Nigel Russell

Nigel Russell
University of Nottingham | Notts · School of Medicine

MD

About

720
Publications
40,250
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
25,356
Citations
Citations since 2016
192 Research Items
9548 Citations
201620172018201920202021202205001,0001,500
201620172018201920202021202205001,0001,500
201620172018201920202021202205001,0001,500
201620172018201920202021202205001,0001,500

Publications

Publications (720)
Article
The survival of acute myeloid leukaemia (AML) patients aged over 60 has been suboptimal historically, whether they are treated using hypomethylating agents, low‐dose cytarabine (LDAC) or venetoclax‐based regimens. Progress is being made, however, for subgroups with favourable molecular or cytogenetic findings. Arginine metabolism plays a key role i...
Article
Full-text available
Clinical recommendations for Acute Myeloid Leukemia (AML) classification and risk-stratification remain heavily reliant on cytogenetic findings at diagnosis , which are present in <50% of patients. Using comprehensive molecular profiling data from 3,653 patients we characterize and validate 16 molecular classes describing 100% of AML patients. Each...
Article
Full-text available
Introduction: Treatment decisions in older adults with acute myeloid leukemia (AML) are challenging, particularly for those who are not candidates for intensive chemotherapy (IC), and the trade-offs patients, their families and physicians consider when choosing a treatment option are not well understood. This qualitative research explored the valu...
Article
The prognosis for younger patients with relapsed acute myeloid leukaemia (AML) is generally dismal. Allogeneic stem cell transplantation is the preferred therapy for these patients. As part of the UK NCRI AML17 trial, daunorubicin/clofarabine (DClo) was compared with fludarabine, cytarabine, granulocyte colony‐stimulating factor with idarubicin (FL...
Article
BACKGROUND A single-group, phase 1–2 study indicated that eltrombopag improved the efficacy of standard immunosuppressive therapy that entailed horse antithymocyte globulin (ATG) plus cyclosporine in patients with severe aplastic anemia. METHODS In this prospective, investigator-led, open-label, multicenter, randomized, phase 3 trial, we compared t...
Article
Background: Many patients with Acute Myeloid Leukemia (AML) diagnosed after 60 years of age are not considered suitable for intensive remission induction chemotherapy, either due to co-morbidities or frailty associated with advanced age. Despite treatment with either a hypomethylating agent or low-dose cytarabine arabinoside (LDAC), survival is usu...
Article
Introduction Allogeneic hematopoietic cell transplant (allo-HCT) in first or second complete remission (CR1 or CR2) plays a fundamental role in the management of FLT3-ITD mutant acute myeloid leukemia (AML). Measurable residual disease (MRD) detected prior to HCT by flow cytometry or NPM1 RT-qPCR indicates a high risk of post-HCT relapse (Dillon et...
Article
Background: Among patients with Acute Myeloid Leukaemia (AML) over the age of 60, a considerable number are not considered suitable for intensive remission-induction chemotherapy. Survival in these patients is poor, whether they are treated using hypomethylating agents or low-dose ara-C (LDAC). The possibility of combination therapy with additional...
Article
Full-text available
Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.1...
Article
Full-text available
Reduced Intensity Conditioning (RIC) transplantation is increasingly offered to older patients with acute myeloblastic leukemia (AML). We have previously shown that a RIC allograft, particularly from a sibling donor is beneficial in intermediate risk patients aged 35-65 years. We here present analyses from the NCRI AML16 trial extending this experi...
Article
7016 Background: AML patients may be treated with intensive chemotherapy (IC), or non-intensive chemotherapy (NIC) or they may receive best supportive care (BSC) or hospice care. Balancing treatment efficacy and toxicities is key in treatment decision-making. IC is efficacious with extensive toxicities, while NIC has lower risk of toxicities but re...
Chapter
Measurable (previously minimal) residual disease (MRD) detection in acute myeloid leukemia (AML) has progressed beyond being a recognized strong prognostic factor. MRD-risk stratification is now incorporated into many treatment schedules and there is ongoing evaluation of MRD-directed therapy. Evolving assay technology such as next-generation seque...
