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Mantle cell lymphoma (MCL) is a non-Hodgkin's lymphoma with an often aggressive course, incurable by chemotherapy. Consolidation with high-dose therapy and autologous stem cell transplantation (autoSCT) has a low transplant-related mortality but does not lead to a survival plateau. Allogeneic stem cell transplantation (alloSCT) is associated with a higher early mortality, but can cure MCL. To investigate alloSCT for therapy of MCL, we conducted two prospective trials for de novo MCL (OSHO#74) and for relapsed or refractory MCL (OSHO#60). Fifteen and 24 patients were recruited, respectively. Induction was mainly R-DHAP alternating with R-CHOP. Conditioning was either Busulfan/Cyclophosphamide or Treosulfan/Fludarabin. Either HLA-identical siblings or matched-unrelated donors with not more than one mismatch were allowed. ATG was mandatory in mismatched or unrelated transplantation. Progression-free survival (PFS) was 62% and overall survival (OS) was 68% after 16.5-year follow-up. Significant differences in PFS and OS between both trials were not observed. Patients below 56 years and patients after myeloablative conditioning had a better outcome compared to patients of the corresponding groups. Nine patients have died between day +8 and 5.9 years after SCT. Data from 7 long-term surviving patients showed an excellent Quality-of-life (QoL) after alloSCT. AlloSCT for MCL delivers excellent long-term survival data. The early mortality is higher than after autoSCT; however, the survival curves after alloSCT indicate the curative potential of this therapy. AlloSCT is a standard of care for all feasible patients with refractory or relapsed MCL and should offer to selected patients with de novo MCL and a poor risk profile. For defining the position of alloSCT in the therapeutic algorithm of MCL therapy, a randomized comparison of autoSCT and alloSCT is mandatory. [ABSTRACT FROM AUTHOR]

This study was conducted in order to evaluate allogeneic stem cell transplantation (alloSCT) as consolidation for patients with mantle cell lymphoma (MCL). Patients with MCL were included into two prospective trials OSHO #060 (refractory/relapsed) and #074 (de novo). Induction was rituximab and chemotherapy. Responding patients proceeded to alloSCT. Minimal residual disease was monitored by quantitative RT-PCR detecting either t(11;14) or clonospecific CDR-III regions. In case of circulating lymphoma cells, immunomodulation (cyclosporine A withdrawal, rituximab, donor lymphocyte infusion) was initiated. Thirty-three of 39 patients underwent alloSCT after myeloablative ( n = 7) or toxicity-reduced ( n = 26) conditioning. Leukocytes engrafted at day +16 (median, range 0-101) and platelets at day +14 (0-142). Acute graft-versus-host disease stages I-II occurred in 42 % and stages III-IV in 15 %. Five patients have relapsed after SCT. The overall mortality after SCT was 24 % ( n = 8). Median follow-up after SCT was 2.8 years (range 0.0-10.9). Five-year progression-free survival was 67 %, and overall survival 73 % after SCT. The results were comparable for primary MCL and refractory/relapsed disease as well as for related vs. unrelated SCT. Younger patients had a significantly better outcome than the elderly. AlloSCT is a feasible and promising consolidation therapy for relapsed and refractory disease and an attractive option for young patients with de novo MCL of high risk. [ABSTRACT FROM AUTHOR]

BACKGROUND: Measures to prevent transfusion-transmitted cytomegalovirus (TT-CMV) infection after hematopoietic stem cell transplantation (HSCT) include transfusion of CMV antibody-negative blood units and/or transfusion of leukoreduced cellular blood products. We assessed the incidence of TT-CMV in CMV-seronegative patients receiving CMV-seronegative HSC transplants, who were transfused with leukoreduced cellular blood products not tested for anti-CMV. STUDY DESIGN AND METHODS: In a prospective observational study between 1999 and 2009, all HSCT patients received leukoreduced cellular blood products not tested for anti-CMV. Patients were screened for CMV serostatus and CMV-negative recipients of CMV-negative transplants were systematically monitored for TT-CMV clinically and by CMV nucleic acid testing. Anti-CMV antibodies (immunoglobulin [Ig]G and IgM) were assessed after three time intervals (Interval 1, study inclusion to Day +30 after HSCT; Interval 2, Day +30-Day +100; Interval 3, after Day +100). RESULTS: Among 142 patients treated with allogeneic HSCT, 23 CMV-negative donor-patient pairs were identified. These 23 patients received 1847 blood products from 3180 donors. All patients remained negative for CMV DNA and none developed CMV-associated clinical complications. This results in a risk for TT-CMV per donor exposure of 0% (95% confidence interval, 0.0%-0.12%). However, 17 of 23 patients seroconverted for anti-CMV IgG, but none for anti-CMV IgM. CMV IgG seroconverters received significantly more transfusions per week than nonconverters. CONCLUSION: The risk of TT-CMV is low in high-risk CMVneg/neg HSCT patients transfused with leukoreduced blood products not tested for anti-CMV. The cause of anti-CMV IgG seroconversion is most likely passive antibody transmission by blood products. [ABSTRACT FROM AUTHOR]

The position of aminoglycosides within interventional antibiosis in the early phase after stem cell transplantation has not been fully clarified so far although their use can induce serious renal impairment. To investigate this question early-infection data from 152 patients undergoing 195 allogeneic and autologous stem cell transplantations were investigated. Prophylaxis and treatment of infections followed international standards; however, aminoglycosides were omitted to avoid additional risks such as ototoxicity and nephrotoxicity and increased selection of resistant pathogens. Costs were another aspect. The overall-incidence of infections was 78% (152/195) and 67 patients showed more than one episode of infection. Fever of unknown origin and bacteriaemia/septicaemia dominated the spectrum of infections. The overall-response to interventional regimen consisting of ß-lactam or carbapenem plus glycopeptides was 48%. Aminoglycosides were given in three patients in the late course of disease. Overall mortality was 15/195 (7.7%) and clearly related to infection in nine cases mostly due tomould infection. A comparison with previous published literature showed no hint for inferiority of 'aminoglycoside-free' antibiotic management in stemcell transplant patients. In conclusion, the present analysis supports the policy to omit aminoglycosides in the therapy of early infections in patients undergoing stem cell transplantation to avoid additional toxicity. [ABSTRACT FROM AUTHOR]

