The level of fatigue, insomnia, depression, anxiety, stress, and the relationship between these symptoms following allogeneic hematopoietic stem cell transplantation: a cross-sectional study.

PURPOSE: This study investigated the incidence of fatigue, insomnia, depression, anxiety, and stress symptoms in patients after allogeneic hematopoietic stem cell transplantation (AHSCT), as well as explored potential relationships among these symptoms. METHODS: A total of 126 patients who had undergone transplantation at a university hospital at least one month prior to the study's commencement were included. The study was conducted as a cross-sectional and relational research, and data were collected using the "Personal Information Form," "Brief Fatigue Inventory," "Insomnia Severity Index," and "Depression Anxiety Stress Scale." Statistical analyses included descriptive statistics, parametric and nonparametric tests, and correlation analyses using the Spearman Correlation Coefficient. Additionally, mediation analyses were conducted using a Structural Equation Model to explore potential causal relationships among the variables. RESULTS: The incidence of fatigue was high among patients, with 94% experiencing this symptom following transplantation. Additionally, 52% had anxiety, 47% had insomnia, 47% had depression, and 34% had stress. Moderate relationships were observed between these symptoms. Regression analysis revealed that one-point increase in fatigue was associated with increases in stress 1.065 points, depression 0.937 points, anxiety 0.956 points, and insomnia 0.138 points (p<0.001). Similarly, one-point increase in insomnia was associated with increases in fatigue 3.342 points, stress 0.972 points, depression 0.885 points, and anxiety 0.816 points (p<0.001). CONCLUSION: After AHSCT, fatigue was the most frequent symptom experienced by patients, followed by insomnia, depression, anxiety, and stress. There was a relationship between these symptoms. Additionally, evidence suggested that insomnia was more strongly associated with fatigue compared to the other symptoms.

Endonasal endoscopic approach for sellar metastatic pathologies: a national observation.

PURPOSE: Sellar metastases are rare lesions. Recent improvements in diagnosis and treatment strategies have prolonged survival but increased the probability of metastatic tumors. Evaluation with clinical symptomatology and meticulous laboratory examination is crucial. We present our multicenter national study on sellar metastases to evaluate and underline the main clinical, endocrine, and radiological considerations regarding the diagnosis and endonasal endoscopic management of such rare lesions. METHODS: A medical literature-based retrospective study was planned across 13 neurosurgical centers in Turkey, where a data survey was conducted to collect information regarding sellar metastases surgically treated using the endoscopic endonasal approach, including clinical presentation, radiographic features, primary tumor origin, histopathological confirmation, time to metastasis, treatment, and patient outcomes. RESULTS: Between 2010 and 2020, 54 patients (22 women [40.7%] and 32 men [59.3%]) who underwent surgery with the endonasal endoscopic approach and had pathologically proven sellar metastases (overall incidence, 0.54%) were included. Of the patients, 59.3% had no known malignancy and presented with new-onset symptoms, 79.6% reported headache, 51.9% complained of some degree of visual deficits, and 50% had cranial nerve symptoms. Tissue biopsy was performed in 7.4% of the patients, whereas gross or subtotal resection was achieved in the remaining patients. CONCLUSION: To our knowledge, this is the largest series of patients surgically treated with the endonasal endoscopic approach for sellar metastases. For these patients, the treatment focus should be on management modalities for increasing quality of life instead radical treatment options with survival benefit.

Allogeneic hematopoietic stem cell transplantation for heavily pretreated patients with mycosis fungoides and Sezary syndrome.

