Haploidentical stem cell transplantation: T cell depleted and repleted.

Allogeneic hematopoietic stem cell transplantation (AHSCT), is a curative treatment option for many hematological diseases. Donor availability is the major limiting factor in the transplantation setting. More than half of the patients do not have a HLA fully matched related/unrelated donor but almost all patients have an haploidentical donor. Haploidentical transplantion can be performed either as T cell depleted or repleted. Despite the promising results in T cell depletion methods, expensive T cell selection and the necessity for experienced staff seem to be the limiting factors. However, a T cell repleted haploidentical stem cell transplantation strategy is simple, cheap and has been preferred by different transplant centers worldwide.

A retrospective analysis of patients treated for gestational trophoblastic diseases: a 4-year experience of a tertiary hospital.

AIM: To study incidence, clinical outcome, and follow-up data of the gestational trophoblastic disease (GTD) in patients diagnosed in the present Department. MATERIALS AND METHODS: This study included the authors' retrospective clinical records regarding the cases of GTD which were diagnosed and followed up between January 2011 and January 2015. Patients' age, gravidity and parity, obstetric history, subgroup of GTD, gestational weeks, management results, and pre-post treatment ß-hCG levels was investigated and an incidence study was constituted. RESULTS: Total of 56 GTD cases were hospitalized and clinical records of 16,840 normal spontaneous deliveries were evaluated during the study period. The incidence of GTD was 3.3/1,000 cases. After histopathological examination, nine of 47 cases were partial molar pregnancy, whereas 38 cases were complete moles. There were no choriocarcinoma and invasive moles. All cases were treated with vacuum curettage without complication. CONCLUSION: The GTD incidence in this clinic is high with a rate of 3.3/1,000 per pregnancy compared to Turkish literature. High birth rates of our population may play a role in high incidence results. Further investigation in this field is essential.

Spatial analysis of perinatal mortality rates with geographic information systems in Kocaeli, Turkey.

OBJECTIVES: To determine the spatial patterns of perinatal mortality in Kocaeli, Turkey using geographic information systems (GIS); to examine whether regional differences exist for the period selected; and whether these differences are linked to regional risk factors. STUDY DESIGN: Ecological research. METHODS: Data were obtained from the linked birth-death records data registry maintained by Kocaeli Provincial Health Directorate. Mortality data are added to the geodatabase on a monthly basis. Spatial patterns of mortality rates were determined with GIS by mapping the case differences in the districts, and spatial autocorrelation was used to examine the spatial pattern of mortality rates in the region. RESULTS: Various risk factors contributing to spatial variation of perinatal mortality were revealed in the region. Districts with high mortality rates were shown to be sensitive to these risk factors. The results of this study confirm the direct link between perinatal mortality and poor environmental conditions in the study region. The analyses applied in the study showed that some complex demographic and socio-economic factors should be associated with perinatal mortality rates to identify the geographic patterns of mortality. CONCLUSIONS: Implementation of spatial tools within GIS for mortality data showed the efficiency of GIS in perinatal mortality surveillance. This study also demonstrated the capability and utility of GIS to clarify the geographical distribution of perinatal mortality rates in the study area.

ABO and Rh blood groups frequency in women with HER2 positive breast cancer.

PURPOSE: The role of genetic factors in the development of cancer is widely accepted. Data on the role of ABO blood group and Rh factor in breast cancer is inconclusive. The aim of this study was to investigate the presence of a possible association between HER2 (+) breast cancer in Turkish women and ABO blood groups and Rh factor. METHODS: In 294 female patients with HER2 (+) breast cancer, ABO blood groups and Rh factor were examined. The relationship of blood groups with age, menopausal status, and family history of cancer, estrogen receptor (ER), progesterone receptor (PR) and HER2 status of these patients was evaluated. Blood groups distribution of 22,821 healthy blood donors was also assessed and compared with the patients' blood groups distribution. RESULTS: The median patient age was 47 years (range 20-80) and 56% of the patients were premenopausal. ER and PR were positive in 50 and 60% of the patients, respectively. Overall, the ABO blood group distribution of the 294 HER2 (+) breast cancer patients was similar to that of the healthy blood donors (p=0.36). Likewise there was no correlation between blood type and ER, PR and menopausal status. Rh (-) patients had more frequent family cancer history and this difference was significant for patients with blood group B Rh (-) and O Rh (-) (p = 0.04). CONCLUSION: In the present study we didn't find any relationship between HER2 status and ABO blood group and Rh factor. However, further studies with larger number of patients are needed to establish the role (if any) of blood groups in patients with breast cancer.