We describe a 57-year-old woman suffering from acute erythroblastic leukaemia. After the first course of high-dose Ara-C containing consolidation therapy, the patient developed multiple skin lesions on the left foot. A skin biopsy revealed a Fusarium infection. The lesions regressed under therapy with caspofungin and voriconazole. Leukaemia relapsed after 1 year and an allogeneic stem cell transplantation was performed for consolidation of leukaemia in second remission. Again, the patient developed macular skin lesions located on the trunk and the extremities with central pallor. Clinical examination showed fever, tachyarrhythmia and a systolic murmur. Fusarium spp. was cultured from blood samples. An antimycotic therapy with amphotericin B, voriconazole and posaconazole failed completely. The patient died in a septic shock with consecutive multiple organ failure. The autopsy (SN 1/06, Institute of Pathology, University of Greifswald) revealed a disseminated infiltration with Fusarium solani including myocardial, endocardial and aortal infection. The involvement of the cardiovascular system is uncommon in fusariosis and has not been described so far. This case confirms other reports describing the high mortality of fusariosis after allogeneic stem cell transplantation. A rapid diagnosis and antimycotics with higher activity against Fusarium spp. are necessary for successful therapy of this severe mould infection in the immunocompromised host. [ABSTRACT FROM AUTHOR]

BACKGROUND: High-dose therapy with autologous stem cell support after standard dose induction is a promising approach for therapy of primary central nervous system lymphoma (PCNSL). High-dose methotrexate (HD-MTX) is a standard drug for induction of PCNSL; however, data about the capacity of HD-MTX plus granulocyte–colony-stimulating factor (G-CSF) to mobilize hemopoietic progenitors are lacking. STUDY DESIGN AND METHODS: This investigation describes the data from stem cell mobilization and apheresis procedures after one or two cycles of HD-MTX for induction of PCNSL within the East German Study Group for Haematology and Oncology 053 trial. Eligible patients proceeded to high-dose busulfan/thiotepa after induction therapy and mobilization. RESULTS: Data were available from nine patients with a median age of 58 years. The maximal CD34+ cell count per µL of blood after the first course of HD-MTX was 13.89 (median). Determination was repeated in six patients after the second course with a significantly higher median CD34+ cell count of 33.69 per µL. Five patients required two apheresis procedures and in four patients a single procedure was sufficient. The total yield of CD34+ cells per kg of body weight harvested by one or two leukapheresis procedures was 6.60 × 106 (median; range, 2.68 × 106-15.80 × 106). The yield of CD34+ cells exceeded the commonly accepted lower threshold of 3 × 106 cells per kg of body weight in eight of nine cases. Even in the ninth, hemopoietic recovery after stem cell reinfusion was rapid and safe. CONCLUSION: HD-MTX plus G-CSF is a powerful combination for stem cell mobilization in patients with PCNSL and permits safe conduction of time-condensed and dose-intense protocols with high-dose therapy followed by stem cell reinfusion after HD-MTX induction. [ABSTRACT FROM AUTHOR]

Background: Microbial safe tap water is crucial for the safety of immunosuppressed patients. Methods: To evaluate the suitability of new, reusable point-of-use filters(Germlyser®, Aquafree GmbH, Hamburg, Germany), three variations of a reusable filter with the same filter principle but with different outlets (with and without silver) and inner surface coating of the filter encasements (with and without nano-crystalline silver) were tested. The filter efficacy was monitored over 1, 4 and 8 weeks operating time in a haematological oncology transplantation unit equipped with 18 water outlets (12 taps, 6 showers). Results: The filtered water fulfilled the requirements of absence of pathogens over time. From 348 samples, 8 samples (2.3%) exceeded 100 cfu/ml (no sample = 500 cfu/ml). As no reprocessed filter exhibited 100% filter efficacy in the final quality control after each reprocessing, these contaminations could be explained by retrograde contamination during use. Conclusion: As a consequence of the study, the manufacturer recommends changing filters after 4 weeks in high risk areas and after 8 weeks in moderate infectious risk areas, together with routine weekly alcohol-based surface disinfection and additionally in case of visible contamination. The filter efficacy of the 3 filters types did not differ significantly regarding total bacterial counts. Manual reprocessing proved to be insufficient. Using a validated reprocessing in a washer/disinfector with alkaline, acid treatment and thermic disinfection, the filters were effectively reprocessable and now provide tap water meeting the German drinking water regulations as well as the WHO guidelines, including absence of pathogens. [ABSTRACT FROM AUTHOR]

Relapse of a preceding fungal infection is a considerable risk during haemopoietic stem cell transplantation. The optimal secondary prophylaxis has not been found so far since the application of standard drugs is hampered by potential ineffectiveness or intolerable side effects. This investigation describes haemopoietic cell transplantation of patients with a history of invasive or systemic fungal infection (IFI). The strategy was either administration of liposomal amphotericin B as secondary prophylaxis or an early switch to liposomal amphotericin B after administration of azoles. The 43 patients had a history of proven (n = 14), probable (n = 14) and possible (n = 15) IFI. Twenty-eight patients (65%) could be discharged from the BMT ward without signs of mycosis. Transplant-related mortality was 35%. Overall, 12 fungus-related (IFI) deaths (28%) occurred. The percentage of fungus-related deaths was highest in the ‘proven’ group with 43% compared to 20 and 21% in the two other groups. Side effects of liposomal amphotericin B were low. A discontinuation of the drug was not necessary in any patient. Serum creatinine showed a slight increase to 128% (median) of the baseline allowing continuous administration of concomitant nephrotoxic drugs such as cyclosporin A. In conclusion, secondary prophylaxis with or early switch to liposomal amphotericin B facilitates allogeneic stem cell transplantation of patients with a history of IFI with minor side effects. However, fungal infections and transplant-related mortality remain major problems in this often heavily pretreated subgroup of patients. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Two patients with persistent disease after allografting for multiple myeloma received donor T-cell lymphocyte infusion (DLI) (1·5 × 108 and 7 × 107) to induce a graft-vs.-myeloma effect for further tumour regression after withdrawal of immunosuppression. The interval between stem cell transplantation and DLI was 8 and 14 months respectively. Both patients converted from partial to complete remission, lasting 12+ and 28+ months. Immunofixation became negative after 3 and 4 months. The main toxicity was grade II and III acute graft-vs.-host disease (GvHD) and limited or extensive chronic GvHD in each patient. We conclude that DLI induced further tumour reduction in patients with persistent disease after allografting for multiple myeloma. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor reporting a case of Epstein-Barr virus reactivation after allogeneic stem cell transplantation without lymph node enlargement.