Allogeneic hematopoietic stem cell transplantation (AHSCT) is a promising strategy for treatment of heavily pretreated mycosis fungoides/Sezary syndrome (MF/SS). Herein, we aimed to evaluate the outcomes of AHSCT for heavily pretreated patients with MF/SS retrospectively. This analysis included consecutive 19 patients with MF/SS who received 20 AHSCT between 2012-2021 in our transplant center. Eight patients have been previously reported. Fifteen patients had diagnosis of MF and referred to SS in five patients. In our cohort, all cases had advanced disease (stages IIB: n = 1, IIIA: n = 7; IIIB: n = 4, IVA: n = 4, and IVB: n = 3). Nine patients (47.4%) had developed large cell transformation. Only two patients received AHSCT in complete response, one very good partial response and two partial response while the others had progressive disease (n = 15) before transplant. Seven (35%) patients were alive at the time of analysis, with a median follow up of 10.5 months (range, 0.3-113 months) after AHSCT. Nine patients (47.4%) died without disease relapse or progression. Non-relapse mortality was 35.9% at 1 year and 26.9% at 3 years and thereafter. For all patients the probability of overall survival was 48.5% and 32.3% at 1- and 5-year post-transplant, respectively. AHSCT for MF/SS resulted in an estimated progression free survival of 45.4% at 1 year. Given the poor prognosis of patients not receiving transplants and in the absence of curative non-transplantation therapies, our results support that AHSCT is able to effectively rescue 32.3% of the population of transplant eligible, heavily pretreated patients in 5 years.

Hematological Malignancies and Fertility.

In the last decades, survival rate of hematological malignancies has been significantly improved and sparing reproductive potential after treatment has become one of the goals in both male and female patients. A comprehensive consultation with reproductive specialists before the onset of any kind of cancer treatment procedure is an essential issue which would increase the likelihood of parenting in survivors. In this context, cryopreservation of oocyte, embryo or ovarian tissue in reproductive aged women and sperm or testicular tissue cryopreservation in adult male are feasible approaches that must be considered before gonadotoxic therapy. Notably, all options should be regarded as experimental during pre-pubertal period. Herein, we aim to review the available literature with regard to safety, efficacy of fertility preservation methods and the pregnancy outcomes in patients with hematological malignancies.

Promising utilization areas of therapeutic plasmapheresis in cardiovascular surgery practice.

OBJECTIVE: Apheresis is performed for treatment of numerous diseases by removing auto-antibodies, antigen-antibody complexes, allo-antibodies, paraproteins, non-Ig proteins, toxins, exogenous poisons. In current study, we present our experience of using therapeutic plasma exchange (TPE) in patients with different types of clinical scenarios. METHODS: Between January 2013 and May 2016, we retrospectively presented the results of 64 patients in whom postoperative TPE was performed in ICU setting after cardiac surgery. Patients were grouped into four as; 1-sepsis (n = 26), 2-hepatorenal syndrome(n = 24), 3-antibody mediated rejection(AMR) following heart transplantation(n = 4) and 4-right heart failure(RHF) after left ventricular asist device(LVAD)(n = 10). Hemodynamic parameters were monitored constantly, pre- and post-procedure peripheral blood tests including renal and liver functions and daily complete blood count (CBC), sedimentation, C-reactive protein and procalcitonin (ng/ml) levels were studied. RESULTS: The mean age was 61 ± 17.67 years old and 56.25% (n = 36) were male. Mean Pre TPE left ventricular ejection fraction (LVEF) (%), central venous pressure (CVP)(mmHg) pulmonary capillary wedge pressure (PCWP)(mmHg) and pulmonary arterial pressure (PAP)(mmHg) were measured as 41.8 ± 8.1, 15.5 ± 4.4, 17.3 ± 3.24 and 39.9 ± 5.4, respectively. Procalcitonin (ng/ml) level of patients undergoing TPE due to sepsis was significantly reduced from 873 ± 401 ng/ml to 248 ± 132 ng/ml. Seventeen (26.5%) patients died in hospital during treatment, mean length of intensive care unit (ICU) stay(days) was 13.2 ± 5.1. CONCLUSION: This study shows that TEP is a safe and feasible treatment modality in patients with different types of complications after cardiac surgery and hopefully this study will lead to new utilization areas.

Adult Stem Cells and Medicine.

