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Objectives: Treatment intensification (including consolidative high‐dose chemotherapy with autologous stem cell transplantation [HDT‐ASCT]) significantly improved outcome in primary central nervous system lymphoma (PCNSL) patients. Methods: We conducted a multicenter, retrospective analysis of newly diagnosed PCNSL patients, treated with intensified treatment regimens. The following scores were evaluated in terms of overall survival (OS) and progression‐free survival (PFS): Memorial Sloan‐Kettering Cancer Center (MSKCC), International Extranodal Lymphoma Study Group (IELSG), and three‐factor (3F) prognostic score. Further, all scores were comparatively investigated for model quality and concordance. Results: Altogether, 174 PCNSL patients were included. One hundred and five patients (60.3%) underwent HDT‐ASCT. Two‐year OS and 2‐year PFS for the entire population were 73.3% and 48.5%, respectively. The MSKCC (p =.003) and 3F score (p <.001), but not the IELSG score (p =.06), had the discriminatory power to identify different risk groups for OS. In regard to concordance, the 3F score (C‐index [0.71]) outperformed both the MSKCC (C‐index [0.64]) and IELSG (C‐index [0.53]) score. Moreover, the superiority of the 3F score was shown for PFS, successfully stratifying patients in three risk groups, which also resulted in the highest C‐index (0.66). Conclusion: The comparative analysis of established PCNSL risk scores affirm the clinical utility of the 3F score stratifying the widest prognostic spectrum among PCNSL patients treated with intensified treatment approaches. [ABSTRACT FROM AUTHOR]

Objectives: Chlorhexidine gluconate (CHG)‐coated gel pad dressings for central venous catheter (CVC) may prevent CVC‐related bloodstream infections (CRBSI). However, real‐world data showing beneficial effects in patients with hematologic malignancies are scarce. Methods: In a matched‐pair analysis with data from a multicenter CVC registry, non‐tunneled jugular and subclavian vein CVC in adults with hematologic malignancies or germ cell tumors (including patients receiving autologous hematopoietic stem cell transplantation [ASCT]) with CHG were compared with non‐CHG dressings. The primary endpoint was definite CRBSI rate within 14 days (dCRBSI14) of CVC insertion; secondary endpoints were combined rate of definite or probable CRBSI within 14 days (dpCRBSI14), overall (dpCRBSI), and CRBSI incidences of all estimates. Results: In total, 2070 CVCs were assessed. There was no statistically significant difference in dCRBSI14 (2.3% vs. 3.5%) between patients with and without CHG gel dressings. Likewise, with regards to dpCRBSI14 (6.2% vs. 6.3%) and the overall dpCRBSI rate (9.2% vs. 10.5%), no significant difference was detected. Furthermore, dCRBSI14 incidence (2.0 vs. 3.2/1000 CVC days), dpCRBSI14 incidence (5.4 vs. 5.6/1000 CVC days), and overall CRBSI incidence (5.5 vs. 6.0/1000 CVC days) showed no significant differences. Conclusions: CRBSI rates were not reduced by the use of CHG gel dressings in patients with hematologic malignancies and/or ASCT. [ABSTRACT FROM AUTHOR]

Introduction: In patients with a clinical indication for autologous hematopoietic stem cell transplantation (ASCT), sufficient mobilization of CD34+ precursor cells into peripheral blood is essential to ensure adequate hematopoietic stem cell (HSC) collection prior to intensive therapy. However, with standard granulocyte-colony stimulating factor (G-CSF)-based mobilization schemes, an important minority of patients fail to mobilize sufficient (e.g., >10/µL) CD34+ cell counts into the peripheral blood and are considered as poor mobilizers (PM). Because failure to achieve sufficient CD34+ cell mobilization can negatively affect important clinical treatment endpoints, the use of plerixafor (PLX) was approved to increase CD34+ mobilization in PM patients. Methods: The German non-interventional, multicenter, open-label, prospective OPTIMOB study evaluated HSC mobilization strategies prior to planned ASCT in adult patients with hematologic malignancies (lymphomas or multiple myeloma [MM]) focusing on PM patients. PM patients were defined as follows: (1) never achieving ≥20 CD34+ cells/µL before 1st apheresis, (2) receiving PLX at any timepoint of mobilization, (3) their initially planned stem cell yield had to be reduced, or (4) they had not received apheresis due to low CD34+ count in peripheral blood. Results: 168 of 475 MM patients (35%) participating in the OPTIMOB study were classified as PM, and 155 of them (92%) received PLX (PM+PLX) during the study. PM patients were 40–78 years old, slightly more often male (n = 97, 58%), mostly newly diagnosed (n = 146, 87%) and received highly individualized previous treatments. Ninety-four of the PMs underwent chemotherapy mobilization (65%), and 51 patients (35%) received steady-state mobilization with G-CSF only during 1st mobilization attempt. 92% of the total PM population (n = 155) underwent apheresis, 78% of them (n = 117) achieved >2.0 × 106 CD34+ cells/kg body weight on the 1st day of apheresis. PM+PLX had a higher median total collection result than those PM patients without PLX support (7.2 vs. 5.7 × 106 CD34+ cells/kg body weight). In total, ASCT was performed in 136 PM+PLX (88%) versus 8 PM−PLX patients (62%). Conclusion: The OPTIMOB study showed that a considerable proportion of adult MM patients in Germany are PMs. Even though most of PMs were supported with PLX in the OPTIMOB study, PM-PLX also successfully mobilized HSCs, allowing ASCT in majority of all PMs. However, further analyses are required for treatment optimization in PMs. [ABSTRACT FROM AUTHOR]

Acute myeloid leukaemias harbouring a rearrangement of the mixed lineage leukaemia gene (MLL) are aggressive haematopoietic malignancies that relapse early and have a poor prognosis (event-free survival less than 50%). Menin is a tumour suppressor, however, in MLL-rearranged leukaemias it functions as a co-factor which is mandatory for the leukaemic transformation by interaction with the N-terminal part of MLL, which is maintained in all MLL-fusion proteins. Inhibition of menin blocks leukaemogenesis and leads to differentiation and, in turn, to apoptosis of leukaemic blasts. Furthermore, nucleophosmin 1 (NPM1) binds to specific chromatin targets, which are co-occupied by MLL, and menin inhibition has been shown to trigger degradation of mNPM1 resulting in a rapid decrease in gene expression and activating histone modifications. Therefore, disruption of the menin-MLL axis blocks leukaemias driven by NPM1 mutations for which the expression of menin-MLL target genes (e.g., MEIS1, HOX etc.) is essential. To date at least six different menin-MLL inhibitors are undergoing clinical evaluation as first- and second-line monotherapy in acute leukaemias: DS-1594, BMF-219, JNJ-75276617, DSP-5336, revumenib, and ziftomenib, however, only for revumenib and ziftomenib early clinical data have been reported. In the revumenib phase I/II AUGMENT-101 trial (N = 68) with very heavily pretreated AML patients the ORR was 53% with a CR rate of 20%. The ORR in patients harbouring MLL rearrangement of mNPM1 was 59%. Patients who achieved a response had a mOS of 7 months. Similar results have been reported for ziftomenib in the phase I/II COMET-001 trial. ORR was 40% and CRc was 35% in AML patients with mNPM1. However, outcome was worse in AML patients with a MLL rearrangement (ORR 16.7%, CRc 11%). Differentiation syndrome was a notable adverse event. The clinical development of novel menin-MLL inhibitors is well in line with the currently ongoing paradigm shift towards targeted therapies seen in the AML treatment landscape. Moreover, the clinical assessment of combinations of these inhibitors with established therapy options in AML could be the fuel for an improved outcome of MLL/NPM1 patients. [ABSTRACT FROM AUTHOR]

