Publications by authors named "Amy A Kirkwood"

Article Synopsis
  • Autologous anti-CD19 CAR T cells are becoming standard treatment for relapsed/refractory large B-cell lymphoma, but serious side effects like cytokine release syndrome (CRS) and neurotoxicity (ICANS) pose risks, often requiring ICU care.
  • In a study involving 925 patients in France, high rates of CRS (84.1%) and ICANS (40.5%) were observed, with significant proportions experiencing severe forms of these conditions.
  • Two prognostic scoring systems (CRS-PSS and ICANS-PSS) were developed to identify patients at higher risk for severe CRS and ICANS based on specific clinical factors, and these scores were validated in other patient groups treated with similar therapies.
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The aim of the study was to assess healthy tissue metabolism (HTM) using 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) positron emission tomography/computed tomography (PET/CT) during chemotherapy in Hodgkin lymphoma (HL) and the association of HTM with baseline metabolic tumour volume (MTV), haematological parameters, adverse events (AEs), early response and progression-free survival (PFS). We retrospectively identified 200 patients with advanced HL from the RATHL trial with [F]FDG-PET/CT before (PET0) and following 2 cycles of chemotherapy (PET2). [F]FDG-uptake was measured in bone marrow (BM), spleen, liver and mediastinal blood pool (MBP).

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CAR T-cell therapy has transformed relapsed/refractory (r/r) B-cell precursor acute lymphoblastic leukaemia (B-ALL) management and outcomes, but following CAR T infusion, interventions are often needed. In a UK multicentre study, we retrospectively evaluated tisagenlecleucel outcomes in all eligible patients, analysing overall survival (OS) and event-free survival (EFS) with standard and stringent definitions, the latter including measurable residual disease (MRD) emergence and further anti-leukaemic therapy. Both intention-to-treat and infused cohorts were considered.

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Risk stratification is crucial to the successful treatment of acute lymphoblastic leukemia (ALL). Although numerous risk factors have been identified, an optimal prognostic model for integrating variables has not been developed. We used individual patient data from 4 contemporary academic national clinical trials, UKALL14, NILG-ALL10/07, GIMEMA-LAL1913, and PETHEMA-ALL-HR2011, to generate and validate the European Working Group for Adult ALL prognostic index (EWALL-PI), which is based on white blood cell count, genetics, and end of induction minimal residual disease (MRD).

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JCO We analyzed long-term results of the response-adapted trial for adult patients with advanced-stage Hodgkin lymphoma. The aim was to confirm noninferiority of treatment de-escalation by omission of bleomycin from doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for interim fluorodeoxyglucose positron emission tomography (iPET)-negative patients and assess efficacy and long-term safety for iPET-positive patients who underwent treatment intensification with escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone (BEACOPP/BEACOPP14). The median follow-up is 7.

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Article Synopsis
  • * In a study of 652 BCP-ALL cases, whole genome sequencing (WGS) revealed cancer-related genetic changes in 51 out of 52 patients classified as B-other, including subtype-defining alterations that were previously overlooked.
  • * The research found that WGS is effective in identifying key genetic drivers in B-other ALL cases and highlights the importance of combining it with RNA sequencing for a more comprehensive understanding of leukemia genetics and patient outcomes.
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Article Synopsis
  • * It analyzed 375 adult patients and found that most received chemotherapy (57%) or radiotherapy (17%) as BT, which was generally safe and linked to a 42% reduction in disease progression and death after CAR-T therapy if there was a positive response to BT.
  • * Key factors predicting a positive response to BT included prior therapy response, absence of bulky disease, and using polatuzumab-containing regimens, with complete or partial response being particularly critical for Tisa-cel patients to avoid relapse
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Stem cell transplant (SCT) outcomes in high-risk and relapsed/refractory (R/R) pediatric acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) have been historically poor. Cord blood (CB) allows T-cell replete CB transplant (TRCB), enabling enhanced graft-versus-leukemia. We consecutively collected data from 367 patients undergoing TRCB (112 patients) or other cell source (255 patients) SCT for pediatric AML/MDS in the United Kingdom and Ireland between January 2014 and December 2021.

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CD19 CAR-T have emerged as a new standard treatment for relapsed/refractory (r/r) large B-cell lymphoma (LBCL). CAR-T real-world (RW) outcomes published to date suggest significant variability across countries. We provide results of a large national cohort of patients intended to be treated with CAR-T in the UK.

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Background: The outcome of chemotherapy in patients older than 40 years with acute lymphoblastic leukaemia is poor and myeloablative allogeneic haematopoietic stem-cell transplantation (HSCT) has a high transplant-related mortality (TRM) in this age cohort. The aim of this study was to assess the activity and safety of reduced-intensity conditioned allogeneic HSCT in this patient population.

Methods: This was a single-arm, prospective study within the UKALL14 trial done in 46 centres in the UK, which recruited patients to the transplantation substudy.

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Background: Treatment for adults with acute lymphoblastic leukaemia requires improvement. UKALL14 was a UK National Cancer Research Institute Adult ALL group study that aimed to determine the benefit of adding the anti-CD20 monoclonal antibody, rituximab, to the therapy of adults with de novo B-precursor acute lymphoblastic leukaemia.

Methods: This was an investigator-initiated, phase 3, randomised controlled trial done in all UK National Health Service Centres treating patients with acute lymphoblastic leukaemia (65 centres).

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In successive UK clinical trials (UKALL 2003, UKALL 2011) for paediatric acute lymphoblastic leukaemia (ALL), polyethylene glycol-conjugated E. coli L-asparaginase (PEG-EcASNase) 1000 iu/m was administered intramuscularly with risk-stratified treatment. In induction, patients received two PEG-EcASNase doses, 14 days apart.

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Prophylactic high-dose methotrexate (HD-MTX) is often used for diffuse large B-cell lymphoma (DLBCL) patients at high risk of central nervous system (CNS) relapse, despite limited evidence demonstrating efficacy or the optimal delivery method. We conducted a retrospective, international analysis of 1384 patients receiving HD-MTX CNS prophylaxis either intercalated (i-HD-MTX) (n = 749) or at the end (n = 635) of R-CHOP/R-CHOP-like therapy (EOT). There were 78 CNS relapses (3-year rate 5.

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Article Synopsis
  • Acute lymphoblastic leukemia (ALL), typically a childhood disease, also affects older adults (60+) who have a second peak in incidence but face worse treatment outcomes.
  • A study analyzing 210 patients aged 60 and older revealed significant genetic abnormalities, including prevalent deletions in driver genes (77% of cases) and specific mutations, with high-risk genetic profiles being notably scarce.
  • The 5-year event-free survival and overall survival rates for this population were low (17% and 24%, respectively), highlighting the urgent need for new treatment approaches.
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Chromosomal abnormalities are established prognostic markers in adult ALL. We assessed the prognostic impact of established chromosomal abnormalities and key copy number alterations (CNA) among 652 patients with B-cell precursor ALL treated on a modern MRD driven protocol. Patients with KMT2A-AFF1, complex karyotype (CK) and low hypodiploidy/near-triploidy (HoTr) had high relapse rates 50%, 60% & 53% and correspondingly poor survival.

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