In contrast to the evidence regarding azacitidine (Aza), there is limited knowledge about the combination of decitabine (DAC) and donor lymphocyte infusions as salvage therapy for relapse after allogeneic stem cell transplantation (allo-SCT) so far. We retrospectively analyzed data of 36 patients with hematological (n = 35) or molecular relapse (n = 1) of acute myeloid leukemia (AML, n = 29) or myelodysplastic syndrome (MDS, n = 7) collected from 6 German transplant centers. Patients were treated with a median of 2 cycles DAC (range, 1 to 11). DAC was the first salvage therapy in 16 patients (44%), whereas 20 patients (56%) had previously received 1 to 5 lines of salvage therapy including 16 of them had been treated with Aza. In 22 patients (61%), a median of 2 DLI per patient (range, 1 to 5) was administered in addition to DAC. As a result, overall response rate was 25% including 6 complete remissions (CR, 17%) and 3 partial remissions (PR, 8%). Three patients within the first-line group achieved CR, while also 3 patients receiving DAC as second-line treatment reached CR including 2 patients with previous Aza failure. Median duration of CR was 10 months (range, 2 to 33) and no patient relapsed so far. The 2-year OS rate was 11% (± 6%) without any difference between first-line and pretreated patients. Incidence of acute and chronic graft-versus-host disease was 19 and 5%. Taken together, DAC exerts clinical efficacy in patients with AML or MDS relapsing after allo-SCT and is able to induce durable remissions in individual patients suggesting that DAC may be an alternative to Aza or even a second choice after Aza failure. [ABSTRACT FROM AUTHOR]

There are no epidemiological data on BK virus associated hemorrhagic cystitis (BKHC) in adult allogeneic stem cell transplantation in Germany available and associations with clinical conditions like GvHD are controversially discussed. Therefore, we conducted a nationwide survey among haematologists and urologists about this disease. We developed two questionnaires, one for haematologists (26 items) and one for urologists (20 items) concerning BKHC in adult allogeneic stem cell transplantation with epidemiological data and clinical implications. The survey was sent out at least three times to EBMT registered centres performing at least five transplantations a year, leading to 39 centres. The recruiting time was between January and June 2016. Total response rates were 76.9% among haematologists and 74.4% among urologists. BKHC seems to appear less frequent in this survey than it is described in the literature. Six deaths in the last 5 years due to this disease have been reported. Interestingly, haematologists as well as urologists mostly think that local therapy is most effective while 50.0% stated that there is no real effective oral or intravenous medication. Associations with other clinical conditions mentioned were heterogeneous, e.g. transplantation type, CMV reactivation, acute GvHD, nephropathy and worse clinical outcome. There was a significant discrepancy between haematologists and urologist concerning the association with acute GvHD (p = 0.004). We need prospective, multicentric clinical studies to evaluate local therapy and for developing a risk stratification model since this disease can be severe with morbidity and rarely mortality. In our opinion, this should be an interdisciplinary approach. [ABSTRACT FROM AUTHOR]

The novel coronavirus SARS-CoV-2 and the associated infectious disease COVID-19 pose a significant challenge to healthcare systems worldwide. Patients with cancer have been identified as a high-risk population for severe infections, rendering prophylaxis and treatment strategies for these patients particularly important. Rapidly evolving clinical research, resulting in the recent advent of various vaccines and therapeutic agents against COVID-19, offers new options to improve care and protection of cancer patients. However, ongoing epidemiological changes and rise of new virus variants require repeated revisions and adaptations of prophylaxis and treatment strategies to meet these new challenges. Therefore, this guideline provides an update on evidence-based recommendations with regard to vaccination, pharmacological prophylaxis and treatment of COVID-19 in cancer patients in light of the currently dominant omicron variants. It was developed by an expert panel of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) based on a critical review of the most recent available data. • Changes in epidemiology of SARS-CoV-2 variants require review of strategies. • Vaccination against COVID-19 is of particular importance in cancer patients. • Early treatment of COVID-19 in cancer patients reduces risk of severe disease. • Long-COVID is common in cancer patients and poses a particular challenge. • Evidence-based recommendations can help clinicians make informed decisions. [ABSTRACT FROM AUTHOR]

Infectious complications after allogeneic haematopoietic stem cell transplantation (allo-HCT) remain a clinical challenge. This is a guideline provided by the AGIHO (Infectious Diseases Working Group) of the DGHO (German Society for Hematology and Medical Oncology). A core group of experts prepared a preliminary guideline, which was discussed, reviewed, and approved by the entire working group. The guideline provides clinical recommendations for the preventive management including prophylactic treatment of viral, bacterial, parasitic, and fungal diseases. The guideline focuses on antimicrobial agents but includes recommendations on the use of vaccinations. This is the updated version of the AGHIO guideline in the field of allogeneic haematopoietic stem cell transplantation utilizing methods according to evidence-based medicine criteria. [ABSTRACT FROM AUTHOR]

Overall, 33 patients (52%) continued treatment beyond investigator assessed PD and a total of 16 patients received additional concomitant radiotherapy and/or chemotherapy. The majority of patients experiencing PD during or after anti-PD1 treatment received additional therapies (21/37, 57%). Outcomes of anti-programmed death 1 treatment for relapsed/refractory Hodgkin lymphoma: A German Hodgkin Study Group multicentre real-world analysis. [Extracted from the article]

Introduction: Allogeneic stem cell transplantation (alloSCT) has become available for elderly patients or for patients with comorbidities by introduction of reduced-intense conditioning. Comorbidity-related prognosis after alloSCT can be estimated by the hematopoietic cell transplantation comorbidity index (HCT-CI). Material and Methods: The charts from 85 patients who have undergone 90 alloSCTs between 1999 and 2011 were analysed. Most patients received a dose-reduced conditioning and a graft from an unrelated donor. Patients were stratified for age, HCT-CI, cGvHD versus no cGvHD, and a modified HCT-CI with a further split high-risk score. Results: Age over 60 years did not affect the outcome. Manifestation of cGvHD improved the prognosis significantly. An additional stratification of the high-risk group of the HCT-CI revealed that even a fraction of these patients can have considerable benefit from an alloSCT. Furthermore, this high-risk collective could be clearly discriminated into two groups with different outcomes. Conclusions: The investigation confirms that age is no absolute risk factor for alloSCT and demonstrates the heterogeneity of the high-risk group of the HCT-CI. A comprehensive investigation of an additional stratification is suggested. Furthermore, the authors encourage early withdrawal of immunosuppression, even in elderly patients and patients with comorbidities to permit graft-versus-leukaemia/lymphoma, since cGvHD is associated with a significantly better prognosis. [ABSTRACT FROM AUTHOR]