Introduction: Successful mobilization and collection of peripheral hematopoietic stem cells (HSCs) are necessary for lymphoma patients eligible for myeloablative chemotherapy with subsequent autologous stem cell transplantation (ASCT). Albeit G-CSF alone or combined with chemotherapy is well-established methods for HSC mobilization, up to 40% of the patients fail to mobilize (poor mobilizer, PM). Plerixafor (PLX) is commonly used in PM patients resulting in increased migration of HSCs into peripheral blood and thus improves the collection outcome. Methods: The prospective, multicenter, open-label, non-interventional OPTIMOB study assessed mobilization and collection parameter of patients with lymphoma or multiple myeloma to get deep insights in the treatment of those patients in clinical routine focusing on PM patients. PM was defined as follows: (1) no achievement of ≥20 CD34+ progenitor cells/µL before first apheresis, (2) PLX administration at any time point during the observational period, (3) reduction of the initially planned CD34+ progenitor cell yield as necessity due to failed mobilization or HSC collection, and (4) no performance of apheresis due to low CD34+ progenitor level. Primary objective of the study was to assess mobilization success by the proportion of PM patients achieving >2 × 106 CD34+ progenitor cells/kg body weight on the first day of apheresis. Here, the data of the lymphoma cohort are presented. Results: Out of 238 patients with lymphoma documented in the study, 32% were classified as PM. 87% of them received PLX. Demographic data revealed no obvious differences between PM and good mobilizing (GM) patients. All patients were treated highly individualized prior to mobilization. Majority of all PM patients were able to undergo apheresis (95%) and reached their individual requested CD34+ progenitor cell target (72%). 57% of the PM patients achieved >2.0 × 106 CD34+ progenitor cells/kg body weight on day 1 of apheresis and nearby 70% of them underwent ASCT. Median time to engraftment was similar in PM and GM patients of the lymphoma cohort. Conclusions: Majority of PM patients with lymphoma were successfully mobilized and underwent ASCT. Most of them received PLX during the study. [ABSTRACT FROM AUTHOR]

Purpose: Overall, insertion of central venous catheter (CVC) into femoral veins (FV) has been shown to be associated with a higher risk of infection compared with subclavian and internal jugular (IJV/SCV) CVC, but no data are available on the impact of the FV insertion site on the CVC-related bloodstream infections (CRBSI) risk in patients with cancer. The objective of the study is to compare CRBSI rates and incidences of FV with those of internal jugular and subclavian vein (IJV/SCV CVC) as observed in the prospective SECRECY registry. Methods: SECRECY is an ongoing observational, prospective, clinical CRBSI registry active in six departments of hematology/oncology in Germany. Each case of FV CVC was matched at a ratio of 1:1 to a case with IJV/SCV CVC. The propensity score was estimated using a multivariable logistic regression model adjusting for age, sex, cancer type, and duration of indwelling catheter. Results: Of 4268 CVCs included in this analysis, 52 (1.2%) were inserted into the FV and 4216 (98.8%) into the IJV/SCV. 52 cases of FV CVC were matched with 52 IJV/SCV CVC. There was no significant difference in the CRBSI rate (3.8% vs. 9.6%), the CRBSI incidence (5.7 vs. 14.2/1000 CVC days), and the median CVC time (5.5 vs. 5 days) between the FV and the IJV/SCV group. Conclusion: Based on this data, inserting FV CVCs in patients with cancer does, at least in the short-term, not appear to be associated with an increased risk of CRBSI as compared to IJV/SCV CVC. [ABSTRACT FROM AUTHOR]

Patients with haematological malignancies (HM) are at high risk of developing invasive fungal disease (IFD) with high morbidity and attributable mortality. We reviewed data published until September 2021 to update the 2017 antifungal prophylaxis recommendations of the German Society of Haematology and Medical Oncology (DGHO). The strong recommendation to administer antifungal prophylaxis in patients with HM with long-lasting neutropenia, i.e. <500 cells/μL for >7 days remains unchanged. Posaconazole remains the drug of choice for mould-active prophylaxis in these patients. Novel treatment options in HM, such as CAR-T-cell treatment or novel targeted therapies for acute myeloid leukaemia (AML) were considered, however, data are insufficient to give general recommendations for routine antifungal prophylaxis in these patients. Major changes regarding specific recommendations compared to the 2017 edition are the now moderate instead of mild support for the recommendations of isavuconazole and voriconazole. Furthermore, published evidence on micafungin allows recommending it at moderate strength for its use in HM. For the first time we included recommendations for non-pharmaceutical measures regarding IFD, comprising the use of high-efficiency particulate air (HEPA) filters, smoking, measures during construction work and neutropenic diets. We reviewed the impact of antifungal prophylaxis with triazoles on drug–drug interactions with novel targeted therapies that are metabolized via cytochrome p450 where triazoles inhibit CYP3A4/5. The working group recommends reducing the dose of venetoclax when used concomitantly with strong CYP3A4 inhibiting antifungals. Furthermore, we reviewed data on the prophylactic use of novel antifungal agents. Currently there is no evidence to support their use in a prophylactic setting in clinical practice. [ABSTRACT FROM AUTHOR]

As stated in Table S1, one centre had a markedly reduced CVC insertion/documentation rate during the pandemic, and the six centres had no similar CRBSI incidences/rates. Central venous catheter, central venous catheter-related bloodstream infection, epidemiology, haematological malignancies, pandemic, SARS-CoV-2 Keywords: central venous catheter; central venous catheter-related bloodstream infection; epidemiology; haematological malignancies; pandemic; SARS-CoV-2 EN central venous catheter central venous catheter-related bloodstream infection epidemiology haematological malignancies pandemic SARS-CoV-2 e16 e20 5 11/11/22 20221115 NES 221115 Patients with haematological malignancies are at increased risk for infectious complications. [Extracted from the article]

