Benefits and risks of clofarabine in adult acute lymphoblastic leukemia investigated in depth by multi-state modeling.

Background: We recently reported results of the prospective, open-label HOVON-100 trial in 334 adult patients with acute lymphoblastic leukemia (ALL) randomized to first-line treatment with or without clofarabine (CLO). No improvement of event-free survival (EFS) was observed, while a higher proportion of patients receiving CLO obtained minimal residual disease (MRD) negativity.

Aim: In order to investigate the effects of CLO in more depth, two multi-state models were developed to identify why CLO did not show a long-term survival benefit despite more MRD-negativity.

10-day decitabine versus 3 + 7 chemotherapy followed by allografting in older patients with acute myeloid leukaemia: an open-label, randomised, controlled, phase 3 trial.

Background: Many older patients with acute myeloid leukaemia die or cannot undergo allogeneic haematopoietic stem-cell transplantation (HSCT) due to toxicity caused by intensive chemotherapy. We hypothesised that replacing intensive chemotherapy with decitabine monotherapy could improve outcomes.

Methods: This open-label, randomised, controlled, phase 3 trial was conducted at 54 hospitals in nine European countries.

Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine.

Treatment choice according to the individual conditions remains challenging, particularly in older patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS). The impact of performance status, comorbidities, and physical functioning on survival is not well defined for patients treated with hypomethylating agents. Here we describe the impact of performance status (14% ECOG performance status 2), comorbidity (40% HCT-comorbidity index ≥ 2), and physical functioning (41% short physical performance battery < 9 and 17% ADL index < 6) on overall survival (OS) in 115 older patients (age ≥ 66 years) treated on a clinical trial with a 10-day decitabine schedule.

Drug-drug interaction: decreased posaconazole trough concentrations during concomitant flucloxacillin treatment.

Background And Objectives: Posaconazole is used as prophylaxis of invasive fungal disease in immune-compromised haematological patients with prolonged neutropenia after intensive chemotherapy. During routine therapeutic drug monitoring of posaconazole, we repeatedly observed low posaconazole serum concentrations in patients that were concomitantly treated with flucloxacillin. A possible interaction between flucloxacillin and posaconazole was explored in this case series.

Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial.

Lenalidomide, an antineoplastic and immunomodulatory drug, has therapeutic activity in acute myeloid leukemia (AML), but definitive studies about its therapeutic utility have been lacking. In a phase 3 study, we compared 2 induction regimens in newly diagnosed patients age 18 to 65 years with AML: idarubicine-cytarabine (cycle 1) and daunorubicin and intermediate-dose cytarabine (cycle 2) without or with lenalidomide (15 mg orally on days 1-21). One final consolidation cycle of chemotherapy or autologous stem cell transplantation (auto-SCT) or allogeneic SCT (allo-SCT) was provided according to a prognostic risk and minimal residual disease (MRD)-adapted approach.

Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS.

Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66-81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg ( = 116), days 1-21.

Ibrutinib added to 10-day decitabine for older patients with AML and higher risk MDS.

The treatment of older, unfit patients with acute myeloid leukemia (AML) is challenging. Based on preclinical data of Bruton tyrosine kinase expression/phosphorylation and ibrutinib cytotoxicity in AML blasts, we conducted a randomized phase 2 multicenter study to assess the tolerability and efficacy of the addition of ibrutinib to 10-day decitabine in unfit (ie, Hematopoietic Cell Transplantation Comorbidity Index ≥3) AML patients and higher risk myelodysplasia patients (HOVON135/SAKK30/15 trial). In total, 144 eligible patients were randomly (1:1) assigned to either 10-day decitabine combined with ibrutinib (560 mg; sequentially given, starting the day after the last dose of decitabine) (n = 72) or to 10-day decitabine (n = 72).

Therapeutic value of clofarabine in younger and middle-aged (18-65 years) adults with newly diagnosed AML.

Clofarabine has demonstrated antileukemic activity in acute myeloid leukemia (AML) but has yet to be critically evaluated in younger adults in the frontline with standard chemotherapy. We compared 2 induction regimens in newly diagnosed patients ages 18 to 65 with acute myeloid leukemia (AML)/high-risk myelodysplastic syndromes, that is, idarubicine-cytarabine (cycle I) and amsacrine-cytarabine (cycle II) without or with clofarabine (10 mg/m on days 1-5 of each of both cycles). Consolidation involved chemotherapy with or without hematopoietic stem cell transplantation.

Comparison of modern and conventional imaging techniques in establishing multiple myeloma-related bone disease: a systematic review.

This systematic review of studies compared magnetic resonance imaging (MRI), (18) F-fluorodeoxyglucose positron emission tomography (FDG-PET), FDG-PET with computerized tomography (PET-CT) and CT with whole body X-Ray (WBXR) or (whole body) CT in order to provide evidence-based diagnostic guidelines in multiple myeloma bone disease. A comprehensive search of 3 bibliographic databases was performed; methodological quality was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria (score 1-14). Data from 32 directly comparative studies were extracted.

¹⁸F-fluoro-deoxyglucose positron emission tomography in assessment of myeloma-related bone disease: a systematic review.

Background: The goal of this study was to conduct a comparative analysis of whole body X-ray (WBXR) and (18) F-fluoro-deoxyglucose positron emission tomography ((18) FDG PET) in staging and response assessment of multiple myeloma.

Methods: We performed a systematic review of studies comparing (18) FDG PET with WBXR and/or magnetic resonance imaging in terms of sensitivity for myeloma-related bone disease at staging and during follow-up.

Results: Eighteen studies involving 798 patients met the inclusion criteria.