Clinical and molecular characterization of TP53-mutant acute lymphoblastic leukemia in adults.

TP53-mutant acute lymphoblastic leukemia (ALL) in adults is a high-risk subtype with poor outcomes, yet its molecular landscape and clinical implications remain incompletely defined. In this multi-institutional study of 830 adult ALL patients treated at eight academic centers between 2010 and 2024, we demonstrated that TP53 mutations are independent predictors of inferior overall survival in both B-ALL (median, 1.9 vs 5 years) and T-ALL (1.

Improved outcomes of acute lymphoblastic leukemia after allogeneic blood or marrow transplantation with high-dose post-transplantation cyclophosphamide in the era of more effective pre-transplant therapy.

The therapeutic landscape in ALL has changed dramatically over the last decade. Allogeneic blood or marrow transplantation (AlloBMT) has also evolved and remains an important option for consolidation. We assessed the interplay between these factors by analyzing the outcomes of 251 adult ALL (214 B and 37 T ALL) patients undergoing alloBMT with post-transplantation cyclophosphamide (PTCy) across two eras: 2008-2014 (ERA1) and 2015-2022 (ERA2).

Recognition, prevention, and management of adverse events associated with asparaginase / pegaspargase treatment of acute lymphoblastic leukemia in adults: consensus of an expert panel.

Asparaginase (ASNase)-based chemotherapy regimens significantly improve survival outcomes in children, adolescent and young adult (AYA), and even adults with acute lymphoblastic leukemia/lymphoma (ALL); however, the incidence and severity of ASNase-associated adverse events (AEs) in adults may differ significantly from those reported in children. Strategies to mitigate, monitor for, and manage toxicities that allow adult ALL patients to receive full ASNase courses are needed. A representative 12-member panel of experts who treat AYA and adult ALL patients, incorporate ASNase into their treatment regimens, and conduct related research was assembled to consider opportunities to optimize the use of pediatric-inspired ALL regimens in these adult patients.

Developing critical enquiry, capacity, capability and confidence in the health and care workforce.

Background: Health and care staff have limited opportunities to design, deliver and lead critical enquiry activities.

Aims: To explore barriers and enablers of building capacity, capability and confidence of these practitioners who wish to undertake critical enquiry activity.

Methods: A realist conceptual framework including the development of middle range theory allowed analysis of the scholarship process and outcomes.

Exploring the sustainable impacts of a clinical healthcare research scholarship programme.

Background: The NHS is the first public body globally to commit to net zero.

Aim: This study aimed to explore the environmental sustainability impact of a hospital scholarship programme.

Method: A sustainable quality improvement value framework was used to measure the programme's environmental, social and financial effects.

AMPK inhibition sensitizes acute leukemia cells to BH3 mimetic-induced cell death.

BH3 mimetics, including the BCL2/BCLX/BCLw inhibitor navitoclax and MCL1 inhibitors S64315 and tapotoclax, have undergone clinical testing for a variety of neoplasms. Because of toxicities, including thrombocytopenia after BCLX inhibition as well as hematopoietic, hepatic and possible cardiac toxicities after MCL1 inhibition, there is substantial interest in finding agents that can safely sensitize neoplastic cells to these BH3 mimetics. Building on the observation that BH3 mimetic monotherapy induces AMP kinase (AMPK) activation in multiple acute leukemia cell lines, we report that the AMPK inhibitors (AMPKis) dorsomorphin and BAY-3827 sensitize these cells to navitoclax or MCL1 inhibitors.

Impact of inotuzumab ozogamicin on outcome in relapsed or refractory acute B-cell lymphoblastic leukemia patients prior to allogeneic hematopoietic stem cell transplantation and risk of sinusoidal obstruction syndrome/venous occlusive disease.

We evaluated 58 patients with relapsed or refractory (r/r) acute B-lymphoblastic leukemia (B-ALL; median age 42.5 years; range, 16-69 years), treated with inotuzumab ozogamicin (INO) between 2016-2022 and who received an allogeneic hematopoietic stem cell transplantation (allo-HCT) consecutively. Forty-seven (81%) of the 58 patients were heavily pretreated receiving intensive chemotherapy +/- tyrosine kinase inhibitor, blinatumomab in 24 (41%) and allo-HCT at first-line in 11 (19%) patients.

A phase 2 and pharmacological study of sapanisertib in patients with relapsed and/or refractory acute lymphoblastic leukemia.

Background: Despite recent approval of several new agents, relapsed acute lymphoblastic leukemia (ALL) remains challenging to treat. Sapanisertib (MLN0128/TAK-228) is an oral TORC1/2 inhibitor that exhibited preclinical activity against ALL.

Methods: We conducted a single-arm multi-center Phase II study of sapanisertib monotherapy (3 mg orally daily of the milled formulation for 21 days every 28 days) in patients with ALL through the Experimental Therapeutics Clinical Trials Network (NCI-9775).

DNA methyltransferase inhibitor exposure-response: Challenges and opportunities.

Although DNA methyltransferase inhibitors (DNMTis), such as azacitidine and decitabine, are used extensively in the treatment of myelodysplastic syndromes and acute myeloid leukemia, there remain unanswered questions about DNMTi's mechanism of action and predictors of clinical response. Because patients often remain on single-agent DNMTis or DNMTi-containing regimens for several months before knowing whether clinical benefit can be achieved, the development and clinical validation of response-predictive biomarkers represents an important unmet need in oncology. In this review, we will summarize the clinical studies that led to the approval of azacitidine and decitabine, as well as the real-world experience with these drugs.