Although not generally recommended, scheduled central venous catheter (CVC) removal is sometimes carried out in order to reduce the CVC-related bloodstream infection (CRBSI) incidence. We conducted a simulation for scheduled CVC removal within the multicenter CRBSI registry (SECRECY). Non-tunneled jugular and subclavian CVC in patients with hematological disease or with germ cell tumors (including patients receiving autologous stem cell transplantation [SCT]) were included. Cases were randomized in a 1:1:1:1 ratio to either a simulated, scheduled CVC removal after 7, 14, and 21 days, or to non-simulated, unscheduled CVC removal (control group). The primary endpoint was definitive CRBSI incidence for a scheduled CVC removal after 14 days (dCRBSI-D14rmv). Among other, secondary endpoints were definite CRBSI incidence for a scheduled removal after 7 days (dCRBSI-D7rmv) and 21 days (dCRBSI-D21rmv). Data on 2984 CVC were included. Patients' median age was 59 (range 16-95) years, 58.8% being male. The vast majority (98.4%) were patients with hematological malignancies. Jugular veins were the main insertion site (93.2%). dCRBSI-D14rmv was 3.10/1000 CVC days as compared to 4.15/1000 CVC days in the control group (p = 0.23). There was a significant difference between dCRBSI-D7rmv (0.86/1000 CVC days) and controls (p < 0.001), but not between dCRBSI-D21rmv (4.10/1000 CVC days) and controls (p = 0.96). Our data suggest that in patients with hematological diseases or autologous SCT recipients scheduled CVC removal after 14 days does not result in a lower CRBSI incidence compared to unscheduled removal.Trial registration: DRKS00006551, 2014/09/29, retrospectively registered. [ABSTRACT FROM AUTHOR]

Clinical reactivations of herpes simplex virus or varicella zoster virus occur frequently among patients with malignancies and manifest particularly as herpes simplex stomatitis in patients with acute leukaemia treated with intensive chemotherapy and as herpes zoster in patients with lymphoma or multiple myeloma. In recent years, knowledge on reactivation rates and clinical manifestations has increased for conventional chemotherapeutics as well as for many new antineoplastic agents. This guideline summarizes current evidence on herpesvirus reactivation in patients with solid tumours and hematological malignancies not undergoing allogeneic or autologous hematopoietic stem cell transplantation or other cellular therapy including diagnostic, prophylactic, and therapeutic aspects. Particularly, strategies of risk adapted pharmacological prophylaxis and vaccination are outlined for different patient groups. This guideline updates the guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) from 2015 "Antiviral prophylaxis in patients with solid tumours and haematological malignancies" focusing on herpes simplex virus and varicella zoster virus. [ABSTRACT FROM AUTHOR]

To ensure the safety of high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT), evidence-based recommendations on infectious complications after HDC/ASCT are given. This guideline not only focuses on patients with haematological malignancies but also addresses the specifics of HDC/ASCT patients with solid tumours or autoimmune disorders. In addition to HBV and HCV, HEV screening is nowadays mandatory prior to ASCT. For patients with HBs antigen and/or anti-HBc antibody positivity, HBV nucleic acid testing is strongly recommended for 6 months after HDC/ASCT or for the duration of a respective maintenance therapy. Prevention of VZV reactivation by vaccination is strongly recommended. Cotrimoxazole for the prevention of Pneumocystis jirovecii is supported. Invasive fungal diseases are less frequent after HDC/ASCT, therefore, primary systemic antifungal prophylaxis is not recommended. Data do not support a benefit of protective room ventilation e.g. HEPA filtration. Thus, AGIHO only supports this technique with marginal strength. Fluoroquinolone prophylaxis is recommended to prevent bacterial infections, although a survival advantage has not been demonstrated. [ABSTRACT FROM AUTHOR]

Summary: Background: Invasive fungal diseases remain a major cause of morbidity and mortality in cancer patients undergoing intensive cytotoxic therapy. The choice of the most appropriate antifungal treatment (AFT) depends on the fungal species suspected or identified, the patient's risk factors (eg length and depth of granulocytopenia) and the expected side effects. Objectives: Since the last edition of recommendations for 'Treatment of invasive fungal infections in cancer patients' of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) in 2013, treatment strategies were gradually moving away from solely empirical therapy of presumed or possible invasive fungal diseases (IFDs) towards pre‐emptive therapy of probable IFD. Methods: The guideline was prepared by German clinical experts for infections in cancer patients in a stepwise consensus process. MEDLINE was systematically searched for English‐language publications from January 1975 up to September 2019 using the key terms such as 'invasive fungal infection' and/or 'invasive fungal disease' and at least one of the following: antifungal agents, cancer, haematological malignancy, antifungal therapy, neutropenia, granulocytopenia, mycoses, aspergillosis, candidosis and mucormycosis. Results: AFT of IFDs in cancer patients may include not only antifungal agents but also non‐pharmacologic treatment. In addition, the armamentarium of antifungals for treatment of IFDs has been broadened (eg licensing of isavuconazole). Additional antifungals are currently under investigation or in clinical trials. Conclusions: Here, updated recommendations for the treatment of proven or probable IFDs are given. All recommendations including the levels of evidence are summarised in tables to give the reader rapid access to key information. [ABSTRACT FROM AUTHOR]

We performed a prospective study to evaluate the types and characteristics of central nervous system (CNS) disorders in patients after hematopoietic stem cell transplantation. The study included 163 episodes of CNS disorders of which 58 (36%) were infections. Proven or probable infections were documented in 34 patients and included fungi (n = 10, 29%), viruses (n = 12, 35%), Toxoplasma spp. (n = 9, 27%) and bacteria (n = 3, 9%). Non-infectious neurological disorders (n = 105, 64%) frequently encompassed metabolic/drug-induced abnormalities (n = 28, 27%) or cerebral vascular events (n = 22, 21%). Median onset times were later for infectious (day + 101) vs non-infectious neurological disorders (day + 50, p = 0.009). An unremarkable cranial CT scan was found in 33% of infection episodes. Absence of cerebrospinal fluid pleocytosis despite a normal or increased peripheral blood white blood cell count occurred in 26% of infections. Day-30 mortality rates were significantly higher for fungal (87%) vs non-fungal infections (40%, p < 0.001). Significantly higher mortality rates were also documented for cerebral vascular events than for other non-infectious disorders (86% vs 34%, p < 0.001). Our prospective study shows that diagnostic findings in CNS infections might differ between hematopoietic stem cell transplant recipients and immunocompetent hosts. Special awareness and timely initiation of adequate diagnostics are crucial to improve the prognosis of these patients. [ABSTRACT FROM AUTHOR]

Introduction: Infections are among the most frequent complications in patients with hematological and oncological diseases. They might be classified as fever of unknown origin and microbiologically or clinically documented infections. Optimal duration of antimicrobial treatment is still unclear in these patients.Areas covered: We provide an overview on the management of febrile neutropenia in the perspective of antimicrobial de-escalation and discontinuation.Expert opinion: Patients with febrile high-risk neutropenia should be treated empirically with an anti-pseudomonal agent such as piperacillin/tazobactam. Several clinical studies support the assumption that the primary antibiotic regimen might be safely discontinued prior to neutrophil reconstitution if the patient is afebrile for several days and all infection-related symptoms have been resolved. Primary empirical treatment with carbapenems or antibiotic combinations should commonly only be considered in selected patient subgroups, such as patients with severe neutropenic sepsis or colonization with multidrug-resistant bacteria. Preemptive antifungal treatment guided by lung imaging and other parameters (e.g. serial Aspergillus galactomannan antigen screening) might reduce the consumption of antifungals compared to the classical empirical approach.Multidrug-resistant pathogens are emerging, and novel anti-infective agents under development are scarce. Therefore, a rational use of antimicrobials based on the principles of antibiotic stewardship is crucial. [ABSTRACT FROM AUTHOR]