A Vehicle Routing Problem with Time Windows and Workload Balancing for COVID-19 Testers: A Case Study.

Due to the COVID-19 pandemic, laboratories have faced unprecedented demand for in-home delivery test services. This drastic demand increase requires a rapid reaction from laboratories to manage their testers in order to respond to the high demand volume and avoid unnecessary costs. This study provides an optimization model based on the vehicle routing problem with time windows by considering the testers' workload balancing to improve laboratories' assignment and routing policies. A medical lab that has faced this situation for its in-home test services is taken as a real-world case in the current study. A mixed-integer programming model is solved for small instances using the CPLEX solver, and an adaptive large neighborhood search algorithm is implemented for large instances. Ultimately, the obtained solutions are compared to the real-world implementation of the lab on a dataset of six consecutive days, and the results are further discussed.

Incremental Multi-Scale Search Algorithm for Dynamic Path Planning With Low Worst-Case Complexity.

Path-planning (equivalently, path-finding) problems are fundamental in many applications, such as transportation, VLSI design, robot navigation, and many more. In this paper, we consider dynamic shortest path-planning problems on a graph with a single endpoint pair and with potentially changing edge weights over time. Several algorithms exist in the literature that solve this problem, notably among them the Lifelong Planning algorithm. The algorithm is an incremental search algorithm that replans the path when there are changes in the environment. In numerical experiments, however, it was observed that the performance of is sensitive in the number of vertex expansions required to update the graph when an edge weight value changes or when a vertex is added or deleted. Although, in most cases, the classical requires a relatively small number of updates, in some other cases the amount of work required by the to find the optimal path can be overwhelming. To address this issue, in this paper, we propose an extension of the baseline algorithm, by making efficient use of a multiscale representation of the environment. This multiscale representation allows one to quickly localize the changed edges, and subsequently update the priority queue efficiently. This incremental multiscale ( for short) algorithm leads to an improvement both in terms of robustness and computational complexity-in the worst case-when compared to the classical . Numerical experiments validate the aforementioned claims.

Effects of ABO incompatibility in allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: The impact of ABO mismatch on outcomes following allo-HSCT remains controversial. In this study, our aim is to define the effect of ABO mismatch on post-transplant outcomes, engraftment kinetics and complications in a large cohort. PATIENTS AND METHODS: We retrospectively identified 1000 patients who underwent allo-HSCT from either bone marrow or peripheral blood stem cells at our center between 1988 and 2016. P<0.05 was considered statistically significant. RESULTS: Five hundred and ninety (59%) patient-donor pairs were ABO matched, 164 (16.4%) were ABO major mismatched (MM), 191 (19.1%) were ABO minor MM, and 55 (5.5%) were ABO bi-directionally MM. ABO matched pairs were more common in transplants from related donors (P<0.001) and using bone marrow as a stem cell source (P<0.001). In minor ABO MM transplantations, mild delayed hemolytic reaction occurred more frequently compared to major and bidirectional ABO MM transplantations (47% vs 35% and 18%, P<0.001). Neutrophil engraftment was slightly delayed in ABO MM patient-donor pairs when compared ABO matched donor pairs according to median engraftment time in all group (167/410, 41% vs 204/590, 35%, P=0.046). Pure red cell aplasia was diagnosed in 6 patients (1%). Higher risk of death was shown in ABO MM transplants compared to ABO matched transplants in overall survival (OS) analysis (HR:1.201, 95% CI:1.004-1.437, P=0.045). The non-relapse mortality (P=0.546) and cumulative incidences of acute graft versus host disease (aGVHD) and chronic (c) GVHD were comparable between ABO MM and ABO matched patient-donor pairs (for aGVHD, P=0.235; for cGVHD, P=0.137). CONCLUSION: ABO MM transplants were associated with decreased OS and slightly delayed neutrophil engraftment. NRM and the risk of GVHD were not related to ABO incompatibility.

