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AbstractBackground:Anaemia is a highly prevalent condition in cancer patients impacting on morbidity, mortality and quality of life. Darbepoetin alfa (DA) 500 µg administered once every 3 weeks (Q3W) has been shown to be effective in patients with chemotherapy-induced anaemia.Objective:This non-interventional study investigated the efficacy and usage patterns of DA 500 µg Q3W in routine clinical practice.Research design and methods:Prospective data on adult anaemic cancer patients receiving DA 500 µg Q3W during chemotherapy was collected. Efficacy of DA treatment was measured as the red blood cell transfusion (RBCT) incidence, the change in Hb over time, hospitalisations for anaemia, and the change in Eastern Cooperative Oncology Group (ECOG) performance status between baseline and study end. Usage patterns were evaluated in Hb categories at baseline and week 16, DA dosage information, and adherence to the guidelines issued by the European Organisation for Research and Treatment of Cancer (EORTC).Results:A total of 309 patients were included. The median study duration was 16 weeks and the overall transfusion rate was 19%. Significantly fewer patients required transfusions when DA was initiated at Hb 9.0–10.0 g/dL (19), as compared to later at a Hb < 9.0 g/dL (50, p  0.0002). Transfusion-independent patients had fewer anaemia-related hospitalisations and better ECOG scores at the end of the study. A total of 83 of patients reached a Hb  11.0 g/dL during weeks 1–16. Physicians’ adherence to Hb thresholds for DA initiation as recommended by the EORTC was observed in 83 of patients.Conclusions:In accordance with the recommended treatment objective for DA to minimise RBCTs, 81 of study patients remained free of RBCTs during DA 500 µg Q3W treatment and at an even higher rate if DA treatment was initiated before Hb fell below 9.0 g/dL. [ABSTRACT FROM AUTHOR]

