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Objectives: Limited data is available on HCV directly acting agents (DAAs) in haematopoietic stem cell transplant (HSCT) recipients. This study aimed at reporting the characteristics, treatment practices and treatment efficacy in HSCT recipients with chronic HCV.Methods: Prospective observational study from EBMT Infectious Diseases Working Party (IDWP). Patients with chronic HCV infection were included.Results: Between 12/2015 and 07/2018, 45 patients were included: male in 53%; median age 49 years (range, 8-75); acute leukaemia in 48.9%, lymphoma in 17.7%, non-malignant disorders in 22.3%; allogeneic HSCT in 84%; 77.8% no immunosuppressive treatment. Genotypes 1, 2, 3 and 4 were detected in 54.5%, 20.5%, 13.6% and 11.4%, respectively; advanced fibrosis in 40%, including cirrhosis in 11.4%. Overall, 37 (82.2%) patients received DAAs, at a median of 8.4 years after HSCT (16.2% within 6 months from HSCT). Sofosbuvir-based treatment was given to 62.2%. Thirty-five patients completed planned treatment course, with sustained virological response (SVR) of 89.1%, and 94.3% (33/35) in those who completed the treatment. Side effects possibly related to DAAs were reported in 5 (14%) and did not require treatment discontinuation.Conclusions: DAAs treatment was effective, safe and feasible in this cohort of mainly allogeneic HSCT recipients with mild/moderate liver damage. [ABSTRACT FROM AUTHOR]

Recent years have brought significant breakthroughs in the understanding of tumor biology, related to discovery of cancer stem cells (CSCs) in acute myelogenous leukemia as well as in a number of solid tumors. This finding revealed that not all tumor cells are able to divide indefinitely, and that the bulk of tumor cells are expanded because of divisions and differentiation of CSC fraction. Although the CSCs identified in acute leukemia have a phenotype of early hematopoietic progenitors, it seems that CSCs in multiple myeloma (MM) may resemble the memory B cell fraction. Previous studies in patients with MM have documented the existence of cells without plasma cell characteristics expressing MM-type immunoglobulin genes—so-called “clonotypic” B cells. These cells have been characterized functionally and phenotypically as chemoresistant recirculating B cells. They have been found to self-renew and to be capable of initiating MM growth in immunocompromised animals. Controversy exists as to whether these cells truly belong to an MM clone, however; they may represent only the remaining clones of premalignant B cells. The identification of MM stem cells responsible for the recurrence of MM is of primary importance in designing targeted therapies to definitely cure this disease. This article summarizes the current state of knowledge on these hypothetical “MM stem cells.” [Copyright &y& Elsevier]

• Anemia is relatively common in patients after hematopoietic stem cell transplantation as well as in kidney transplant recipients. • Chronic kidney disease remains a significant complication of hematopoietic stem cell transplantation, affecting the outcome of transplant patients. • In chronic kidney disease and coexistent anemia, nephrology referral is to be considered to optimize therapy, including nephroprotection. Hematopoietic stem cell transplant (HSCT) is the treatment of choice in various hematologic diseases, and kidney transplantation (KTx) is the best therapy for end-stage kidney disease. Chronic kidney disease (CKD) occurs relatively often after both types of transplantations. Anemia after both HSCT and KTx may be due to CKD and other reasons. This study aimed to assess the prevalence of anemia to CKD in 156 prevalent patients after HSCT and 80 after KTx. According to the World Health Organization's definition (hemoglobin <13 g/dL for men and <12 g/dL for women), the prevalence of anemia in the studied cohort after HSCT was 13% in women and 35% in men and for those after KTx, it was29% in men and 11%. Anemia in KTx was found in 46% of patients, whereas CKD was present in 53%. After HSCT, anemia was associated with CKD in 56% of women and 17% of men. In KTx, anemia and CKD was diagnosed in 21% of patients. Patients with anemia after KTx had significantly lower glomerular filtration rate (GFR), hemoglobin, and significantly higher creatinine levels. Age was related to the estimated GFR (eGFR; r = –0.39, P <.001) in patients who underwent HSCT and had anemia. In patients without anemia, age was negatively related to eGFR (r = –0.56, P <.001) and the hemoglobin-to-platelet count (r = 0.62, P <.001). In KTx, hemoglobin was related to eGFR (r = 0.35, P <.001), and age was related to eGFR (r = –0.20, P <.05). The type of induction therapy immunosuppressive regimen (anti-thymocyte globulin vs basiliximab vs no induction) did not affect the prevalence of anemia in the KTx population studied. Anemia is relatively common in CKD after HSCT. In both CKD and coexistent anemia, nephrology referral is to be considered to optimize therapy, including nephroprotection. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