Stem cells can be either totipotent, pluripotent, multipotent or unipotent. Totipotent cells have the capability to produce all cell types of the developing organism, including both embryonic and extraembryonic tissues. The Hematopoietic Stem Cells (HSC) are the first defined adult stem cells (ASC) that give rise to all blood cells and immune system. Use of HSCs for treatment of hematologic malignancies, which is also called bone marrow (BM) transplantation or peripheral blood stem cells (PBSC) transplantation is the pioneer of cellular therapy and translational research. However, stem cell research field is developing so fast that, innovative approaches using HSCs for treatment of refractory diseases are growing rapidly. Hematopoietic stem cell transplantation (HSCT) has been widely used to achieve cure in different hematological diseases. Applications include the treatment of marrow failure syndromes, leukemia, lymphoma, multiple myeloma (MM), certain inherited blood disorders, autoimmune diseases and as an enzyme replacement in metabolic disorders. Innovative approaches such as haploidentical stem cell transplantation, new monoclonal antibodies and immunotherapies as well as Chimeric Antigen Receptor T-cell (CAR-T cell) therapies are on the way as promising treatment options especially for patients with refractory hematologic malignancies and even in solid tumors. However, there are still some challenges remaining before some of these therapies are translated into clinical application. In this paper, HSCs including its properties, niches, clinical usage and its contribution to modern medicine today and in the future will be discussed.

A review of infectious complications after haploidentical hematopoietic stem cell transplantations.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation from haploidentical donor is a feasible option for patients with hematological diseases who lack a suitable HLA-matched donor, but viral and fungal infections are still the most common causes of morbidity and mortality in haploidentical transplantation setting because of delayed immune reconstitution, increased risk of graft vs host disease (GvHD) or systemic steroid use. Therefore, this review will focus on the infectious complications after haploidentical hematopoietic stem cell transplantation (HSCT). MATERIALS AND METHODS: Electronic publications were searched until February 2017 throughout databases, including Pubmed, Cochrane, and Embase. The following keywords were used 'haploidentical transplantation', 'infection', 'T cell replete', and 'T cell deplete'. RESULTS: An increased incidence of bacterial, fungal, or viral infections is detected in haplo-HSCT compared to related, unrelated, or cord blood transplantations. Neutropenia and use of systemic steroid for GvHD and delayed immune reconstitution are important risk factors for infection after haplo-HSCT. CONCLUSION: A shift towards T cell repletes haplo-HSCT with post-transplant cyclophosphamide (CY) for GvHD has been emerged in recent years, in which the incidence of viral and fungal infections is detected to be lower. Prophylaxis and pre-emptive treatment strategies should be applied according to patient status.

A rare complication after allogeneic stem cell transplantation: post-transplant erythrocytosis.

Post-transplant erythrocytosis is an infrequent complication and has been reported after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in aplastic anemia, acute myeloid leukemia, and chronic myeloid leukemia. The pre-disposing factors and treatment are not clearly defined. We present 11 post-transplant erythrocytosis cases. More studies should be conducted to distinguish the pathogenesis and follow-up for this rare complication.

Does defibrotide prophylaxis decrease the risk of acute graft versus host disease following allogeneic hematopoietic cell transplantation?

There is some preliminary evidence, that veno-occlusive disease prophylaxis with defibrotide (DF) may also have a role in decreasing risk of acute graft-versus-host disease (aGvHD) by preventing tissue damage. In this study, we aimed to investigate the role of DF prophylaxis on the development of aGvHD at D+180. One hundred ninety-five consecutive adult patients receiving allogeneic HCT were retrospectively evaluated in 3 groups: no DF, DF/post-HCT (DF D+1 to D+14) and DF/pre-HCT (DF for 14 days concurrently with conditioning). The total (p: 0.057) and grades III/IV (p: 0.051) aGvHD rates at D+180 were 46.5%, 40%, 25.5% and 15.5%, 11.2%, 0% in patients on no DF, DF/post-HCT and DF/pre-HCT. DF may have a role in decreasing incidence and severity of aGvHD, especially if used concurrently with conditioning regimen.

Peripheral blood stem cell mobilization and collection from elderly patients and elderly healthy donor.

The impact of age on peripheral blood stem cell mobilization has been reported with contradictory results. We aimed to revise these data about stem cell mobilization in elderly patients and healthy donors.

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.

Which regimen is better for stem cell mobilization of lymphoma patients?

