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OBJECTIVES: To investigate attrition at the finally selected donor stage among British Bone Marrow Registry (BBMR) donors, all recruited from blood donors. BACKGROUND: The success of searches for unrelated stem cell donors relies on the existence of large international donor registries and the availability of registered donors when matched with a patient. Withdrawal of donors may adversely affect patient outcomes. MATERIALS/METHODS: Data on 2942 planned donations were analysed to assess donor-related deferral rates and associated factors. RESULTS: Overall, 20·2% of requests were cancelled. Transplant centres activated more than half of the cancellations (52·6%). Donor reasons accounted for 46·7% of cancellations (9·4% of requests), of which 61·7% happened for medical and 38·3% for personal reasons. Medical ineligibility of the donor was associated with increasing age (odds ratio [OR] = 1·36, P = 0·011) and peripheral blood stem cell source (OR = 2·22, P = 0·006), and there was some evidence of association with low blood donation reliability (OR = 1·52, P = 0·054). The blood donor reliability score relates to blood donation, and the score worsens if donors consistently fail to attend a donation session when invited. Withdrawal on personal grounds showed associations with donor age (OR = 1·72, P = 0·017, 30-40 years vs other ages), peripheral blood stem cell source (OR = 2·43, P = 0·010) and low blood donor reliability (OR = 1·94, P = 0·007). CONCLUSIONS: To our knowledge, this is the first report on all-cause cancellation at the finally-selected donor stage for international stem cell donor provision, showing 9·4% donor-related cancellation rate. Scores associated with blood donation reliability may be useful to predict stem cell donor withdrawal.
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Seleção do Doador , Células-Tronco de Sangue Periférico , Sistema de Registros , Doadores de Tecidos , Adulto , Fatores Etários , Medula Óssea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reino UnidoRESUMO
INTRODUCTION: Engaging with patients when designing a clinical or research project is beneficial; feedback from the intended audience provides invaluable insight form the patients' perspective. Working with patients can result in developing successful research grants and interventions. The benefit of including the voice of the patient in the Yorkshire Cancer Research funded PREHABS study is described in this article. METHODS: Patients were included in the PREHABS study from inception to completion. The Theory of Change methodology was used to provide a framework to implement patient feedback to refine the study intervention. RESULTS: In total, 69 patients engaged with the PREHABS project. Two patients were recruited as co-applicants on the grant and were members on the Trial Management Group. Six patients attended the pre application workshop and provided feedback on their lived experiences of being a lung cancer patient. Commentary from the patients influenced the interventions selected and the design of the prehabs study. Following ethical approval (21/EE/0048) and informed written consent, 61 patients were recruited into the PREHABS study between October 2021 and November 2022. The breakdown of recruited patients was 19 males: mean age 69.1 years (SD 8.91) and 41 females; mean age 74.9 years (SD 8.9). CONCLUSION: It is practicable and beneficial to include patients at all stages of designing and delivering a research study. Patient feedback can help refine the study interventions to allow for maximum acceptance, recruitment and retention. IMPLICATIONS FOR PRACTICE: Including patients in the design of radiotherapy research studies can provide invaluable insight that can support the selection and delivery of interventions that are acceptable to the patient cohort.
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Neoplasias , Projetos de Pesquisa , Masculino , Feminino , Humanos , Idoso , Neoplasias/radioterapiaAssuntos
Transplante de Medula Óssea/métodos , Dermatologia/organização & administração , Dermatopatias/terapia , Adolescente , Adulto , Idoso , Transplante de Medula Óssea/psicologia , Dermatologistas/organização & administração , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Satisfação do Paciente , Dermatopatias/psicologia , Transplantados/psicologia , Transplante Homólogo/métodos , Adulto JovemRESUMO
ASTRACT: Granulocyte-Colony-Stimulating factor (G-CSF) is currently the standard mobilising agent for peripheral blood stem cell (PBSC) donation. Concerns that it may trigger chromosome aberrations similar to those observed in leukaemia patients were refuted but long-term effects of G-CSF mobilisation on genome integrity remains unclear. In the setting of a multi-centre clinical trial we screened blood samples from 50 PBSC donors at cellular and gene level for aberrations common in haematological malignancies using fluorescence in situ hybridisation (FISH) and next generation sequencing (NGS) assays. Analysis of samples collected before, on the day of donation, 90 and 180 days after G-CSF admission confirmed the absence of short-term effects in PBSC donors on both quiescent and dividing cells. This data did not differ from the results of 50 individuals tested 3-5 years after bone marrow donation and 50 healthy persons. NGS using a panel targeting 54 genes recurrently affected in myeloid disorders (TruSight Myeloid panel, Illumina) showed that the gene profiles of samples from 48 PBSC donors remained stable throughout the study period. These data strongly indicate absence of detrimental effects on the genome integrity caused by PBSC donation.