• ECP was able to increase Tfh cells to ameliorate GvHD. • Upregulation of Th22 cells was observed in aGvHD patients with CR. • Tim-3 expression was downregulated on effector T cells by ECP. • ECP shows immunomodulatory effects in GvHD setting. Extracorporeal photopheresis (ECP), a personalized cellular immunotherapy, constitutes a promising treatment for steroid-refractory/-resistant graft-versus-host disease (SR-GvHD), with encouraging clinical response rates. To further investigate its mechanism of action, ECP's effects on T helper (Th) cells as well as on expression of immune checkpoint (PD-1 and Tim-3) and apoptotic (Fas receptor [FasR]) molecules were investigated in 27 patients with SR-GvHD. Our data show that GvHD patients had significantly higher levels of Th2, Th17, Th22 and granulocyte-macrophage colony-stimulating factor (GM-CSF)-positive Th (ThG) cells and clearly lower levels of T follicular helper (Tfh) cells, including Th1- and Th2-like cells, compared with healthy donors. ECP therapy for GvHD was effective through the modulation of different Th subsets: increases of Th22 (1.52-fold) and Tfh cells (1.48-fold) in acute GvHD (aGvHD) and increases of Th2-like Tfh cells (1.74-fold) in chronic GvHD (cGvHD) patients were associated with clinical response. Expression of FasR was further upregulated in CD4+CD8+ T cells. Additionally, Tim-3–expressing effector T cells associated with the severity of GvHD were reduced. Taken together, these data show that ECP therapy exerts immunomodulatory effects by promoting a balanced immune reconstitution and inducing immune tolerance. Therefore it represents an attractive option for the treatment of GvHD. [ABSTRACT FROM AUTHOR]

We evaluated the cytomegalovirus (CMV) serostatus as a risk factor for survival and treatment-related mortality (TRM) in 125 patients allografted from an unrelated donor between 1994 and 1999. All patients received pretransplant in vivo T-cell depletion using rabbit anti-thymocyte globulin (ATG). Only one patient had primary graft failure and severe grade III/IV graft-versus-host disease occurred in 14% of the patients. The overall survival (OS) at 3 years was 70% for CMV-negative patients (n = 76) and 29% in the seropositive cohort (n = 49) (P > 0·001). In multivariate analyses, CMV seropositivity remained an independent negative prognostic factor for OS (RR: 2·1; CI: 1·2–3·8; P = 0·014), apart from age > 20 years (RR: 2·74; CI: 1·2–3·8; P = 0·004) and late leucocyte engraftment (RR: 2·4; CI: 1·2–4·9; P = 0·015). The TRM for all patients was 27%. Despite monitoring for CMV antigenaemia and preemptive therapy with ganciclovir when reactivation occurred, seropositive patients had a three times higher risk of fatal treatment-related complications than seronegative patients. In multivariate analyses, CMV seropositivity remained the strongest independent negative factor for TRM (RR: 5·3; CI: 1·9–14·6; P = 0·002), followed by age > 20 years (RR: 4·8; CI: 1·3–18·1; P = 0·02) and delayed leucocyte engraftment (RR: 3·6; CI: 1·2–11; P = 0·02). The TRM was identical in seropositive patients with (n = 27) or without (n = 22) CMV reactivation (44% versus 50%). We conclude that CMV seropositivity, despite preemptive ganciclovir therapy and even without reactivation, is a major negative prognostic factor for survival as well as for TRM in unrelated stem cell transplantation using pretransplant in vivo T-cell depletion with ATG. [ABSTRACT FROM AUTHOR]

To evaluate the schedule dependency of granulocyte colony-stimulating factor (G-CSF) (filgrastim) for stem cell mobilization, we conducted a randomized comparison in 50 healthy donors, with one subcutaneous daily injection of 10 µg/kg G-CSF (n = 25) compared with twice injections daily of 5 µg/kg G-CSF (n = 25). The two groups were well balanced for age, body weight and sex. G-CSF application was performed on an out-patient basis and leukapheresis was started in all donors on day 5. The most frequent side-effects of G-CSF were mild to moderate bone pain (88%), mild headache (72%), mild fatigue (48–60%) and nausea (8%) without differences between the two groups. The CD34+ cell count in the first apheresis was 5·4 × 106/kg donor weight (range 2·8–13·3) in the 2 × 5 µg/kg group compared with 4·0 × 106/kg (range 0·4–8·8) in the 1 × 10µg/kg group (P = 0·007). The target of collecting > 3·0 × 106 CD34+ cells/kg donor weight with one apheresis procedure was achieved in 24/25 (96%) donors in the 2 × 5 µg/kg group and in 17/25 (68%) donors in the 1 × 10 µg/kg group. The target of collecting > 5·0 × 106 CD34+ cells/kg in the first apheresis was achieved in 64% in the 2 × 5µg/kg group, but in only 36% in the 1 × 10 µg/kg group. The progenitor cell assay for granulocyte–macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) was higher in the 2 × 5 µg/kg group than in the 1 × 10 µg/kg group (7·0 vs. 3·5 × 105/kg, P = 0·01; 6·6 vs. 5·0 × 105/kg; P = 0·1). Administering G-CSF (filgrastim) at a dosage of 5 µg/kg twice daily rather than 10 µg/kg once daily is recommended; this leads to a higher CD34+ cell yield and requires fewer apheresis procedures without increasing toxicity or cost. [ABSTRACT FROM AUTHOR]

Haematopoietic stem-cell transplantation (HSCT) is performed mainly in patients diagnosed with malignancies or some severe congenital diseases. Significant reduction of red blood cell transfusion requirements by changing from a double-unit to a single-unit transfusion policy in patients receiving intensive chemotherapy or stem cell transplantation. Patients with PRCA can become RBC transfusion dependent for a long period, suffering an important long-term iron overload, alloimmunization and transfusion reactions [15]. [Extracted from the article]

- We systematically monitor the efficacy of platelet transfusions by a post-transfusion platelet count at 20 h after transfusion. The efficacy of platelet transfusions is not routinely measured by a post-platelet transfusion increment (PPI), however if there are any concerns regarding the daily platelet counts (e.g. persisting low counts after prior transfusion such that the patient is requiring very frequent transfusions), we would perform platelet increment testing at 30-60 min post-transfusion. We advise monitoring of post-transfusion platelet counts (15-60 min post) in "high-use alert cases" (three consecutive days with >=1 platelet transfusion per day), or in the evaluation of immune-selected single donor apheresis platelets (to assess the in vivo efficacy of products which had been selected to circumvent the last known array of HLA- and/or HPA-specific antibodies). We systematically monitor the efficacy of platelet transfusions in patients undergoing HSCT by a post-transfusion platelet count about an hour after finishing the transfusion. At our institution, if a patient is independent of RBC transfusion for 90 days and no incompatible isohemagglutinins against the new RBC phenotype are detected in two consecutive blood samples, then the patient's native blood type is switched to the donor type for future transfusion. [Extracted from the article]

A letter to the editor is presented in response to previous issue concerning a 49-year old man who had Erdheim-Chester disease with hemophagocytosis in the June 2006.

