The impact of patient ethnicity on haematopoietic cell transplantation outcome: a retrospective cohort study on the UK experience.

Background: Patient ethnicity has been correlated with different outcomes after haematopoietic cell transplantation (HCT), with patients from minority ethnic backgrounds reported to have worse outcomes compared with White patients. To date, studies have been predominantly done in the USA, where health-care models are different to many European countries, including the UK. We aimed to evaluate the impact of patient-reported ethnicity on autologous and allogeneic HCT outcomes in the UK.

The presentation of results from studies in clinical haematology.

Research is based on trying to find answers to specific questions or to test hypotheses. Studies are thus undertaken to generate data which, with appropriate statistical methods, will help to determine the validity of the science under investigation. The aim of this paper is not to provide answers on which statistical methods to use, but will concentrate on suggesting the best ways of presenting the results of appropriately analysed data.

The accuracy of haemoglobin A measurements in the presence and absence of haemoglobin S.

The quantification of haemoglobin A by high-performance liquid chromatography (HPLC) was compared with quantification by capillary electrophoresis for control subjects and patients with sickle cell trait or sickle cell anaemia. Significant differences were found, with estimated values being higher by HPLC for control subjects and higher by capillary electrophoresis for sickle cell trait and sickle cell anaemia patients. There is an ongoing need for improved standardisation and alignment of methods.

Systems medicine dissection of chr1q-amp reveals a novel PBX1-FOXM1 axis for targeted therapy in multiple myeloma.

Understanding the biological and clinical impact of copy number aberrations (CNAs) on the development of precision therapies in cancer remains an unmet challenge. Genetic amplification of chromosome 1q (chr1q-amp) is a major CNA conferring an adverse prognosis in several types of cancer, including in the blood cancer multiple myeloma (MM). Although several genes across chromosome 1 (chr1q) portend high-risk MM disease, the underpinning molecular etiology remains elusive.

Fecal Microbiota Transplant Mitigates Adverse Outcomes Seen in Patients Colonized With Multidrug-Resistant Organisms Undergoing Allogeneic Hematopoietic Cell Transplantation.

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. We performed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy for MDRO-colonized patients with hematological malignancy.

Diagnostic application of transcripts associated with antibody-mediated rejection in kidney transplant biopsies.

Background: The diagnosis of antibody-mediated rejection (AMR) is reached using the Banff Classification for Allograft Pathology, which now includes gene expression analysis. In this study, we investigate the application of 'increased expression of thoroughly validated gene transcripts/classifiers strongly associated with AMR' as diagnostic criteria.

Method: We used quantitative real-time polymerase chain reaction for 10 genes associated with AMR in a retrospective cohort of 297 transplant biopsies, including biopsies that met the full diagnostic criteria for AMR, even without molecular data (AMR, n = 27), biopsies that showed features of AMR, but that would only meet criteria for AMR with increased transcripts [suspicious for AMR (AMRsusp), n = 49] and biopsies that would never meet criteria for AMR (No-AMR, n = 221).

Presence of donor-encoded centromeric KIR B content increases the risk of infectious mortality in recipients of myeloablative, T-cell deplete, HLA-matched HCT to treat AML.

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 analysis establishing the effect of donor KIR motifs on the outcomes of 119 HLA-matched, unrelated donor HCT for adult acute myeloid leukaemia (AML) using myeloablative conditioning (MAC) in a predominantly T-cell deplete (TCD) cohort. We observed that HCT involving donors with at least one KIR B haplotype were more likely to result in non-relapse mortality (NRM) than HCT involving donors with two KIR A haplotypes (p = 0.

Recipients Receiving Better HLA-Matched Hematopoietic Cell Transplantation Grafts, Uncovered by a Novel HLA Typing Method, Have Superior Survival: A Retrospective Study.

HLA matching at an allelic-level resolution for volunteer unrelated donor (VUD) hematopoietic cell transplantation (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 been previously characterized in HCT. Our aim was to explore the extent of diversity outside of the ARD and determine the impact of this diversity on transplant outcome.

FOXM1 modulates 5-FU resistance in colorectal cancer through regulating TYMS expression.

Resistance to 5-Fluoruracil (5-FU) has been linked to elevated expression of the main target, thymidylate synthase (TYMS), which catalyses the de novo pathway for production of deoxythymidine monophosphate. The potent oncogenic forkhead box transcription factor, FOXM1 is is regulated by E2F1 which also controls TYMS. This study reveals a significant role of FOXM1 in 5-FU resistance.

Impact of route and adequacy of nutritional intake on outcomes of allogeneic haematopoietic cell transplantation for haematologic malignancies.

Background: Allogeneic haematopoietic cell transplantation (HCT) is often associated with poor oral intake due to painful mucositis and gastrointestinal sequalae that occur following a preparative regimen of intensive chemotherapy and/or total body radiation. Although attractive to assume that optimal nutrition improves HCT outcomes, there are limited data to support this. It is also unclear whether artificial nutrition support should be provided as enteral tube feeding or parenteral nutrition (PN).