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Células-Tronco de Sangue Periférico , Doadores não Relacionados , Medula Óssea , Fator Estimulador de Colônias de Granulócitos , Mobilização de Células-Tronco Hematopoéticas , Humanos , Coleta de Tecidos e ÓrgãosAssuntos
Criopreservação/métodos , Criopreservação/normas , Células-Tronco Hematopoéticas/citologia , Gestão da Qualidade Total/métodos , Gestão da Qualidade Total/normas , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/normas , Humanos , Masculino , Controle de Qualidade , Transplante HomólogoRESUMO
PURPOSE: T-prolymphocytic leukemia (T-PLL) is an aggressive malignancy of mature T cells refractory to conventional chemotherapy, with a median survival duration of 7.5 months. We report here promising results with the use of a genetically reshaped human CD52 antibody, CAMPATH-1H. PATIENTS AND METHODS: Fifteen patients with T-PLL, most of whom had received the purine analog deoxycoformycin (DCF), were treated with CAMPATH-1H. Results were compared with those of 25 patients treated with DCF. RESULTS: Major responses occurred in 11 patients (73%) treated with CAMPATH-1H compared with 40% with DCF. Complete remissions (CRs) were documented in nine (60%) of the CAMPATH-1H cases and only three (12%) were obtained with DCF. CRs with CAMPATH-1H were durable, and re-treatment with the antibody resulted in second CRs in three relapsed patients. Two of them were successfully autografted with peripheral-blood and bone marrow stem cells collected during the first CR. Apart from first-dose reactions, infusions of CAMPATH-1H were well tolerated. However, two responding patients developed severe bone marrow aplasia that was fatal in one; the second remained moderately pancytopenic 21 weeks after stopping CAMPATH-1H therapy. The cause of this adverse effect is unknown. CONCLUSION: CAMPATH-1H is an effective agent in T-PLL and represents a significant improvement over other types of therapy. However, CAMPATH-1H alone is not sufficient for long-term remissions, and the role of autologous stem-cell transplantation needs further investigation.
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Anticorpos Monoclonais/uso terapêutico , Anticorpos Antineoplásicos/uso terapêutico , Antineoplásicos/uso terapêutico , Leucemia Prolinfocítica/tratamento farmacológico , Leucemia de Células T/tratamento farmacológico , Adulto , Idoso , Alemtuzumab , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Anticorpos Antineoplásicos/efeitos adversos , Antineoplásicos/efeitos adversos , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Transplante Autólogo , Resultado do TratamentoRESUMO
The possible involvement of the human T lymphotropic viruses type I and II (HTLV-I and -II) in lymphoproliferative disorders of mature T cells other than adult T cell leukemia/lymphoma (ATLL) has been controversial. Most studies have focused primarily on the cutaneous T cell lymphomas. However, skin involvement is a frequent feature of T prolymphocytic leukemia (T-PLL) and antibodies against HTLV-I and -II have been reported in individuals with large granular lymphocytic (LGL) leukemia. We examined 36 patients with T-PLL and 28 with LGL leukemia for evidence of HTLV-I and -II. Polymerase chain reaction (PCR) was performed on DNA from fresh peripheral blood mononuclear cells (PBMCs) and PBMCs after short-term culture (STC) using primers against all parts of the HTLV-I genome (LTR, gag, env, pol, tax/rex) and against HTLV-II pol and gag. Reverse transcriptase (RT) activity was measured on supernatants from STCs using a sensitive PCR-based technique. No HTLV-I or -II sequences were found by PCR nor RT activity detected in the 64 cases. Our findings do not provide evidence of HTLV-I or -II infection in T-PLL and LGL leukemia patients from an HTLV-I nonendemic area. Previous positive reports on these disorders may represent technical artefacts, detection of endogenous HTLV-like sequences or reflect patients from endemic areas and a variable etiology of T cell diseases.