• Kidney damage remains a significant complication of HCT affecting the mortality of transplant patients. • Identifying risk factors and markers of kidney injury, understanding the causes and appropriate treatment of kidney injury are important to the safety of the HSCT procedure. • RBP4 was significantly higher in patients after HSCT when compared to healthy volunteers. • Nephroprotective strategies are key to prevent chronic kidney disease. Hematopoietic stem cell transplantation could be complicated by acute kidney injury and chronic kidney disease. It may be due to either previous chemotherapy or exposure to a variety of nephrotoxic drug or other causes. The aim of the study was to assess biomarkers of kidney injury in patients at least 3 months after hematopoetic stem cell transplantation (HSCT) under ambulatory care of the Hematology, Transplantation and Internal Medicine Department. We studied 80 prevalent patients after allogeneic HSCT and 32 healthy volunteers to obtain normal ranges of biomarkers. In this cross-sectional study we assessed retinol-binding protein 4 (RBP4), a biomarker of kidney injury in urine using commercially available assays. It was significantly higher in patients after HSCT when compared to healthy volunteers. When we divided patients according to kidney function (below and over 60 mL/min/1.72 m2), we found that the concentration of RBP4 was significantly higher in 23 patients with chronic kidney disease stage 3 compared to patients with estimated glomerular filtration (eGFR) over 60 mL/min/1.72 m2. In univariate correlations RBP4 was positively related to serum creatinine (r = 0.34, P <.01) and inversely to eGFR (r = −0.20, P <.05). Patients after allogeneic HSCT despite normal or near normal kidney function show evidence of kidney injury. [ABSTRACT FROM AUTHOR]

Despite new treatment strategies, graft-versus-host disease (GvHD) remains a formidable complication after allogeneic hematopoietic stem cell transplantation (HSCT). This study aimed to investigate the impact of polymorphisms and expression of MICA and NKG2D receptor on the development of GvHD in allogeneic HSCT recipients. Soluble MICA (sMICA) concentration was measured in serum collected 30 days after transplantation and the genetic variability of MICA and NKG2D genes was evaluated. The frequency of NKG2D+NK cells was determined by flow cytometry before and (21, 30, 60 and 90 days) after transplantation. Recipients with acute GvHD grades II-IV carried the NKG2D rs1049174 C allele more frequently than controls or patients with no or mild disease. Patients with chronic GvHD had higher frequency of NKG2D expressing NK cells posttransplant, reflecting increased activity of their NK cells. Although no direct relationship between MICA SNPs and GvHD were observed, the presence of MICA rs1051792 GG genotype correlated with elevated sMICA levels and increased serum level of sMICA was associated with higher risk of chronic GvHD. Our findings suggest that sMICA concentration may serve as a potential biomarker for chronic GvHD and emphasize the impact of genetic variability of NKG2D and its surface expression on the HSCT outcome. [ABSTRACT FROM AUTHOR]

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 14C-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. [ABSTRACT FROM AUTHOR]