Objective: Patients suffering from haemato‐oncological diseases tend to have a weakened immune system after the end of their therapy. To avoid infections, patients are advised to limit contact with other people. This poses the question whether a stay at a rehabilitation facility can be recommended. Methods: We report about 134 rehabilitation stays of patients. Premature discontinuation of the rehabilitation stay was selected as the criterion for a serious complication during the rehabilitation, and the underlying reasons were analysed. Results: Compared to the discontinuation rates of patients suffering from solid tumours (2.4%), the percentage of haemato‐oncological patients ending prematurely their rehabilitation stay (8.2%) is significantly increased. This rises to 17.1% for patients who have undergone an allogeneic stem cell transplantation. The analysis of the discontinuation reasons revealed that they were not directly connected to the rehabilitation. Apart from the already known risk factors for premature termination of the rehabilitation stay, we have identified the period (days) between the last therapy and the beginning of the rehabilitation stay as a risk factor. Conclusions: We show for the first time that a rehabilitation stay does not pose additional risks for patients suffering from haemato‐oncological diseases. [ABSTRACT FROM AUTHOR]

Objective. Steroid-resistant graft-versus-host disease (GvHD) is a major challenge after allogeneic stem cell transplantation and associated with significant morbidity and mortality. There is no therapeutic standard defined beyond calcineurin inhibitors (CNI) and steroids. Furthermore, some patients may have contraindications against CNI or high-dose steroids. Efficacy of ruxolitinib against GvHD has been described recently. Methods. Ruxolitinib was used for treatment of acute or chronic GvHD in eight patients. The patients either needed intensification of therapy or had contraindications against use of CNI or high-dose steroids. Results. Supplementation of therapy in acute GvHD with severe diarrhea with ruxolitinib was unsuccessful. All these patients died from acute GvHD. Introduction of ruxolitinib into therapy and relapse prophylaxis in other patients was successful in 4/4 cases (CR=3, PR=1). Indications for ruxolitinib were contraindications against CNI due to aHUS in two cases and the need for steroid sparing in two other cases. None of these patients suffered from diarrhea at the initiation of ruxolitinib. Conclusion. Ruxolitinib was effective for therapy of acute and chronic GvHD in higher lines in patients without severe diarrhea. Ruxolitinib could replace successfully CNI and high-dose steroids. Further investigations are necessary to define the position of ruxolitinib in GvHD-therapy. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: BK polyomavirus can lead to hemorrhagic cystitis (BKPyV‐HC) in allogeneic stem cell transplantation and therefore to increased morbidity. No causal therapy has been established yet. Cidofovir (CDV) is a nucleotide analog of cytosine that is active against various DNA viruses and it has been described for therapy of BKPyV‐HC using 2 admission routes: intravenous and intravesical. Methods: We performed a systematic review regarding the comparison of intravenous or intravesical cidofovir in the treatment of BKPyV‐HC following adult allogeneic stem cell transplantation. Since there is a lack of randomized controlled trials, we considered all kinds of studies for this review. Due to heterogeneity of the data, we were not able to perform a meta‐analysis, so the results are shown descriptively. Results: The literature search for primary studies yielded 232 results. Finally, 9 studies where considered which included a total of 189 adult patients with BKPyV‐HC after allogeneic stem cell transplantation. We could only identify retrospective studies for this review. A total of 172 patients received intravenous CDV, 17 patients received intravesical CDV, and 2 patients received CDV in both admission routes. In 68.0% of the cases, a complete response for intravenous CDV was documented and in 88.2% for intravesical CDV. Interestingly, no kidney toxicity was mentioned in intravesical CDV. 9.3% of the intravenously treated patients had renal failure. Conclusion: There is only weak evidence for the use of CDV. The intravesical admission route should be further investigated because of a good toxicity profile. [ABSTRACT FROM AUTHOR]

Objective: There is a substantial lack of data about men's health in adult allogeneic stem cell transplantation. Methods: We conducted prospective unicentric non-interventional clinical study on men's health with a follow-up time of 1 year. Results: Between 11/2013 and 12/2015, we were able to include 27 patients. AML was the most frequent underlying disease (25.9%), and we mainly used intermediate intense conditioning protocols (77.8%). Erectile dysfunction, loss of libido, and loss of efficiency were the most frequent symptoms of hypogonadism. At inclusion of the study, hypogonadism was already frequent. Primary hypogonadism was found in eight cases (29.6%) and secondary hypogonadism in one case (3.7%). We did not observe hypogonadism 6 months after inpatient treatment anymore, but there might still be the impairment of fertility because of still rising FSH levels at the end of the observation period. There were no significant associations of hypogonadism with myeloablative conditioning or kind of donor. Interestingly, there is a significant association with nicotine abuse (P = .049). Conclusions: On the whole, male hypogonadism was found in one-third of the patients who underwent allogeneic stem cell transplantation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Alemtuzumab as part of the conditioning protocol is effective in reducing graft‐versus‐host disease (GvHD), but may be associated with increased infection rates, especially when using high doses (ie, 100 mg). Methods: We performed a retrospective, single‐center, case‐control study analyzing the rates of neutropenic fever, cytomegalovirus (CMV) reactivation, Epstein‐Barr virus (EBV) reactivation, clinical manifest toxoplasmosis, and clinical manifest human herpesvirus‐6 (HHV6) infection using low‐dose alemtuzumab in comparison with anti‐thymocyte globulin (ATG) as GvHD prophylaxis before allogeneic stem cell transplantation. Forty‐four patients transplanted from unrelated donors between 2001 and 2012 were matched by age, diagnosis, and conditioning regimen and treated either with alemtuzumab 10 mg at day −2 (respectively, 20 mg in case of mismatch transplantation) or ATG. ATG Fresenius (10 mg/kg for 3 days) or Thymoglobulin (2 mg/kg for 3 days) were used. Results: Rates of CMV reactivation, EBV reactivation, and clinical manifest HHV6 infection or toxoplasmosis did not differ significantly between both groups until 2 years after transplantation. No case of post‐transplant lymphoproliferative disorder was observed. Also, rates of neutropenic fever during inpatient treatment after transplantation did not differ significantly in both groups. Conclusion: We saw no indication of increased infections rates when using low‐dose alemtuzumab as GvHD prophylaxis before allogeneic stem cell transplantation in this retrospective analysis. [ABSTRACT FROM AUTHOR]