Article
Full-text available
In acute myeloid leukaemia (AML) t(8;16)(p11;p13)/MYST3-CREBBP is a very rare abnormality. Previous small series suggested poor outcome. We report on 59 patients with t(8;16) within an international, collaborative study. Median age was 52 (range: 16-75) years. AML was de novo in 58%, therapy-related (t-AML) in 37% and secondary after myelodysplasti...
Article
Full-text available
Background Carfilzomib is a second-generation irreversible proteasome inhibitor that is efficacious in the treatment of myeloma and carries less risk of peripheral neuropathy than first-generation proteasome inhibitors, making it more amenable to combination therapy. Methods and findings The Myeloma XI+ trial recruited patients from 88 sites acros...
Article
PURPOSE The optimum number of treatment courses for younger patients with acute myeloid leukemia (AML) is uncertain. The United Kingdom National Cancer Research Institute AML17 trial randomly assigned patients who were not high risk to a total of three versus four courses. PATIENTS AND METHODS Patients received two induction courses based on dauno...
Article
Introduction Molecular MRD assays targeting NPM1 mutant (mut) transcripts have an established role for monitoring treatment efficacy in patients with NPM1mut AML. Approximately 25% of NPM1mut patients show persistent MRD level in the bone marrow (BM) at the end of treatment (EOT), which is associated with a higher risk of relapse (Ivey, NEJM 2016;...
Article
Full-text available
The reported influence of donor Killer-cell Immunoglobulin-like Receptor (KIR) genes on the outcomes of haematopoietic cell transplantation (HCT) are contradictory, in part due to diversity of disease, donor sources, era and conditioning regimens within and between different studies. Here, we describe the results of a retrospective clinical analysi...
Article
Full-text available
Despite the substantial clinical activity of fms-related tyrosine kinase 3 (FLT3) inhibitors in relapsed or refractory (R/R) FLT3-ITD‒positive acute myelogenous leukemia (AML), durable remissions and prolonged survival in this population require allogeneic hematopoietic stem cell transplantation (allo-HSCT). Quizartinib, a once-daily oral, highly p...
Conference Paper
Introduction: We evaluated the impact of baseline (BL) co-mutations and FLT3-ITD VAF on overall survival (OS) and response (composite complete remission [CRc]) to quizartinib and SC in the phase III QuANTUM-R trial. Methods: We analyzed 37 recurrently mutated genes in AML in BL samples from 304 patients (pts) (83% of ITT population) with R/R FLT3-I...
Article
Full-text available
Second‐generation immunomodulatory agents, such as lenalidomide, have a more favourable side‐effect profile than the first‐generation thalidomide, but their optimum combination and duration for patients with newly diagnosed transplant‐ineligible myeloma (ND‐TNE‐MM) has not been defined. The most appropriate delivery and dosing regimens of these the...
Article
Full-text available
The optimal way to use immunomodulatory drugs as components of induction and maintenance therapy for multiple myeloma is unresolved. We addressed this question in a large phase III randomized trial, Myeloma XI. Patients with newly diagnosed multiple myeloma (n = 2042) were randomized to induction therapy with cyclophosphamide, thalidomide, and dexa...
Article
7520 Background: Current treatment options for acute myeloid leukemia (AML) are diverse, including intensive chemotherapy (IC), low intensity therapy, best supportive care (BSC), and hospice care. Despite continued development of new therapies, recent data suggest that approximately 60% of older US patients remain untreated, but reasons for this ar...
Article
Full-text available
Based on promising results in older adults with acute myeloid leukaemia (AML), we treated patients with NPM1mut measurable residual disease (MRD) using off‐label venetoclax in combination with low‐dose cytarabine or azacitidine. Twelve consecutive patients were retrospectively identified, including five with molecular persistence and seven with mol...
