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Gene mutations independent of BCR::ABL1 have been identified in newly diagnosed patients with chronic myeloid leukemia (CML) in chronic phase, whereby mutations in epigenetic modifier genes were most common. These findings prompted the systematic analysis of prevalence, dynamics, and prognostic significance of such mutations, in a clinically well-characterized patient population of 222 CML patients from the TIGER study (CML-V) by targeted next-generation sequencing covering 54 myeloid leukemia-associated genes. In total, 53/222 CML patients (24%) carried 60 mutations at diagnosis with ASXL1 being most commonly affected (n = 20). To study mutation dynamics, longitudinal deep sequencing analysis of serial samples was performed in 100 patients after 12, 24, and 36 months of therapy. Typical patterns of clonal evolution included eradication, persistence, and emergence of mutated clones. Patients carrying an ASXL1 mutation at diagnosis showed a less favorable molecular response to nilotinib treatment, as a major molecular response (MMR) was achieved less frequently at month 12, 18, and 24 compared to all other patients. Patients with ASXL1 mutations were also younger and more frequently found in the high risk category, suggesting a central role of clonal evolution associated with ASXL1 mutations in CML pathogenesis.

Reliable automated blood cell characterization and quantification remain challenging in pathologic samples, whereas slide reviews due to unnecessary flagging should be avoided. We compared 4 modern hematology analyzers—Abbott Sapphire, Siemens Advia 120, Sysmex XE-2100, and Beckman Coulter DxH 800—regarding complete blood cell count (CBC), leukocyte differential count, and flagging efficacy in a total of 202 samples from hematology patients and normal controls. Manual differential count was used as reference. The analyzers exhibited very good correlation for CBC parameters. Neutrophils and eosinophils also showed very good correlations, whereas lymphocytes and monocytes correlated fairly. The Advia 120 displayed notably lower measurements for both parameters, which is attributable to classification of some events as large unstained cells. Basophil counts were unreliable with all analyzers. Flagging for blasts and immature granulocytes showed moderate sensitivity and specificity. Operators must not rely on blast flagging alone to detect leukemic samples with any analyzer.

Background One challenge in caring for cancer patients with incurable disease is the adequate identification of those in need for specialized palliative care (SPC). The study’s aim was to validate an easy to use phenomenological screening tool. Methods The German tool is based on the National Comprehensive Cancer Network (NCCN) Palliative Care guidelines and contains ten items in five domains that focus e.g. on diagnosis, functional status, complications, comorbidities, and palliative care relevant problems such as symptom management, distress, and support of family and team members. Sum score ranges from 0 to 14 (no need to great need). Assessment to identify SPC needs was done in university hospital wards between 1 and 08/2017 by health care professionals on admission of the patient if the disease was incurable and expected prognosis < 12 months. The Integrated Palliative Outcome Scale (IPOS, staff version), an outcome assessment instrument for palliative care that consists of ten items, served as external criterion; in sub samples inter-rater/test-retest were performed. Results Data from 208 patients with incurable disease and life expectancy < 12 months (54.8% female; average age 63.5 years, range 21–96) were assessed using the tool. The tool has good convergent validity; the correlation between the sum scores of IPOS and our tool showed a significant and substantial effect. The sum score was independent of the patient’s age, gender and primary diagnosis. Patients who already were in contact with SPC had significantly higher screening scores than patients without. With a cut point of  ≥ 5, 80.8% of the screened patients were in need for SPC. Cronbach’s alpha was α = .600. Rater agreement (inter-rater, test-retest) varied between single items. Correlation coefficients showed significant substantial effects. Conclusions This is the first validation of a screening procedure in German language identifying SPC needs of adult patients with advanced cancer and the first using filter questions as a pre-screening. Proxy assessment of SPC needs by physicians in cancer care settings is feasible and the suggested tool presents a valid instrument to trigger a PC consultation. Trial registration The study was not registered.

Allogeneic hematopoetic stem cell transplantation (allo SCT) is a treatment option with a unique chance of cure for patients with high-risk AML or MDS. However, the optimal path for an individual patient on its way to allo SCT is far from clear and subject of ongoing debates. Upfront transplantation “as soon as possible” competes with strategies to achieve deep remission or at least stabilization of the disease. In this context, we performed a survey among German transplant centers to assess their preferred strategies for patients before SCT in five typical scenarios of AML and MDS. We obtained replies from 22 centers, revealing a heterogenous use of possible strategies. Upfront transplantation was a preferred option (68%) in intermediate risk MDS, chemotherapy was preferred (64%) as bridging for AML in remission, whereas hypomethylating agents (HMA) and induction chemotherapy for relapsed AML were highly controversial. Further prospective evaluation of different options is desirable.