Understanding the impact of induction and maintenance therapy on patients' quality of life (QoL) is important for treatment selection. This study aims to compare patient-reported QoL between patients treated with KTd or KRd induction therapy and K maintenance therapy or observation. QoL was assessed using the EORTC QOL-C 30 and QOL-MY20 questionnaires in the AGMT-02 study, in which 123 patients with newly diagnosed transplant ineligible multiple myeloma were randomized to nine cycles of either KTd or KRd induction therapy, followed by 12 cycles of K maintenance therapy, or observation. Longitudinal assessments showed statistically significant improvements in global health-related QoL, various disease symptoms and pain for both treatment regimens. KTd improved insomnia and fatigue, and KRd improved physical functioning. Cross-sectional comparisons indicated a "slight" superiority of KTd over KRd in several scales, with the exception of higher neuropathy scores with KTd. During maintenance, longitudinal comparisons showed no statistically significant changes. Cross-sectional comparisons revealed a "slight" improvement in cognitive functioning during carfilzomib therapy, but a worsening in most other QoL scales. Induction therapy led to improvements in most QoL items, while maintenance therapy with K maintenance was associated with "slight" or "moderate" impairments in several QoL scales compared with the observation group., Competing Interests: The study was supported by AMGEN which provided support for the conduct and analysis of the trial, and by the Austrian Forum against Cancer which supported in part the scientific assistance of HL. HL declares receiving honoraria for lectures or advisory boards from Janssen, BMS, Takeda, Pfizer, Sanofi, and Stem line and research support from AMGEN and Sanofi. TM received honoraria from AbbVie and BMS. MS received honoraria from Janssen, AbbVie, BMS, and Pfizer. BH received honoraria from BMS, Amgen, AbbVie, and Janssen‐Cilag. KP received research funding and honoraria for consultancy from Amgen, BMS, Janssen, and Roche. WW is an employee of syndena GmbH and received research funding from Amgen, Takeda, BMS‐Celgene, Janssen‐Cilag, Novartis, Roche, Sanofi, and oncotyrol and received honoraria for participation in steering and safety committees from Amgen, BMS‐Celgene, and Morphosys and received honoraria for consultancy from Amgen, Takeda, BMS‐Celgene, EUSA Pharma, Gilead, AbbVie, Janssen‐Cilag, GSK, Incyte, Kite, Novartis, Morphosys, Merck, Pfizer, Roche, Sandoz, and Sanofi, and received honoraria from Fujimoto and Myelom‐ und Lymphomselbsthilfe. MTK received research funding from Janssen and honoraria from GSK, Sanofi, Pfizer, Janssen, Amgen, BMS‐Celgene, and Takeda. AP received honoraria for participation in advisory boards from Novartis, Kite‐Gilead, Amgen, Celgene, Janssen, Roche, Sandoz, AstraZeneca, AbbVie, Takeda, Sanofi, Pfizer, Saegen, Daiichi Sankyo, and received travel support from Kite‐Gilead, Janssen, Roche, AstraZeneca, Pfizer, and Daiichi Sankyo. CS received research funding from AstraZeneca, Janssen‐Cilag, and Roche, and received honoraria for consultancy from AbbVie, AstraZeneca, BMS‐Celgene, Janssen‐Cilag, Roche, and Takeda. SMS received honoraria for consultancy from Jazz Pharmaceuticals, Novartis, Amgen, BMS, and Gilead. HA received research funding from Janssen and received honoraria from Janssen, Amgen, BMS, and Takeda. SK received honoraria from Amgen, BMS‐Celgene, and Sanofi, and received travel grants from BMS and Sobi. RG received research funding, travel support, and honoraria for consultancy and participation in advisory boards from AbbVie, Takeda, Daiichi Sankyo, Gilead, MSD Merck, BMS‐Celgene, Novartis, AstraZeneca, Janssen‐Cilag, and Hoffmann‐La Roche. The remaining authors declare no conflict of interest., (© 2024 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Multiple myeloma (MM) is characterized by serial relapses, necessitating the application of sequential lines of therapy (LoT). Reports on attrition rates (ARs) vary widely. The present study analysed ARs from the Austrian Myeloma Registry. Attrition was defined as being either deceased, progressive without having received another LoT, or lack of follow-up for ≥5 years. A total of 571 patients diagnosed between January 2009 and August 2021 were included (median age: 72 years; median follow-up: 50.8 months). Some 507 patients received at least one LoT. Of the total, 43.6% underwent autologous stem cell transplantation (SCT, transplant eligible = TE)) with primarily VRd (Bortezomib/Lenalidomide/Dexamethasone) given as induction (26.5%), followed by lenalidomide maintenance in 55.7% of cases. Transplant-ineligible (NTE) patients were predominantly treated with Vd (Bortezomib/Dexamethasone, 21.6%), receiving maintenance in 27.1%. A total of 37.5% received a second LoT. ARs across one to five LoTs were 16.7-27%. Frontline induction/ SCT followed by maintenance reduced ARs associated with age and achievement of deep remission in the frontline. Deep remission prolongs follow-up and time-to-next-treatment (TTNT), while high-risk-cyctogenetics negatively affected these outcomes. Our results demonstrate considerably lower ARs for MM patients within the AMR data versus other healthcare systems. Young age and the achievement of significant remissions after optimal frontline therapy resulted in particularly low ARs. These promising results support a key role for the ease of drug access and reimbursement policies in governing long-term MM patient outcomes.

Objectives: Cell counts have a significant impact on the complex mechanism of thrombosis in patients with essential thrombocythemia (ET). We recently demonstrated a considerable impact of white blood cell (WBC) counts on thrombotic risk in patients with optimized platelet counts by analysing a large anagrelide registry. In contrast, the current analysis of the registry aimed to estimate the influence of platelet counts on thrombotic risk in patients with optimized WBC counts., Methods: Cox regression analysis and Kaplan-Meier plot were applied on all patients in the registry with optimized WBC counts., Results: By using the calculated cut-off of 593 G/L for platelets, Cox regression analysis revealed a clear influence of elevated platelet counts on the occurrence of a major thrombotic event (P < .001). A Kaplan-Meier plot revealed a markedly shorter time to a major thrombotic event for patients with platelet counts above the cut-off (P < .001)., Conclusions: The data show clear impact of platelet lowering on the thrombotic risk in ET patients with normal WBC counts. Therefore, selective platelet lowering with anagrelide appears sufficient for thrombotic risk reduction in WHO-diagnosed ET patients lacking leukocytosis., (© 2020 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Objectives: Risk of thrombosis is significantly enhanced by both elevated platelet (PLT) and white blood cell (WBC) counts according to a retrospective analysis of a large anagrelide registry in thrombocythemic MPN patients. We were interested in the impact of elevated WBC counts on thrombosis risk in patients where PLT counts were reduced below the calculated cutoff of 574.5 G/L by treatment with anagrelide., Methods: Cox regression analysis and Kaplan-Meier plot were applied on all patients in the registry with optimized PLT counts., Results: Using the calculated cutoff of 9.66 G/L for WBC, Cox regression analysis revealed a clear influence of elevated WBC counts on the occurrence of a major thrombotic event (P = .012). A Kaplan-Meier plot revealed a markedly shorter time to a major thrombotic event for patients with WBC counts above the cutoff (P = .001)., Conclusions: These data suggest that additional correction of elevated WBC counts is mandatory in patients with optimally managed PLT counts to reduce thrombotic risk. This study is the first investigation in a prospectively observed large patient cohort which was treated homogenously allowing for evaluation of single parameters for an effect on thrombophilia., (© 2018 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.)

