Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
1.
EJHaem ; 2(2): 261-265, 2021 May.
Article in English | MEDLINE | ID: mdl-35845286

ABSTRACT

Accurate, reproducible diagnoses can be difficult to make in haemato-oncology due to multi-parameter clinical data, complex diagnostic criteria and time-pressured environments. We have designed a decision tree application (DTA) that reflects WHO diagnostic criteria to support accurate diagnoses of myeloid malignancies. The DTA returned the correct diagnoses in 94% of clinical cases tested. The DTA maintained a high level of accuracy in a second validation using artificially generated clinical cases. Optimisations have been made to the DTA based on the validations, and the revised version is now publicly available for use at http://bit.do/ADAtool.

2.
Br J Haematol ; 184(4): 547-557, 2019 02.
Article in English | MEDLINE | ID: mdl-30467838

ABSTRACT

Allogeneic haematopoietic stem cell transplant (allo-HSCT) offers potentially curative therapy for patients with relapsed/refractory lymphoid malignancies. Reduced-intensity conditioning (RIC) with Alemtuzumab reduces transplant-related mortality and graft-versus-host disease (GvHD), but may be associated with increased risk of relapse. With the aim of studying the effect of GVHD and donor lymphocyte infusions (DLI) on relapse, we performed a retrospective study of 288 patients (57% non-Hodgkin lymphoma, 24% Hodgkin lymphoma and 19% chronic lymphocytic leukaemia; 58% were relapsed/refractory) who underwent RIC-Alemtuzumab-HSCT between 2000 and 2012. Median follow-up time for survivors was 64 months. Five-year overall survival, relapse incidence, GvHD/relapse-free survival and non-relapse mortality were 47%, 33%, 37% and 28% respectively. Cumulative incidence of grade II-IV acute and extensive chronic GvHD was 22% and 21% at 100 days and 5 years respectively. On multivariate analysis, presence of GvHD (P = 0·03) and unrelated donor type (P = 0·03) were protective of relapse. 62/288 patients received DLI for either mixed donor chimerism (prophylactic DLI, n = 37) or clinical relapse (therapeutic DLI, n = 25). Prophylactic and therapeutic DLI successfully converted the patient to full or stable mixed donor chimerism in 78% and 56% of patients respectively. These data demonstrate good long-term outcomes and support the concept of the graft-vs-lymphoma effect as a key protective factor against relapse following RIC-Alemtuzumab allo-HSCT for patients with mature lymphoid malignancies.


Subject(s)
Alemtuzumab/administration & dosage , Graft vs Tumor Effect , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Lymphoma/therapy , Transplantation Conditioning , Adolescent , Adult , Aged , Allografts , Disease-Free Survival , Female , Hematologic Neoplasms/mortality , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Lymphoma/mortality , Male , Middle Aged , Recurrence , Survival Rate
6.
Clin Med (Lond) ; 13(2): 188-92, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23681871

ABSTRACT

The myeloproliferative neoplasms that are associated with the JAK2 mutation are a heterogeneous group of disorders. The additional mutations that result in the clinical phenotype are still the subject of research. As more than one mutation is involved, and as JAK2 has a necessary physiological role (unlike BCR-ABL), the development of targeted therapy remains a challenge. Although new drugs are being developed, treatment at present is predominantly with agents that have been in use for many years. An understanding of the need to control the thrombotic risk has, however, led to improved survival rates such that ET and PV can be seen as chronic diseases.


Subject(s)
Janus Kinase 2/genetics , Polycythemia Vera/diagnosis , Primary Myelofibrosis/diagnosis , Thrombocythemia, Essential/diagnosis , Hematocrit , Humans , Mutation , Polycythemia Vera/genetics , Polycythemia Vera/therapy , Primary Myelofibrosis/genetics , Primary Myelofibrosis/therapy , Prognosis , Thrombocythemia, Essential/drug therapy , Thrombocythemia, Essential/genetics
7.
Int J Hematol ; 94(3): 266-278, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21898174

ABSTRACT

We investigated the contributions of methotrexate (MTX) and ciclosporin (CsA) prophylaxis to acute/chronic graft-versus-host disease (a/cGvHD) prevention following reduced-intensity conditioned allogeneic haematopoietic stem cell transplant (HSCT). Ninety-two fludarabine-melphalan sibling allo-SCT received CsA. Nine, 30 and 47 patients received no MTX, 2-3 doses and 4 doses, respectively. Cumulative CsA blood level to day 21 (CsA(21)) was calculated. Grades II-IV aGvHD incidence was 37.2%. In multivariate analysis, MTX omission and increasing donor age significantly associated with aGvHD incidence whilst MTX reduction and CsA(21) did not. Median duration of first immunosuppressive therapy (IST) for aGvHD was 68 days; duration of first IST was significantly longer in older patients but was not associated with MTX or CsA(21). Extensive cGvHD incidence was 60.6% at 1 year. Reduction of MTX to 2-3 doses, but not MTX omission or CsA(21), was associated with greater incidence of cGvHD affecting ≥3 organs. Median IST duration was 22 months; neither MTX nor CsA(21) influenced this. IST duration was significantly greater in patients receiving a CD34 dose below median. Neither MTX nor CsA(21) altered survival or relapse outcomes. MTX influences GvHD following T-replete RIC sibling HSCT.