Differential in vitro inhibitory effects of anticancer drugs on tumor-associated carbonic anhydrase isozymes CA IX and CA XII.

Carbonic anhydrase IX (CA IX) and, to a lesser extent, carbonic anhydrase XII (CA XII) are highly overexpressed in hypoxic tumors. In this study, the inhibitory effects of 11 different anticancer drugs including paclitaxel, amethopterin, etoposide, irinotecan, gemcitabine, 5-fluorouracil, oxaliplatin, epirubicin, cisplatin and carboplatin on the tumor-associated carbonic anhydrase isozymes CA IX and CA XII and cytosolic carbonic anhydrases I and II have been investigated. SX.18MV-R Applied Photophysics stopped-flow instrument was used for measuring the initial velocities for the CO2 hydration reaction catalyzed by different CA isozymes, by following the change in the absorbance of a pH indicator. CA IX and CA XII were the most affected by carboplatin and cisplatin amongst the panel of anticancer drugs. Moreover, the cytosolic carbonic anhydrases I and II can also be affected. Consequently, CA IX and CA XII are interesting targets for anticancer drug development, although more selective and powerful CA inhibitors could prove useful for elucidating the role of the protein in hypoxic cancers, for controlling the pH imbalance in tumor cells and for developing diagnostic or therapeutic applications for the management of hypoxic tumors, generally unresponsive to classical chemo- and radiotherapy.

Comparison of performance and abnormal cell flagging of two automated hematology analyzers: Sysmex XN 3000 and Beckman Coulter DxH 800.

INTRODUCTION: The purpose was to evaluate the analytical performances of Sysmex XN 3000 and UniCel DxH 800 comparing the obtained results with manual counting and between each other. Also flagging capabilities of abnormal cells were compared for both analyzers. METHODS: Two thousand one hundred and forty-two whole-blood samples were analyzed for evaluation. The samples flagged due to blast, atypical lymphocyte (AL), immature granulocyte (IG), or nucleated red blood cells (NRBC) were microscopically reviewed (n=102). RESULTS: The within-run and between-day coefficient of variations (CV%) of XN 3000 for hemoglobin, RBC, MCV, WBC, and platelets were lower than 5% and for WBC differentials lower than 10% except monocytes which was 15.6% at low level. The precision results of DxH 800 were also lower than 5.0% except platelets (9.5%) and monocytes (45%) at low level. The comparison of analyzers revealed good agreement (R>.86), except monocytes and basophils. The flagging sensitivities of XN 3000 were higher for IGs, blasts, and ALs than those of DxH 800 and almost similar for NRBC. CONCLUSION: The XN 3000 and DxH 800 are accurate, highly precise systems and can be used effectively in high-volume laboratories. The flagging sensitivity of XN 3000 was higher in detecting blasts, IGs, and ALs than that of DxH 800. The detection of abnormal cells with high sensitivity may improve laboratory workflow with a reduced slide review and accelerated turnaround time.

Extracorporeal photochemotherapy in mycosis fungoides.

