17 results found
May P, Reid A, Robinson M, et al., 2023, FISH-negative BCR::ABL1-positive e19a2 chronic myeloid leukaemia: the most cryptic of insertions, BMC Medical Genomics, Vol: 16, Pages: 1-6, ISSN: 1755-8794
Background:Chronic myeloid leukaemia (CML) is one of the most well characterised human malignancies. Most patients have a cytogenetically visible translocation between chromosomes 9 and 22 which generates the pathognomonic BCR::ABL1 fusion gene. The derivative chromosome 22 (‘Philadelphia’ or Ph chromosome) usually harbours the fusion gene encoding a constitutively active ABL1 kinase domain. A small subset of patients have no detectable translocation. Historically, these ‘Philadelphia chromosome negative’ patients caused diagnostic confusion between CML and other myeloproliferative neoplasms; it is now well established that the BCR::ABL1 fusion gene can be generated via submicroscopic intrachromosomal insertion of ABL1 sequence into BCR, or, more rarely, of BCR into ABL1. The fusion genes arising from cryptic insertions are not detectable via G-banded chromosome analysis [karyotype] but can nevertheless always be detected using fluorescence in situ hybridisation (FISH) and/or qualitative reverse transcriptase PCR.Case presentation:A 43-year-old female presented with suspected CML in 2007; however, contemporaneous gold standard laboratory investigations, G-banded chromosome analysis and FISH, were both negative. The reverse transcriptase quantitative PCR (RT-qPCR) assay available at the time, which was capable of detecting the common BCR::ABL1 transcripts (e13a2/e14a2), was also negative. Upon review in 2009, the newly recommended reverse transcriptase multiplex PCR (capable of detecting all BCR::ABL1 transcripts including the atypical ones) subsequently detected an e19a2 fusion. The patient then responded to tyrosine kinase inhibitor therapy. In contrast, FISH studies of both samples with three commercially available probes remained consistently negative.Retrospective whole genome sequencing, undertaken as part of the 100,000 Genomes Project, has now revealed that the patient’s BCR::ABL1 fusion gene arose via a uniquely small insertion
Cook L, O'dell G, Vourvou E, et al., 2022, Third primary SARS-CoV-2 mRNA vaccines enhance antibody responses in most patients with haematological malignancies, Nature Communications, Vol: 13, Pages: 1-6, ISSN: 2041-1723
SARS-CoV-2 infection, and resulting disease, COVID-19, has a high mortality amongst patients with haematological malignancies. Global vaccine rollouts have reduced hospitalisations and deaths, but vaccine efficacy in patients with haematological malignancies is known to be reduced. The UK-strategyoffered a third, mRNA-based, vaccine as an extension to the primary course in these patients. The MARCH database is a retrospective observational study of serological responses in patients with blood disorders. Here we present data on 381 patients with haematological malignancies. By comparison with healthy controls, we report suboptimal responses following two primary vaccines, with significantly enhanced responses following the third primary dose. These responses however are heterogeneous and determined by haematological malignancy sub-type and therapy. We identify a group of patients with continued sub-optimal vaccine responses who may benefit from additional doses, prophylactic extended half-life neutralising monoclonal therapies (nMAB) or prompt nMAB treatment in the event of SARS-CoV-2 infection.
- Novel long-acting coronavirus prophylactic monoclonal antibodytherapies have been shown to be effective in preventing COVID19 in immunocompromised individuals who are at increased riskfrom SARS-CoV-2.- Prophylactic antibody therapies should be made available in atimely manner to give an antibody immunity boost to vulnerablepatients.- Real world evaluations should be co-implemented to provideconfidence of ongoing effectiveness.- Successful delivery of a coronavirus prophylactic antibodytherapy programme would deliver significant benefits tohealthcare systems, communities and immunocompromisedindividuals.
Innes AJ, Mullish BH, Ghani R, et al., 2021, Fecal microbiota transplant mitigates adverse outcomes in patients colonized with multidrug-resistant organisms undergoing allogeneic hematopoietic cell transplantation, Frontiers in Cellular and Infection Microbiology, Vol: 11, Pages: 1-8, ISSN: 2235-2988
The gut microbiome can be adversely affected by chemotherapy and antibiotics prior to hematopoietic cell transplantation (HCT).This affects graft success and increases susceptibility to multidrug-resistant organism (MDRO) colonization and infection. Weperformed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy forMDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDROgroup), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival wassignificantly higher in the FMT-MDRO group (70% versus 36% p = 0.044). Post-HCT, fewer FMT-MDRO patients required intensivecare (0% versus 46%, P = 0.045) or experienced fever (0.29 versus 0.11 days, P = 0.027). Intestinal MDRO decolonization occurred in25% of FMT-MDRO patients versus 11% non-FMT MDRO patients. Despite the significant difference and statistically comparablepatient/transplant characteristics, as the sample size was small, a matched-pair analysis to non-MDRO colonized control cohorts(2:1 matching) was performed. At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4%versus 61.9% respectively, p=0.012), and higher non relapse mortality (NRM; 60.2% versus 16.7% respectively, p=0.009) than theirpaired non-colonized cohort. There was no difference in survival (70% versus 43.4%, p=0.14) or NRM (12.5% versus 31.2%respectively, p=0.24) between the FMT-MDRO group and their paired cohort. Negative outcomes, including mortality associatedwith MDRO colonization, may be ameliorated by pre-HCT FMT, despite lack of intestinal decolonization. Further work is needed toexplore the observed benefit.