Subject(s)
Cyclosporine/administration & dosage , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation , Methotrexate/administration & dosage , Transplantation Conditioning , Adult , Aged , Cause of Death , Female , Graft vs Host Disease/epidemiology , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/mortality , Humans , Immunosuppressive Agents/administration & dosage , Kaplan-Meier Estimate , Male , Middle Aged , Recurrence , Siblings , Transplantation Conditioning/adverse effects , Transplantation, Homologous , Young Adult
8.
Cytometry B Clin Cytom ; 80(4): 230-7, 2011.
Article in English | MEDLINE | ID: mdl-21462308

ABSTRACT

BACKGROUND: Both chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) are CD5/19 positive. The t(11;14) MCL translocation is identified by fluorescent in situ hybridization (FISH) and can distinguish the two disorders. We attempted to identify flow cytometric and other markers predictive of a positive FISH test. METHODS: We examined 100 atypical CLL/MCL cases for demographic, hematological, and cytometric variables, 96 were FISH tested for t(11;14) and four were known MCL. RESULTS: Twenty-two cases were confirmed as MCL. Multivariate analysis identified four variables associated with MCL: thrombocytopenia (taken as Plt < 150 × 109/L), CD23 negative, CD20 strong, and CD38 positive, with these variables a four-point score was devised. By ROC analysis, the MCL score was superior in differentiating MCL to the Marsden CLL score (AUC 0.95 vs. 0.78). MCL score ≥ 2 showed sensitivity 1, specificity 0.66, positive predictive value (PPV) 0.49, and negative predictive value (NPV) 1 for MCL. The score was then prospectively validated on an independent cohort of 44 cases of atypical CLL/MCL. No MCL had a score < 3. Validation PPV/NPV of score ≥ 3 were 0.5/1. Overall survival in MCL was shorter compared to t(11;14) negative patients (median 3.3 vs. 4.2 years, HR 2.2, 95% CI 0.87-5.5, P = 0.1). CONCLUSIONS: The score described can be used to identify cases of CD5/19 positive lymphoproliferative disorders likely to be t(11;14) positive MCL.


Subject(s)
ADP-ribosyl Cyclase 1/metabolism , Antigens, CD20/metabolism , Lymphoma, Mantle-Cell/diagnosis , Receptors, IgE/metabolism , Translocation, Genetic , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Humans , Immunophenotyping , Kaplan-Meier Estimate , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Lymphoma, Mantle-Cell/metabolism , Lymphoma, Mantle-Cell/mortality , Male , Middle Aged , Multivariate Analysis , Platelet Count , ROC Curve
9.
J Immunol ; 174(4): 1791-800, 2005 Feb 15.
Article in English | MEDLINE | ID: mdl-15699105

ABSTRACT

Cathepsin E is an aspartic proteinase that has been implicated in Ag processing within the class II MHC pathway. In this study, we document the presence of cathepsin E message and protein in human myeloid dendritic cells, the preeminent APCs of the immune system. Cathepsin E is found in a perinuclear compartment, which is likely to form part of the endoplasmic reticulum, and also a peripheral compartment just beneath the cell membrane, with a similar distribution to that of Texas Red-dextran within 2 min of endocytosis. To investigate the function of cathepsin E in processing, a new soluble targeted inhibitor was synthesized by linking the microbial aspartic proteinase inhibitor pepstatin to mannosylated BSA via a cleavable disulfide linker. This inhibitor was shown to block cathepsin D/E activity in cell-free assays and within dendritic cells. The inhibitor blocked the ability of dendritic cells from wild-type as well as cathepsin D-deficient mice to present intact OVA, but not an OVA-derived peptide, to cognate T cells. The data therefore support the hypothesis that cathepsin E has an important nonredundant role in the class II MHC Ag processing pathway within dendritic cells.


Subject(s)
Antigen Presentation , Cathepsin E/biosynthesis , Cathepsin E/physiology , Dendritic Cells/enzymology , Dendritic Cells/immunology , Animals , Antigen Presentation/genetics , Aspartic Acid Endopeptidases/antagonists & inhibitors , Cathepsin D/deficiency , Cathepsin D/genetics , Cathepsin E/genetics , Cathepsin E/metabolism , Cells, Cultured , Dendritic Cells/metabolism , Down-Regulation/genetics , Down-Regulation/immunology , Humans , Intracellular Fluid/enzymology , Intracellular Fluid/metabolism , Mice , Mice, Inbred BALB C , Mice, Knockout , Mice, Transgenic , Ovalbumin/immunology , Ovalbumin/metabolism , Pepstatins/pharmacology , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...