Emre Tekgündüz

Dengue virus transmission by blood stem cell donor after travel to Sri Lanka; Germany, 2013.

Three days after donation of peripheral blood stem cells to a recipient with acute myeloblastic leukemia, dengue virus was detected in the donor, who had recently traveled to Sri Lanka. Transmission to the recipient, who died 9 days after transplant, was confirmed.

Dorsal sural nerve conduction study in vitamin B12 deficiency with megaloblastic anemia

Abstract  Peripheral neuropathy is frequently observed in B12 deficiency. In spite of this, there is little knowledge about peripheral neuropathy in B12 deficiency because the severity of clinical involvement of the central nervous system clearly outweighs signs and symptoms due to peripheral nervous system involvement. We primarily investigated peripheral neuropathy with dorsal sural conduction study, which is a new method for detection of early peripheral neuropathy, in B12 deficiency with megaloblastic anemia. Conventional nerve conduction studies and tibial sensory‐evoked potential (SEP) recording were also performed. Twenty‐eight B12‐deficient patients (15 male, 13 female, mean age 65.8 years) with megaloblastic anemia and 18 age‐ and sex‐matched controls were included in the study. Although dorsal sural sensory nerve action potentials (SNAPs) were not recorded in 15 (54%) of 28 patients, only 9 (32%) of them were found to have polyneuropathy by conventional conduction studies. Furthermore, patients with dorsal sural SNAP had mean lower amplitude, mean longer latency, and slower velocity response when compared with controls. Twenty patients (71%) were diagnosed as having myelopathy by the combination of tibial SEP and neurological findings. Two patients whose dorsal sural SNAPs were not recorded had normal tibial SEP responses; therefore, these patients were considered to have isolated peripheral neuropathy. As a result, we conclude that dorsal sural nerve conduction study is a reliable method for detection of early peripheral neuropathy in B12 deficiency.

Predicting the successful peripheral blood stem cell harvesting.

Several previously defined factors affecting the mobilization success include age, prior chemotherapy lines, exposure to myelotoxic agents, extended field radiotherapy and bone marrow infiltration with the primary disease. The purpose of this study was to retrospectively analyze the influence of the predictive factors for a successful peripheral stem cell mobilization. We enrolled a total of 145 patients into the study (non-Hodgkin lymphoma (n: 40), Hodgkin lymphoma (n: 36), myeloma (n: 64), solid tumors (n:5)) who received autologous stem cell transplantation between 2009 and 2012. In multivariate analysis only platelet count was found to be related with mobilization outcome (p<0.05). Knowing predictive factors for successful mobilization may be useful to define the best timing for mobilization and the most appropriate mobilizing agents for proper patient population.

Microbial contamination of hematopoietic progenitor cell products

INTRODUCTION Microbial screening for contamination is a part of hematopoietic progenitor cell (HPC) collection and infusion procedure. We aimed to find out our microbial contamination rates during collection, processing and infusion steps of HPC products. We also evaluated the clinical course of patients who received contaminated HPC products. PATIENTS-METHODS We retrospectively analyzed microbial contamination records of HPC grafts between 2010 and 2012. HPC products of autologous donors were evaluated for contamination at three steps: at the end of mobilization, following processing with DMSO and just before stem cell infusion. Grafts of allogeneic donors were assessed only before HPC transplantation (HCT). Microbiological analysis of HPC samples were performed with an automated system (BacT/Alert®). RESULT During the study period a total of 492 mobilization procedures were performed on 329 (214 autologous and 115 allogeneic) donors. Bacterial contamination has been detected in 103 of 1630 samples (6%). Ninety-seven out of 1162 blood samples (8%) from 265 patients who were treated with HCT were contaminated. Forty-six patients (41 autologous and 5 allogeneic) were transplanted with contaminated HPC products. During HCT 42 patients experienced febrile neutropenic attack and 34 of them had positive blood culture results. In none of these 34 patients the isolated pathogens were the same organisms with those found in the final contaminated stem cell product before stem cell infusion. None of the patients who received contaminated products died because of sepsis within the posttransplant 30days. There was no significant difference between patients who received contaminated and non-contaminated products in terms of the first day of fever, duration of fever, engraftment kinetics and duration of hospitalization. CONCLUSION Our results suggest that microbial contamination of HPC products is an issue to be prevented, although it may not have a major impact on the general success of HCT.

What is the most appropriate source for hematopoietic stem cell transplantation? Peripheral stem cell/bone marrow/cord blood.