It has been shown recently that donor and/or recipient cytomegalovirus (CMV) seropositivity is associated with a significant overall survival (OS) decline in acute leukemia patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We now analyzed the prognostic impact of the donor/recipient CMV serostatus in 6968 patients with chronic hematological malignancies who underwent allo-HSCT. Donor and/or recipient CMV seropositivity was associated with a significantly reduced 2-year progression-free survival (PFS, 50% vs. 52%, p = 0.03) and OS (62% vs. 65%, p = 0.01). Multivariate Cox regression analyses showed an independent negative prognostic impact of donor and/or recipient CMV seropositivity on PFS (HR, 1.1; 95% CI, 1.0-1.2; p = 0.03), OS (HR, 1.1; 95% CI, 1.0-1.2; p = 0.003), and non-relapse mortality (HR, 1.2; 95% CI, 1.0-1.3; p = 0.02). OS decline was strongest for CMV-seropositive recipients with a CMV-seronegative donor (HR, 1.2; 95% CI, 1.1-1.3), followed by CMV-seropositive patients with a CMV-seropositive donor (HR, 1.1; 95% CI, 1.0-1.2). Conversely, OS did not differ significantly between CMV-seronegative recipients allografted from a CMV-seropositive donor (HR, 1.0; 95% CI, 0.9-1.2) and patients with donor/recipient CMV seronegativity (p = 0.001 for the four groups together). Non-relapse mortality was also significantly (p = 0.01) higher for CMV-seropositive patients with a CMV-seronegative graft (HR, 1.2; 95% CI, 1.1-1.4) than for CMV-seropositive patients with a CMV-seropositive graft (HR, 1.1; 95% CI, 0.9-1.2) or CMV-seronegative recipients with a CMV-seropositive graft (HR, 1.0; 95% CI, 0.8-1.2). Donor and/or recipient CMV seropositivity still results in an OS decline in patients with chronic hematological malignancies who have undergone allo-HSCT. However, this OS decline seems to be lower than that described for acute leukemia patients previously. [ABSTRACT FROM AUTHOR]

Summary: Invasive fungal diseases (IFD) are a primary cause of morbidity and mortality in patients with haematological malignancies. These infections are mostly life‐threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However, other Non‐Aspergillus moulds are increasingly identified in case of documented IFD. For definite diagnosis of IFD, a combination of diagnostic tools have to be applied, including conventional mycological culture and non‐conventional microbiological tests such as antibody/antigen and molecular tests, as well as histopathology and radiology. Although varying widely in cancer patients, the risk of invasive fungal infection is highest in those with allogeneic stem cell transplantation and those with acute leukaemia and markedly lower in patients with solid cancer. Since the last edition of Diagnosis of Invasive Fungal Diseases recommendations of the German Society for Hematology and Oncology in 2012, integrated care pathways have been proposed for the management and therapy of IFDs with either a diagnostic driven strategy as opposed to a clinical or empirical driven strategy. This update discusses the impact of this additional evidence and effective revisions. [ABSTRACT FROM AUTHOR]

Objective Analysis of the efficiency and toxicity of cyclophosphamide-based stem cell mobilization in patients with relapsed multiple myeloma ( RMM). Methods Peripheral blood stem cells ( PBSCs) were mobilized with high dose cyclophosphamide (2 g/m2 daily on days 1 and 2) and G- CSF plus pre-emptive/rescue plerixafor in RMM patients (first to third relapse) treated within the Re LApsE trial of the German-Speaking Myeloma Multicenter Group ( GMMG). Results Mobilization was initiated with high-dose cyclophosphamide (HD-CY) and G- CSF in 30 patients. Fifteen patients received additional pre-emptive/rescue administration of plerixafor. Stem cell collection was successful (≥2×106 CD34+ cells per kg bw) in 77% (23/30 patients). Patients with prior high-dose melphalan collected a significantly lower median total number of PBSCs than patients without prior high-dose melphalan (3.3×106 vs 17×106 CD34+ cells/kg bw). Toxicity of HD-CY was frequent with 12 serious adverse events ( SAE) in 37% of patients (11/30 patients). Infections accounted for the majority of SAE reports. In two patients, SAEs were lethal (septic shock). Conclusions These data proof feasibility of PBSC collection at relapse but emphasize the importance of collection and storage of additional PBSC transplants during first-line treatment when mobilization is more efficient and less toxic. [ABSTRACT FROM AUTHOR]

The combination of lenalidomide (Revlimid®, R) and dexamethasone (d) is a standard regimen for patients with relapsed/refractory multiple myeloma (rr MM). With this regimen, only a small fraction of patients will achieve high quality responses [≥ very good partial response ( VGPR)]. The combination of bendamustine (B), lenalidomide and dexamethasone ( BRd) has shown high efficacy in patients with advanced rr MM. However, dose-limiting haematotoxicity restricted its use in extensively pre-treated patient populations. This prospective, multicentre Phase II study evaluated the efficacy and safety of BRd in rr MM patients with one prior line of therapy. Fifty patients were enrolled (median age 68·5 years [range 46-83]) and were treated with B 75 mg/m2 days 1, 2; R 25 mg days 1-21 and d (40/20 mg) days 1, 8, 15 and 22, for 6 28-day induction cycles, followed by 12 cycles with Rd alone. Pegfilgrastim was administered according to protocol-defined criteria. The study aimed to demonstrate a complete response ( CR)/ VGPR rate of >40% after induction therapy. Of 45 evaluable patients, 23 (51%) achieved a CR/ VGPR. Grade 4 neutropenia or thrombocytopenia occurred in 17 (34%) and 8 (16%) of patients, respectively. BRd is a safe and efficacious regimen as a second line treatment for rr MM, leading to high quality responses in a considerable proportion of patients. [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]

Background: Multiple myeloma is a malignant disease of plasma cells with a worldwide incidence of 6-7 cases per 100 000 persons per year. It is among the 20 most common types of cancer in Germany. Methods: This review is based on pertinent publications up to December 2015 that were retrieved by a selective search of PubMed employing the terms "multiple myeloma" AND "therapy" OR "diagnostic." Systematic reviews, meta-analyses, randomized controlled trials, and treatment recommendations from Germany and abroad were considered. Results: The diagnostic evaluation of multiple myeloma comprises thorough history-taking and physical examination, various laboratory tests including analysis of a 24-hour urine sample, a bone-marrow biopsy, and skeletal radiography. Systemic treatment should be administered only when organ damage has been diagnosed. The type of treatment to be given is chosen individually on the basis of the patient's age, comorbidities, and risk profile. High-dose therapy with autologous stem-cell transplantation remains the treatment of choice for patients under age 70 who are otherwise in good health. For patients who are not candidates for high-dose therapy or who have had a recurrence of multiple myeloma after prior high-dose therapy, there are a number of further conventional treatment options. Patients need not only systemic antineoplastic treatment, but also supportive treatment for the prevention of treatment-induced toxicity and myeloma-associated organ damage. Conclusion: Recent therapeutic advances have made the treatment of multiple myeloma both more complex and more costly. In particular, the median survival of patients with multiple myeloma has been markedly prolonged through the use of targeted drugs such as proteasome inhibitors and immune modulators. [ABSTRACT FROM AUTHOR]