OBJECTIVES: Extracorporeal photo-chemotherapy (ECP, photopheresis) is an approved treatment modality for mycosis fungoides (MF). Our aim is to present our ECP data for MF. METHODS: We retrospectively evaluated 50 MF patients who received ECP for clinical activity, toxicity, and response and outcome rates, and we compared these with combination therapies. RESULTS: The overall response rate (ORR) was 42% (21/50), while the median time to response was 11months (range, 3-48months). Ten of the responders (48%) had 3 or more treatment lines prior to ECP. Eight patients (16%) had adverse events related to ECP. The overall survival (OS) of 50 patients was 72months (range, 3-211). There was no statistically significant difference in the OS in early-stage vs late-stage patients (77 vs 69months, P=0.077). The stage 3 and 4 patients received an average of 31 cycles compared to 55 cycles in stage 1 and 2 patients (P=0.006). The increased extent of ECP was not correlated with the response. Combined treatment with ECP significantly improved the OS (84months vs 62months, P=0.005). DISCUSSION: A low frequency of side effects and improved OS observed in combination therapy makes ECP a favorable option for treating MF.

Tuberculosis in stem cell transplant patients.

Tuberculosis (TB) is an increasing health problem, and patients undergoing stem cell transplantation (SCT) are at high risk of acquiring TB. Following a review of the medical literature, this article reports the current situation of TB in SCT patients. A PubMed search was undertaken using the keywords 'tuberculosis', 'stem cell transplantation' and 'bone marrow transplantation', and cases with meaningful data for analysis were included. The medical literature contains relatively few data on TB and SCT. Although there is a risk of TB in allogeneic SCT patients, this is less than in solid organ transplant patients, and the risk in autologous SCT patients is similar to the risk in the general population. The incidence of TB in SCT patients is proportional to the incidence of TB in the general population. Evidence favouring TB prophylaxis is not well established. While allogeneic transplantation carries a risk of TB, this is not true for autologous transplantation. Prophylaxis can only be an option for selected patients or countries with high rates of TB.

Late coronary stent dislodgement following coronary artery stenting.

Recently, coronary artery stenting has been successful when used as an intervention for percutaneous coronary artery disease. However, the procedure may frequently produce complications. Although rare, stent dislodgement is one such complication, which may result in serious problems including coronary artery dissection, myocardial infarction, peripheral embolisation and death. Stent dislodgement is known to be an early complication of the coronary artery stenting procedure. In this case report, we present a 53-year-old male with late coronary stent dislodgement. To the best of our knowledge, no such case has been addressed in the literature to date.

Brain SPECT evaluation of the visual cortex in amblyopia.

UNLABELLED: In amblyopia, the number of visual cortical neurons are reduced and abnormal or absent sensitivity to retinal light stimulation of the amblyopic eye is demonstrated. Ten amblyopic patients were studied to evaluate the response of the visual cortex to visual stimulation. METHODS: All patients with unilateral amblyopia received 500-550 MBq 99mTc-HMPAO during visual stimulation. Strobe light flashing was used as the stimulus for five patients and a checkerboard pattern reversal was used in the other five patients, closing one eye. For both groups a 2-Hz frequency was used. One week later, the same procedure was repeated with the opposite eye closed. SPECT images were reconstructed with prefiltering techniques and sliced along the orbitomeatal line. RESULTS: For all patients, the amblyopic eye demonstrated less radioactivity in the visual cortex than in the normal eye. The mean cerebral-to-cerebellar ratios were 0.95 +/- 0.05 and 1.09 +/- 0.07 for amblyopic and normal eyes, respectively (p < 0.0001). CONCLUSION: Visual cortex response of the amblyopic eye to light stimulation was severely reduced when compared to the normal eye.

Erythrocyte antigen and reticulocyte engraftment after allogeneic hematopoietic stem cell transplantation.