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Vírus Linfotrópico T Tipo 1 Humano , Vírus Linfotrópico T Tipo 2 Humano , Leucemia Linfoide/virologia , Leucemia Prolinfocítica/virologia , Transtornos Linfoproliferativos/virologia , Humanos , Reação em Cadeia da Polimerase , RNA Viral/análise , DNA Polimerase Dirigida por RNA/análiseRESUMO
We report the clinical, ultrastructural, immunophenotypic and virological features of nine cases of a rare type of mature T cell disorder formerly designated Sezary cell leukaemia. All patients presented with lymphocytosis ranging from 12.7 to 133 x 10(9)/l, bone marrow infiltration, splenomegaly and lymphadenopathy. Skin involvement was absent at presentation but developed as a terminal event in two patients, one of whom showed a pattern of dermal infiltration different from that characteristic of Sezary syndrome. Cells from eight cases bore a mature T cell phenotype and electronmicroscopy revealed lymphocytes with cerebriform nuclei resembling Sezary cells. All cases except one were HTLV-I negative. Patients were treated with various chemotherapy regimens but with poor outcome, the median survival being 13 months. Laboratory and clinical data suggest great similarity between Sezary cell leukaemia and T prolymphocytic leukaemia (T-PLL), namely coexpression of CD4 and CD8 (3/9 cases), identical chromosomal abnormalities in the three cases studied (isochromosome 8q plus inversion 14 or t(X;14)(q28;q11)) and a remarkable sensitivity to CAMPATH-1H (complete remission of 21 months' duration in one patient), suggesting that this entity could be considered a variant form of T-PLL. The alternative diagnosis of adult T cell leukaemia/lymphoma could not be excluded in one patient in whom positive HTLV-I serology was documented.
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Leucemia Prolinfocítica/diagnóstico , Leucemia de Células T/diagnóstico , Síndrome de Sézary/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Leucemia Prolinfocítica/imunologia , Leucemia Prolinfocítica/patologia , Leucemia de Células T/imunologia , Leucemia de Células T/patologia , Masculino , Pessoa de Meia-Idade , Síndrome de Sézary/patologiaRESUMO
Deficiency of any of the vitamins and minerals essential for normal erythropoiesis (haematinics), including iron, copper, cobalt, vitamins A, B12, B6, C, E, folic acid, riboflavin and nicotinic acid, may be associated with defective erythropoiesis and anaemia. Iron, vitamin B12 and folate are the haematinics for which deficiency states manifest most often clinically and are the focus of this review. The normal absorption of these haematinics and gastrointestinal causes of their deficiency are described. Investigations, including the use of homocysteine metabolite levels and new techniques such as serum transferrin receptor assays, and treatment of haematinic deficiency are discussed in detail.
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Deficiências Nutricionais/fisiopatologia , Eritropoese/fisiologia , Gastroenteropatias/fisiopatologia , Deficiências Nutricionais/diagnóstico , Deficiências Nutricionais/terapia , Diagnóstico Diferencial , Deficiência de Ácido Fólico , Gastroenteropatias/diagnóstico , Gastroenteropatias/terapia , Hematínicos , Humanos , Deficiências de Ferro , Receptores da Transferrina/análise , Deficiência de Vitamina B 12RESUMO
The last decade has seen a dramatic improvement in prognosis of hairy cell leukaemia (HCL) but concern has emerged with regard to the incidence of second malignancy. A recent report found an 18.8% incidence of second cancers and suggested a possible role for alpha-interferon (IFN) in their pathogenesis. We reviewed our larger series of 200 patients with HCL. We found second malignancies in 8 cases (4.0%), all but one of whom had received IFN. However, when compared to age- and sex- matched population data this represents no increase in relative risk of second cancer in patients with HCL and provides no evidence of a role for IFN in the pathogenesis of these second malignancies.
