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.

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 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.

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.

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.

Is cytomegalovirus a risk factor for haemorrhagic cystitis in allogeneic haematopoietic stem cell transplantation recipients?

BACKGROUND: Haemorrhagic cystitis (HC) is usually a serious complication in allogeneic haematopoietic stem cell transplantation (allo-HSCT) recipients. In this study, our aim was to define risk factors and outcomes for patients with HC in an allo-HSCT setting. METHODS: We retrospectively evaluated 249 allo-HSCTs performed between 2011 and 2016 in our centre. RESULTS: HC was diagnosed in 98 patients (39%) at a median of 119 days (range 5-580) and 91 (93%) of the patients had late onset disease. In univariate analysis, HC was related to cytomegalovirus (CMV) reactivation (P<0.001) and BK viraemia (P<0.001); in multivariate analysis, the presence of CMV reactivation was determined to be an independent risk factor (odds ratio: 22.1; 95% CI 1.73, 282.44; P=0.017). There was no association detected between acute graft versus host disease and patients diagnosed with HC within 100 days of transplant. HC was significantly increased by the presence of myelo-ablative conditioning (odds ratio: 31.28; 95% CI 3.98, 246.87; P=0.001) and BK viraemia (odds ratio: 3.93; 95% Cl 1.10, 14.05; P=0.035) in patients with HC grade II and beyond. Forced hydration was recommended in all patients with grade I HC. Patients with HC and clots were treated with continuous bladder irrigation, and 14 of 44 patients with BK viraemia received cidofovir ± ribavirin. Eight of these patients (57%) responded to treatment. Refractory HC was detected in 17 patients (17%) and resolved by a variety of procedures. CONCLUSIONS: This study suggests that CMV reactivation is associated with increased risk of HC in multivariate analysis, however, this result is not confirmed in patients with HC grade II and beyond.

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.

Upper respiratory viral infections in patients with haematological malignancies after allogeneic haematopoietic stem cell transplantation: a retrospective study.

BACKGROUND: Community respiratory viruses (CRVs) are associated with upper respiratory viral infections (URI), pneumonia or life-threatening respiratory disease in patients with allogeneic haematopoietic stem cell transplantation (allo-HSCT). Our aim is to demonstrate our URI experience related to CRVs after allo-HSCT. METHODS: From January 2013 to November 2015, 39 post allo-HSCT patients with acute URI symptoms were included in the study. We evaluated CRVs by multiplex PCR from nasopharyngeal wash and throat swabs. RESULTS: The median age of the patients was 39 (range 20-67 years). A total of 25 patients (64%) had viral panel positivity at a median 140 days post-transplant (range 3-617 days). The most common agents detected were respiratory syncytial virus (32%) and parainfluenza (32%). The patients with viral panel positivity had significantly lower lymphocyte count (1.05×109/l versus 3.09×109/l; P=0.013). During follow-up, 20 patients (80%) were diagnosed with pneumonia. Patients with concurrent bacterial or fungal infections were more likely to have pneumonia (100% versus 68%; P=0.023). 10 patients (40%) died due to pneumonia and related complications. Lower lymphocyte counts and higher C-reactive protein levels at the time of viral panel positivity were risk factors for mortality (1.5×109/l versus 0.39×109/l, P=0.007; 74.2 versus 199.7, P=0.006). CONCLUSIONS: The viral panel was positive in 64% of patients with acute URI symptoms. Lower lymphocyte count was detected in CRV-positive patients. The onset of concomitant bacterial or fungal infections increased the risk of lower respiratory infection disease. Indeed, prospective studies should be designed for risks and outcomes of CRVs in allo-HSCT recipients.

Treatment with methotrexate, rituximab, and cytosine arabinoside followed by autologous stem cell transplantation in primary central nervous system lymphoma: A single-center experience.

OBJECTIVE/BACKGROUND: Primary central nervous system lymphoma (PCNSL) is associated with worst prognosis compared with other aggressive non-Hodgkin's lymphomas. However, recent trials have demonstrated that long-term progression-free survival can be achieved by immunochemotherapy. Our goal is to present our experience in aggressive PCNSL in this study. METHODS: We retrospectively evaluated the clinical features and management of 13 PCNSL patients who were diagnosed and treated between 2006 and 2015. RESULTS: Nine patients received rituximab (R) 375mg/m2/day on Day 1, methotrexate (MTX) 3.5g/m2/day and cytosine arabinoside (ARA-C) 4.4g/m2/day on Day 2, as well as ARA-C 4.4g/m2/day on Day 3 every 28days, and underwent autologous stem cell transplantation. Two patients received procarbazine instead of ARA-C. One patient relapsed, and allogeneic hematopoietic stem cell transplantation was performed. All nine patients are followed in complete remission. Two of 13 patients received one course of MTX and 36-45Gy radiotherapy and died. One patient with renal transplantation had progressive disease and died. Grade 3-4 hematological toxicity was detected in 11 (85%), Grade 3-4 mucositis in 11 (85%), and febrile neutropenia in 12 (92%) patients. The median overall survival in the R-MTX-ARA-C/procarbazine group was 28±16months. CONCLUSION: R-MTX-ARA-C followed by autologous stem cell transplantation seems a promising strategy with high response rates in PCNSL.

Allogeneic hematopoietic stem cell transplantation for refractory mycosis fungoides (MF) and Sezary syndrome (SS).

Cutaneous T cell lymphoma is a heterogeneous group of lymphoproliferative disorders with different clinical behavior and prognosis in which malignant T cells accumulate in the skin. In the relapsed/refractory stage, treatment strategy varies depending on clinical perspective. We retrospectively evaluated advanced stage relapse or refractory mycosis fungoides and Sezary syndrome patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our hospital. The overall response rate was 25%, while the disease progressed and relapsed after transplant in 38% of patients. Allo-HSCT may be a reasonable treatment option in the relapsed/refractory stage.

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.

Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in Daily Practice: A Multicenter Experience.

BACKGROUND: The prognosis of Philadelphia-positive acute lymphoblastic leukemia (Ph(+) ALL) is generally poor. Currently, allogeneic hematopoietic cell transplantation (allo-HCT) is the only accepted therapy with curative potential. PATIENTS AND METHODS: Herein, we report our multicenter, retrospective experience with 46 (23 female; 23 male) Ph(+) ALL patients, who were treated off-study between 2005 and 2012. RESULTS: The median age of the patients was 46 years (range, 19-73 years). During induction, 30 (65%), 13 (28%), and 3 (7%) patients received tyrosine kinase inhibitors (TKIs) concurrent with chemotherapy (TKIs/chemotherapy), chemotherapy only, and TKIs only, respectively. Following induction, rates of complete remission (CR) of the study population were 85% (n = 39). CR rate in patients receiving TKIs during induction (n = 33) was significantly higher compared with patients who received chemotherapy only (n = 13; P = .011). Taking TKIs during induction significantly reduced induction mortality (3.3% vs. 38%; P = .01). Allo-HCT was performed subsequently in 21 (46%) patients. More patients who received TKIs with or without chemotherapy (19/33; 58%) during induction were able to undergo to allo-HCT compared with patients who received chemotherapy only (2/13; 15%; P = .005). Median overall survival of patients who were treated with TKIs during induction and received allo-HCT (not reached; NR) was significantly prolonged compared with patients who received allo-HCT but without TKIs during induction (23.2 months) and to the rest of the cohort (21.2 months; P = .019). CONCLUSIONS: Current state-of-the art management of Ph(+) ALL in real-life seems to be incorporation of TKIs to chemotherapy regimens and proceeding to allo-HCT, whenever possible.

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.

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.

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.