Purpose: Allogeneic stem cell transplantation may cure approximately 50% of patients, however, a significant part of the other half might benefit from a high-quality palliative care medicine at the end of life. Somatic, psychic and spiritual needs of these patients may differ from those of patients suffering from incurable solid tumours and are not comprehensively evaluated so far. Methods: To address this question, data from charts of 123 patients who have died after allogeneic stem cell transplantation were extracted. In detail, the time line of the clinical course, the symptoms, the administered drugs and other applied procedures were analysed. Results: Approximately one half of the patients, who have died after stem cell transplantation, did not live more than 5 months. Two-thirds of patients died within 14 months after SCT. 28.5% of the patients could not be discharged after transplantation. However, a significant proportion had a low ECOG-score (0-1) prior to death, indicating a high degree of mobility. Major symptoms were weakness, fatigue and need for aid at daily activities. Severe pain, dyspnoea and obstipation, as known from patients suffering from advanced solid tumours, were rare. In consequence, use of opioids seemed to be less frequent than in patients with solid tumours. Measures of intensive care and i.v.-drug administration were applied to a significant proportion of patients. Conclusion: The present investigation indicates that the somatic, psychic and spiritual end-of-life-care after allogeneic stem cell transplantation could be optimised. A significant problem for the transplantation team seems to be the realisation of necessity to switch the curative concept into a palliative ambition. Requirements are a subsequent prospectively conducted investigation and an intensification of cooperation between transplant and palliative care teams. [ABSTRACT FROM AUTHOR]

4381549 8 Pandey RK, DiPippo A, Kadia T. Nelarabine-related rhabdomyolysis in a patient with T-cell acute lymphoblastic leukemia. Computed tomography showed a complete remission after consolidation I and marrow cytology and histology were negative for T-LBL blasts. [Extracted from the article]

Background: The association of polyomaviruses BK and JC with other opportunistic infections and graft-versus-host disease (GvHD) in allogeneic stem cell transplantation is controversially discussed. Methods: We conducted a retrospective study of 64 adult patients who received their first allogeneic stem cell transplantation between March 2010 and December 2014; the follow-up time was 2 years. Results: Acute leukemia was the most frequent underlying disease (45.3%), and conditioning included myeloablative (67.2%) and nonmyeloablative protocols (32.8%). All patients received 10 mg of alemtuzumab on day -2 (20 mg in case of mismatch) as GvHD prophylaxis. Twenty-seven patients (41.5%) developed cytomegalovirus (CMV) reactivation. BKPyV-associated hemorrhagic cystitis was diagnosed in 10 patients (15.6%). Other opportunistic infections caused by viruses or protozoa occurred rarely (<10%). There was no association of BKPyV or JCPyV with CMV reactivation, Epstein-Barr virus reactivation, human herpes virus 6, or parvovirus B19 infection requiring treatment. There was a significant correlation of BKPyV-associated hemorrhagic cystitis with toxoplasmosis (p = 0.013). Additionally, there was a significant link of simultaneous BKPyV and JCPyV viruria with toxoplasmosis (p = 0.047). BKPyV and JCPyV were not associated with GvHD, relapse, or death. Conclusion: We found no association of BKPyV or JCPyV with viral infections or GvHD. Only the correlation of both polyomaviruses with toxoplasmosis was significant. This is a novel and interesting finding. [ABSTRACT FROM AUTHOR]

Every year 50,000 patients receive a stem cell transplantation worldwide, but there is lack of data pertaining to urological complications. Methods: We performed a retrospective analysis of all adult patients undergoing their first allogenic stem cell transplantation from January 2011 to June 2013 in our institution. Statistical tests performed were Pearson's correlation, chi-square testing and logistic regression using SPSS 22.0. Results: We identified 39 patients (22 males, 17 females). Twenty four patients (61.5%) had a urological complication. Most frequent urologic complications were bacterial urinary tract infection (n = 13; 33.3%), acute renal failure (n = 6; 15.4%) and BK virus-associated haemorrhagic cystitis (n = 5; 12.8%). BK viruria was detected in 12 patients (30.8%). We observed an association of creatinine increase (about 20 µmol/l at time of onset of BK viruria) with BK viruria (Pearson's correlation 0.64; p = 0.01), and BK viruria is significantly linked to acute renal failure (Pearson's correlation 0.35; p = 0.029). In univariate regression, BK viruria is significantly linked to urological complication (p = 0.025). Conclusions: We suggest that BK virus infection during stem cell transplantation can lead to BK virus associated nephropathy, which is so far only known from patients after kidney transplantation. [ABSTRACT FROM AUTHOR]

BK polyomavirus-associated haemorrhagic cystitis (BKHC) is a complication after allogeneic stem cell transplantation, which can occur in 5–60% of the cases. BK viruria alone can also occur in up to 100%. BKHC can lead to severe morbidity in stem cell-transplanted patients, but data about this disease is limited. Consequently, we conducted a prospective unicentric non-interventional trial on BKHC as well as BK viruria after first adult allogeneic stem cell transplantation with a follow-up time of 1 year after inpatient treatment. Between November 2013 and December 2015, we were able to include 40 adult patients with a mean age of 52.8 years. Twenty-seven (67.5%) of these patients were male and 13 (32.5%) were female. Acute myeloid leukaemia was the most frequent underlying disease (n = 15; 37.5%). Only 1 patient developed BKHC during inpatient treatment (n = 1; 2.5%), but BK viruria was frequent (n = 11; 27.5%) during inpatient treatment as well as in the follow-up time (n = 14; 35%). Interestingly, BK viruria was significantly associated with mucositis (p = 0.038) and number of transfused platelet concentrates (p = 0.001). This unexpected association will be discussed and needs further investigation. [ABSTRACT FROM AUTHOR]

Purpose: In patients undergoing allogeneic stem cell transplantation, conditioning regimens containing alemtuzumab instead of anti-thymocyte globulin (ATG) may result in an earlier platelet engraftment and a reduced number of platelet transfusions. Methods: We performed a retrospective, single-center, case-control study analyzing time to engraftment and transfusion needs using alemtuzumab in comparison with ATG as part of conditioning protocol. Results: Median values for time to platelet engraftment, number of transfused platelet concentrates and number of transfused red cell concentrates were 12 versus 19.5 days ( p < 0.001), 2 versus 14 ( p < 0.001) and 6 versus 14.5 ( p = 0.003) in the alemtuzumab and ATG group. Time to leukocyte engraftment did not differ with median 15 days in both groups. Patients in the ATG group showed a significant higher decrease in platelet count during conditioning (68 vs. 29 %, p = 0.001), leading to significant lower median platelet counts at the day of stem cell infusion (38 vs. 95.5 Gpt/l, p = 0.008), and higher values for median C-reactive protein after first antibody infusion (69.0 vs. 43.6 mg/l, p = 0.001) compared with alemtuzumab group. Test for significance was done by using Wilcoxon rank-sum test. Subgroup analysis considering the type of ATG used (Thymoglobulin vs. ATG Fresenius) revealed that differences between alemtuzumab and ATG group were more due to effects of ATG Fresenius than Thymoglobulin. Conclusions: The use of alemtuzumab in comparison with ATG as part of the conditioning regimen may be an approach to reduce the number of transfused platelet and red cell concentrates after allogeneic stem cell transplantation. [ABSTRACT FROM AUTHOR]

The Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) here presents its updated recommendations for the treatment of documented fungal infections. Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. In recent years, new antifungal agents have been licensed, and agents already approved have been studied in new indications. The choice of the most appropriate antifungal treatment depends on the fungal species suspected or identified, the patient's risk factors (e.g., length and depth of neutropenia), and the expected side effects. This guideline reviews the clinical studies that served as a basis for the following recommendations. All recommendations including the levels of evidence are summarized in tables to give the reader rapid access to the information. [ABSTRACT FROM AUTHOR]

Antibody-mediated in vivo T cell depletion is common prior to unrelated (URD) or mismatched allogeneic stem cell transplantation (alloSCT) and optional in HLA-identical sibling (FAM) alloSCT. While anti-thymocyte globulin (ATG) is the current standard, alemtuzumab is an alternative. The optimal dose of alemtuzumab has not been defined. This retrospective analysis compares low-dose alemtuzumab with ATG in URD alloSCT and with no antibody in FAM alloSCT. Twenty-eight patients treated with alemtuzumab (10 mg; HLA mismatch, 20 mg) were matched to 28 patients who have either received ATG (URD) or no antibody (noAB) according to disease, disease stage, age, transplant type and risk state. Both groups were compared for engraftment, outcome, disease-free (DFS) and overall survival (OS), graft-versus-host disease (GvHD), freedom from GvHD (ffGvHD) and transplant-related mortality (TRM). No significant differences were found between the groups for leukocyte engraftment, GvHD, ffGvHD, TRM, DFS and OS. There was a trend for reduction of cGvHD by alemtuzumab ( p = 0.05). A transplant-type stratified subanalysis consolidated equivalency of alemtuzumab and ATG in URD-SCT and indicates possible superiority of low-dose alemtuzumab compared to noAB in FAM-SCT. Low-dose alemtuzumab, as part of conditioning regimen prior to alloSCT, is safe and comparable to standard ATG. Prospective trials, particularly comparing alemtuzumab vs. noAB in FAM alloSCT, should be conducted. [ABSTRACT FROM AUTHOR]

More than 18,000 autolgous transplantation were performed in Europe in the year 2009. It as a routine procedure in experienced centres. Even if there is a low mortality rate, infections are a major issue after transplantation, occurring in more than 60 % of the patients. In this review we discuss all aspects of infections after autologous stem transplantation, including epidemiology, diagnostics, therapeutic algorithms, prophylaxis and supportive therapy. [ABSTRACT FROM AUTHOR]

Toxoplasmosis is a rare but possibly underestimated complication following allogeneic stem cell transplantation with a high mortality rate. One reason might be the limitation of the diagnostic instruments relying mainly on imaging and molecular-based techniques. In this report, we present three cases of toxoplasmosis identified among 155 allograft recipients treated at Greifswald University Hospital. Widely disseminated toxoplasmosis was detected post-mortem in two patients allografted for high-risk multiple myeloma. Clinical signs suspicious for toxoplasmosis occurred after days +32 and +75, respectively. In one case, serology and conventional Toxoplasma gondii PCR, targeting the B1 gene, revealed negative results, while in the other patient, toxoplasmosis was not investigated. Both patients received pentamidine for Pneumocystis jirovecii pneumonia (PcP) prophylaxis. The third patient, a 68-year-old woman allografted for AML, developed cerebral toxoplasmosis from day +395 after allogeneic SCT with typical signs in magnetic resonance tomography. Toxoplasma DNA was amplified from one of two samples of cerebrospinal fluid. The patient died of disseminated toxoplasmosis despite immediate initiation of therapy. Retrospective comparative testing of clinical specimens by the conventional T. gondii PCR and by a real-time PCR targeting a 529-bp genomic fragment suggests a higher sensitivity of the latter method in our patients. In conclusion, we suggest a rigorous real-time PCR monitoring for high-risk patients or patients with signs of infections suspicious for toxoplasmosis, even though low-copy results are presently difficult to interpret. Our reported cases might also encourage the use of trimethoprim-sufmethoxazole instead of pentamidine for PcP prophylaxis in those patients. [ABSTRACT FROM AUTHOR]

Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. Early antifungal treatment is mandatory to improve survival. Today, a number of effective and better-tolerated but more expensive antifungal agents compared to the former gold standard amphotericin B deoxycholate are available. Clinical decision-making must consider results from numerous studies and published guidelines, as well as licensing status and cost pressure. New developments in antifungal prophylaxis improving survival rates result in a continuous need for actualization. The treatment options for invasive Candida infections include fluconazole, voriconazole, and amphotericin B and its lipid formulations, as well as echinocandins. Voriconazole, amphotericin B, amphotericin B lipid formulations, caspofungin, itraconazole, and posaconazole are available for the treatment of invasive aspergillosis. Additional procedures, such as surgical interventions, immunoregulatory therapy, and granulocyte transfusions, have to be considered. The Infectious Diseases Working Party of the German Society of Hematology and Oncology here presents its 2008 recommendations discussing the dos and do-nots, as well as the problems and possible solutions, of evidence criteria selection. [ABSTRACT FROM AUTHOR]

Summary: Cell–cell and cell–matrix interactions, which are mediated by cell adhesion molecules, play a fundamental role during many cellular processes including growth, differentiation, cell migration and cancer metastasis. One molecule playing a major role in these processes is the CD44 surface receptor, which is expressed in a wide range of cells including many cells of the hemopoietic system, where it mediates the interaction with its major ligand, hyaluronate. However, little is known about CD44 and hyaluronate in bone marrow and this was investigated immunohistochemically in trephine biopsies and in cultivated human bone marrow stromal cells. In biopsy specimens, patches of hyaluronate deposition were detected in the extracellular matrix (ECM). However, most of the areas of the ECM were devoid of hyaluronate. Single mast cells and lymphocytes scattered throughout the marrow were CD44 immunopositive. Marrow-derived stromal cells (MDSC) expanded in cell culture were immunopositive for CD44, hyaluronate synthase, and hyaluronate. Hence, a marked difference between CD44 immunolocalisation and hyaluronate deposition can be observed between in situ and under cell culture conditions. Since in normal marrow in situ the number of CD44 immunopositive cells was low, interactions of CD44 and hyaluronate would appear to not to play a major role in cell adhesion in the normal bone marrow. [Copyright &y& Elsevier]