Harvests from bone marrow donors who weigh less than their recipients are associated with a significantly increased probability of a suboptimal harvest yield.

Background: Previous studies have demonstrated the importance of bone marrow (BM) harvest yield in determining transplant outcomes, but little is known regarding donor and procedure variables associated with achievement of an optimal yield. We hypothesized that donor demographics and variables relating to the procedure were likely to impact the yield (total nucleated cells [TNCs]/kg recipient weight) and quality (TNCs/mL) of the harvest.

Study Design And Methods: To test our hypothesis, BM harvests of 110 consecutive unrelated donors were evaluated.

The finer points of writing and refereeing scientific articles.

Writing scientific papers is a skill required by all haematologists. Many also need to be able to referee papers submitted to journals. These skills are not often formally taught and as a result may not be done well.

A donor-specific epigenetic classifier for acute graft-versus-host disease severity in hematopoietic stem cell transplantation.

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological conditions. Acute graft-versus-host disease (aGVHD) is a prevalent immune-mediated complication following HSCT. Current diagnostic biomarkers that correlate with aGVHD severity, progression, and therapy response in graft recipients are insufficient.

Predonation health-related quality of life scores predict time to recovery in hematopoietic stem cell donors.

The physical reactions to hematopoietic stem cell donation have been extensively studied, but less is known about factors that predict poorer donation experiences. The aim of this prospective study was to examine demographic and health-related quality of life (HRQOL) factors that might be associated with recovery and side effects. We also described the changes in HRQOL during the donation process.

Female donors and donors who are lighter than their recipient are less likely to meet the CD34+ cell dose requested for peripheral blood stem cell transplantation.

Background: It is of clinical relevance to recognize donors who are unlikely to meet the requested stem cell dose for transplantation, as this group may benefit from an alternative mobilization regimen. This study was performed to evaluate the frequency of unrelated donor peripheral blood stem cell (PBSC) collections that meet the target yield and the impact of donor factors on this.

Study Design And Methods: All sequential PBSC collections facilitated by the national registry (n = 323) from January through December 2011 were analyzed.

Night-time immobilization of the distal interphalangeal joint reduces pain and extension deformity in hand osteoarthritis.

Objective: DIP joint OA is common but has few cost-effective, evidence-based interventions. Pain and deformity [radial or ulnar deviation of the joint or loss of full extension (extension lag)] frequently lead to functional and cosmetic issues. We investigated whether splinting the DIP joint would improve pain, function and deformity.

Assessment of BCR-ABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors.

Purpose: We studied BCR-ABL1 transcript levels in patients with chronic myeloid leukemia in chronic phase (CML-CP) at 3, 6, and 12 months after starting imatinib to identify molecular milestones that would predict for overall survival (OS) and other outcomes more reliably than serial marrow cytogenetics.

Patients And Methods: We analyzed 282 patients with CML-CP who received imatinib 400 mg/d as first-line therapy followed by dasatinib or nilotinib if treatment with imatinib failed. We used a receiver operating characteristic curve to identify the cutoffs in transcript levels at 3, 6, and 12 months that would best predict patient outcome.

Reduced-intensity conditioning before allogeneic hematopoietic stem cell transplantation in patients over 60 years: a report from the SFGM-TC.

This retrospective multicenter report assessed the outcome of 600 patients with hematologic diseases older than 60 years who received reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT), with the specific aim to compare outcomes of patients between 60 and 65 years old (N = 493) with those older than 65 years (N = 107). Except for donor age, there were no significant differences between the groups regarding patients, diseases, and allo-HSCT characteristics. At time of RIC allo-HSCT, 276 patients (46%) were in complete remission.

Three decades of transplantation for chronic myeloid leukemia: what have we learned?

Last year marked 30 years of hematopoietic stem cell transplantation as a curative treatment of chronic myeloid leukemia (CML). Initially studies used stem cells from identical twins but techniques rapidly developed to use cells first from HLA-identical siblings and later unrelated donors. During the 1990s CML became the most frequent indication for allogeneic transplantation worldwide.

LACE-conditioned autologous stem cell transplantation for relapsed or refractory diffuse large B-cell lymphoma: treatment outcome and risk factor analysis from a single centre.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a recognized treatment option for patients with relapsed diffuse large B-cell lymphoma. We have analysed 51 patients who underwent ASCT after LACE (lomustine (CCNU), cytarabine (Ara-C), cyclophosphamide, etoposide) conditioning for relapsed (n = 34, 67%) or primary refractory (n = 17, 33%) diffuse large B-cell lymphoma. With a median follow-up of 60 months (range 2-216) the probabilities of overall survival (OS) and progression-free survival (PFS) at 5 years were 47 and 42%, respectively.