BCG vaccination alters the epigenetic landscape of progenitor cells in human bone marrow to influence innate immune responses.

Although the Bacille-Calmette-Guérin (BCG) vaccine is used to prevent tuberculosis, it also offers protection against a diverse range of non-mycobacterial infections. However, the underlying protective mechanisms in humans are not yet fully understood. Here, we surveyed at single-cell resolution the gene expression and chromatin landscape of human bone marrow, aspirated before and 90 days after BCG vaccination or placebo.

Decitabine in older patients with AML: quality of life results of the EORTC-GIMEMA-GMDS-SG randomized phase 3 trial.

We hypothesized that fit older patients with acute myeloid leukemia (AML) treated with decitabine (DEC) would report better health-related quality of life (HRQoL) outcomes than those receiving intensive chemotherapy (IC). We conducted a phase 3 randomized trial to compare DEC (10-day schedule) with IC (3+7) in older fit patients with AML. HRQoL was a secondary end point, and it was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in conjunction with its elderly module (EORTC QLQ-ELD14).

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.

Significant impact of antibiotic exposure on GI-GVHD, NRM, and GRFS following allogeneic HCT with non-myeloablative Flu-TBI conditioning.

Background: Acute gastro-intestinal graft--host disease (GI-GVHD) and non-relapse mortality (NRM) after allogeneic HCT are closely related to loss of microbial diversity and intestinal dominance by single taxa resulting from the use of antibiotics, dietary changes, and mucosal barrier injury. There is a paucity of data on the impact of use of antibiotics in HCT after Flu-TBI-based non-myeloablative (NMA) conditioning where there is absence of mucositis and limited malnutrition.

Methods: We did a retrospective single-center analysis of patients receiving Flu-TBI-based NMA HCT for a high-grade myeloid malignancy, mostly AML, and MDS, or acute lymphoblastic leukemia (ALL).

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.

Platelet Transfusion before CVC Placement in Patients with Thrombocytopenia.

Background: Transfusion guidelines regarding platelet-count thresholds before the placement of a central venous catheter (CVC) offer conflicting recommendations because of a lack of good-quality evidence. The routine use of ultrasound guidance has decreased CVC-related bleeding complications.

Methods: In a multicenter, randomized, controlled, noninferiority trial, we randomly assigned patients with severe thrombocytopenia (platelet count, 10,000 to 50,000 per cubic millimeter) who were being treated on the hematology ward or in the intensive care unit to receive either one unit of prophylactic platelet transfusion or no platelet transfusion before ultrasound-guided CVC placement.

A difficult to treat relapse after allogeneic stem cell transplantation.

Here we describe a complicated case of a relapsed infection after an allogeneic stem cell transplantation (allo-SCT) for primary myelofibrosis. Three years earlier the patient had been diagnosed with a hemophagocytic lymphohistiocytosis secondary to a visceral infection, for which he was effectively treated with a cumulative dose of 40 mg/kg liposomal amphotericin B. During the first disease episode he was also diagnosed with primary myelofibrosis for which he received medical follow-up.

Clinical Impact of Polymerase Chain Reaction-Based Aspergillus and Azole Resistance Detection in Invasive Aspergillosis: A Prospective Multicenter Study.

Background: Invasive aspergillosis (IA) by a triazole-resistant Aspergillus fumigatus is associated with high mortality. Real-time resistance detection will result in earlier initiation of appropriate therapy.

Methods: In a prospective study, we evaluated the clinical value of the AsperGenius polymerase chain reaction (PCR) assay in hematology patients from 12 centers.

Invasive Fungal Disease in Patients with Myeloid Malignancies: A Retrospective Cohort Study of a Diagnostic-Driven Care Pathway Withholding Mould-Active Prophylaxis.

Objectives: Patients receiving remission induction therapy for acute myeloid leukaemia (AML) are at high risk of developing invasive fungal disease (IFD). Newer therapies with targeted antileukemic agents and the emergence of azole resistance pose a challenge to the strategy of primary antifungal prophylaxis. We report the experience of a diagnostic-driven care pathway (DCP) for the management of IFD in these patients, using only culture-directed mould inactive prophylaxis.