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Fatores Imunológicos/efeitos adversos , Interferon-alfa/efeitos adversos , Leucemia de Células Pilosas/terapia , Segunda Neoplasia Primária/induzido quimicamente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Fatores Imunológicos/uso terapêutico , Incidência , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/epidemiologia , Estudos Retrospectivos , RiscoRESUMO
Adult T-cell leukemia/lymphoma (ATLL) is uncommon in the United Kingdom and has so far been restricted to people of Afro-Caribbean extraction. Between 1981 and 1995, 21 cases presented to 2 inner London teaching hospitals where 17% of the population are of Afro-Caribbean origin. Clinical presentations were similar to those of the disease in HTLV-I-endemic areas. Major responses (CR + PR) were obtained in 10/16 assessable patients (63%) treated with combination chemotherapy. However, median survival was only 5.5 months. Disease progression and opportunistic infection were the major causes of treatment failure and death. Three patients (14%) relapsed in the central nervous system (CNS). Our cases confirm the profound immunosuppression in ATLL. The poor prognosis of acute and lymphoma types of ATLL highlight the need for new approaches to treatment such as zidovudine and alpha-interferon, incorporating prophylaxis against CNS disease and opportunistic infections.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Adulto , Idoso , População Negra , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/complicações , Londres , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/complicações , Resultado do TratamentoRESUMO
Primary T-cell lymphoma of the central nervous system (CNS) is an extremely rare tumour. The Human T-cell lymphoma virus type 1 associated Adult T-cell lymphoma/leukaemia (ATLL) often involves the CNS during its course but disease limited to the CNS is exceptional. Using clinicopathological and molecular biological information we describe a case of primary CNS ATLL with infiltration of the brainstem associated with an atypical Herpes simplex encephalitis the distribution of which corresponded to that of the tumour. CNS involvement in ATLL is discussed.
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Neoplasias Encefálicas/virologia , Infecções por Deltaretrovirus/complicações , Vírus Linfotrópico T Tipo 1 Humano , Linfoma de Células T/virologia , Adulto , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , DNA Viral/análise , DNA Viral/genética , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Linfoma de Células T/diagnóstico , Linfoma de Células T/patologia , Imageamento por Ressonância Magnética , MasculinoRESUMO
The World Marrow Donor Association (WMDA) fosters collaboration between international registries to facilitate the exchange of hematopoietic stem cell products for unrelated stem cell donor transplantation. As indications for hematopoietic SCT grow, the movement of products across the world will increase. Although competent authorities may regulate products within their country, there is a need to protect the best interests of donors and recipients by identifying universal donor medical suitability criteria. Within this report the WMDA provides a background to unrelated adult donor and recipient safety, recommends a common framework for assessing the health of unrelated adult donors at each stage of the donation pathway and presents a novel mechanism for sharing international consensus criteria for individual medical and lifestyle conditions. Wherever possible, these criteria are evidence-based. By establishing a donor medical suitability working group, the WMDA has developed a process through which donor centers and registries may request a consensus opinion on conditions not already listed, as well as challenge existing criteria. Guidance from the WMDA is intended to complement, not supersede, guidance from national competent authorities and international regulatory bodies.
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Transplante de Células-Tronco Hematopoéticas/normas , Condicionamento Pré-Transplante/normas , Doadores não Relacionados , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Condicionamento Pré-Transplante/métodos , Transplante HomólogoRESUMO
As part of the national Hepatitis C (HCV) Lookback Programme, HCV-infected donors donating blood after September 1991 were identified and the fate of their previous donations received at a single hospital were traced; 123 of 160 implicated blood components were traceable and transfused. Only 19 recipients were alive and traceable and were tested for HCV. Nine of the 14 recipients (64%) of HCV-positive donations and 2 of 5 recipients (40%) of HCV-indeterminate donations had evidence of HCV infection. Neither the number of donor exposures nor the type of component was predictive of recipient HCV status. Three recipients have chronic active hepatitis. The Hepatitis C Lookback Programme successfully identifies some but not all cases of transfusion-transmitted HCV. Transfusion records, particularly in the medical case notes, should be substantially improved. Many of the traced recipients are young, so that identification of HCV is of great importance.