Objectives: Although guidelines recommend normalization of platelet counts as an appropriate endpoint for treatment in high-risk essential thrombocythemia (ET), retrospective studies could not prove a correlation of diagnostic platelet counts with an increased thrombotic rate. There is, however, an increasing evidence that leukocytosis is an important risk factor for arterial thrombosis in myeloproliferative neoplasms., Methods: This study considers the Austrian cohort of a European registry regarding the platelet-lowering therapeutic anagrelide. Influence of platelet and white blood cell (WBC) counts on thrombotic risk was assessed., Results: Using the calculated cutoffs of 574.5 G/L for platelets and 8.48 G/L for WBC counts, respectively, the Cox regression analysis revealed a clear influence of elevated platelets (P = 0.008) and WBC counts (P = 0.011) on the occurrence of major thrombotic events. The time to a major thrombotic event was shortest (P < 0.001) and the frequency related to 100 patient-years was highest (P = <0.001) when both platelet and WBC counts ranged above the calculated cutoffs., Conclusion: Our data add evidence to the impact of platelet and WBC counts on thrombosis in ET. We suspect a particular interaction between platelets and WBC which might be based on a biological interplay depending on particular cell counts., (© 2016 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.)

Immune Thrombocytopenia (ITP) is a rare and - in most patients - mild disease, but might be associated with severe or even life-threatening bleeding complications. The treatment of ITP has partly changed in recent years, due to new therapeutic options. International guidelines changed accordingly. This consensus statement by the Austrian Society of Hematology and Oncology (OEGHO) is not a new evaluation of the current evidence, but rather tries to discuss the available international guidelines and adapt them to the situation in Austria. The subject is primary ITP in adults only. Classification, epidemiology, clinical presentation and diagnostics of ITP, and especially the management of this disease, are discussed in detail. This includes current aspects of first, second, and third line therapies, splenectomy with its indications and contraindications, and the use of new therapeutic options like thrombopoetin receptor agonists (TRA).

Background: Anaemia is a highly prevalent condition in cancer patients impacting on morbidity, mortality and quality of life. Darbepoetin alfa (DA) 500 µg administered once every 3 weeks (Q3W) has been shown to be effective in patients with chemotherapy-induced anaemia., Objective: This non-interventional study investigated the efficacy and usage patterns of DA 500 µg Q3W in routine clinical practice., Research Design and Methods: Prospective data on adult anaemic cancer patients receiving DA 500 µg Q3W during chemotherapy was collected. Efficacy of DA treatment was measured as the red blood cell transfusion (RBCT) incidence, the change in Hb over time, hospitalisations for anaemia, and the change in Eastern Cooperative Oncology Group (ECOG) performance status between baseline and study end. Usage patterns were evaluated in Hb categories at baseline and week 16, DA dosage information, and adherence to the guidelines issued by the European Organisation for Research and Treatment of Cancer (EORTC)., Results: A total of 309 patients were included. The median study duration was 16 weeks and the overall transfusion rate was 19%. Significantly fewer patients required transfusions when DA was initiated at Hb 9.0-10.0 g/dL (19%), as compared to later at a Hb < 9.0 g/dL (50%, p = 0.0002). Transfusion-independent patients had fewer anaemia-related hospitalisations and better ECOG scores at the end of the study. A total of 83% of patients reached a Hb ≥ 11.0 g/dL during weeks 1-16. Physicians' adherence to Hb thresholds for DA initiation as recommended by the EORTC was observed in 83% of patients., Conclusions: In accordance with the recommended treatment objective for DA to minimise RBCTs, 81% of study patients remained free of RBCTs during DA 500 µg Q3W treatment and at an even higher rate if DA treatment was initiated before Hb fell below 9.0 g/dL.