Background: Despite novel therapeutic agents, most multiple myeloma (MM) patients eventually relapse. Two large phase III trials have shown significantly improved response rates (RR) of lenalidomide/dexamethasone compared with placebo/dexamethasone in relapsed MM (RMM) patients. These results have led to the approval of lenalidomide for RMM patients and lenalidomide/dexamethasone has since become a widely accepted second-line treatment. Furthermore, in RMM patients consolidation with high-dose chemotherapy plus autologous stem cell transplantation has been shown to significantly increase progression free survival (PFS) as compared to cyclophosphamide in a phase III trial. The randomized prospective ReLApsE trial is designed to evaluate PFS after lenalidomide/dexamethasone induction, high-dose chemotherapy consolidation plus autologous stem cell transplantation and lenalidomide maintenance compared with the well-established lenalidomide/dexamethasone regimen in RMM patients.Methods/design: ReLApsE is a randomized, open, multicenter phase III trial in a planned study population of 282 RMM patients. All patients receive three lenalidomide/dexamethasone cycles and--in absence of available stem cells from earlier harvesting--undergo peripheral blood stem cell mobilization and harvesting. Subsequently, patients in arm A continue on consecutive lenalidomide/dexamethasone cycles, patients in arm B undergo high dose chemotherapy plus autologous stem cell transplantation followed by lenalidomide maintenance until discontinuation criteria are met. Therapeutic response is evaluated after the 3(rd) (arm A + B) and the 5(th) lenalidomide/dexamethasone cycle (arm A) or 2 months after autologous stem cell transplantation (arm B) and every 3 months thereafter (arm A + B). After finishing the study treatment, patients are followed up for survival and subsequent myeloma therapies. The expected trial duration is 6.25 years from first patient in to last patient out. The primary endpoint is PFS, secondary endpoints include overall survival (OS), RR, time to best response and the influence of early versus late salvage high dose chemotherapy plus autologous stem cell transplantation on OS.Discussion: This phase III trial is designed to evaluate whether high dose chemotherapy plus autologous stem cell transplantation and lenalidomide maintenance after lenalidomide/dexamethasone induction improves PFS compared with the well-established continued lenalidomide/dexamethasone regimen in RMM patients.Trial Registration: ISRCTN16345835 (date of registration 2010-08-24). [ABSTRACT FROM AUTHOR]

Background: The prevalence of extended-spectrum β-lactamase producing Enterobacteriaceae (ESBL-E) is increasing worldwide. ESBL-E are known to colonize different body sites and cause bloodstream infections (BSI), pneumonia, intra-abdominal infections and urinary tract infections. Even though ESBL-E-related morbidity and mortality in high-risk patients – patients receiving immunosuppressants or chemotherapy, as well as those treated in an ICU – is considerable, the management of ESBL-E in these populations has not been systematically reviewed.Methods: For the purpose of this review, ICU patients, patients in hematology and oncology wards and transplant recipients were considered high-risk. An English-language Medline search was conducted to identify literature on epidemiology, risk factors, clinical impact and measures of infection control regarding ESBL-E in high-risk patients published between June 2002 and May 2013.Results: Using the above described methodology, 43 relevant articles regarding high-risk patients and – for areas where literature on exclusively high-risk patients is scarce – 17 articles in standard risk settings were identified. The evidence on epidemiology, associated risk factors, treatment and hygiene measures were summarized.Discussion: This review gives a complete overview on the management of ESBL-E in the high-risk setting. [ABSTRACT FROM PUBLISHER]

Targeting tyrosine kinases represents a highly specific treatment approach for different malignancies. This also includes non-Hodgkin lymphoma since it is well known that these enzymes are frequently involved in the lymphomagenesis. Hereby, tyrosine kinases might either be dysregulated intrinsically or be activated within signal transduction pathways leading to tumor survival and growth. Among others, Bruton's tyrosine kinase (Btk) is of particular interest as a potential therapeutic target. Btk is stimulated by B-cell receptor signaling and activates different transcription factors such as nuclear factor κB. The Btk inhibitor ibrutinib has been approved for the treatment of chronic lymphocytic leukemia and mantle-cell lymphoma recently. Numerous clinical trials evaluating this agent in different combinations (eg, with rituximab or classical chemotherapeutic agents) as a treatment option for aggressive and indolent lymphoma are under way. Here, we summarize the role of tyrosine kinase inhibitors in the treatment of indolent and other non-Hodgkin lymphomas (eg, mantle-cell lymphoma). [ABSTRACT FROM AUTHOR]

Background: Alterations and senescence in bone marrow mesenchymal stromal cells of multiple myeloma patients (MM-BMMSCs) have become an important research focus. However the role of senescence in the pathophysiology of MM is not clear. Methods: Correlation between senescence, cell cycle and microRNA expression of MM-BMMSCs (n = 89) was analyzed. Gene expression analysis, copy number analysis and methylation specific PCR were performed by Real-Time PCR. Furthermore, cyclin E1, cyclin D1, p16 and p21 genes were analyzed at the protein level using ELISA. Cell cycle and senescence were analyzed by FACS. MiRNA transfection was performed with miR-485-5p inhibitor and mimic followed by downstream analysis of senescence and cell cycle characteristics of MM-BMMSCs. Results were analyzed by Mann–Whitney U test, Wilcoxon signed-rank test and paired t-test depending on the experimental set up. Results: MM-BMMSCs displayed increased senescence associated β-galactosidase activity (SA-βGalA), cell cycle arrest in S phase and overexpression of microRNAs. The overexpressed microRNAs miR-485-5p and miR-519d are located on DLK1-DIO3 and C19MC, respectively. Analyses revealed copy number accumulation and hypomethylation of both clusters. KMS12-PE myeloma cells decreased SA-βGalA and influenced cell cycle characteristics of MM-BMMSCs. MiR-485-5p was significantly decreased in co-cultured MM-BMMSCs in connection with an increased methylation of DLK1-DIO3. Modification of miR-485-5p levels using microRNA mimic or inhibitor altered senescence and cell cycle characteristics of MM-BMMSCs. Conclusions: Here, we show for the first time that MM-BMMSCs have aberrant methylation and copy number of the DLK1-DIO3 and C19MC genomic region. Furthermore, this is the first study pointing that multiple myeloma cells in vitro reduce both the senescence phenotype of MM-BMMSCs and the expression of miR-223 and miR-485-5p. Thus, it is questionable whether senescence of MM-BMMSCs plays a pathological role in active multiple myeloma or is more important when cell interaction with myeloma cells is inhibited. Furthermore, we found that MiR-485-5p, which is located on the DLK1-DIO3 cluster, seems to participate in the regulation of senescence status and cell cycle characteristics of MM-BMMSCs. Thus, further exploration of the microRNAs of DLK1-DIO3 could provide further insights into the origin of the senescence state and its reversal in MM-BMMSCs. [ABSTRACT FROM AUTHOR]