PRDM16 (PR Domain Containing 16) is a transcription factor that plays a critical role in hematopoietic stem cell maintenance. In acute myeloid leukemia (AML), PRDM16 overexpression is linked to specific cytogenetic risk groups and poor prognosis. However, in NPM1 -mutated AMLs, PRDM16 expression varies widely, with no consensus on its prognostic significance. To understand molecular and clinical associations of PRDM16 expression in this relevant subgroup, we screened 503 adult NPM1 -mutant AML patients. High PRDM16 expression was associated with mutations in DNMT3A (57% vs 22%; p  < 0.0001) and FLT3 -ITD (51% vs 37%; p  = 0.0258), and therefore a higher rate of ELN2022 intermediate-risk (42% vs 26%; p  = 0.01), compared to low PRDM16 expression. Accordingly, PRDM16 overexpression was not associated with clinical outcome in multivariable analysis adjusting for ELN2022 risk in the unselected NPM1 -mutant AML cohort. However, within the double-mutant NPM1 / FLT3 -ITD subgroup (n = 200), low PRDM16 expression was an independent prognostic factor for longer survival (hazard ratio [95%-CI] 0.467 [0.270–0.807]; p  = 0.006). On a molecular level, low PRDM16 expression was associated with mutations in epigenetic regulators ( TET2 , IDH1 / 2 ) and increased PRDM16 promoter methylation, suggesting impaired TET/IDH-mediated DNA-demethylation as underlying mechanism. Notably, IDH1 R132C and IDH2 R140Q alterations particularly contributed to higher PRDM16 promoter methylation and reduced expression. These results suggest an association of PRDM16 overexpression with the NPM1 / FLT3 -ITD/ DNMT3A triple-mutant AML genotype, typically linked to high leukemia stem cell frequencies and poor prognosis. Importantly, within this adverse AML subtype low PRDM16 expression is an independent prognostic marker for favorable outcome, supporting an anti-leukemic mechanism in AMLs with repressed PRDM16 transcription. Graphical Abstract

Major molecular remission (MMR) is an important therapy goal in chronic myeloid leukemia (CML). So far, MMR is not a failure criterion according to ELN management recommendation leading to uncertainties when to change therapy in CML patients not reaching MMR after 12 months. At monthly landmarks, for different molecular remission status Hazard ratios (HR) were estimated for patients registered to CML study IV who were divided in a learning and a validation sample. The minimum HR for MMR was found at 2.5 years with 0.28 (compared to patients without remission). In the validation sample, a significant advantage for progression-free survival (PFS) for patients in MMR could be detected (p-value 0.007). The optimal time to predict PFS in patients with MMR could be validated in an independent sample at 2.5 years. With our model we provide a suggestion when to define lack of MMR as therapy failure and thus treatment change should be considered. The optimal response time for 1% BCR-ABL at about 12–15 months was confirmed and for deep molecular remission no specific time point was detected. Nevertheless, it was demonstrated that the earlier the MMR is achieved the higher is the chance to attain deep molecular response later.

Background Allogeneic stem cell transplantation (aSCT) frequently leads to prolonged impaired quality of life (Qol) and depression. To reduce symptom burden and improve Qol, we implemented a complementary medicine approach (TriCAM). Methods In a randomized, controlled clinical trial (NCT02976558), we enrolled 36 patients undergoing aSCT. In addition to standard care, the intervention group received Traditional Chinese Medicine acupuncture (TCMA), music therapy (TaKeTiNa) and active clown role playing. FACT-G was used to assess Qol and HADS-D to asses anxiety and depression. We monitored safety of TCMA as well as typical complications during aSCT. Results TCMA did not result in more hematomas, soft tissue infections or bacteriaema. Clinical depression was reduced in the intervention group compared to the control group ( p  = 0.01). There was a trend towards improvement of Qol over time ( P  = 0.10) and in reducing aGvHD ( P  = 0.084) in the intervention group compared to the control group. Conclusions Our trial is the first to show TCMA to be safe in aSCT. TriCAM showed a trend towards mitigating the loss of QoL and significantly reduced depression in patients undergoing aSCT. The promising results of this pilot study give a first positive signal for safety and efficacy allowing for the design of larger studies to confirm the results and support this particularly vulnerable patient group. Trial registration ClinicalTrials.gov NCT02976558. Registered 29 November 2016.

