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G J Mufti

Publications and source records attributed to G J Mufti.

At least 127 records · Page 7Linked to original sources
PubMed1989

Clinical-cytogenetic correlations in myelodysplasia (preleukemia).

Cytogenetic studies detected abnormalities in 107 (43%) of the 247 patients in this series. Some degree of overt clinical progression occurred in 55 patients (22%), this being 29% of those patients with cytogenetic abnormalities and 17% of those with normal chromosomes. The presence and complexity of a clonal cytogenetic abnormality correlated with shorter survival. In each clone category of a complexity classification (simple, complex, very complex), patients with some normal cells appeared to have better survival than those with none. In multiple regression analyses, the prognostic value of chromosomes was independent of (and second in importance to) the FAB type of myelodysplastic syndrome (MDS) whichever chromosome classification was used. Patients with refractory anemia (RA) had the lowest incidence of chromosome abnormalities and no cases were found to have only abnormal cells (AA). A greater proportion of patients with refractory anemia with an excess of blasts (RAEB) and RAEB in transformation (RAEB-t) had clonal abnormalities. Morphology alone is not at present able to distinguish between RA or refractory anemia with ringed sideroblasts and similar disorders that may not be MDS in the strict sense. Demonstration of a clonal cytogenetic abnormality remains a positive indication of the presence of the neoplastic nature of the disease.

Adult↗
PubMed1989

Coulter S Plus STKR histograms detect spurious elevation of leucocyte and platelet counts associated with cryoglobulinaemia.

Abnormalities in the size frequency histogram generated by the Coulter S Plus STKR at room temperature raised the possibility of the presence of a cryoglobulinaemia in a man admitted to the hospital with pneumonia. The leucocyte and platelet counts generated by the Coulter S Plus STKR were higher when counts were done at room temperature than counts done at 37 degrees C. Further investigation of the patient revealed the presence of Non-Hodgkin's Lymphoma which had not been suspected on clinical grounds. The importance of testing samples at 37 degrees C, where an abnormality in the Coulter S Plus STKR histogram has been detected at room temperature, is emphasized.

Aged↗
PubMed1989

Myelofibrosis in primary myelodysplastic syndromes: a clinico-morphological study of 10 cases.

We describe 10 cases of primary myelodysplastic syndrome in which marrow fibrosis was striking at presentation. All the cases showed trilineage dysplasia with increased megakaryopoiesis and marked reticulin fibrosis. Significant organomegaly was notably absent. This association has hitherto not been highlighted and it is important to distinguish these cases from those of idiopathic myelofibrosis with which they may be confused. Furthermore, their comparatively long survival distinguishes these cases from those previously described as acute myelodysplasia with myelofibrosis and malignant myelosclerosis. The pathogenesis of fibrosis in these cases may be related to disordered megakaryopoiesis and the platelet-derived cytokines that may be released. The treatment of these fibrotic cases remains problematical and further investigation is required.

Adult↗
PubMed1989

Development of polycythaemia vera in a patient with myelofibrosis.

In March 1981, a 53-year-old man presented with itching and was diagnosed as having myelofibrosis. There was gradual enlargement of the spleen over the following 5 yr. His spleen had to be removed in February 1986 because of physical discomfort. 3 months post-splenectomy he became polycythaemic. Bone marrow examination was consistent with severe myelofibrosis. It was possible to demonstrate erythropoietin-independent BFU-E from peripheral blood, and ferrokinetic studies showed that erythropoiesis was localised to the liver with little bone marrow activity. Thus, despite severe marrow fibrosis, liver erythropoiesis was now polycythaemic, suggesting the coexistence of myelofibrosis and polycythaemia vera.

Bone Marrow↗
PubMed1989

Bilateral adrenal lymphoma presenting as Addison's disease.

We describe an unusual case of non-Hodgkin's lymphoma of the adrenals which presented as Addison's disease. Examination of tissue taken by computed tomography guided biopsy revealed a high grade B cell centroblastic lymphoma. The patient was treated with chemotherapy but died from invasive aspergillosis. Autopsy confirmed bilateral adrenal involvement by lymphoma.

Addison Disease↗
PubMed1989

Clonal analysis of myelodysplastic syndromes: evidence of multipotent stem cell origin.

Restriction fragment length polymorphisms (RFLPs) of the X-chromosome genes hypoxanthine phosphoribosyl transferase (HPRT) and phosphoglycerate kinase (PGK) were studied in 34 female patients with primary myelodysplastic syndromes (MDS). Twelve patients (35%) were heterozygous at the HPRT or PGK loci for BamHI or BglI RFLPs, respectively. In eight patients showing PGK polymorphisms, clonality was determined by X-chromosome inactivation analysis. These included patients from different morphologic subtypes: four with refractory anemia (RA), two with RA and ring sideroblasts (RARS), one patient with RA with excess of blasts (RAEB), and one with chronic myelomonocytic leukemia (CMML). A monoclonal pattern of X-chromosome inactivation was observed in seven cases. In a further case characterized by bone marrow hypoplasia, peripheral blood (PB) leukocytes were polyclonal in origin. Following low-dose cytarabine therapy, reversion to polyclonal hematopoiesis was observed in a case of RAEB indicating the presence of residual normal hematopoietic stem cells with the capacity for marrow reconstitution. The clonal relation of lymphoid and granulocyte/monocyte lineages was studied directly in two cases of CMML exhibiting somatic mutations of N-ras or Ki-ras oncogenes. By selective oligonucleotide hybridization to ras gene sequences amplified in vitro by the polymerase chain reaction, a mutated ras allele was demonstrated in PB granulocytes, monocytes, and B and T lymphocytes of both patients. We conclude that MDS arise from a multipotent hematopoietic stem cell with the potential for myeloid and lymphoid differentiation.

