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C Pocock

Publications and source records attributed to C Pocock.

10 recordsLinked to original sources
PubMed2003

Mosaic trisomy 2 in myelodysplastic syndromes and acute myeloblastic leukemias.

We present a short report here of two more patients with trisomy 2 as the sole chromosomal abnormality in a hematologic malignancy. Although trisomy 2 is a recognized abnormality in neoplasms, particularly hepatoblastomas, to the best of our knowledge only three other cases have been reported with trisomy 2, in patients with a hematologic malignancy. The two cases presented here of myelodysplastic syndrome transforming to acute myeloblastic leukemia and chronic myelomonocytic leukemia showed trisomy 2 as the sole abnormality.

Aged↗
PubMed2001

Early detection of BCR-ABL transcripts by quantitative reverse transcriptase-polymerase chain reaction predicts outcome after allogeneic stem cell transplantation for chronic myeloid leukemia.

The reverse transcriptase-polymerase chain reaction (RT-PCR) has become widely used for monitoring minimal residual disease after allogeneic stem cell transplantation (SCT) for chronic myeloid leukemia (CML). However, most of these studies were performed using qualitative RT-PCR, and the interpretation of the results obtained has been conflicting. The correlation of a quantitative RT-PCR test performed early after SCT (at 3 to 5 months) and long-term outcome of CML patients surviving for more than 6 months was studied. Between January 1991 and June 1999, data from 138 CML patients who received allografts were evaluated. Early RT-PCR results were classified as (1) negative if there were no BCR-ABL transcripts detected (n = 61), (2) positive at low level if the total number of BCR-ABL transcripts was less than 100 per microg RNA and/or the BCR-ABL/ABL ratio was less than 0.02% (n = 14), or (3) positive at high level if transcript levels exceeded the thresholds defined above (n = 63). Three years after SCT the cumulative incidence of relapse was 16.7%, 42.9%, and 86.4%, respectively (P =.0001). The relationship between BCR-ABL transcript level and probability of relapse was apparent whether patients had received sibling or unrelated donor SCT and also whether or not the transplantation was T cell depleted. The results suggest that quantitative RT-PCR performed early after SCT is useful for predicting outcome and may help to define the need for further treatment.

Actuarial Analysis↗
PubMed2001

Immune haemolytic anaemia following T cell-depleted allogeneic bone marrow transplantation for chronic myeloid leukaemia: association with leukaemic relapse and treatment with donor lymphocyte infusions.

Immune haemolytic anaemia (IHA) is a recognised complication after allogeneic stem cell transplantation (SCT) and occurs more frequently if marrow cells have been subjected to T cell depletion (TCD). Among 58 consecutive patients who underwent TCD-allogeneic SCT from volunteer unrelated donors for the treatment of CML at the Hammersmith Hospital during a 3-year period (1 March 1996 to 28 February 1999) we identified nine cases of IHA. All patients had a strongly positive direct and indirect antiglobulin test and in eight patients the serological findings were typical of warm-type haemolysis often with antibody specificities within the Rh system. All nine cases had clinically significant haemolysis and were treated initially with prednisolone and immunoglobulin. The onset of IHA coincided with the occurrence of leukaemic relapse in six cases, and the presence of host haemopoiesis confirmed by lineage-specific chimerism in all four cases studied. Five patients received donor lymphocyte infusions (DLI); in three molecular remission and the restoration of full donor chimerism coincided with resolution of haemolysis. We conclude that in the context of leukaemic relapse, DLI is an effective therapy for IHA following allografts involving TCD.

Adolescent↗
PubMed2001

Stem cell transplantation for chronic myeloid leukaemia: the role of infused marrow cell dose.

INTRODUCTION: Allogeneic stem cell transplantation is a potentially curative option for patients with CML. The optimal donor is an HLA-identical sibling but transplants using unrelated volunteers can also be successful. The factors influencing survival after allogeneic SCT for CML are reasonably well defined. Recently however, the Seattle group have emphasised the influence of a high marrow cell dose on outcome following volunteer unrelated donor SCT for high risk acute leukaemia. MATERIALS AND METHODS: We have sought to define factors impacting on transplant related mortality (TRM) in a population of CML patients after allografting with matched sibling or alternative stem cell donors at a single centre over a 20-year period, with emphasis on infused marrow cell dose. Factors entered into a multivariate analysis were: recipient age, recipient CMV serostatus, disease phase, donor sex, cell dose and frequency of CTLP reactivity. RESULTS: In multivariate analysis four factors had an adverse effect on TRM when using a VUD: low marrow cell dose (<3.65 x 10(8) TNC/kg, relative risk 2.05, CI 1.08-3.90, P = 0.029), late disease phase (relative risk 1.68, CI 1.03-2.74, P = 0.038), patient CMV seropositivity (relative risk 1.98, CI 1.25-3.13, P = 0.004) and high frequency of CTLP (relative risk 1.93, CI 1.18-3.13, P = 0.008). For HLA-identical sibling donor transplants the only factor that adversely impacted on TRM was late disease phase (P = 0.0004 in univariate analysis). CONCLUSION: High infused cell dose is a new modifiable factor associated with reduced TRM following allogeneic SCT using an unrelated donor for the treatment of CML. The data support the recommendation that bone marrow harvest teams should aim to collect the highest possible number of nucleated cells for recipients of unrelated donor transplants.

Adult↗
PubMed2001

Correction of stromal cell defect after bone marrow transplantation in aplastic anaemia.

