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Biomedical subjects

J Amess

Publications and source records attributed to J Amess.

31 records · Page 2Linked to original sources

High dose cytosine arabinoside in the initial treatment of adults with acute lymphoblastic leukaemia.

In a study conducted at St Bartholomew's Hospital between 1972 and 1982, using moderately intensive therapy (OPAL/HEAV'D), a low blast count at presentation (less than 10 x 10(9) 1(-1)) and common ALL (C-ALL) phenotype correlated favourably with duration of remission. Fifty-four patients (age range 15-57, median 32) subsequently received a modification of the previous treatment programme which included high-dose ara-C 2 g m-2 b.d. for 6 days as cycle 3 (OPAL + HD ARA-C). CR was achieved in 36/54 (67%) patients, response correlating favourably with younger age (15-30 years vs 31-57 years, P = 0.02). Three patients died in CR. Overall, there was no difference in survival or remission duration between patients who received high dose ara-C and those in the control group. However, in contrast to the early results, there was a reversal in the relevance of the prognostic factors with a trend in favour of high blast count (greater than 10 x 10(9) 1(-1)) and T-cell phenotype in terms of remission duration. Moreover, comparison of duration of remission for the previously defined prognostic groups according to therapy suggests that the prognosis of patients with 'high risk' disease (T, B, null ALL or high blast count) is improved with more intensive therapy. In contrast, those with 'low risk' disease (C-ALL and low blast count) have a better prognosis with less intensive therapy. These observations confirm those of others and allow for individualization of therapy on the basis of pre-treatment variables.

Adolescent↗

Duplication of one of the products of the t(8;21) translocation in a patient with refractory anemia with excess blasts in transformation.

A 34-year-old man with refractory anemia with excess blasts in transformation is reported, having a t(8;21) translocation and a duplication of one of the products, der(21). The duplicated product had not been observed at presentation in malignant disease, as far as we are aware; thus, the findings are discussed with regard to this case and other possible smoldering leukemias. The diagnostic use of cytogenetics is also considered.

Adult↗

Incidence of the 15q+;17q- chromosome translocation in acute promyelocytic leukaemia (APL).

Cytogenetic analysis was carried out on peripheral blood cultures from seven patients with acute promyelocytic leukaemia (APL-M3). A reciprocal 15;17 chromosome translocation, t(15q+;17q-), was found in all cases, and the breakpoints estimated to be 15q22 and 17q12-21. In addition to the t(15q+;17q-), trisomy 10 was found in 50% of cells analysed in one case. These results suggest that the 15;17 chromosome translocation may be observed in most cases of APL where the leukaemic cells are cultured before cytogenetic analysis is performed. The use of conditioned media in the culture of leukaemic cells is also described.

Adult↗

ALL masquerading as AUL.

Of 597 cases of acute leukaemia in adults (greater than 16 years) seen at St. Bartholomew's Hospital, London, between May 1973 and January 1982, 412 were diagnosed as AML, 103 as ALL and 58 as Philadelphia chromosome positive blast crisis of CML (13 presenting as acute leukaemia and 45 having a prior chronic phase). The remaining 24 cases were considered to be acute undifferentiated leukaemia. Twenty-one of the latter were investigated using a panel of immunological markers at diagnosis and/or retrospectively using frozen cell suspensions. Eighteen out of 21 were shown to have a predominantly 'lymphoid' phenotype which comprised 12 cases of common ALL (two of whom were Ph1 positive), three cases of null-ALL, one case with a probable early thymic phenotype, and two cases with a monoclonal B lymphoblast phenotype. One 'common ALL' and one 'null-ALL' had a significant proportion of pre-B (cytoplasmic mu chain+) cells. One other case reacted with anti-myeloid sera. Leukaemic blasts from two patients were unreactive with all markers tested. No cases of glycophorin positive erythroleukaemia or anti-platelet (glycoprotein I) positive leukaemia were detected. These observations suggest that the overwhelming majority of acute leukaemias have an identifiable affiliation to the lymphoid or myeloid lineages and that patients diagnosed haematologically as 'AUL' might benefit by therapy appropriate for their leukaemic cell type.

Acute Disease↗

Hairy cell leukemia--mediastinal involvement. A report of two cases and review of the literature.

The clinical features of two patients with hairy cell leukemia involving the mediastinum are described. Both patients presented with acute chest pain 2-3 months prior to diagnosis being made. In one patient mediastinal disease was recorded only by computerized tomography of the thorax. There was good response of mediastinal disease to alpha-interferon in both patients, in spite of persisting bone marrow involvement with hairy cell leukemia.