Adult↗
PubMed1989

Chronic dialysis in patients with multiple myeloma and renal failure: a worthwhile treatment.

Severe renal failure is a life-threatening complication of multiple myeloma. Aggressive treatment can reverse acute renal failure in many cases but the prognosis for those who require chronic renal replacement therapy is not clear. We have reviewed the treatment of these patients in the Brighton, Dulwich and Guy's Hospitals renal units. Twenty-three patients were treated for a total of 385 months. Over half presented with end-stage renal failure and required dialysis immediately. Fifteen patients died during the study period and actuarial survival was 45 per cent at one year; six have survived for longer than two years. No prognostic features at presentation were identified but those who responded to chemotherapy survived significantly longer than those who did not. Haemodialysis and continuous ambulatory peritoneal dialysis (CAPD) appeared to be equally effective treatments. Complications from dialysis were more common than in patients with renal failure from other causes. Infection in those treated by CAPD was a serious problem and may be exacerbated by aggressive chemotherapy. Maintenance dialysis offers some patients with multiple myeloma long-term survival and should be offered to all patients who are considered to warrant continuing treatment for their underlying disease.

Actuarial Analysis↗
PubMed1988

Prognostic features of chronic myelomonocytic leukaemia: a modified Bournemouth score gives the best prediction of survival.

We have studied the clinical and laboratory features of 53 cases of chronic myelomonocytic leukaemia (CMML) defined according to the FAB criteria. A granulocyte count of greater than 16 X 10(9)/l or a monocyte count of greater than 2.6 X 10(9)/l correlated with a poorer survival, but the best predictor of poor survival was the modified 'Bournemouth' score in which one point each was allocated for Hb less than 10 g/dl, neutrophils less than 2.5 X 10(9)/l or greater than 16 X 10(9)/l, platelets less than 100 X 10(9)/l and bone marrow blasts greater than 5%. A score of 2 or more was predictive of poor survival (Chi2 = 10.25; P less than 0.001). Those patients with low monocyte and neutrophil counts and a low modified Bournemouth score tended to have a clinical course similar to refractory anaemia (RA) with an indolent course not requiring treatment and long survival whereas those with high monocyte and neutrophil counts and a high modified 'Bournemouth' score have a clinical course resembling that of refractory anaemia with excess of blasts (RAEB).

Aged↗
PubMed1988

Mutation of Ki-ras and N-ras oncogenes in myelodysplastic syndromes.

Somatic mutation of the N-ras oncogene occurs frequently in de novo acute myeloid leukemia (AML). By virtue of their relation to AML, myelodysplastic syndromes (MDS) provide an in vivo model of human leukemogenesis. By using a strategy for analysis of gene mutation based on in vitro amplification of target sequences by the polymerase chain reaction (PCR) and selective oligonucleotide hybridization we analyzed the mutational status of codons 12, 13, and 61 of Ha-ras, K-ras, and N-ras in peripheral blood (PB) and/or bone marrow (BM) in 34 cases of primary MDS. Mutations at codon 12 of Ki-ras or N-ras were detected in three cases (9%): one of six cases of refractory anemia with excess blasts (RAEB) and two of nine cases of chronic myelomonocytic leukemia (CMML). The nucleotide substitution differed in each. In all cases the mutant allele was detectable in PB cells. A sustained hematologic remission was achieved after low-dose cytarabine therapy in the case of RAEB. Neither case of CMML exhibited signs of disease progression during follow-up at 7 and 12 months. In contrast, four of 31 patients without the ras mutation underwent transformation to AML within 12 months of genetic analysis. We conclude that ras mutations in MDS are heterogeneous and may develop at an early stage during the evolution of MDS. Their detection in PB cells illustrates the potential utility of ras mutation as a clonal marker in myeloid malignancy.

Genes, ras↗
PubMed1987

Differentiation induction in myelodysplasia and acute myeloid leukaemia: use of synergistic drug combinations.

DNA synthesis inhibitors and vincristine greatly enhance the response of leukaemic and dysplastic cells to differentiation inducing agents such as retinoic acid (RET). Differentiation induction therapy is an attractive therapeutic approach in myelodysplasia (MDS) and in acute myeloid leukaemia (AML) in the elderly, since it should be possible to increase the production of mature cells, at the expense of precursor cells, without incurring the complications of intensive cytotoxic therapy. Single agent differentiation therapy has, however, not been highly successful. We have therefore investigated the use of synergistic combinations of agents. We treated nine patients (6 with MDS, 3 with AML) with 13-cis-retinoic acid (up to 100 mg/m2/day) in combination with either 6-thioguanine (20-40 mg/day in 14-57 day courses) or with vincristine (1-2 mg as a single injection during a four-day course of RET). Seven patients responded with an increase in the mature cells of at least one haemopoietic lineage. A concomitant decrease in marrow blasts was observed in 3/4 responding patients. The retention of dysplastic and karyotypic abnormalities and lack of a hypoplastic phase all suggested that differentiation induction was occurring in vivo. Prior failure to respond to therapy with single agents (RET in two and cytosine arabinoside in five patients) suggests that the synergy observed in vitro operates in vivo. In-vitro studies on marrow cells from seven patients demonstrated synergistic differentiation induction in 6/7 samples. The seventh patient was one of the two who did not respond clinically. The second of these clinically unresponsive patients had cells which were relatively refractory to RET in vitro, suggesting that in-vivo and in-vitro responses may be related.

Adult↗