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Biomedical subjects

G J Mufti

Publications and source records attributed to G J Mufti.

At least 19 recordsLinked to original sources
PubMed2006

Lamivudine prophylaxis and treatment of hepatitis B Virus-exposed recipients receiving reduced intensity conditioning hematopoietic stem cell transplants with alemtuzumab.

Individuals with past exposure to hepatitis B virus (HBV) may reactivate HBV following bone marrow transplantation. Alemtuzumab (CAMPATH)-based reduced intensity conditioning bone marrow transplantation has been associated with a high incidence of viral infections. Lamivudine prophylaxis for HBV should be instituted in this setting. The management of 240 CAMPATH-based reduced intensity conditioning bone marrow transplantation, carried out over an 8-year period at Kings College Hospital, was reviewed. Hepatitis B core total antibody (anti-HBc) testing identified recipients and donors with previous HBV exposure. Fifteen donor-recipient pairs were identified as being at risk of HBV reactivation. Eight recipients of anti-HBc negative donors were HBsAg negative, anti-HBc positive pre-transplantation. Five anti-HBc negative recipients received transplants from HBsAg negative, anti-HBc positive donors. Two HBV carrier recipients had one anti-HBc negative and one positive donor, respectively. Pre-transplant lamivudine prophylaxis was given to 8/10 (80%) anti-HBc positive recipients. Although HBsAg and HBV DNA were detected 4 months after bone marrow transplantation in one patient who did not receive prophylaxis, a good antiviral response was documented on starting lamivudine. The two HBV carrier recipients had stopped lamivudine at 8 and 31 months post-bone marrow transplantation, respectively, and died of liver failure with a sharp rise in HBV DNA levels. The five anti-HBc negative recipients with anti-HBc positive donors remained HBsAg and HBV DNA negative. Although lamivudine prophylaxis prevented HBV reactivation, it is unclear at what stage post-transplantation prophylaxis can be discontinued. Close monitoring of liver function tests (LFTs), HBsAg, and HBV DNA must be undertaken even after stopping antiviral prophylaxis.

Adolescent↗
PubMed2006

Topical issues in unrelated donor haematopoietic stem cell transplants: a report from a workshop convened by the Anthony Nolan Trust in London - 2005.

Over more than three decades, The Anthony Nolan Trust (ANT) has provided an unrelated donor (UD) for over 4000 children and adults lacking a suitable family member donor, and has remained at the forefront of developments in haematopoietic stem cell transplantation (HSCT) and bone marrow register management. These three decades have seen major changes in clinical practice of UD-HSCT, including new indications, increased use of alternative haematopoietic cell sources, significant improvement of the outcome as a result of better support care, less-toxic conditioning regimens, and better donor selection, and expansion to older patients with higher comorbidities. In order to foster our goal of improving UD-HSCT availability and outcome in a progressively more complex clinical scenario, a new initiative from ANT was launched in 2005 to convene an experts workshop to address the topical issues in this field. Four consecutive panels addressed factors influencing donor selection and transplant outcome, the use of cord blood, regulatory and accreditation issues, and future developments in this field. This report summarizes the discussions held in this workshop, which will likely develop into a periodic event where transplant clinicians, scientists and registry members will meet to share their experience and vision in the field of UD-HSCT.

Donor Selection↗
PubMed2006

A novel MHC-associated proteinase 3 peptide isolated from primary chronic myeloid leukaemia cells further supports the significance of this antigen for the immunotherapy of myeloid leukaemias.

Three of the most promising antigens for immunotherapy of chronic myelogenous leukaemia (CML) include the specific fusion-protein, Bcr/Abl, and the overexpressed proteins WT1 and Proteinase 3. The clinical significance of Proteinase 3 as a target in myelogenous leukaemias has been bolstered by detection of high frequencies of cytotoxic CD8+ lymphocytes specific for this antigen in patients undergoing immune therapies. Our investigation aimed to directly identify MHC-ligands derived from these antigens and presented on CML blasts by means of affinity-purification and mass spectrometric peptide-sequencing. Although no known or potential new epitopes were discovered for Bcr/Abl or WT1, a novel peptide from Proteinase 3 was detected among the more abundant MHC-ligands. Additionally, MHC-ligands derived from known immunogenic proteins overexpressed as a result of Bcr/Abl transformation were also identified. Our investigation is the second of only a small number of studies to identify a peptide from Proteinase 3 among the more abundant MHC-associated peptides and thus implies that peptides from this antigen are among the more abundantly presented of the known leukaemic antigens. Taken in conjunction with clinical observations of functional Proteinase 3 specific CTL in patients', these data further support the application of this antigen as an immunotherapeutical target for myelogenous leukaemias.

Epitopes↗
PubMed2006

Cutaneous manifestations of granulocyte colony-stimulating factor.

Granulocyte colony-stimulating factor (GCSF) is a recombinant human growth factor widely used in haematology. It is known to cause cutaneous vasculitis and neutrophilic dermatoses. We present three cases of Sweet's syndrome (SS) associated with GCSF use. Raised GCSF levels have been demonstrated in patients with SS. GCSF is the best understood mechanism by which neutrophil accumulation occurs and shows a dose-dependent effect in provoking SS.

