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Renal impairment (RI) is one of the multiple myeloma (MM)-defining events for initiating therapy. After induction therapy, high-dose chemotherapy followed by autologous peripheral blood stem cell transplant (ASCT) remains the standard of care for transplant-eligible patients with MM. According to the International Myeloma Working Group (IMWG), the organ criterion for kidney damage is defined by a serum creatinine concentration (CrC)2 mg/dL or estimated glomerular filtration rate (eGFR) 40 mL/min. In this long-term study, we evaluated the impact of CrC and eGFR calculated by the Modification of Diet in Renal Disease equation on progression-free and overall survival using a lower threshold than the IMWG criteria.We studied the longitudinal outcomes as measured by progression-free survival and overall survival in 59 transplant-eligible patients with MM: 38 patients with normal renal function and 21 patients with RI defined as a CrC higher than upper limit of normal (≥ 1.1 mg/dL), eGFR 60 mL/min, treated with ASCT from 1998 to 2004.The risk of disease progression and death following ASCT increased by 16.5% (P = .005) and 19% (P .0009) per 1 mg/dL of CrC, respectively. The thresholds for the association of renal insufficiency and negative outcomes were CrC1.4 mg/dL and eGFR 55mL/min.We observed a negative correlation between minimal renal insufficiency and long-term outcomes. Management of patients with even marginally increased CrC and/or decreased eGFR not fulfilling IMWG RI criteria requires more concentrated effort to reverse even minimal renal insufficiency.

Background Multiple myeloma (MM) has become a chronic disease in majority of patients, and remission consolidation with autologous hematopoietic stem cell transplant (ASCT) remains the backbone of treatment in transplant-eligible patients. Objective The aim of this multicenter cross-sectional nationwide retrospective study was to evaluate the epidemiology, etiology, and outcome of infections in patients with MM undergoing ASCT in 13 Polish transplant centers, carried out on behalf of the Infectious Complications Study Group of the Polish Adult Leukemia Group. Methods A total number of consecutive 1374 patients with MM treated in Polish adult transplant centers from 2012 to 2014 were followed for infectious complications up to day +100 after ASCT in nationwide study. Results Altogether 490 infection episodes in 336 patients (49% male, aged 21-72 years) were reported, including 145 episodes of neutropenic fever (103 patients) and 34 episodes of clinically documented infections (CDIs) (27 patients). Among microbiologically confirmed infections there were 251 episodes of bacterial infections (180 patients), 42 episodes of fungal infections (38 patients), and 18 episodes of viral infections (17 patients). The overall incidence of infections reached 13.1% for bacterial, 3.6% for fungal, and 1.3% for viral infections. There were 16 cases of infection-related deaths after ASCT (1.2%). The mortality risk factors included multidrug-resistant bacteria etiology (odds ratio [OR], 3.5; P = .033), coexistence of bacterial and fungal infection (OR, 6.3; P = .002), and CDI (OR, 5.5; P = .007). Conclusion ASCT in patients with MM was connected with low risk of life-threatening infections. However, multidrug-resistant bacteria bacterial etiology, mixed etiology, and CDI increased the risk of fatal outcome.

Background Primary refractory acute myeloid leukemia (AML) is associated with dismal prognosis. No standard treatment options are available, and it remains an unmet clinical need. Here, we report a case of a tandem allogeneic hematopoietic stem cell transplantation (allo-HSCT) performed in a patient who did not achieve remission after 2 courses of induction chemotherapy. Methods Case report The treatment was approved by the Bioethical Commission of the Medical University of Warsaw and was performed in accordance with the Declaration of Helsinki. The patient gave informed consent. Results A 41-year-old woman was diagnosed with AML, high cytogenetic risk, with concomitant skin and central nervous system involvement, bone marrow necrosis, and hemophagocytic lymphohistiocytosis. She received “3+7” induction and HAM (cytarabine, mitoxantrone) reinduction, after which she did not achieve remission and hematopoietic recovery. Tandem allo-HSCT was performed from the same HLA-identical brother---the first after reduced intensity conditioning (cladribine, cytarabine, mitoxantrone, melphalan) and the second after myeloablative conditioning (BuCy--busulphan, cyclophosphamide). The patient obtained complete remission after the first allo-HSCT and remains disease-free after the second for 5 years Conclusion Tandem allo-HSCT may be a treatment option for primary refractory AML.