Multiparameter flow cytometry is a cornerstone of B cell non-Hodgkin lymphoma (B-NHL) diagnostics, but interpretation requires substantial expertise and is complicated by high-dimensional data, variable sample quality, limited data for rare entities, and evolving clinical classification systems. Current artificial intelligence approaches often require large training datasets and provide limited insight into the rationale behind individual diagnostic decisions. We developed FlowXAI, a self-explaining artificial intelligence system designed to support B-NHL classification while explicitly reporting case-level diagnostic trustworthiness. FlowXAI combines unsupervised structural analysis with a clinically motivated, multi-level diagnostic framework reflecting routine diagnostic priorities. An unsupervised Tile Mining (TM) procedure performs pre-diagnostic sample-quality assessment by identifying structurally atypical samples. TM is applied to filter training data, enabling substantial reduction of training requirements while preserving unbiased evaluation on independent test samples. FlowXAI was evaluated using repeated cross-validation on 19,493 peripheral blood samples and further assessed on an independent external benchmark dataset generated at a separate diagnostic center using a different antibody panel. Across diagnostic levels, FlowXAI achieved performance comparable to a deep learning-based system despite requiring approximately two orders of magnitude fewer training samples. When predictions were classified as confident by the system's internal self-assessment, diagnostic performance exceeded that of the neural network baseline. Unsupervised structural analysis demonstrated clear separation between normal controls and selected lymphoma entities such as chronic lymphocytic leukemia-like lymphomas and hairy cell leukemia, while other entities were not clearly separable using the antibody panels studied. FlowXAI provides accurate, data-efficient, and transparent support for B-NHL immunophenotyping from nonstandardized flow cytometry data. By combining interpretable decision logic with explicit self-assessment, FlowXAI offers a clinically meaningful framework for diagnostic support and training, particularly in settings with limited expert availability or rare lymphoma subtypes. The main limitation is the retrospective evaluation using specific antibody panels, and FlowXAI requires prospective validation as a decision-support tool within integrated diagnostic workflows.

Immunocompromised patients are at high risk of invasive fungal infections (IFI), in particular those with haematological malignancies undergoing remission-induction chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) and recipients of allogeneic haematopoietic stem cell transplants (HSCT). Despite the development of new treatment options in the past decades, IFI remains a concern due to substantial morbidity and mortality in these patient populations. In addition, the increasing use of new immune modulating drugs in cancer therapy has opened an entirely new spectrum of at risk periods. Since the last edition of antifungal prophylaxis recommendations of the German Society for Haematology and Medical Oncology in 2014, seven clinical trials regarding antifungal prophylaxis in patients with haematological malignancies have been published, comprising 1227 patients. This update assesses the impact of this additional evidence and effective revisions. Our key recommendations are the following: prophylaxis should be performed with posaconazole delayed release tablets during remission induction chemotherapy for AML and MDS (AI). Posaconazole iv can be used when the oral route is contraindicated or not feasible. Intravenous liposomal amphotericin B did not significantly decrease IFI rates in acute lymphoblastic leukaemia (ALL) patients during induction chemotherapy, and there is poor evidence to recommend it for prophylaxis in these patients (CI). Despite substantial risk of IFI, we cannot provide a stronger recommendation for these patients. There is poor evidence regarding voriconazole prophylaxis in patients with neutropenia (CII). Therapeutic drug monitoring TDM should be performed within 2 to 5 days of initiating voriconazole prophylaxis and should be repeated in case of suspicious adverse events or of dose changes of interacting drugs (BIItu). General TDM during posaconazole prophylaxis is not recommended (CIItu), but may be helpful in cases of clinical failure such as breakthrough IFI for verification of compliance or absorption.

Hematologic and oncologic patients with chemo- or immunotherapy-related immunosuppression are at substantial risk for bacterial infections and Pneumocystis jirovecii pneumonia (PcP). As bacterial resistances are increasing worldwide and new research reshapes our understanding of the interactions between the human host and bacterial commensals, administration of antibacterial prophylaxis has become a matter of discussion. This guideline constitutes an update of the 2013 published guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO). It gives an overview about current strategies for antibacterial prophylaxis in cancer patients while taking into account the impact of antibacterial prophylaxis on the human microbiome and resistance development. Current literature published from January 2012 to August 2020 was searched and evidence-based recommendations were developed by an expert panel. All recommendations were discussed and approved in a consensus conference of the AGIHO prior to publication. As a result, we present a comprehensive update and extension of our guideline for antibacterial and PcP prophylaxis in cancer patients.