Objectives: Highly differing rates of cardiac complications associated with high-dose cyclophosphamide (CY) have been reported, and only one clinical study has been performed on the cardiotoxic effects of CY monotherapy following total body irradiation (TBI)., Patients and Methods: We prospectively evaluated the potential cardiotoxic effects of conditioning with fractionated total body irradiation and high-dose cyclophosphamide (TBI/CY) by serial measurement of serum cardiac troponin T (cTnT), assessment of systolic and diastolic echocardiographic parameters and analysis of ventricular repolarisation indices (QT-dispersion and corrected QT-dispersion) in 30 adult patients with haematological malignancies undergoing haematopoietic stem cell transplantation., Results: There was no evidence of pretreatment cardiac dysfunction in any patient. Although cTnT was determined serially for a median of 14 d after completion of conditioning, no elevated levels were observed. Echocardiographic parameters did not show any significant change at a median follow-up of 5 months except for one patient with evidence of impaired diastolic filling. No significant differences for mean values before and after high-dose CY were noted for ventricular repolarisation indices. Two patients had a significant increase in corrected QT-dispersion after CY without any other signs of cardiotoxicity. Congestive heart failure or arrhythmias were not observed., Conclusions: These data suggest that TBI/CY is safe with respect to cardiotoxicity in patients without pre-existing cardiac dysfunction. Hitherto unknown synergistic cardiotoxic effects of CY with other cytostatic drugs may constitute the major pathogenic factor of myocardial dysfunction after high-dose chemotherapy.

Ineffective hematopoiesis leading to profound cytopenias represents a major clinical problem in the management of patients with myelodysplastic syndrome (MDS). The aminothiol amifostine has shown to promote multilineage hematopoiesis both in vivo and in vitro in patients with MDS. We have treated 10 patients with 250 mg/m2 amifostine thrice weekly in combination with erythropoietin for 4 consecutive weeks followed by 2 weeks observation. Responding patients received the same 6 week schedule, while nonresponder received G-CSF in addition to erythropoietin and amifostine during the second treatment course. All patients experienced single or multilineage hematologic improvement, but only 2 reached transfusion independency. Moreover, response was durable only in a minority of patients and thus additional studies are warranted to further define the potential interaction of amifostine and growth factors.

The aim of the present study was to investigate loss of heterozygosity (LOH) or microsatellite instability in chronic myeloid leukaemia (CML) blast crisis at genomic locations which are known or postulated to harbour tumour suppressor genes. We studied 48 patients in blast crisis of myeloid (n = 31), lymphoid (n = 15), megakaryocytic (n = 1), or mixed lineage (n = 1) phenotype by comparing constitutional DNA extracted from buccal epithelial cells or chronic phase leucocytes with DNA obtained from blast crisis leucocytes. Twelve variable number tandem repeat loci from six different chromosomes were amplified by polymerase chain reaction using labelled primers, and fractionated on polyacrylamide gels. After autoradiography, length as well as intensity of the amplified products were compared between constitutional and blast crisis samples. LOH was scored as complete, partial or none in informative patients. Complete LOH was found in one patient at 8p22 and another at 13q14; partial LOH was detected in three patients at 11p13 and/or 11p15. No LOH was found at 6q27, 8p21, 18q21, 22q11-12 and 22q13 in any patient. Furthermore, no consistent difference in allelic length was observed in 517 paired amplifications indicating no microsatellite instability. We conclude that the Rb gene at 13q14, the Wilms tumour gene at 11p13, the DCC gene at 18q21, the neurofibromatosis 2 gene at 22q11-13 and uncloned tumour suppressor genes at 6q27, 8p21-22 and 11p15, as well as genes responsible for microsatellite instability, are unlikely to be involved in the progression of CML to blast crisis in the majority of patients.