• Kidney damage remains a significant complication of hematopoietic stem cell transplantation (HSCT), affecting the mortality of transplant patients. • Identifying risk factors and markers of kidney injury and understanding the causes and appropriate treatment of kidney injury are important to the safety of HSCT. • All of the biomarkers studied were significantly higher in patients after hematopoietic stem cell transplant when compared with healthy volunteers. • Nephroprotective strategies are key to preventing chronic kidney disease. Kidney function in patients undergoing hematopoietic stem cell transplant (HSCT) is frequently worsened by previous chemotherapy and exposure to a variety of nephrotoxic drugs. The aim of the study was to assess biomarkers of kidney injury in patients at least 3 months after HSCT under ambulatory care of the Hematology, Oncology and Internal Medicine Department. We studied 80 prevalent patients after allogeneic HSCT and 32 healthy volunteers to obtain normal ranges for biomarkers. In this cross-sectional study, the following biomarkers of kidney injury in urine were evaluated using commercially available assays: IGFBP7 and TIMP2 , netrin-1, and semaphorin A2. All of the biomarkers studied were significantly higher in patients after HSCT compared with the healthy volunteers. When we divided patients according to kidney function (below and over 60 mL/min/1.73m2), we found that only concentration of IGFBP7 was significantly higher in 23 patients with chronic kidney disease (CKD) stage 3 relative to patients with an estimated glomerular filtration rate (eGFR) over 60 mL/min/1.73m2. All biomarkers in both subgroups of patients with eGFRs below and over 60 mL/min/1.73m2 were significantly higher relative to healthy volunteers. In univariate correlations, semaphorin A2 was related to netrin-1 (r = 0.47, P <.001), IGFBP7 (r = 0.35, P <.01), and TIMP2 (r = 0.32, P <.01), whereas IGFBP7 was positively related to serum creatinine (r = 0.38, P <.001) and inversely to eGFR (r = -0.36, P <.001). Patients after allogeneic HSCT, despite normal or near normal kidney function, show evidence of kidney injury. [ABSTRACT FROM AUTHOR]

• Kidney damage remains significant complication of hematopoietic cell transplant affecting the mortality of transplant recipients. • Chronic graft-vs-host disease is common, and serious complication of allogeneic hematopoietic cell transplant occurs in about 60% to 80% of patients. • A total of 30% to 60% of patients with acute graft-vs-host disease progressed to chronic disease, with about 20% requiring lifelong immunosuppressive therapy that had toxic effects on kidney function. • It is very important to consider a comprehensive approach to develop and update treatment regimens and constantly monitor drug levels. Hematopoietic stem cell transplant (HSCT) is used in advanced hematologic diseases to restart the immune system. Kidney damage remains significant complication of hematopoietic cell transplant (HCT) affecting the mortality of transplant recipients. The aim of the study was to assess the advancement of chronic kidney disease (CKD) in patients after HSCT. We studied 150 patients who underwent allo-HSCT treatment in our center in years 1995 to 2020 because of acute myeloid leukemia in 47% of patients, acute lymphoblastic leukemia in 19%, and lymphoma in 32%. The mean age of patients with acute leukemia is 48 years (including acute myeloid leukemia it is 47 years, and including acute lymphoblastic leukemia it is 32 years). The mean age of lymphoma patients is 34 years. We studied the prevalence and stages of CKD. CKD stage 3a and 3b was found in 24.6%. None of the patients studied had CKD stage 4 or 5. In patients after HSCT because of both acute myeloid leukemia and acute lymphoblastic leukemia, CKD stage 3a was found in 19% and stage 3b in 7.3%. Estimated glomerular filtration rate (eGFR) >90 mL/min/1.73 m2, was found in 36.8% of this population, whereas eGFR between 90 and 60 mL/min/1.73 m2 was observed in 36.8%. In patients with lymphoma who underwent HSCT, CKD stage 3a was found in 18%, while CKD stage 3b was diagnosed in 27% of the patients. An eGFR >90 mL/min/1.73 m2, was found in 27% of this population, whereas eGFR between 90 and 60 mL/min/1.73 m2 was observed in 27% of patients. The categorization of patients according to the underlying disease is important because other drugs are used in therapy of conditioning before HCT. CKD in patients after allogeneic HSCT is common, although advanced stages were not observed, probably because the age of the population studied was not advanced. CKD in these vulnerable patients may be because of prior chemotherapy, conditioning regimen, post-HSCT calcineurin therapy, and other possible nephrotoxic drugs. [ABSTRACT FROM AUTHOR]