Adult↗

Recombinant human granulocyte macrophage colony stimulating factor following alternating non cross resistant chemotherapy in Hodgkin's disease.

Fourteen patients with Hodgkin's disease (two previously untreated, 12 following relapse or with refractory disease) were treated with a combination chemotherapy regimen comprising chlorambucil, vinblastine, procarbazine, prednisolone, etoposide, vincristine and adriamycin administered on days 1-8. Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) (mammalian glycosylated, Sandoz/Schering-Plough) was administered after alternate cycles of chemotherapy from day 10 for 7 days by continuous intravenous (i.v.) infusion in 12 patients in a dose finding study (dose: 2 micrograms/kg/day in four patients, 4 micrograms/kg/day in four patients and 8 micrograms/kg/day in four patients) and by daily subcutaneous (s/c) injections in two patients (8 micrograms/kg/day). There was a rapid peripheral leucocytosis following the rhGM-CSF, reaching a peak at 1-2 days in 12/14 patients. The initial leucocytosis was composed of neutrophils followed by a rise in immature myeloid cells. There was no difference observed in the duration or depth of the nadir following chemotherapy or in the rate of recovery of peripheral white cell counts between cycles with and without rhGM-CSF in patients treated with 2 and 4 micrograms/kg/day. At the dose of 8 micrograms/kg/day, 3/6 patients had a shorter nadir duration in the cycle with rhGM-CSF, compared with cycle without rhGM-CSF. There was no difference in frequency of infection in cycles with and without rhGM-CSF. Following chemotherapy, six patients achieved clinical remission, six partial remission and two had progressive disease.

Adult↗

The management of chronic lymphocytic leukemia at a single centre over a 24-year period: prognostic factors for survival.

Over a 24-year period, 137 patients were referred for management of newly diagnosed chronic lymphocytic leukemia. One hundred and nineteen patients have been reviewed in terms of response to therapy and prognostic factors for survival; 18 patients were excluded either because lymph node biopsy was not compatible with the diagnosis of CLL (11 patients), or because the lymphocyte count at presentation was < 5 x 10(9)/l (seven patients). Patients were staged retrospectively according to both the Rai and Binet Classifications. Forty-eight per cent (57/119) were deemed not to be in need of any treatment at presentation, 36 per cent (43/119) have never received any specific therapy. The majority of patients received chlorambucil alone, at a dose of 10 mg daily given for 6 weeks, followed by a 2-week interval, followed by three, 2-week cycles. The overall response rate (complete+partial remission) was 38 per cent. In terms of survival, there was a trend in favour of patients who responded to treatment in comparison with those who did not but this did not reach statistical significance (P = 0.07). Correlations with stage were highly significant, the median survivals for patients with stage A, B and C disease (Binet) were 12.5, 8 and 3.5 years respectively. On univariate analysis, the absolute lymphocyte count at presentation was the most significant prognostic factor for survival, patients presenting with an absolute lymphocyte count above 50 x 10(9)/l having a less favourable prognosis (P = 0.002). However, on multivariate analysis, older age, a low hemoglobin, low platelet count, and the presence of lymphadenopathy and fever at presentation correlated adversely with survival. Overall, 40 patients died as a consequence of CLL or from disease-related causes, 34/40 dying of infection. Twenty-one patients developed second cancers. With a median follow-up of 13 years, these results confirm that the two staging systems can separate patients into prognostic groups, however in practice, there is heterogeneity of outcome within stage. New approaches are urgently needed.

Adult↗

HLA class I and class II antigen associations in acute leukaemias.

HLA-A,B,C and DR antigen frequencies were determined in a group of 188 patients suffering from acute myeloid (AML) and acute lymphoid leukaemia (ALL). These antigen frequencies were compared with those obtained on a panel of normal individuals (n = 109) of the same ethnic origin. The significance of the differences in the antigen distribution and the strength of the associations between particular HLA antigens and the disease were then calculated. The results obtained show a decreased frequency of HLA-Aw19 in the overall group of patients and the group of patients with ALL. In addition, the antigen frequency of the HLA-B18 and DR5(DRw11) antigens was also decreased in the overall group of patients and in those patients with AML but not in the patients with ALL. The results suggest that the antigen Aw19 may confer some degree of resistance to the development of ALL and that the HLA-B18 and/or DR5 antigens may be resistance factors for the development of AML.

Adolescent↗