Maynard S, Ros-Soto J, Chaidos A, et al., 2021, The role of ibrutinib in COVID-19 hyperinflammation: a case report, International Journal of Infectious Diseases, Vol: 105, Pages: 274-276, ISSN: 1201-9712
Continuing ibrutinib in patients with COVID-19 may be advantageous given its immunomodulatory properties and withdrawal of ibrutinib therapy may be detrimental. Further evidence is required to explore the potential therapeutic impact of BTKis and other immunomodulatory agents on the clinical course of COVID-19 as is currently being carried out in a number of clinical trials.
Ghani R, Mullish B, Innes A, et al., 2021, Faecal microbiota transplant (FMT) prior to allogeneic haematopoietic cell transplantation (HCT) in patients colonised with multidrug-resistant organisms (MDRO) results in improved survival, ECCMID
Pavlu J, Auner H, Szydlo RM, et al., 2017, Analysis of hematopoietic recovery after autologous transplantation as method of quality control for long-term progenitor cell cryopreservation., Bone Marrow Transplantation, Vol: 52, Pages: 1599-1601, ISSN: 1476-5365
Hematopoietic precursor cells (HPC) are able to restore hematopoiesis after high-dose chemotherapy and their cryopreservation is routinely employed prior to the autologous hematopoietic cell transplantation (AHCT). Although previous studies showed feasibility of long-term HPC storage, concerns remain about possible negative effects on their potency. To study the effects of long-term cryopreservation, we compared time to neutrophil and platelet recovery in 50 patients receiving two AHCT for multiple myeloma at least 2 years apart between 2006 and 2016, using HPC obtained from one mobilization and collection attempt before the first transplant. This product was divided into equivalent fractions allowing a minimum of 2 × 106 CD34+ cells/kg recipient’s weight. One fraction was used for the first transplant after median storage of 60 days (range, 17–165) and another fraction was used after median storage of 1448 days (range, 849–3510) at the second AHCT. Neutrophil recovery occurred at 14 days (median; range, 11–21) after the first and 13 days (10–20) after the second AHCT. Platelets recovered at a median of 16 days after both procedures. Considering other factors, such as disease status, conditioning and HPC dose, this single institution data demonstrated no reduction in the potency of HPC after long-term storage.
Chapman MS, Innes A, Milojkovic, et al., 2017, A retrospective analysis of patients testing positive for the JAK2 V617F mutation: correlation between mutant allele burden and disease phenotype, 57th Annual Scientific Meeting of the British Society for Haematology, ISSN: 0007-1048
Beckerson J, Szydlo RM, Hickson M, et al., 2016, Impact of Nutrition on Non-Relapse Mortality and Acute Graft Versus Host Disease during Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies, 59th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH)/Symposium on the Basic Science of Hemostasis and Thrombosis, Publisher: American Society of Hematology, Pages: 2226-2226, ISSN: 0006-4971
Rohman PJ, Szydlo RM, Hobbs E, et al., 2016, Preconditioning Neutropenia Is a Key Prognostic Factor in Allogeneic Hematopoietic Cell Transplantation for High Risk Acute Myeloid Leukemia, 59th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH)/Symposium on the Basic Science of Hemostasis and Thrombosis, Publisher: American Society of Hematology, Pages: 3411-3411, ISSN: 0006-4971
Monsalvo S, Sevillano B, Innes AJ, et al., 2016, The Intensive Care Trial for Critically Ill Onco-Haematologic Patients: The Need for Response Criteria at 5 Days of Full Treatment to Separate Good Risk Patients and Avoid Futile Intensive Care Interventions, 59th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH)/Symposium on the Basic Science of Hemostasis and Thrombosis, Publisher: American Society of Hematology, Pages: 5987-5987, ISSN: 0006-4971
Claudiani S, Apperley JF, Deplano S, et al., 2016, Cognitive dysfunction after withdrawal of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia, American Journal of Hematology, Vol: 91, Pages: E480-E481, ISSN: 1096-8652
Neelakantan P, Rezvani K, May P, et al., 2014, Excellent outcome after repeated changes of tyrosine kinase inhibitor therapy for chronic myeloid leukaemia in complete cytogenetic response due to minor side effects, BRITISH JOURNAL OF HAEMATOLOGY, Vol: 164, Pages: 608-610, ISSN: 0007-1048
Bain B, Khoder A, Milojkovic D, et al., 2013, Systemic mastocytosis - the importance of looking within bone marrow fragments: AJH Educational Material, American Journal of Hematology, ISSN: 0361-8609
Milojkovic D, Apperley J, 2008, State-of-the-art in the treatment of chronic myeloid leukaemia, CURRENT OPINION IN ONCOLOGY, Vol: 20, Pages: 112-121, ISSN: 1040-8746
De Melo VA, Milojkovic D, Khorashad JS, et al., 2007, Philadelphia-negative clonal haematopoiesis is a significant feature of dasatinib therapy for chronic myeloid leukaemia, Blood, Vol: 110, Pages: 3086-3087
Loubeyre C, Belle L, Savary D, et al., 2007, Transradial approach in percutaneaous coronary intervention following pre-hospital fibrinolysis reduce vascular access site complication: Data from the french national OPTIMAL study, 56th Annual Scientific Session of the American-College-of-Cardiology, Publisher: ELSEVIER SCIENCE INC, Pages: 185A-185A, ISSN: 0735-1097
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