A 42-year-old woman received a simultaneous pancreas and kidney transplantation (SPK). Immunosuppression consisted of tacrolimus modified release, prednisone, mycophenolate mofetil (MMF), and thymoglobulin as induction. The function of both grafts was good. Eight months after SPK, the patient suffered from weakness and arthralgia. Normocytic anemia with reticulocytopenia was revealed. In a bone marrow examination, giant pronormoblasts were found. Immunohistochemical staining of bone marrow and serum examination were positive for Parvovirus B19 (Parvo B19) confirming diagnosis of pure red cell aplasia (PRCA).The treatment consisted of MMF withdrawal, red-cell transfusions, immunoglobulins subcutaneously (SCIg) and immunosuppression reduction. Rapid improvement was observed with the rise of reticulocyte count and hemoglobin. Two months after the achievement of remission, the low dose of everolimus was added considering the high risk of rejection and antiviral potential of mTOR inhibitors. Three months later, PRCA relapsed. Retherapy with SCIg was still effective. Subsequent SCIg was supplemented due to low reticulocyte count and recurrent herpes zoster. The replication of Parvo B19 was persistent (serum qualitative test). Everolimus was withdrawn after 9 months of therapy due to the recurrence of PRCA and serious infections. The observation period after PRCA diagnosis lasts for 15 months. The patient is in good condition with no anemia and excellent grafts function. In conclusion, pure red cell aplasia related to Parvo B19 infection should be considered in transplant recipients with normocytic anemia and reticulocytopenia. The treatment with immunoglobulin G and immunosuppression reduction is an effective therapy. The role of everolimus in Parvo B19 infection requires future studies. [ABSTRACT FROM AUTHOR]

• Low bone mineral density (BMD) is frequent after hematopoietic cell transplantation (HCT). • There is inconsistency of practice in relation to guidelines on BMD after HCT. • There is a lack of familiarity with BMD guidelines among European HCT centers. Reduced bone mineral density (BMD) is a well-recognized complication of hematopoietic cell transplantation (HCT), with significant drops in BMD occurring within the first 12 months after HCT. Guidance on identifying and managing this complication is available in several published guidelines. In this study, we investigated current practices in the investigation and management of low BMD in centers registered with the European Society for Blood and Marrow Transplantation (EBMT). A questionnaire about bone health was sent to all registered centers, and responses were received from 99 centers in 25 countries (52%) currently registered with the EBMT. Our data highlight considerable heterogeneity in practices across European centers in relation to investigations, management, and use of guidelines. Our data demonstrate the need for better dissemination and implementation of existing guidelines and also for the development of multidisciplinary guidelines with input from all relevant stakeholders. [ABSTRACT FROM AUTHOR]