Sepsis is a major cause of mortality during the neutropenic phase after intensive cytotoxic therapies for malignancies. Improved management of sepsis during neutropenia may reduce the mortality of cancer therapies. Clinical guidelines on sepsis treatment have been published by others. However, optimal management may differ between neutropenic and non-neutropenic patients. Our aim is to give evidence-based recommendations for haematologist, oncologists and intensive care physicians on how to manage adult patients with neutropenia and sepsis. [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]

We analyzed the prognostic impact of donor and recipient cytomegalovirus (CMV) serostatus in 16628 de novo acute leukemia patients after allogeneic stem cell transplantation (allo-SCT). Compared with CMV-seronegative recipients who underwent allograft from a CMV-seronegative donor, cases of CMV seropositivity of the donor and/or the recipient showed a significantly decreased 2-year leukemia-free survival (44% vs 49%, P< .001) and overall survival (50% vs 56%, P< .001), and increased nonrelapse mortality (23% vs 20%, P< .001). Both groups showed a comparable relapse incidence and 2-year probability of graft-versus-host disease. The negative prognostic effects of CMV seropositivity of the donor and/or the recipient (vs CMV seronegativity of both) were significantly stronger for acute lymphoblastic leukemia (ALL) than for acute myeloid leukemia (AML), resulting in a markedly reduced 2-year overall survival (46% vs 55% for ALL compared with 52% vs 56% for AML). The important prognostic impact of donor/recipient CMV serostatus remained in a multivariate Cox regression analysis including the other prognostic variables. We conclude that donor and/or recipient CMV seropositivity is still associated with an adverse prognosis in de novo acute leukemia patients after allo-SCT despite the implementation of sophisticated strategies for prophylaxis, monitoring, and (preemptive) treatment of CMV. [ABSTRACT FROM AUTHOR]

We analyzed cytomegalovirus (CMV) infection risk factors and immune reconstitution kinetics in 89 patients after allogeneic stem cell transplantation (allo-SCT). The use of alemtuzumab for in vivo T cell depletion (TCD) had, besides the donor/recipient CMV serostatus, the strongest influence on the CMV infection risk in univariate and multivariate analyses. In comparison to without use of in vivo TCD, the CMV infection risk [hazard ratio (HR)] was 4.82-fold after TCD with alemtuzumab, but only 1.40-fold after TCD with antithymocyte globulin (ATG). Alemtuzumab strongly depressed CD4(+) and CD8(+) T cell reconstitution, whereas ATG only delayed CD4(+) T cell reconstitution. Considering the reconstitution kinetics of CD4(+) and CD8(+) T cells, CMV-specific CD8(+) T cells, NK cells and the IgG concentration, only a low day +60 NK cell count (< or =161 versus >161/microl) was significantly associated with CMV infection development (HR 2.92, p = 0.034). CMV-specific CD8(+) T cells were detected in 57% of patients with a CMV-seropositive donor, but in none of the patients with a CMV-seronegative donor on day +30 (p = 0.01). Our data indicate that the type of in vivo TCD (alemtuzumab or ATG) differentially influences both the CMV infection risk and CD4(+)/CD8(+) T cell reconstitution kinetics in patients after allo-SCT. [ABSTRACT FROM AUTHOR]

Abstract: We analyzed karyotype stability in 22 patients with acute leukemia at relapse or disease progression after allogeneic stem cell transplantation (allo-SCT). Karyotypes before and at relapse after allo-SCT were different in 15 patients (68%), the most frequent type being clonal evolution either alone or combined with clonal devolution (13 patients). Patients with and without a karyotype change did not differ significantly in overall survival (OS) (median, 399 vs. 452 days; P = 0.889) and survival after relapse (median, 120 vs. 370 days; P = 0.923). However, acquisition of additional structural chromosome 1 abnormalities at relapse after allo-SCT occurred more frequently than expected and was associated with reduced OS (median, 125 vs. 478 days; P = 0.008) and shorter survival after relapse (median, 37 vs. 370 days; P = 0.002). We identified a previously undescribed clonal evolution involving t(15;17) without PML-RARA rearrangement in an AML patient. We conclude that a karyotype change is common at relapse after allo-SCT in acute leukemia patients. Moreover, our data suggest that additional structural chromosome 1 abnormalities are overrepresented at relapse after allo-SCT in these patients and, in contrast to a karyotype change per se, are associated with reduced OS and shorter survival after relapse. [Copyright &y& Elsevier]

A letter to the editor is presented on the results of a clinical trial conducted on patients for antibacterial prophylaxis with levofloxacin after allogeneic stem cell transplantation and neutrophil reconstitution.

Reduced-intensity conditioning with fludarabine and treosulfan before allogeneic stem cell transplantation (SCT) was introduced several years ago. Although its feasibility has recently been proven, only limited data are available on myelotoxicity, engraftment kinetics, and the significance of hematopoietic chimerism using this novel conditioning regimen. To clarify these open questions, we analyzed 27 patients with various hematological diseases, who received allogeneic SCT preceded by fludarabine/treosulfan conditioning. Further assessment endpoints included graft-vs-host disease (GvHD), mortality, and overall survival (OS). Allogeneic SCT was followed by neutropenia (absolute neutrophil count ≤ 0.5 × 109/l) and thrombocytopenia (platelets ≤ 20 × 109/l) in all patients. All patients showed stable neutrophil engraftment, and all except one had stable platelet engraftment. Grades II–IV acute GvHD was found in 48% of patients, whereas 52% developed chronic GvHD. The treatment-related mortality on day +100, 1 year after SCT, and at the last follow-up was 11, 26, and 33%, respectively. We found complete chimerism rates of 46, 57, and 72% on days +28, +56, and at the last follow-up or before death, respectively. The underlying malignancy tended to relapse more frequently in patients with mixed chimerism than in those with complete chimerism on day +28 as well as on day +56 (not significant). Additionally, no significant association was found between hematopoietic chimerism and donor type, GvHD, or OS, respectively. We conclude that reduced-intensity conditioning with fludarabine and treosulfan before allogeneic SCT is myeloablative, provides stable engraftment, and leads to complete chimerism in the majority of patients. [ABSTRACT FROM AUTHOR]

Abstract: Acute hemolysis due to AB0-incompatibility caused by transfusion of red blood cell concentrates (RBCC) to the wrong recipient is one of the major causes of transfusion-related death. As part of our policy to improve quality and safety in emergency transfusion, we have developed a standardized surveillance system for supplying RBCC in emergency situations. This surveillance system involves the implementation of a standardized set of basic data transmitted from the requesting unit to the blood bank by phone and a scoring system to check for compliance with guidelines and errors in daily routines. Communication deficiencies and delayed pretransfusion sampling were the most common errors. [Copyright &y& Elsevier]