Posaconazole bioavailability of the solid oral tablet is reduced during severe intestinal mucositis.

Objectives: This study aimed to describe the absolute oral bioavailability of the solid oral formulation of posaconazole and the impact of severe intestinal mucositis in haematology patients. This study also aimed to describe posaconazole protein binding in haematology patients.

Methods: A pharmacokinetic study was performed of patients receiving induction chemotherapy or a haematopoietic cell transplantation who were randomized to receive 7 days of intravenous posaconazole therapy followed by 9 days of oral therapy, or vice versa.

Anti-thymocyte globulin with CsA and MMF as GVHD prophylaxis in nonmyeloablative HLA-mismatched allogeneic HCT.

Nonmyeloablative regimens are used for allogeneic hematopoietic cell transplantation (HCT) of older or medically unfit patients, but successful outcome is still hindered by graft-versus-host disease (GVHD), especially in the setting of HLA-mismatched HCT. New GVHD prophylaxis strategies are emerging, including the triple drug strategy, that improve the GVHD-free and relapse-free survival (GRFS). Because the impact of ATG in HLA-mismatched Flu-TBI-based nonmyeloablative HCT has not been investigated, we did a retrospective analysis in three Dutch centers.

Low relapse risk in poor risk AML after conditioning with 10-day decitabine, fludarabine and 2 Gray TBI prior to allogeneic hematopoietic cell transplantation.

Patients with poor risk acute myeloid leukemia (AML) have a dismal outcome. We hypothesized that combining decitabine with a standard non-myeloablative (NMA) conditioning regimen prior to allogeneic hematopoietic cell transplantation (allo HCT), might decrease the relapse incidence. We conducted a multicenter prospective phase II study (NCT02252107) with 10-day decitabine (20 mg/m/day) integrated in a standard non-myeloablative conditioning regimen (3 days fludarabine 30 mg/m with 2 Gray total body irradiation (TBI)).

Pretransplantation MRD in Older Patients With AML After Treatment With Decitabine or Conventional Chemotherapy.

The predictive value of measurable residual disease (MRD) for survival in acute myeloid leukemia (AML) has been firmly established in younger patients treated with intensive chemotherapy. The value of MRD after treatment with decitabine in older patients is unknown. This retrospective analysis included patients ≥60 years of age with AML who received an allogeneic hematopoietic cell transplantation (alloHCT) after treatment with decitabine or intensive chemotherapy.

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.

Anakinra: efficacy in the management of fever during neutropenia and mucositis in autologous stem cell transplantation (AFFECT-2)-study protocol for a multicenter randomized double-blind placebo-controlled trial.

Background: Since decades, fever and infections have been the most important complications of intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) in the treatment of hematologic malignancies. Neutropenia has long been considered to be the most important risk factor for these complications. However, recent studies have shown that not neutropenia, but the development of mucositis is the most important cause of these complications.

BCG Vaccination in Humans Elicits Trained Immunity via the Hematopoietic Progenitor Compartment.

Induction of trained immunity by Bacille-Calmette-Guérin (BCG) vaccination mediates beneficial heterologous effects, but the mechanisms underlying its persistence and magnitude remain elusive. In this study, we show that BCG vaccination in healthy human volunteers induces a persistent transcriptional program connected to myeloid cell development and function within the hematopoietic stem and progenitor cell (HSPC) compartment in the bone marrow. We identify hepatic nuclear factor (HNF) family members 1a and b as crucial regulators of this transcriptional shift.

Association of Serum Ferritin Levels Before Start of Conditioning With Mortality After alloSCT - A Prospective, Non-interventional Study of the EBMT Transplant Complications Working Party.

Elevated serum ferritin levels occur due to iron overload or during inflammation and macrophage activation. A correlation of high serum ferritin levels with increased mortality after alloSCT has been suggested by several retrospective analyses as well as by two smaller prospective studies. This prospective multicentric study aimed to study the association of ferritin serum levels before start of conditioning with alloSCT outcome.