• The 3-year overall survival probability was 88.9% in patients with classic paroxysmal nocturnal hemoglobinuria (cPNH) and 85.1% in those with bone marrow failure-associated PNH (BMF/PNH). • The PNH clone was reduced to <1 in 96% of patients with cPNH and in 95% of patients with BMF/PNH. • The incidence of acute graft-versus-host disease (GVHD) grade II-IV was 23%, and that of extensive chronic GVHD at 1 year was 9%. • Reduced-toxicity conditioning with treosulfan was safe and effective. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the sole potential cure for paroxysmal nocturnal hemoglobinuria (PNH); however, the data on its utility in PNH are limited. This retrospective analysis of patients with PNH who underwent allo-HSCT in 11 Polish centers between 2002 and 2016 comprised 78 patients with PHN, including 27 with classic PNH (cPNH) and 51 with bone marrow failure-associated PNH (BMF/PNH). The cohort was 59% male, with a median age of 29 years (range, 12 to 65 years). There was a history of thrombosis in 12% and a history of hemolysis in 81%, and 92% required erythrocyte transfusions before undergoing allo-HSCT. No patient received eculizumab, and 26% received immunosuppressive treatment. The median time from diagnosis to allo-HSCT was 12 months (range, 1 to 127 months). Almost all patients (94%) received reduced-toxicity conditioning, 66% with treosulfan. The stem cell source was peripheral blood in 72% and an identical sibling donor in 24%. Engraftment occurred in 96% of the patients. With a median follow-up of 5.1 years in patients with cPNH and 3.2 years in patients with BMF/PNH, 3-year overall survival (OS) was 88.9% in the former and 85.1% in the latter (P = not significant [NS]). The 3-year OS for patients with/without thrombosis was 50%/92% (P = NS) in the cPNH group and 83.3%/85.3% (P = NS) in the BMF/PNH group. The 3-year OS for in the BMF/PNH patients with/without hemolysis was 93.9%/62.9% (hazard ratio,.13; P =.016). No other factors impacted OS. After allo-HSCT, the frequency of the PNH clone was reduced to 0%, <1%, and <2.4% in 48%, 48%, and 4% of cPNH patients and in 84%, 11%, and 5% of BMF/PNH patients, respectively. The frequency of acute graft-versus-host disease (GVHD) grade II-IV was 23%, and the cumulative 1-year incidence of extensive chronic GVHD was 10.8% in the BMF/PNH group and 3.7% in the cPNH group. Allo-HSCT is a valid option for PNH patients, effectively eliminating the PNH clone with satisfactory overall survival and acceptable toxicity. Reduced-toxicity conditioning with treosulfan is effective and safe in patients with cPNH and BMF/PNH. [ABSTRACT FROM AUTHOR]

Objectives: We performed a systematic review of health state utility values (HSUVs) obtained using the EQ-5D questionnaire for patients with hematologic malignancies.Methods: The following databases were searched up to September 2018: MEDLINE, EMBASE, The Cochrane Library, and the EQ-5D publications database on the EuroQol website. Additional references were extracted from reviewed articles. Only studies presenting EQ-Index results were incorporated. In view of the heterogeneity across the included publications, we limited ourselves to a narrative synthesis of original HSUVs found.Results: Fifty-nine studies (described in 63 articles) met the inclusion criteria. Data from 21 635 respondents provided 796 HSUV estimates for hematologic malignancy patients. EQ-Index scores ranged from -0.025 to 0.980. The most represented area was multiple myeloma (4 studies, 11 112 patients, and 249 HSUVs). In clinical areas such as chronic myeloid leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and mantle cell lymphoma, we described over 50 health utilities in each. In contrast, we identified only 13 HSUVs (based on 4 studies and the data of 166 patients) for Hodgkin lymphoma. Areas without EQ-5D-based health utilities comprised: polycythemia vera, primary myelofibrosis, essential thrombocythemia, mastocytosis, myeloid sarcoma, chronic myelomonocytic, eosinophilic leukemia, and neutrophilic leukemia.Conclusions: There is a wide range of HSUVs available for hematologic cancer patients with different indications. The review provides a catalog of utility values for use in cost-effectiveness models for hematologic malignancies. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the sole curative option for many hematological malignancies and other diseases. Nevertheless, its application is limited due to the risk of life-threatening complications, mainly graft-versus-host disease (GVHD). Currently, in clinical practice, the risk of developing GVHD is estimated for every patient based on factors related to the donor and the host. In our prospective, observational study, we analyzed serum from 38 patients undergoing allo-HCT at our institution. We compared the metabolic profiles of patients who developed acute GVHD (aGVHD) with those without such complication by identification and comparison of metabolites masses on the XCMS platform. We observed that patients diagnosed with aGVHD had different metabolic profiles compared to the remaining patients and this alteration was noticeable already 7 days before the procedure. We identified dysregulated metabolites involved in bile acid transformation and cholesterol synthesis. Our study of the untargeted metabolome in allo-HCT recipients has revealed a potential link between lipid metabolism, specifically involving bile acid transformation and cholesterol synthesis, and the development of aGVHD. This finding might be an important indication for future research focused on understanding GVHD development, discovering prediction models, and investigating possible prophylactic interventions. • Patients diagnosed with aGVHD have different metabolic profiles compared to the patients without aGVHD. • Metabolic changes are observed already in the pre-transplant period. • Identified dysregulated metabolites are involved in bile acid transformation and cholesterol synthesis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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 Tandem allo-HSCT may be a treatment option for primary refractory AML. • Primary refractory acute myeloid leukemia is associated with a dismal prognosis. • As no standard treatment options are available, it remains an unmet clinical need. • Tandem allogeneic hematopoietic stem cell transplantation may be an option. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 < .001) and multivariate (hazard ratio, 3.53; 95% confidence interval, 1.71 to 7.28; P < .001) analyses. Nonrelapse mortality was significantly higher in colonized than in noncolonized patients (42% versus 11% at 24 months, P = .001). Colonized patients more frequently experienced bacteremia (48% versus 24%, P = .01), and more deaths were attributable to infectious causes in the colonized group (42% versus 11% of patients and 67% versus 29% of deaths, P < .05). We observed a significantly higher incidence of grades II to IV acute GVHD in colonized than in noncolonized patients (42% versus 23%, P < .05), especially involving the gastrointestinal system (33% versus 13.5%, P = .07). In summary, we determined that gut colonization by antibiotic-resistant bacteria decreases the overall survival of patients undergoing alloSCT by increasing nonrelapse mortality and the incidences of systemic infection and acute GVHD. [ABSTRACT FROM AUTHOR]