Hematopoietic stem cell transplantation (HSCT) patients can suffer from various musculoskeletal problems resulting in long-term functional incapacity. Physical therapy (PT), as a part of the healthcare team, has been historically advocated for regaining functional capacity and improving quality of life post-HSCT. Because of the nature of this condition and the burden of post-transplant complications, this patient group requires a unique approach toward their rehabilitation that takes into account their complex musculoskeletal presentation ranging from fascia, muscle, tendons, bones, and ligaments. However, to our knowledge there is no universal standardized PT protocol or pathway to help guide rehab specialists to achieve optimal gains for this patient group, and anecdotal evidence suggests that these patients do not always receive the PT care they require. Hence, in collaboration with the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation, the Survivorship Special Interest Group of the American Society of Blood and Marrow Transplantation, and the Quality of Life Committee of the Eastern Mediterranean Blood and Marrow Transplantation, herein the Physical Therapy Association for Graft Versus Host Disease provides a brief review on role of PT in mitigating musculoskeletal complications in HSCT patients and makes evidence-based recommendations for incorporation of PT into routine HSCT care. ispartof: Biol Blood Marrow Transplant vol:25 issue:6 pages:e191-e198 ispartof: location:United States status: published

Ocular graft-versus-host disease (GVHD) occurs in more than one-half of patients who develop chronic GVHD after allogeneic hematopoietic cell transplantation (HCT), causing prolonged morbidity that affects activities of daily living and quality of life. Here we provide an expert review of ocular GVHD in a collaboration between transplantation physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Recent updates in ocular GVHD regarding pathophysiology, preclinical models, risk factors, prevention, screening, diagnosis, response criteria, evaluation measures, and treatment are discussed. Ocular GVHD involves at least 3 biological processes: lacrimal gland dysfunction, meibomian gland dysfunction, and corneoconjunctival inflammation. Preclinical models have identified several novel pathogenic mechanisms, including the renin angiotensin system and endoplasmic reticulum stress signaling, which can be targeted by therapeutic agents. Numerous studies have identified reliable tests for establishing diagnosis and response assessment of ocular GVHD. The efficacy of systemic and topical treatment for ocular GVHD is summarized. It is important that all health professionals caring for HCT recipients have adequate knowledge of ocular GVHD to provide optimal care.

Background There are only a few cases of pericarditis complications following allogeneic bone marrow transplantation described in the literature and there are no data available on the risk and frequency of this condition. The aim of this study was to assess the frequency of exudative pericarditis complicating chronic graft-vs-host disease in allogeneic hematopoietic cell transplant recipients. Methods Retrospective analysis involved a group of 105 patients of the Outpatient Transplantation Service of the Department of Hematology, Medical University of Warsaw, who received transplants in the years 2010–2016 and were evaluated for the years 2014–2016. In this group, 50 patients suffered from chronic graft-vs-host disease (cGVHD), including 24 with moderate or severe disease. Cardiology parameters evaluated included electrocardiography, echocardiography, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and systematic clinical follow-up. Results Pericarditis was diagnosed in 6 patients (aged 20–56 years) within 4 to 23 months after allogenic hematopoietic stem cell transplantation. All patients suffered from severe cGVHD with involvement of at least 2 organs but none had earlier history of heart disease. All patients had elevated NT-proBNP and demonstrated signs of heart insufficiency grade II or III according to the New York Heart Association. There were no major changes in electrocardiogram. Only 1 patient improved following glucocorticosteroids as monotherapy, while others required complex approaches including tacrolimus plus sirolimus, rituximab, and extracorporeal photopheresis. Conclusion Late pericarditis may occur in up to 5% of allogenic hematopoietic stem cell transplantation survivors, primarily affecting patients with moderate and severe grade cGVHD. It requires escalation of immunosuppressive treatment but usually has favorable outcome. Early diagnosis may be achieved by systematic NT-proBNP testing and periodic echocardiograph evaluation.

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and nonmalignant diseases. Despite increasing survival rates, long-term morbidity after HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction after HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction after HCT. In this review we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Finally, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae after HCT.

Introduction: Gut colonization with antibiotic-resistant bacteria (ARB) is associated with a significantly decreased overall survival in adult patients undergoing allo-HCT because of an increased treatment-related mortality. Objective: The objective of this multicenter study was the analysis of impact of gut colonization status and the use of antibiotics on development of gastro-intestinal (GI) graft-versus-host disease (GVHD) of allo-HCT in children. Methods: All consecutive patients who underwent allo-HCT over a period of three years in all pediatric HCT centers in Poland were analyzed for the impact of gut colonization on GI GVHD, with respect to standard of care including prophylaxis of infections and supportive therapy. Results: At the time of allo-HCT, 44.2% of pediatric patients were colonized by ARB. Decontamination therapy with antibiotics was applied in 78% of children. Gut decontamination prophylactic therapy with antibiotics decreased the risk of acute GI GVHD. The use of gentamicin contributed to decreased rate of GVHD, while the use of ciprofloxacin and colistin contributed to increased incidence of GVHD after allo-HCT in children. Sepsis with ARB and non-MFD transplant contributed significantly to worse survival, while neither colonization nor gut decontamination had an impact on overall survival. Conclusions: Gut decontamination therapy contributed to lower incidence of acute GI GVHD in children undergoing allo-HCT, and the use of specific antibiotics might be responsible for this effect.