Article
Full-text available
Introduction In QuANTUM-R, the once-daily, oral, highly potent and selective FLT3 inhibitor Q improved clinical benefit vs SC (median overall survival [mOS], 6.2 vs 4.7 mo [HR, 0.76 (95% CI, 0.58-0.98); P = .02]) in R/R FLT3-ITD AML (NCT02039726). Before randomization, 25% (Q) and 23% (SC) of pts had 1 prior HSCT. Objective To describe post hoc an...
Article
Full-text available
Relapse remains the most common cause of treatment failure for patients with acute myeloid leukaemia (AML) who undergo allogeneic stem cell transplantation (alloSCT) and carries a grave prognosis. Multiple studies have identified the presence of measurable residual disease (MRD) assessed by flow cytometry (FCM) prior to alloSCT as a strong predicto...
Article
We evaluated the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in transplant-naïve patients with relapsed/refractory Hodgkin lymphoma (HL) who failed to attain metabolic complete response (mCR) to 1 to 2 lines of salvage chemotherapyThose with residual but nonprogressive disease assessed by positron emission tomography/comp...
Article
Introduction: Molecular MRD monitoring in NPM1 mutant (mut) AML is now standard of care in many countries as prospective clinical trials have demonstrated that suboptimal reduction and/or rising levels of NPM1mut transcript are associated with disease relapse (Ivey, NEJM 2016; Balsat, JCO 2017). Higher levels of NPM1mut MRD positivity are associate...
Article
Introduction: Patients (pts) with relapsed/refractory (R/R) acute myeloid leukemia (AML) with FLT3-ITD mutations have a dismal prognosis and limited treatment options. Given the aggressiveness of FLT3-ITD AML, therapies that produce rapid and sustained disease control are needed. Quizartinib (Q), a once-daily, oral, highly potent and selective FLT3...
Article
Background: Immunomodulatory (IMiD) compounds are effective therapies for multiple myeloma (MM) acting via modulation of the CUL4 E3-ubiquitin ligase cereblon. Based on their structure individual IMiD compounds have different substrate specificities altering both their efficacy and side effect profile. These mechanistic differences impact the optim...
Article
INTRODUCTION: Allogeneic stem cell transplantation (allo-SCT) is an important curative strategy in adults with high risk acute myeloid leukemia (AML) and myelodysplasia (MDS). Disease relapse represents the major cause of treatment failure and whilst retrospective analyses have identified that pre-transplant measurable residual disease (MRD) is an...
Article
Background: The impact of the selective pressure of maintenance Lenalidomide has the potential to enhance disease aggressiveness at relapse and if this were the case would shorten the time to next therapy. Previously we have shown that Lenalidomide maintenance therapy in myeloma is associated with improved progression-free survival (PFS). This init...
Article
Background: Quizartinib is a once-daily, oral, highly potent and selective FLT3 inhibitor with proven single-agent activity and a manageable safety profile in FLT3-ITD R/R AML. In the global, phase 3 QuANTUM-R study, quizartinib demonstrated a significant survival benefit over salvage chemotherapy(Cortes, et al. Lancet Oncol, 2019; NCT02039726). Ad...
Article
Introduction: Multiple myeloma (MM) is more common in men than women but the mechanism(s) driving this are not understood. In our previous study (Myeloma IX) we found sex disparities in the cytogenetic lesions present in myeloma cells at the time of diagnosis and that female sex was associated with reduced overall survival in the context of treatme...
Article
INTRODUCTION: Acute myeloid leukemia (AML) is a rare hematologic cancer primarily affecting older people, with a median age at diagnosis of 67 years old (Almeida & Ramos, 2016). Heterogeneity in the presentation, functional status and presence of comorbidities among AML patients presents unique challenges for treatment. Intensive chemotherapy (IC),...
Article
Introduction: R/R FLT3-ITD AML is an aggressive hematologic malignancy with a generally poor prognosis and high relapse rate even after allogeneic hematopoietic stem cell transplantation (HSCT). QuANTUM-R (NCT02039726), a large, global, phase 3, randomized, controlled trial, showed that single-agent quizartinib significantly prolonged overall survi...