Chronic graft-vs.-host disease (cGVHD) occurs in 20–50% of patients who survive for at least 100 d after allogeneic stem cell transplantation (SCT). cGVHD includes scleroderma-like skin changes, chronic cholangitis, obstructive lung disease and general wasting syndrome. Polymyositis or myopathy are rare manifestations of cGVHD with approximately 40 reported cases. Polymyositis accompanied by hemosiderin deposits in cGVHD has been reported only once, and there are no reports on lipofuscin deposits in skeletal muscle cells in cGVHD. We report here on a 56-yr-old male who underwent allogeneic SCT in 1999 for osteomyelofibrosis and progressive hematopoietic insufficiency. In February 2004, the patient was hospitalized for progressive muscular weakness with loss of the ability to walk. Laboratory tests demonstrated normal values for serum creatine kinase, aldolase and lactic dehydrogenase; the ferritin level was highly elevated. The femoral muscle biopsy showed mostly perifascicular atrophy as well as numerous subsarcolemmal hemosiderin and lipofuscin deposits. Intravenous administration of the chelating agent deferoxamine was ineffective. Three weeks later the patient died of aspiration pneumonia. Interestingly, autopsy disclosed moderate hemosiderin deposits in the liver, the organ usually involved in hemosiderosis. [ABSTRACT FROM AUTHOR]

Acute graft- versus-host disease (aGVHD) occurs in up to 80% of patients who undergo allogeneic stem cell transplantation (SCT) and contributes significantly to transplant-related mortality (TRM). We conducted a prospective phase II trial to assess the efficacy and feasibility of treating steroid-refractory aGVHD with basiliximab, a chimaeric monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor. Basiliximab was administered intravenously at a dose of 20 mg on days 1 and 4. Twenty-three patients were enrolled between October 1999 and July 2004. We found a primary overall response rate of 82·5% with four patients (17·5%) showing a complete response and 15 patients (65%) a partial response. Six patients were again treated successfully with an IL-2 receptor antagonist because of recurrence of aGVHD. The rates of infections, chronic GVHD, malignancy recurrence and 1-year TRM following immunosuppression with basiliximab were comparable with those found with other treatment modalities for aGVHD. We conclude that basiliximab is efficient and feasible for steroid-refractory aGVHD and merits further evaluation. [ABSTRACT FROM AUTHOR]

Simple Summary: Extramedullary disease can occur either in multiple myeloma at the initial diagnosis or relapse or as primary extramedullary plasmocytoma/solitary osseous plasmocytoma. The exact molecular mechanisms underlying extramedullary spread of clonal plasma cells are not fully understood. The aim of our study was to assess further insights into clinical and biological characteristics of different types of extramedullary plasma cell disorders. We show that expression profiles of molecules involved in homing and cytogenetic abnormalities differ between various types of plasma cell dyscrasias, indicating the contrasting biology of these diseases. Background: Extramedullary plasma cell (PC) disorders may occur as extramedullary disease in multiple myeloma (MM-EMD) or as primary extramedullary plasmocytoma (pEMP)/solitary osseous plasmocytoma (SOP). In this study, we aimed to obtain insights into the molecular mechanisms of extramedullary spread of clonal PC. Methods: Clinical and biological characteristics of 87 patients with MM-EMD (n = 49), pEMP/SOP (n = 20) and classical MM (n = 18) were analyzed by using immunohistochemistry (CXCR4, CD31, CD44 and CD81 staining) and cytoplasmic immunoglobulin staining combined with fluorescence in situ hybridization (cIg-FISH). Results: High expression of CD44, a cell-surface glycoprotein involved in cell-cell interactions, was significantly enriched in MM-EMD (90%) vs. pEMP/SOP (27%) or classical MM (33%) (p < 0.001). In addition, 1q21 amplification by clonal PC occurred at a similar frequency of MM-EMD (33%), pEMP/SOP (57%) and classical MM (44%). Conversely, del(17p13), t(4;14) and t(14;16) were completely absent in pEMP/SOP. Besides this, 1q21 amplification was identified in 64% of not paraskeletal samples from MM-EMD or pEMP compared to 9% of SOP or paraskeletal MM-EMD/pEMP and 44% of classical MM samples, respectively (p = 0.02). Conclusion: Expression of molecules involved in homing and cytogenetic aberrations differ between MM with or without EMD and pEMP/SOP. [ABSTRACT FROM AUTHOR]

Hydroxyethyl starch (HES) is usually considered to be associated with limited side effects. Generalized foamy cell macrophage syndrome after HES therapy has rarely been reported since Schaefer first described it as ‘hydrops lysosomalis generalisatus’ in 1982. We present a 19-yr-old male who received large amounts of HES. A bone marrow and a liver biopsy were performed because of persistent thrombocytopenia and liver dysfunction. We found severe infiltration of foamy cell degenerated macrophages in both organ systems, indicating that sequelae of HES therapy have to be included in the differential diagnosis of bone marrow and liver dysfunction. [ABSTRACT FROM AUTHOR]

Leukemic meningitis is a rare manifestation of chronic lymphocytic leukemia (CLL) and typically occurs in advanced stages. We report the case of a 71-year-old male in whom Binet A, Rai 1 stage CLL was diagnosed in June 2002. The stage called for a “watch and wait” strategy. Six months later the patient presented with paraparesis. Magnetic resonance imaging of the lumbar spine revealed no abnormalities. Lumbar puncture disclosed xanthochromic cerebrospinal fluid (CSF) with 1003 cells/µl, 95% atypical lymphocytes. Flow cytometry confirmed typical features of CLL. Intrathecal injections of methotrexate, cytosine arabinoside and corticosteroids did not substantially reduce the CSF cell count and failed to improve the neurological symptoms. Two weeks later the patient developed a pulmonary embolism complicated by fatal secondary pneumonia. Leukemic meningitis is a rare manifestation of CLL, especially in early stages. Selective spinal paraparesis as the first symptom of meningitis in CLL is even rarer and has been reported only once. [ABSTRACT FROM AUTHOR]