The introduction of peripheral stem cell (PSC) and cord blood (CB) as an alternative to bone marrow (BM) recently has caused important changes on hematopoietic stem cell transplantation (HSCT) practice. According to the CIBMTR data, there has been a significant decrease in the use of bone marrow and increase in the use of PSC and CB as the stem cell source for HSCT performed during 1997–2006 period for patients under the age of 20. On the other hand, the stem cell source in 70% of the HSCT procedures performed for patients over the age of 20 was PSC and the second most preferred stem cell source was bone marrow. CB usage is very limited for the adult population. Primary disease, stage, age, time and urgency of transplantation, HLA match between the patient and the donor, stem cell quantity, and the experience of the transplantation center are some of the associated factors for the selection of the appropriate stem cell source. Unfortunately, there is no prospective randomized study aimed to facilitate the selection of the correct source between CB, PSC, and BM. In this paper, we would like to emphasize the data on stem cell selection in light of the current knowledge for patient populations according to their age and primary disease.

Differences in platelet-leukocyte aggregates among subtypes of acute cerebral ischemia.

BACKGROUND Acute cerebral ischemia is caused by different pathophysiological mechanisms. The role of platelets and other blood cells can be different among the stroke subtypes. METHODS Seventy-two patients with acute ischemic cerebrovascular disease, including 31 patients with large vessel disease, 21 patients with cardioembolic disease, and 20 patients with small vessel disease, were evaluated. P-selectin (CD62P) expression and platelet leukocyte aggregates were measured with flow cytometry at the acute phase after the ischemic event. Markers were also measured in 37 control subjects. In all subjects, the serum high-sensitivity C-reactive protein (CRP) was also measured. RESULTS The platelet-monocyte aggregates (PMA) and platelet-granulocyte aggregates (PGA) in the large vessel disease group were higher than in control group (P=0.002, and P<0.0001, respectively). The PMA and PGA in the small vessel disease group were also higher than in the control group (P=0.004 and P<0.0001, respectively). In contrast, in the cardioembolic disease group, the PMA and PGA were not significantly different from the control group. CD62P expression was higher in all of the patient groups relative to the control group (P<0.05 for all comparisons). Serum CRP levels were also higher in all of the patient groups than in the control group (P<0.0001 for all comparisons). CONCLUSIONS In contrast to large vessel and small vessel disease, it seems that platelet-leukocyte association does not play a crucial role in the pathogenesis of cardioembolic stroke.

Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience

Background Reed-Sternberg cells of classical Hodgkins lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. Patients and methods We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. Results Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. Conclusions Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity.

The current status in hematopoietic stem cell mobilization

Hemotopoietic stem cell mobilization with cytokines alone, has still been widely accepted as the initial attempt for stem cell mobilization. Chemotherapy based mobilization can be preferred as first choice in high risk patients or for remobilization. But mobilization failure still remains to be a problem in one third of patients. Salvage mobilization strategies have been composed to give one more chance to ‘poor mobilizers’. Synergistic effect of a reversible inhibitor of CXCR4, plerixafor, with G‐CSF has opened a new era for these patients. Preemptive approach in predicted poor mobilizers, immediate salvage approach for patients with suboptimal mobilization or remobilization approach of plerixafor in failed mobilizers have all been demonstrated convincing results in various studies. Alternative CXCR4 inhibitors, VLA4 inhibitors, bortezomib, parathormone have also been emerged as novel agents for mobilization failure. J. Clin. Apheresis 30:273–280, 2015.

Pandemic 2009 H1N1 Influenza in Patients with Hematopoietic Stem Cell Transplantation and Hematologic Malignancy: Single Center Experience

Although valuable information on many aspects of the pandemic 2009 H1N1 influenza came to light in a relatively short period of time, the disease course among immunocompromised patients is largely unknown. In this study, we present the results of active H1N1 surveillance in 32 patients who were treated at our hematology/stem cell transplantation clinic between December 2009 and January 2010. We also report the clinical and laboratory features of patients with laboratory-proven disease and try to define the impact of novel H1N1 disease on their outcome. Eight patients in the hematology clinic and 7 patients in the hematology/stem cell transplantation unit tested positive for pandemic H1N1 infection. Patients were treated with oral oseltamivir for 5–15 days. In 10 patients the infection was limited to the upper respiratory tract. But in 5 patients it was complicated with lower respiratory diseases. Three of them required intensive care support with mechanic ventilation and all died during follow-up. As the clinical and radiological findings of H1N1 infection are nonspecific in nature, we should have a high index of suspicion in immunocompromised patients. Therefore, beginning empiric oseltamivir therapy while waiting for laboratory results and increasing the dose/duration of therapy in laboratory-confirmed cases could be life saving.

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.