Although chemotherapy combined with G-CSF is an effective method for hematopoietic stem cell mobilization, standard chemotherapy protocol leading to best stem cell yield is not defined. In our study, we aimed to assess the impact of chemotherapy choice on mobilization outcome in lymphoma patients. Patients were mobilized with cyclophosphamide (n:15), ASHAP (n:11) or VGEPP (n:12) protocols. Groups were similar according to collected CD34+ cell count, total nucleated cell count and median apheresis days. Five out of fifteen (33%) patients could not be mobilized in Cy group but there was only one failed mobilization attempt in both salvage groups (9% with ASHAP vs 8% with VGEPP). In conclusion, we showed that VGEPP and ASHAP are safe protocols in terms of stem cell mobilization and have similar mobilization capacity as cyclophosphamide alone.

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.

How Does Influenza A (H1N1) Infection Proceed in Allogeneic Stem Cell Transplantation Recipients?

The clinical course of influenza A (H1N1) infection in allogeneic hematopoietic stem cell transplantation (AHSCT)recipients is not clearly known. We report 3 AHSCT recipients that were infected with influenza A (H1N1). Each of thepatients had a different hematological disease and was at a different post-transplantation stages. All the patients weretreated with oseltamivir, and zanamivir was switched to oseltamivir in 1 patient. All the patients survived without anycomplications. The course of swine flu can vary and progress with bacterial or other viral infections in immunosuppressedpatients.

Alpha-1-Antitrypsin Experience for Steroid-Resistant Acute Graft-Versus-Host Disease.

Steroid-refractory acute graft-versus-host disease (SR-aGVHD) treatment has a low response rate and a high risk of infection in allogeneic hematopoietic stem cell transplantation. The standard approach to be applied in this situation is uncertain. This study aims to evaluate the effectiveness and safety of alpha-1-antitrypsin (AAT). In the study, the results of five SR-aGVHD patients received AAT evaluated. Complete response was seen 2 of four patients with gastrointestinal (GI) aGVHD, partial response in one GI and one liver aGVHD. The overall response rate was 80%. AAT is an effective and safe treatment option in SR-aGVHD.

Pretransplant Consolidation Therapies Improve the Outcome of Myeloablative Allogeneic Transplantation in Adults with Ph-negative Acute Lymphoblastic Leukemia.

BACKROUND AND AIM: The benefit of pre-transplant consolidation in patients with acute lymphoblastic leukemia (ALL) who achieved first complete remission (CR1) has not yet been clearly demonstrated. Here, we aimed to investigate the relationship between the treatments received before transplantation and transplant outcome in Ph-ALL patients who underwent myeloablative allo-HSCT in CR1. PATIENTS AND METHODS: A total of 55, 32 (58.2%) men and 23 (41.8%) women, who underwent allo-HSCT with the diagnosis of Ph-ALL were evaluated retrospectively. All patients underwent to allo-HSCT with myeloablative conditioning regimen in the 1st CR from the available donor. RESULTS: In patients who received >2 consolidation, the 2-year and 3-year OS was 69% and 65%, respectively, while the 2-year and 3-year OS was 39% and 26%, respectively, in those who received < 2 consolidation (P =.03). RFS was similar in both groups (P = .8). One year- NRM was found 28% in patients who received ≥ 2 consolidations, and 37% in patients who received <2 consolidation (P =.06). L-asparaginase, high dose methotrexate, and cranial treatments given before transplantation had no effect on transplant outcomes (P > .05). CONCLUSION: Contrary to the belief that pre-transplant consolidation is not beneficial in ALL patients who proceed with allo-HCST in CR1, our results showed that consolidation treatments reduce NRM and improve the survival.

Allogeneic stem cell transplantation for relapsed primary central nervous system lymphoma: Is it feasible?

Primary central nervous system lymphoma (PCNSL), has an aggressive course and in untreated patients median survival is limited to three months. For relapsed PCNSL, the treatment options are few and results are usually unsatisfactory. Allogeneic Hematopoietic Stem Cell Transplantation (allo-HCT) has been widely used for treatment of relapsed/refractory NHL patients. However there are limited data whether graft versus lymphoma effect can work in PCNSL patients. Here, we present a relapsed refractory PCNSL case treated by allo-HCT.