The risk of infection after allogeneic stem cell transplantation is determined by the underlying disease, the intensity of previous treatments and complications that may have occurred during that time, but above all, the risk of infection is determined by the selected transplantation modality (e.g. HLA-match between the stem cell donor and recipient, T cell depletion of the graft, and others). In comparison with patients treated with high-dose chemotherapy and autologous stem cell transplantation, patients undergoing allogeneic stem cell transplantation are at a much higher risk of infection even after hematopoietic reconstitution, due to the delayed recovery of T and B cell functions. The rate at which immune function recovers after hematopoietic reconstitution greatly influences the incidence and type of post-transplant infectious complications. Infection-associated mortality, for example, is significantly higher following engraftment than during the short neutropenic period that immediately follows transplantation. [ABSTRACT FROM AUTHOR]

Morbidity and mortality in patients with malignancies, especially leukemia and lymphoma, are increased by invasive fungal infections. Since diagnosis of invasive fungal infection is often delayed, antifungal prophylaxis is an attractive approach for patients expecting prolonged neutropenia. Antifungal prophylaxis has obviously attracted much interest resulting in dozens of clinical trials since the late 1970s. The non-absorbable polyenes are probably ineffective in preventing invasive fungal infections, but may reduce superficial mycoses. Intravenous amphotericin B and the newer azoles were used in clinical trials, but their role in antifungal prophylaxis is still not well defined. Allogeneic stem cell transplant recipients are at particularly high risk for invasive fungal infections. Other well described risk factors are neutropenia >10 days, corticosteroid therapy, sustained immunosuppression, graft versus host disease, and concomitant viral infections. The enormous study efforts are contrasted by a scarcity of risk stratified evidence based recommendations for clinical decision making. The objective of this review accumulating information on about 10.000 patients is to assess evidence based criteria primarily regarding the efficacy of antifungal prophylaxis in neutropenic cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Allogeneic stem cell transplantation is a curative treatment option for several hematological diseases. Data about health status and late complications of long-term survivors of this therapy are limited, so we conducted a prospective study. This analysis focusses on kidney function and urological complications. Interestingly, the BK polyomavirus plays an important role in this patient population and can lead to severe impairment of kidney function. This was only previously described in the acute situation following transplantation. Further studies should address causal therapy development for this severe viral infection. Background: Allogeneic stem cell transplantation (aSCT) is a common treatment for a variety of hematological diseases. Advances in transplantation practices have led to an increasing number of long-term aSCT survivors, but data about health status and late complications are sparse. This analysis focusses on kidney function and urological complications in this population. Methods: This study is a prospective unicentric non-interventional trial. Before starting the study, we obtained the approval of the local ethics review board. Furthermore, the study was registered at WHO Clinical Trial Registry. The study protocol is available via UTN. Results: We were able to include 33 patients with a mean age of 60.5 years (SD 11.1). The median survival time following allogeneic stem cell transplantation was 9.0 years (IQR 8.5–13.0). Five patients (15.2%) had BKPyV viruria with mean 218.3 (SD 674.2) copies/mL. BKPyV viruria was significantly linked to pre-existing chronic kidney failure (p = 0.019), creatine > 100 µmol/L (p < 0.001), and cystatin c > 1.11 mg/L (p = 0.021), respectively. We were not able to identify a single risk factor for BKPyV viruria in univariate or multivariate Cox regression. Conclusions: BKPyV-associated nephropathy might be one reason for impaired kidney function in long-term survivors of aSCT. [ABSTRACT FROM AUTHOR]

Haemophagocytic lymphohistiocytosis (HLH) is an autosomal recessive disease with histiocytic and lymphocytic infiltrations in multiple organs. Cure seems possible only by allogeneic bone marrow transplantation (BMT), but matched sibling donors (MSD) are restricted and high mortality rates are associated with BMT from unrelated donors (URD). We report on 12 consecutive HLH patients with an improved outcome following URD transplants. Eight patients received BMT from URD, four from MSD. Five patients had signs of active HLH at the time of BMT. The conditioning regimen consisted of 20 mg/kg busulphan, 60 mg/kg VP-16 and 120 mg/kg cyclophosphamide and, in case of URD, 90 mg/kg antithymocyte globulin. The doses of busulphan and VP-16 were reduced during the programme to 16 mg/kg and 30 mg/kg, respectively. Using a fivefold graft-versus-host disease (GVHD) prophylaxis, GVHD was absent or mild in 10, and moderate or severe in two patients undergoing unrelated transplants. One patient with URD experienced graft failure and was retransplanted on day 37. Major toxicities were hepatic veno-occlusive disease in five, capillary leak syndrome in two, pneumonia in three, sepsis in one, severe mucositis in one and seizures in two patients. All patients are alive without HLH after a median follow-up of 24.5 months. One patient has chronic GVHD, another patient has severe retardation. Three patients show slight to moderate development delay. These results indicate that in HLH, BMT from matched unrelated donors should be performed. Incomplete resolution of disease activity need not impede a successful outcome. [ABSTRACT FROM AUTHOR]

• Establishment of a 3D organotypic model of primary urothialial cells and fibrobasts. • Establishment of first infection modell of archetype BK polyomavirus in urothelium. • Infection model could be used to study viral life cycle and drug development. • BKPyV infected urothial cells enhance proliferation while reducing differentiation. • STAT3 pathway seems to be involved in BK polyomavirus infection in urothelium. 3D organotypic cell cultures offer the possibility to study cell growth in a more in vivo like situation. To our knowledge no 3D culture of primary urothelial cells has been established yet. BK Polyomavirus (BKPyV), replicating in urothelial cells, may cause haemorrhagic cystitis in immunocompromised patients. Establishment of a 3D organotypic cell culture of primary urothelial cells and fibroblasts; use of this model as infection model for archetype BKPyV; description of first parts of viral life cycle with identification of therapeutic targets. This is an experimental study. Primary urothelial cells were purchased from CellnTec, Bern, Switzerland; fibroblasts were isolated from the ureter of patients with no urothelial malignancy in their medical history. As main methods we used quantitative real-time PCR and immunohistochemistry. Outcomes were analysed using SPSS 23.0. We were able to develop a 3D organotypic culture for primary urothelium. An infection with archetype BKPyV was established in this model with virus replication rates up to 6.41 × 108 copies/ml on day 9 following Infection. Interestingly, proliferation rate of the urothelial cells is significantly (p = 0.049 at day 6 following infection) elevated while cells are losing differentiation under infection. Phosphorylated STAT3 is also significantly elevated (p < 0.0001) during infection. The established of urothelial 3D cultures is a new method to study several urothelial diseases. The archetype BKPyV infection model is novel and the first method to study archetype viral life cycle. The STAT3 pathway might be an interesting target for the development of a causal therapy. [ABSTRACT FROM AUTHOR]