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Doadores de Sangue , Transfusão de Sangue , Hepatite C/transmissão , Hospitais , Adolescente , Adulto , Idoso , Transfusão de Eritrócitos , Hepacivirus/genética , Hepatite C/diagnóstico , Anticorpos Anti-Hepatite C/sangue , Humanos , Prontuários Médicos , Pessoa de Meia-Idade , Transfusão de Plaquetas , RNA Viral/sangueRESUMO
Acute leukaemias in relapse after allogeneic stem cell transplantation (SCT) respond poorly to donor leucocyte infusions (DLI) compared with chronic myeloid leukaemia (CML), at least in part because of faster disease kinetics. Fludarabine-containing 'non-myeloablative' chemotherapy followed by further allo SCT may offer more rapid and effective disease control. We report 14 patients with relapse after allo SCT for acute leukaemia [seven acute myeloid leukaemia (AML), five acute lymphoblastic leukaemia (ALL)] or refractory anaemia with excess blasts in transformation (RAEB-t, n = 2) treated with fludarabine, high-dose cytosine arabinoside (ara-C) and granulocyte colony-simulating factor (G-CSF) with (n = 10) or without (n = 2) idarubicin (FLAG +/- Ida) or DaunoXome (FLAG-X) (n = 2) and second allo SCT from the original donor. Donors were fully human leucocyte antigen (HLA) -matched in 13 cases with a single class A mismatch in one. Actuarial overall survival was 60% and disease-free survival was 26% at 58 months. Remissions after the second SCT were longer than those after the first bone marrow transplantation (BMT) in eight of the 13 assessable patients to date. Haematopoietic recovery was rapid. Transplants were well tolerated with no treatment-related deaths. The major complication was graft-versus-host disease (GvHD, acute >/= grade II-2 cases, chronic - eight cases, two limited, six extensive) although there have been no deaths attributable to this. FLAG +/- Ida and second allo SCT is a safe and useful approach and may be more effective than DLI in the treatment of acute leukaemias relapsing after conventional allo SCT.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Medula Óssea , Citarabina/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Idarubicina/administração & dosagem , Leucemia/terapia , Condicionamento Pré-Transplante/métodos , Vidarabina/análogos & derivados , Vidarabina/administração & dosagem , Doença Aguda , Adulto , Anemia Refratária com Excesso de Blastos/terapia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Filgrastim , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Leucemia Mieloide/terapia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Proteínas Recombinantes , Recidiva , Reoperação , Estudos Retrospectivos , Taxa de Sobrevida , Transplante HomólogoRESUMO
Association between mycosis fungoides (MF), its leukaemic variant Sezary syndrome (SS) and the human T-cell lymphotropic virus type-I (HTLV-I) has been controversial, with the reported incidence of infection varying between 0% and nearly 100%. We studied 127 patients (85 MF, 28 SS, five Sezary cell leukaemia, four lymphomatoid papulosis, and five unspecified cutaneous T-cell lymphomas (CTCL)) originating from Europe (France, Spain, U.K., Portugal) or from U.S.A. (California) for the presence of HTLV-I infection markers. HTLV-I and -II serology were performed on 78 patients using standard immunological methods. Reverse transcriptase (RT) assay was also performed in 26 cases using an RT-PCR-based method of high sensitivity. Molecular analyses were performed on 215 DNA samples (121 from fresh PBMCs, 26 from PBMCs after short-term culture and 68 from skin lesions) by PCR amplification using HTLV-I and -II gag, pol, env, pX and LTR specific primers. Immunological tests were negative except for two sera which were indeterminate. PCR with all HTLV-I and -II primer pairs showed negative results in all 215 samples investigated. No RT activity was detected in short-term PBMC cultures of any of the 26 cases studied. The results of this large study from five different countries clearly indicate that MF and SS are not associated with HTLV-I infection.