Defects in stromal cell function have been demonstrated in a number of aplastic anaemia (AA) patients. Here we have studied a patient with severe AA and abnormal stromal cell function who underwent bone marrow transplantation (BMT). The objective of this study was to investigate the timing and the mechanism of correction of the stromal defect after transplantation. The patient, a 25-year-old woman with severe AA, underwent BMT from her brother. BM was obtained from the patient on five occasions: 2 weeks pre BMT, and 3, 8, 16 and 21 months post BMT. Stromal cells were grown to confluence and recharged with purified CD34+ cells from normal donors. The support of such cells, as assessed by weekly colony-forming assay (CFU) of non-adherent cells, was compared with that of stromal layers grown from normal BM. A novel technique of combined fluorescence in situ hybridization (FISH) and immunocytochemistry was used to determine the origin of specific stromal cell types on cytospins of stroma post BMT. Stromal function was defective at 2 weeks pre BMT and at 3 months post BMT, but returned to normal at 8 and 16 months post BMT. At 21 months post BMT, stromal fibroblasts and endothelial cells were shown to be of recipient origin, and macrophages and T cells were of donor origin. We present here evidence in a case of severe AA for defective stromal function before BMT and delayed normalization of function after BMT. This correlated with engraftment of donor macrophages and T cells, but not fibroblasts and endothelial cells.

Adult↗
PubMed2000

Estimating leukemia-free survival after allografting for chronic myeloid leukemia: a new method that takes into account patients who relapse and are restored to complete remission.

A significant number of patients who relapse after allogeneic stem cell transplantation (SCT) for chronic myeloid leukemia (CML) will achieve sustained remissions after treatment with interferon-alpha, second transplants, or donor lymphocyte infusions (DLI) from the original stem cell donor. Because leukemia-free survival (LFS) is at present defined as survival without evidence of relapse at any time posttransplant, patients who relapse but are then restored to complete remission are treated as failures when estimating LFS. We have established a new category of LFS, termed current LFS (CLFS), which we define as survival without evidence of leukemia at the time of most recent assessment. To gauge the contribution of treatment for relapse to the efficacy of allogeneic SCT in the management of CML in chronic phase, we compared conventional LFS and CLFS in 189 consecutive patients who underwent SCT over a 7-year period with a minimum follow-up of 3 years. Patients with sibling donors (n = 111) received cyclosporine and methotrexate as prophylaxis for graft versus host disease; patients with unrelated donors (n = 78) also received Campath-1G or 1H as intravenous T-cell depletion. The 5-year LFS defined conventionally was 36% (CI: 29% to 43%) versus a 5-year CLFS of 49% (CI: 36% to 62%). This new method of defining LFS confirms the view that appropriate "salvage" therapy, principally DLI, makes a major contribution to the capacity of allogeneic SCT to produce long-term LFS in patients who receive SCT for CML and emphasizes the importance of redefining LFS to take account of successful treatment of relapse.

Adolescent↗
PubMed2000

The patient with a systolic murmur: severe aortic stenosis may be missed during cardiovascular examination.

Significant aortic stenosis is prevalent amongst elderly people. It may be subclinical, manifesting only as a murmur, but can still cause unexpected death with little warning after symptoms develop. Recent studies have highlighted the unreliability of the classical clinical signs of severe aortic stenosis, leading to concern that some patients may not be referred appropriately for echocardiography. Here, we review the evidence for the accuracy of each sign. We suggest that the assessment of the patient with a systolic murmur should be reappraised, and offer guidelines toward improving the recognition of aortic stenosis in the community.

Aged↗
PubMed1994

Antisense oligonucleotides suppress B-cell lymphoma growth in a SCID-hu mouse model.

The t(14;18) translocation is found in the majority follicular lymphomas and some high grade B-cell lymphomas. This is results in deregulation of the BCL-2 gene and appears to play a role in oncogenesis. Various numbers of cells from a cell line derived spontaneously from a patient with B-cell lymphoma bearing the t(14;18) translocation and negative for the Epstein-Barr virus (EBV) were injected by IP, IV, and SC routes into SCID mice. The mice developed lymphoma bearing the t(14;18) translocation with as few as 5 x 10(6) cells within 28 days. This was determined by histological examination. The higher the cell inoculation the more rapidly the lymphoma developed. Engraftment of the tumour cells was determined by PCR for the t(14;18) breakpoint region on peripheral blood samples and could be detected prior to development of overt lymphoma. Having established a lymphoma model the cells were treated with antisense oligonucleotides to the first open reading frame of the BCL-2 gene prior to inoculation of the SCID mice. Control treatments with sense and nonsense oligonucleotides was also performed. At 28 days the sense, nonsense and untreated cell SCID mice had developed lymphoma, however, the antisense treated group failed to develop lymphoma. The findings demonstrate the modelling of B-cell lymphoma bearing the t(14;18) translocation and the ability to modify the lymphoma process with the use of antisense oligonucleotides to the BCL-2 gene. Reduction of the BCL2 protein suppresses the oncogenic potential of these lymphoma cells confirming that it plays an essential role in the development of malignancy.

Animals↗
PubMed1991

Microangiopathic haemolysis associated with occult carcinoma.

Microangiopathic haemolytic anaemia (MAHA) is a well recognized complication of disseminated carcinoma and its treatment. It is however, rarely seen with localized carcinoma. The case presented here is a previously unreported association of a patient, who having been successfully treated for MAHA, was found to have occult breast carcinoma on a routine screening mammogram six months after the haemolytic episode.

Adenocarcinoma↗