The aim of this study was to study the usefulness of erythrocyte antigen (EA) measurement to study engraftment after allogeneic HSCT. In all, 31 consecutive patients receiving HLA-identical bone marrow (BM) (n=13) or peripheral blood stem cells (n=18) were investigated. Apart from the ABO group, 15 EAs representing six minor blood groups were followed by the simple tube agglutination technique. A total of 20 (64.5%) patients received ABO-identical, eight (25.8%) received ABO minor and three (9.7%) received ABO major mismatched grafts. In all, 29 patients were followed for a median of 12 (6-16) months; 65% of the patients expressed donor type EA 1 month and almost all did so 6 months after transplant. Reticulocyte engraftment was significantly shorter than EA engraftment (median 18 vs 35 days) (P=0.001). Patients who received PB stem cells showed significantly faster EA and reticulocyte engraftment than patients who received BM stem cells (P=0.038 and 0.025). ABO compatibility did not have an impact on reticulocyte and EA engraftment (P=0.4 and 0.55). The earliest donor type EA detected was from the Rh and Kidd system. These data suggest that EA and reticulocyte assays are useful in monitoring engraftment.

Aerobic bacterial and fungal infections in peripheral blood stem cell transplants.

Allogeneic and autologous peripheral blood stem cell transplants are frequently complicated by infections. This study was performed to evaluate early and late infections in 74 patients who underwent peripheral blood stem cell transplantation (PBSCT). Fifty-eight patients received allogeneic and 16 autologous PBSCT. All patients received fluconazole, ciprofloxacin and acyclovir prophylaxis. 93.1% of alloPBSCT patients and 87.5% of autoPBSCT patients developed fever. Febrile episodes were commonly seen in the week of transplantation (66%). There was a median of 3 days with fever in alloPBSCT, and 2 days in autoPBSCT. Period of neutropenia was 15 days for AlloPBSCT and 12 days for AutoPBSCT. The microbiological identification rate was 47% (32/68). Gram-positive infections dominated the early period (50%) and Gram-negative bacterial infections dominated the late period (50%). All our patients had Hickman-type catheters and 26 infections involving catheters were seen. Sixteen occurred in the early, and 10 in the late period. Ten of 14 (71.4%) late bacterial infections were catheter-related. The dominance of Gram-positive infections and high rates of methicillin resistance warranted the use of vancomycin extensively. Surveillance cultures were found to be useful in selected patients. Although slime factor is an important virulence factor, there was no difference between slime factor positive and negative coagulase-negative staphylococci isolated during infections. In conclusion, febrile episodes are the most frequent complication of PBSCT and Gram-positive microorganisms remain the main pathogen in these patients because of catheter use, mucositis and ciprofloxacin prophylaxis. Methicillin resistance is increasing and glycopeptides remain the only choice for treating such infections. Although the infection rate is high, measures taken to prevent and treat infections result in very low rates of mortality from infection in PBSCT patients.

High-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous peripheral blood stem cell transplantation in patients with lymphoma -- a retrospective evaluation.

The purpose of this evaluation was to investigate the efficacy of high-dose chemotherapy with thiotepa, melphalan, and carboplatin (TMCb), and of autologous peripheral blood stem cell (PBSC) infusion in patients with aggressive non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). A total of 42 patients, 23 with intermediate-grade NHL and 19 with HD, received thiotepa (500 mg/m2), melphalan (100 mg/m2), and carboplatin (1050-1350 mg/m2) followed by autologous PBSC infusion. Of 21 patients with more advanced disease, four had primary refractory disease, one was in complete remission (CR)-2, 11 were in first refractory relapse, and five were beyond first relapse. Of 21 patients with less advanced disease, two were in CR-1, four were in CR-2, and 15 were in first responding relapse. In all, 14 patients (33%) had received prior radiotherapy prohibiting a total-body irradiation (TBI)-based conditioning regimen. The projected 2-year probabilities of survival, event-free survival (EFS), and relapse for all patients were 0.65, 0.60, and 0.21 (0.85, 0.80, and 0.10 for patients with less advanced disease and 0.47, 0.42, and 0.33 for patients with more advanced disease). The probability of nonrelapse mortality in the first 100 days was 0.12. Grade 3-4 regimen-related toxicities (RRT) occurred in five of 42 (12%) patients and death due to grade-4 RRT occurred in only one (2.5%) patient. These preliminary data suggest that 0.42% EFS in this study for advanced disease patients is highly encouraging and high-dose TMCb followed by autologous PBSC transplantation is well tolerated as well as an effective regimen in patients with intermediate-grade NHL or HD, and may be comparable to some previously used regimens including TBI-based regimens.