Secondary central nervous system lymphoma (SCNSL) confers a dismal prognosis and treatment advances are constrained by the lack of prospective studies and real-world treatment evidence. Patients with SCNSL of all entities were included at first diagnosis and patient characteristics, treatment data, and outcomes were prospectively collected in the Secondary CNS Lymphoma Registry (SCNSL-R) (NCT05114330). 279 patients from 47 institutions were enrolled from 2011 to 2022 and 243 patients (median age: 66 years; range: 23–86) were available for analysis. Of those, 49 (20 %) patients presented with synchronous (cohort I) and 194 (80 %) with metachronous SCNSL (cohort II). The predominant histology was diffuse large B-cell lymphoma (DLBCL, 68 %). Median overall survival (OS) from diagnosis of CNS involvement was 17·2 months (95 % CI 12–27·5), with longer OS in cohort I (60·6 months, 95 % CI 45·5-not estimable (NE)) than cohort II (11·4 months, 95 % CI 7·8–17·7, log-rank test p < 0.0001). Predominant induction regimens included R-CHOP/high-dose MTX (cohort I) and high-dose MTX/cytarabine (cohort II). Rituximab was used in 166 (68 %) of B-cell lymphoma. Undergoing consolidating high-dose therapy and autologous hematopoietic stem cell transplantation (HDT-ASCT) in partial response (PR) or better was associated with longer OS (HR adjusted 0·47 (95 % CI 0·25–0·89), p = 0·0197). This study is the largest prospective cohort of SCNSL patients providing a comprehensive overview of an international real-world treatment landscape and outcomes. Prognosis was better in patients with SCNSL involvement at initial diagnosis (cohort I) and consolidating HDT-ASCT was associated with favorable outcome in patients with PR or better. • Large prospective study in SCNSL, including n = 243 patients diagnosed from 2011 to 2022. • Providing real-world data from an international registry. • Reporting patient characteristics, treatments and outcomes in SCNSL. • High-dose therapy followed by stem cell transplant is associated with better survival. [ABSTRACT FROM AUTHOR]

There are limited data guiding choice of re-induction therapies for patients with relapsed/refractory multiple myeloma (RRMM) prior to stem cell transplantation (SCT). We performed a retrospective medical chart review of 171 patients with RRMM in Germany who received re-induction therapy in second line (78%; n = 134) or third line (22%; n = 37) prior to re-SCT. Index therapy was defined as first completed re-induction therapy for planned myeloablative conditioning and SCT in second/third line within the eligibility period (1/2016-12/2019). Most common pre-index first line and maintenance therapy used were bortezomib-based combinations (91%; n = 155/171) and lenalidomide (55%; n = 29/53), respectively. Median duration of index therapy line was 9 months; carfilzomib-based combinations were the most widely used in second/third line re-induction therapy (49%; n = 83/171), followed by daratumumab-based combinations (21%; n = 36/171). Overall response rates in second/third line were 87% after re-induction and 96% after SCT; median time to next treatment line after start of index therapy was 31 months; median progression-free survival (PFS) was 29 months; and median overall survival after index date was not reached. Based on these data, re-induction therapy with salvage SCT appears to be beneficial in selected patients with RRMM in clinical practice in Germany, translating into deep responses, long PFS and prolonged time to next treatment., (© 2024. The Author(s).)

We retrospectively studied 125 patients with acute myeloid leukemia and trisomy 4 (median age at diagnosis, 58 years; range, 16-77 years) treated between 2000 and 2019 within a multicenter study. Trisomy 4 was the sole abnormality in 28 (22%) patients and additional abnormalities were present in 97 (78%) patients. Twenty-two (22%) and 15 (15%) of 101 tested patients harbored NPM1 and FLT3-ITD mutations. Two (3%) of 72 tested patients had double CEBPA mutations. Data on response to intensive anthracycline-based induction therapy were available for 119 patients. Complete remission was achieved in 67% (n=80) and the early death rate was 5% (n=6). Notably, patients with trisomy 4 as sole abnormality had a complete remission rate of 89%. Allogeneic hematopoietic cell transplantation was performed in 40 (34%) patients, of whom 19 were transplanted in first complete remission. The median follow-up of the intensively treated cohort was 5.76 years (95% confidence interval [95% CI]: 2.99-7.61 years). The 5-year overall survival and relapse-free survival rates were 30% (95% CI: 22-41%) and 27% (95% CI: 18-41%), respectively. An Andersen-Gill regression model on overall survival revealed that favorable-risk according to the European LeukemiaNet classification (hazard ratio [HR]=0.34; P=0.006) and trisomy 4 as sole abnormality (HR=0.41; P=0.01) were favorable factors, whereas age with a difference of 10 years (HR=1.15; P=0.11), female gender (HR=0.74; P=0.20) and allogeneic hematopoietic cell transplantation (HR=0.64; P=0.14) did not have an significant impact. In our cohort, patients with trisomy 4 as their sole abnormality had a high complete remission rate and favorable clinical outcome. Allogeneic hematopoietic cell transplantation did not seem to improve overall survival.

The role of salvage high-dose chemotherapy and autologous stem cell transplantation (sHDCT/ASCT) for relapsed and/or refractory multiple myeloma (RRMM) in the era of continuous novel agent treatment has not been defined. This randomized, open-label, phase III, multicenter trial randomized patients with 1st-3rd relapse of multiple myeloma (MM) to a transplant arm (n = 139) consisting of 3 Rd (lenalidomide 25 mg, day 1-21; dexamethasone 40 mg, day 1, 8, 15, and 22; 4-week cycles) reinduction cycles, sHDCT (melphalan 200 mg/m 2 ), ASCT, and lenalidomide maintenance (10 mg/day) or to a control arm (n = 138) of continuous Rd. Median PFS was 20.7 months in the transplant and 18.8 months in the control arm (HR 0.87; 95% CI 0.65-1.16; p = 0.34). Median OS was not reached in the transplant and 62.7 months in the control arm (HR 0.81; 95% CI 0.52-1.28; p = 0.37). Forty-one patients (29%) did not receive the assigned sHDCT/ASCT mainly due to early disease progression, adverse events, and withdrawal of consent. Multivariate landmark analyses from the time of sHDCT showed superior PFS and OS (p = 0.0087/0.0057) in patients who received sHDCT/ASCT. Incorporation of sHDCT/ASCT into relapse treatment with Rd was feasible in 71% of patients and did not significantly prolong PFS and OS on ITT analysis while patients who received sHDCT/ASCT may have benefitted.

Baseline chest computed tomography (BCT) in high-risk hematology patients allows for the early diagnosis of invasive pulmonary aspergillosis (IPA). The distribution of BCT implementation in hematology departments and impact on outcome is unknown. A web-based questionnaire was designed. International scientific bodies were invited. The estimated numbers of annually treated hematology patients, chest imaging timepoints and techniques, IPA rates, and follow-up imaging were assessed. In total, 142 physicians from 43 countries participated. The specialties included infectious diseases ( n = 69; 49%), hematology ( n = 68; 48%), and others ( n = 41; 29%). BCT was performed in 57% ( n = 54) of 92 hospitals. Upon the diagnosis of malignancy or admission, 48% and 24% performed BCT, respectively, and X-ray was performed in 48% and 69%, respectively. BCT was more often used in hematopoietic cell transplantation and in relapsed acute leukemia. European centers performed BCT in 59% and non-European centers in 53%. Median estimated IPA rate was 8% and did not differ between BCT (9%; IQR 5-15%) and non-BCT centers (7%; IQR 5-10%) (p = 0.69). Follow-up computed tomography (CT) for IPA was performed in 98% ( n = 90) of centers. In high-risk hematology patients, baseline CT is becoming a standard-of-care. Chest X-ray, while inferior, is still widely used. Randomized, controlled trials are needed to investigate the impact of BCT on patient outcome.