Article
Background: Quizartinib, a once-daily, oral, highly potent and selective FLT3 inhibitor, demonstrated a significant improvement in survival vs SC in FLT3-ITD-positive R/R AML in the global, randomized, phase 3 QuANTUM-R study (Cortes et al. Lancet Oncol, 2019; NCT02039726). Patients with R/R FLT3-ITD-positive AML were randomized 2:1 to receive sing...
Article
Introduction: In the phase 3 QuANTUM-R trial, once-daily, oral, highly potent and selective FLT3 inhibitor Q improved clinical benefits vs SC (median overall survival [mOS], 6.2 vs 4.7 mo [HR, 0.76 (95% CI, 0.58-0.98); P = .02]; composite complete remission [CRc], 48% vs 27%; median duration of CRc, 12.1 vs 5.0 wk) in 367 pts with R/R FLT3-ITD AML...
Article
Key Points Flt3L is a biomarker of progenitor cell mass in AML. Measurement of Flt3L during induction chemotherapy and follow-up provides prognostic information.
Article
Background FLT3-ITD mutations occur in about 25% of patients (pts) with acute myeloid leukemia (AML) and are associated with poor outcomes. Pts with relapsed/refractory (R/R) FLT3-ITD AML have worse prognosis and high unmet medical need. Quizartinib (Q) is a potent and selective FLT3i with promising activity and a manageable safety profile. QuANTUM...
Article
Full-text available
Background: Multiple myeloma has been shown to have substantial clonal heterogeneity, suggesting that agents with different mechanisms of action might be required to induce deep responses and improve outcomes. Such agents could be given in combination or in sequence on the basis of previous response. We aimed to assess the clinical value of maximi...
Article
Cohesin complex disruption alters gene expression, and cohesin mutations are common in myeloid neoplasia, suggesting a critical role in hematopoiesis. Here, we explore cohesin dynamics and regulation of hematopoietic stem cell homeostasis and differentiation. Cohesin binding increases at active regulatory elements only during erythroid differentiat...
Article
Acute myeloid leukemia (AML) with t(6;9)(p22;q34) is a distinct entity accounting for 1-2% of AML cases. A substantial proportion of these patients have a concomitant FLT3-ITD. While outcomes are dismal with intensive chemotherapy, limited evidence suggests allogeneic hematopoietic cell transplantation (allo-HCT) may improve survival if performed e...
Article
Full-text available
HLA matching at an allelic-level resolution for volunteer unrelated donor (VUD) hematopoietic cell transplanta-tion (HCT) results in improved survival and fewer post-transplant complications. Limitations in typing technologies used for the hyperpolymorphic HLA genes have meant that variations outside of the antigen recognition domain (ARD) have not...
Article
Since the comprehensive recommendations for the management of acute promyelocytic leukemia (APL) reported in 2009, several studies have provided important insights, particularly regarding the role of arsenic trioxide (ATO) in frontline therapy. Ten years later, a European LeukemiaNet expert panel has reviewed the recent advances in the management o...
Article
Full-text available
Acute myeloid leukaemia (AML) cells often up-regulate pro-survival members of the BCL-2 protein family, such as BCL-2 and MCL-1, to avoid apoptosis. Venetoclax (ABT-199) targets BCL-2 and has shown promising efficacy in AML but over-expression of MCL-1 can cause resistance. A co-operative approach, targeting both BCL-2 and MCL-1 may therefore prove...
Article
Full-text available
Background Patients with multiple myeloma treated with lenalidomide maintenance therapy have improved progression-free survival, primarily following autologous stem-cell transplantation. A beneficial effect of lenalidomide maintenance therapy on overall survival in this setting has been inconsistent between individual studies. Minimal data are avai...
Article
Introduction Relapse remains the most common cause of treatment failure for patients with acute myeloid leukaemia (AML) who undergo allogeneic stem cell transplantation (SCT) and carries a grave prognosis. Multiple studies have identified the presence of minimal residual disease (MRD) prior to SCT assessed by flow cytometry (FCM) as a strong predic...