Anti-CD20 monoclonal antibodies (mAbs) are successfully used in the management of non-Hodgkin lymphomas and chronic lymphocytic leukemia. We have reported previously that statins induce conformational changes in CD20 molecules and impair rituximab-mediated complement-dependent cytotoxicity. Here we investigated in more detail the influence of farnesyltransferase inhibitors (FTIs) on CD20 expression and antitumor activity of anti-CD20 mAbs. Among all FTIs studied, L-744,832 had the most significant influence on CD20 levels. It significantly increased rituximab-mediated complement- dependent cytotoxicity against primary tumor cells isolated from patients with non-Hodgkin lymphomas or chronic lymphocytic leukemia and increased CD20 expression in the majority of primary lymphoma/leukemia cells. Incubation of Raji cells with L-744,832 led to up-regulation of CD20 at mRNA and protein levels. Chromatin immunoprecipitation assay revealed that inhibition of farnesyltransferase activity was associated with increased binding of PU.1 and Oct-2 to the CD20 promoter sequences. These studies indicate that CD20 expression can be modulated by FTIs. The combination of FTIs with anti-CD20 mAbs is a promising therapeutic approach, and its efficacy should be examined in patients with B-cell tumors. [ABSTRACT FROM AUTHOR]

Fludarabine and lenalidomide are essential drugs in the front-line treatment of non-Hodgkin lymphoma (NHL) and multiple myeloma (MM), respectively. Data suggests that fludarabine and lenalidomide therapy may have a deleterious effect on stem cell mobilization. In the European compassionate use program, 48 patients (median age 57 years) previously treated with fludarabine (median 5 cycles; range: 1-7 cycles) were given plerixafor plus granulocyte colony-stimulating factor (G-CSF) for remobilization following a primary mobilization attempt. The overall median number of CD34+ cells collected was 2.3 × 106/kg (range: 0.3-13.4). The minimum required number of CD34+ cells (≥2.0 × 106/kg) was collected from 58% of patients in a median of 2 days. Thirty-five patients (median age = 57 years) previously treated with lenalidomide (median 5 cycles; range: 1-10 cycles) were given plerixafor plus G-CSF for remobilization. The overall median number of CD34+ cells collected was 3.4 × 106/kg (range: 1.1-14.8). The minimum required number of CD34+ cells (≥2.0 × 106 per kg) was collected from 69% of patients in a median of 2 days. In conclusion, salvage mobilization with plerixafor plus G-CSF is successful in the majority of patients with MM previously treated with lenalidomide. In fludarabine-exposed patients, only 58% of patients will achieve successful salvage mobilization with plerixafor plus G-CSF, suggesting the need for novel mobilization regimens algorithms in this subgroup of patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]