Hepatitis B virus infection in allogeneic bone marrow transplantation.

Fourty-four patients who underwent allogeneic bone marrow transplantation (alloBMT) were studied for hepatitis B virus (HBV)-related complications. The mean follow-up period was 15.3 months. Positivity for HBV surface antigen (HBsAg) was observed in 10 patients (22.7%) throughout the study. Four of the 10 patients were HBsAg carriers before alloBMT, while the remaining six became HBsAg(+) after alloBMT. During the follow-up period (from 6 months to 45 months), an elevation in serum ALT activity was observed in the four carriers when immunosuppression was reduced or withdrawn. All of the four HBsAg carriers developed hepatitis, but none of them died of liver failure due to HBV. Only one death due to GVHD and diabetic ketoacidosis was observed in this group. Two of the four carriers received marrow from anti-HBs positive donors and one of them cleared HBsAg from his serum via adoptive immunity 8 months after transplantation. The remaining six patients acquired HBV after alloBMT, but we were unable to demonstrate the source of HBV. Five of them had a moderate increase in serum ALT activity while the other patient had a normal ALT. Two patients seroconverted to anti-HBs spontaneously. Two patients died during the follow-up, one due to intracranial hemorrhage and the other due to GVHD and accompanying pulmonary infection. The rest of the study group (34 patients) remained HBsAg(-) throughout the study. Two of them had an HBsAg(+) donor, but neither developed HBV infection in their follow-up period. The acquisition rate of HBV infection was relatively low in recipients who were positive for anti-HBs compared to those who were negative for anti-HBs (8 vs 19%). Anti-HBs positivity remained for a longer period in recipients who received marrow from anti-HBs positive donors compared to those recipients who had anti-HBs negative donors (median 12 vs 3 months). We think that HBV is a frequent cause of liver dysfunction in alloBMT patients where HBV infection is endemic. Whether the disease is in the form of reactivation of HBsAg-positive recipients, or is acquired from unknown sources in recipients who never had contact with the virus, the course of the disease is not fatal. Silent serologic changes can be demonstrated if viral serologic markers are sought serially. Among them, the disappearance of serum anti-HBs may be important as it increases the risk of HBV contamination in recipients.

Role of pretransplant interferon-alpha(IFN) treatment in the outcome of stem cell transplantation (SCT) from related donors in chronic myelogenous leukemia (CML): results from three Turkish transplant centers.

Since transplantation cannot be performed immediately after the diagnosis of chronic myelogenous leukemia (CML), interferon treatment is usually required. This study aims to analyze the effects of interferon-alpha (IFN) treatment on allogeneic stem cell transplantation (SCT) outcome. A total of 106 patients aged 16-47 years and transplanted from HLA-identical sibling donors for CML in chronic phase (CP) were evaluated. In all, 48 had received IFN-alpha for a median duration of 5 months (1-18 months) until a median of 1 month prior to transplantation. Of the patients, 50 have received bone marrow transplant (BMT) whereas 56 have received peripheral blood stem cells (PBSCT) between 1991 and 1999 in three major transplant centers in Turkey. Patient characteristics in both groups were similar. More hematological responders were present in the IFN(+) patients (P=0.0001). No difference was found in engraftment kinetics. The incidences of acute or chronic graft-versus-host disease (GVHD), relapse and graft failure were similar in all patients regardless of stem cell source. Overall survival (OS) and disease-free survival (DFS) at 2 years were similar for both IFN(+) or (-) patients following SCT. With multivariate analysis, pretransplant IFN-alpha use, stem cell source, transplant year and CD34+ cell content were not found to be risk factors for OS. In conclusion, prior IFN exposure did not impair BMT or PBSCT outcome.