There are many reports on factors predicting the outcome of PBSC (peripheral blood stem cell) mobilization, such as the donor's gender, age, weight, white blood cell count, platelets pre apheresis, LDH and iron status. Although there are reports of seasonal variation in the physiology of the human immune system and hematopoiesis there are no data that such differences play a role in the response to G-CSF in healthy hematopoietic stem cell donors. The response to G-CSF could also impact the collection results during different seasons. To assess the possible impact of seasonal variation we performed a retrospective, single-center analysis of mobilization and harvest of PBSC in 330 healthy unrelated donors. We found no significant differences in the number of CD34+ cells in peripheral blood after G-CSF mobilization and in collection results when all donors were analyzed. In the subgroup of male donors the number of CD34+ stem cells after G-CSF mobilization was higher than average in summer and autumn (p = 0.036), however, it did not translate into clinically relevant differences in stem cell harvest. We conclude that although there is possible seasonal variation in the response to G-CSF in male donors there is no impact on PBSC harvest in healthy unrelated donors.

Gut colonization by antibiotic-resistant bacteria may underlie hard-to-treat systemic infections. There is also accumulating evidence on the immunomodulatory function of gut microbiota after allogeneic stem cell transplantation (alloSCT) and its impact on graft-versus-host disease (GVHD). We investigated the epidemiology and clinical impact of gut colonization after alloSCT and retrospectively analyzed data on 107 alloSCTs performed at a single transplant center. Pretransplant microbiology screening identified colonization in 31% of cases. Colonization had a negative impact on overall survival after alloSCT in univariate (34% versus 74% at 24 months, P

Background Infections with human β-herpesviruses are common worldwide and are still frequent in patients after hematopoietic stem cell transplantation. Some data suggest that HHV-6 and HHV-7 could take part in CMV reactivation from latency and/or progression of CMV disease in immunosupressed patients. Objectives The aims of this study were: (1) to summarise retrospectively the results of β-herpesviruses DNA detection in a large group of adult allogeneic haematopoietic stem cell transplant recipients; and (2) to find a potential correlation between viruses belonging to this subfamily. Study design AlloHSCT recipients ( N =142) were examined in the early post-transplant period (median=89 days). The presence of CMV, HHV-6 and HHV-7 was confirmed through detection and quantification of viral DNA, isolated from 1679 sera samples. Results CMV DNA alone was detected in 23.9% of patients, while single HHV-6 and HHV-7 were detected in 14.8% and 9.9% of individuals, respectively. The reactivation of more than one virus was identified in 31% of analysed patients. In cases of concurrent infection, HHV-7 was detected at the same time as HHV-6, and both of them were usually reactivated before CMV. The kinetics of virus reactivation and measured viral load may suggest a potential role of HHV-6 and HHV-7 as co-factors in CMV reactivation. Conclusions The observed kinetics of virus reactivation may strongly suggest a potential role of HHV-6 and/or HHV-7 as co-factors of CMV reactivation. The co-infection with these β-herpesviruses could predispose patients after hematopoietic stem cell transplantation to a longer and more severe CMV infection.

Despite undisputed success of tyrosine kinase inhibitors in the therapy of chronic myeloid leukemia (CML), development of drug resistance and inability to cure the disease challenge clinicians and researchers. Additionally, recent reports regarding cardiovascular toxicities of second and third generation tyrosine kinase inhibitors prove that there is still a place for novel therapeutic combinations in CML. We have previously shown that statins are able to modulate activity of chemotherapeutics or antibodies used in oncology. Therefore, we decided to verify that statins are able to potentiate antileukemic activity of imatinib, still a frontline treatment of CML. Lovastatin, a cholesterol lowering drug, synergistically potentiates antileukemic activity of imatinib in cell lines and in primary CD34+ CML cells from patients in different phases of the disease, including patients resistant to imatinib with no detectable mutations. This effect is related to increased intracellular concentration of imatinib in CD34+ CML cells and cell lines measured using uptake of 14 C-labeled imatinib. Lovastatin does not influence influx but significantly inhibits efflux of imatinib mediated by ATP-binding cassette (ABC) transporters: ABCB1 and ABCG2. The addition of cholesterol completely reverses these effects. Statins do not affect expression of ABCB1 and ABCG2 genes. The effects are drug-class specific, as observed with other statins. Our results suggest that statins may offer a valuable addition to imatinib in a select group of CML patients.

Patriarca et al. recently showed that gut colonization or infection by multidrug-resistant gram-negative bacteria in patients undergoing allogeneic hematopoietic stem cell transplantation has no influence on the rates and severity of acute graft-versus-host disease. On the contrary, we analyzed 145 consecutive adult patients and found that gut colonization represents an independent risk factor for gastrointestinal graft-versus-host disease. In the letter to the editor we show our data and discuss possible reasons for discrepancies between these two studies.