Detection of an atypical BCR::ABL1 fusion in a patient with secondary B-cell acute lymphoblastic leukemia/lymphoma following multiple myeloma treatment.

Secondary hematologic malignancies, such as B-cell acute lymphoblastic leukemia/lymphoma (B-ALL), have been reported following multiple myeloma. Tyrosine kinase inhibitors have improved clinical outcomes of patients with Philadelphia-positive (Ph+) B-ALL. Therefore, recognition of the Ph chromosome in B-ALL patients is important for both prognosis and therapies.

Embedding research (ER) led by nurses, midwives and allied health professionals (NMAHPs): the NMAHP-ER model.

Background: Previous embedded researcher models have focused predominantly on an individual being a temporary team member and embedded for a project-limited short-term placement.

Aim: To develop an innovative research capacity building model to address the challenges of developing, embedding and sustaining, research led by Nurses, Midwives, and Allied Health Professionals (NMAHPs) in complex clinical environments. This healthcare and academic research partnership model offers an opportunity to support the 'how' of enabling NMAHP research capacity building from within the researchers' clinical area of expertise.

Venetoclax in combination with hypomethylating agent for the treatment of advanced myeloproliferative neoplasms and acute myeloid leukemia with extramedullary disease.

The combination of venetoclax and hypomethylating agent (HMA/venetoclax) has emerged as a treatment option for patients with de novo acute myeloid leukemia (AML) who are unfit to receive intensive chemotherapy. In this single-center retrospective study, we evaluated clinical outcomes following treatment with HMA/venetoclax in 35 patients with advanced myeloproliferative neoplasms, myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes or AML with extramedullary disease. The composite complete remission (CR) rate (including confirmed/presumed complete cytogenetic response, acute leukemia response-complete, CR and CR with incomplete hematologic recovery) was 42.

Allogeneic Blood or Marrow Transplantation with High-Dose Post-Transplantation Cyclophosphamide for Acute Lymphoblastic Leukemia in Patients Age ≥55 Years.

Patients age ≥55 years with acute lymphoblastic leukemia (ALL) fare poorly with conventional chemotherapy, with a 5-year overall survival (OS) of ∼20%. Tyrosine kinase inhibitors and novel B cell-targeted therapies can improve outcomes, but rates of relapse and death in remission remain high. Allogeneic blood or marrow transplantation (alloBMT) provides an alternative consolidation strategy, and post-transplantation cyclophosphamide (PTCy) facilitates HLA-mismatched transplantations with low rates of nonrelapse mortality (NRM) and graft-versus-host disease (GVHD).

Hyperphosphatemic Tumoral Calcinosis With Pemigatinib Use.

Background/objective: Pemigatinib, a fibroblast growth factor receptor (FGFR) 1-3 inhibitor, is a novel therapeutic approach for treating cholangiocarcinoma when an FGFR fusion or gene rearrangement is identified. Although the most reported side effect of pemigatinib is hyperphosphatemia, tumoral calcinosis with soft tissue calcifications is not widely recognized as a complication. We report a case of patient with hyperphosphatemic tumoral calcinosis on pemigatinib.

'Guiding Lights for effective workplace cultures': enhancing the care environment for staff and patients in older people's care settings.

While much attention has been given to organisational culture, there has been less focus on workplace culture. Yet workplace culture strongly influences the way care is delivered, received and experienced. An effective workplace culture is crucial for the well-being of individual staff members and teams as well as for patients' experiences and outcomes of care.

A thematic analysis of system wide learning from first wave Covid-19 in the East of England.

Background: The Covid-19 pandemic has created an unprecedented challenge for health and social care systems globally. There is an urgent need for research on experiences of COVID-19 at different levels of health systems, including lessons from professional, organisational and local system responses, that can be used to inform managerial and policy responses.

Methods: This paper presents the findings from a thematic analysis of front-line staff experiences working across the Norfolk and Waveney integrated care system (ICS) in the East of England during April and October 2020 to address the question "What are the experiences and perceptions of partner organisations and practitioners at multiple levels of the health system in responding to COVID-19 during the first wave of the pandemic?" This question was posed to learn from how practitioners, interdependent partner organisations and the system experienced the pandemic and responded.

Genomic landscape of myelodysplastic/myeloproliferative neoplasm can predict response to hypomethylating agent therapy.

There are currently no known predictors of myelodysplastic syndrome (MDS)/myeloproliferative overlap neoplasm (MPN) patients' response to hypomethylating agents (HMA). Forty-three patients with MDS/MPN who were treated with HMA during chronic phase and had next-generation sequencing using the established 63-genes panel were identified. Complete and partial remission and marrow response were assessed based on the MDS/MPN International Working Group response criteria.

Post-Transplantation Cyclophosphamide-Based Graft- versus-Host Disease Prophylaxis with Nonmyeloablative Conditioning for Blood or Marrow Transplantation for Myelofibrosis.

We describe outcomes after post-transplantation cyclophosphamide and nonmyeloablative conditioning-based allogeneic blood or marrow transplantation for myelofibrosis using matched or mismatched related or unrelated donors. The conditioning regimen consisted of fludarabine, cyclophosphamide, and total body irradiation. Forty-two patients were included, with a median age of 63 years, of whom 19% had Dynamic International Prognostic Scoring System (DIPSS)-plus intermediate-1 risk, 60% had intermediate-2 risk, and 21% had high-risk disease, and 60% had at least 1 high-risk somatic mutation.