Adjuvants, Immunologic↗
PubMed2005

Isochromosome of a deleted 20q: a rare but recurrent chromosome abnormality in myelodysplastic syndromes.

Interstitial deletion of the long arm of chromosome 20, as the sole abnormality, is commonly observed in myeloid malignancies, including myeloproliferative disorder, myelodysplastic syndrome, and acute myeloid leukemia. The breakpoints of the deletion are typically located in the region 20q11.2 approximately q13.3, although smaller deletions within this region have also been reported. We present here 4 patients with myelodysplastic syndrome with an isochromosome of the deleted long arm of chromosome 20: ider(20)(q10)del(20)(q11q13). Fluorescence in situ hybridization studies were performed on the bone marrow samples from these patients to prove the identity of this unusual chromosome abnormality.

Adult↗
PubMed2005

Cardiac presentation of ALK positive anaplastic large cell lymphoma.

Cardiac involvement as an initial presentation of malignant lymphoma is a rare occurrence. We report the case of an immunocompetent 29-year-old male who presented with syncope and arrythmias secondary to a ventricular cardiac mass. Transcutaneous cardiac biopsy was non-diagnostic, therefore an open cardiac biopsy was performed from which a provisional diagnosis of a cardiac inflammatory pseudotumour was made. Six months after presentation, he developed several subcutaneous lesions with systemic symptoms. Histological and immunophenotypic review of the initial cardiac biopsy revealed features consistent with a diagnosis of CD30, ALK1 positive anaplastic large cell lymphoma (ALCL). Despite intensive treatment with combination chemotherapy, there was significant progression of disease, and he died 11 months after diagnosis. The overall prognosis of cardiac lymphoma remains poor, which may be due to the often late presentation of the tumour. To our knowledge, this is the first reported case of a cardiac ALK positive ALCL. Although rare, cardiac presentation of ALCL should be added to the list of differential diagnoses of cardiac lymphomas.

Activin Receptors, Type I↗
PubMed2004

Differentially expressed genes in adult familial myelodysplastic syndromes.

The precise genetic events leading to myelodysplastic syndromes (MDSs) and leukemic transformation remain poorly defined. Even less is known about adult familial MDS. We report an adult MDS family in whom enriched tissue-specific transcripts were derived by subtractive hybridization of cDNA from the mononuclear and CD34+ cells of affected and unaffected family members. These expression libraries were then hybridized to Genome Discovery arrays containing 18 404 genes and expressed sequence tags, and several clusters of differentially expressed genes were identified. A group of 21 genes was underexpressed (>5-fold) in affected vs unaffected family members, and among these were transcription factors and genes involved in myeloid differentiation, such as ZNF140 and myeloid nuclear differentiation antigen (MNDA). Another group of 36 genes was overexpressed (>5-fold), and these encoded proteins belonging to signaling pathways, such as Ras- and Fos-related genes. The top two genes downregulated in this MDS family, ZNF140 and MNDA, were similarly altered in another MDS family, and in some cases of sporadic MDS. Our data suggest that we have identified genes differentially expressed in adult familial MDS, and that alteration of some of these genes may also be important for the evolution of different stages or severity of sporadic MDS.

Adolescent↗
PubMed2003

Epstein-Barr virus-related post-transplant lymphoproliferative disorder with t(9;14)(p11-12;q32).

The immunoglobulin heavy chain gene locus on 14q32 is known to be involved in translocations that are associated with B-lymphoproliferative disorders, typically Burkitt lymphoma and B-cell acute lymphoblastic leukemia. Several cytogenetic abnormalities have been described in post-transplant lymphoproliferatve disease (PTLD), some of which include this locus. To our knowledge, we report the first case of translocation t(9;14)(p11-12;q32) in a PTLD that developed after orthoptic liver transplantation.

Biliary Atresia↗
PubMed2003

Reduced-intensity rituximab-BEAM-CAMPATH allogeneic haematopoietic stem cell transplantation for follicular lymphoma is feasible and induces durable molecular remissions.

The indolent non-Hodgkin's lymphomas are theoretically curable through allogeneic haematopoietic stem cell transplantation (allo-HSCT). The applicability of standard conditioning allo-HSCT is, however, restricted by its toxicity. Recently, reduced-intensity conditioning regimens have demonstrated efficacy with significantly reduced early morbidity and mortality. We examined the safety and efficacy of rituximab-BEAM-CAMPATH as reduced-intensity conditioning for allo-HSCT in follicular lymphomas. Minimal residual disease was assessed by polymerase chain reaction (PCR) for bcl-2/IgH translocations, and chimerism by X,Y-FISH or PCR amplification of short tandem repeat sequences. At a median follow-up of 521 days (371-719), four of five patients were alive and three were in complete molecular remission. Three patients required pre-emptive treatment for CMV reactivation. One succumbed to a perforated viscus and one had slowly progressive disease. A graft-versus-lymphoma effect was demonstrable and quantitative PCR for bcl-2/IgH may allow better accuracy in scheduling post-allograft rituximab and/or donor lymphocyte infusions. Although follow-up is short, reduced-intensity allo-HSCT with BEAM-CAMPATH conditioning appears to be safe, effective in inducing a molecular remission and is potentially curative. Further recruitment and much longer follow-up will be necessary to determine if this impacts favourably upon disease-free and overall survival.

Adult↗