficiency. However, we could not find any relationship between serum cytokine levels and autonomic dysfunction by EPS.

Early Diagnostic Markers for Detection of Acute Kidney Injury in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

OBJECTIVES: Acute kidney injury is a relatively frequent complication of allogenic hematopoietic stem cell transplant, resulting in increased risk of morbidity and mortality. Early diagnosis and management of acute kidney injury is of great importance for prevention of poor outcomes in these transplant recipients. MATERIALS AND METHODS: Fifty consecutive patients, hospitalized for allogenic hematopoietic stem cell transplant at the Bone Marrow Transplantation Unit of Gazi University Faculty of Medicine, were included in this prospective study. Serial measurements of serum creatinine and creatinine clearance were obtained before administration of conditioning regimen and at 0, 7, 14, 21, and 28 days after start of conditioning. Blood and urine samples were also obtained for the measurement of serum cystatin C and urine neutrophil gelatinase-associated lipocalin levels before conditioning and 24 hours before each serum creatinine measurement. RESULTS: During the median 25 days of follow-up, acute kidney injury developed in 19 patients: 10 patients had stage 1, 7 had stage 2, and 2 had stage 3 acute kidney injury according to the Acute Kidney Injury Network classification. There were significant positive correlations between serum cystatin C levels and serum creatinine levels and negative correlations with creatinine clearance levels at each time point (P < .001), whereas no statistically significant associations were observed with urinary neutrophil gelatinase-associated lipocalin levels. Both univariate and multivariate Cox regression models showed a statistically significant association between serum cystatin C levels and development of acute kidney injury, whereas urine neutrophil gelatinase-associated lipocalin levels did not show any significant associations. CONCLUSIONS: Serum cystatin C levels might be a useful marker for early detection of acute kidney injury in adult allogenic hematopoietic stem cell transplant recipients. Close monitoring of kidney function by sensitive biomarkers might provide early recognition and timely management of acute kidney injury in high-risk patient populations.

Intercontinental study on pre-engraftment and post-engraftment Gram-negative rods bacteremia in hematopoietic stem cell transplantation patients: Risk factors and association with mortality.

OBJECTIVES: We present here data on Gram-negative rods bacteremia (GNRB) rates, risk factors and associated mortality. METHODS: Data on GNRB episodes were prospectively collected in 65 allo-/67 auto-HSCT centers in 24 countries (Europe, Asia, Australia). In patients with and without GNRB, we compared: demography, underlying disease, HSCT-related data, center` fluoroquinolone prophylaxis (FQP) policy and accreditation status, and involvement of infection control team (ICT). RESULTS: The GNRB cumulative incidence among 2818 allo-HSCT was: pre-engraftment (pre-eng-allo-HSCT), 8.4 (95% CI 7-9%), post-engraftment (post-eng-allo-HSCT), 5.8% (95%CI: 5-7%); among 3152 auto-HSCT, pre-eng-auto-HSCT, 6.6% (95%CI: 6-7%), post-eng-auto-HSCT, 0.7% (95%CI: 0.4-1.1%). GNRB, especially MDR, was associated with increased mortality. Multivariate analysis revealed the following GNRB risk factors: (a) pre-eng-allo-HSCT: south-eastern Europe center location, underlying diseases not at complete remission, and cord blood source; (b) post-eng-allo-HSCT: center location not in northwestern Europe; underlying non-malignant disease, not providing FQP and never accredited. (c) pre-eng-auto-HSCT: older age, autoimmune and malignant (vs. plasma cell) disease, and ICT absence. CONCLUSIONS: Benefit of FQP should be explored in prospective studies. Increased GNRB risk in auto-HSCT patients transplanted for autoimmune diseases is worrying. Infection control and being accredited are possibly protective against bacteremia. GNRB are associated with increased mortality.

Allogeneic stem cell transplantation for severe aplastic anemia: graft rejection remains a problem.

We reviewed the outcome in 15 consecutive patients with severe aplastic anemia with a median age of 23 years who received matched sibling peripheral blood stem cell transplantation. Conditioning regimen was cyclophosphamide (Cy)+anti-thymocyte globulin (ATG). Cumulative incidence of transplant related mortality, graft failure, acute and chronic GVHD were 20%, 33%, 25%, and 8.3%, respectively. Conditioning with Cy only, resulted in higher rejection rate compared to Cy plus ATG (75% versus 12.5%, p=0.03). Eighty percent of patients are alive with a median follow-up of 19.5 (4.6-35.6) months. Two of the three patients who were re-transplanted with fludarabine had sustained donor chimerism.

Bortezomib-induced perivascular dermatitis in a patient with multiple myeloma.

Bortezomib is a potent, selective proteasome inhibitor. It is usually well tolerated, and bortezomib-induced skin lesions are less well known. A 59-year-old man with multiple myeloma underwent autologous hematopoetic stem cell transplantation (AHSCT). Administration of bortezomib was started after AHSCT as his disease progressed despite thalidomide maintenance. He developed a rash afer the third cycle of bortezomib. A biopsy showed superficial and deep perivascular dermatitis. The rash resolved within 4 days; complete response of myeloma was obtained after 8 cycles of bortezomib. The benign clinical course did not require interruption of the treatment, which in turn resulted in complete remission of myeloma.