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Biomedical subjects

A G Prentice

Publications and source records attributed to A G Prentice.

At least 73 records · Page 4Linked to original sources
PubMed1989

Clonal evolution in Ph-negative, bcr-positive chronic myeloid leukaemia before and after bone marrow transplantation.

A 26-year-old man, who presented with bilateral fundal haemorrhages, was found to have chronic myeloid leukaemia (CML). The Ph chromosome was not present but a clone with t(1;9) (p32;q34) was detected. On referral for bone marrow transplant (BMT) he was found to be in accelerated phase with clonal evolution in three cell lines inv(3)(q21q26); inv(3)(q),i(17q); inv(3q)+8. Molecular investigation revealed a breakpoint on chromosome 22 within the breakpoint cluster region (bcr) similar to that found in Ph+ cases. After BMT, from an HLA-identical sister, successful engraftment (46,XX) was accompanied by evidence of a residual host cell population with further evolution (del(7)(q22)) and persistence of the bcr+ clone. Acute myeloid leukaemia, detected 5 months later, was associated with predominance of the clone 46XY,t(1;9),inv(3q),del(7)(q22) which failed to respond to treatment and the patient died 6.5 months after BMT. This case indicates that BMT, after the acquisition of additional chromosomal change in accelerated phase, may fail owing to persistence of the leukaemic clone. In addition the BMT conditioning regimen may produce further abnormalities which confer drug resistance on the persisting clone, which can emerge as an intractable myeloid blast crisis.

Adult↗
PubMed1988

Acute myeloblastic leukaemia in the elderly.

Acute myeloblastic leukaemia (AML) is a disease of the elderly with a median age at presentation in the seventh decade and a peak incidence in the U.K. of greater than 20 patients per 100,000 population per yr between the ages of 80 and 84. Most major AML trials are carried out on a younger population of patients with low recruitment of the elderly. The results in older patients are much worse than younger patients and often no better than the natural history of the disease. These poor results may be partly due to poor tolerance of treatment in the elderly, but are also due to intrinsic differences between AML in the elderly and AML in younger patients. These problems all justify randomised, prospective trials designed specifically for elderly patients to test prognostic scoring and various levels of intensity of therapy.

Aged↗
PubMed1988

Treatment of acute myeloid leukaemia with early intensive induction therapy.

Patients with primary acute myeloid leukaemia were treated with induction therapy consisting of daunorubicin 50 mg/m2 (days 1 and 2) and continuous cytosine arabinoside 400 mg/m2 (days 1-5) with a 7-10-day gap between courses. Consolidation therapy consisted of one further similar course and a final course of cytosine 1 g/m2 infusion (days 1-5). Patients were randomised to receive no further treatment or monthly maintenance therapy consisting of thioguanine 100 mg/m2 twice daily and etoposide 100 mg/m2 twice daily (days 1-5) alternating with CCNU 50 mg/m2 once to a total of 6 courses. 64 patients entered the study; median age was 54 years (range 18-74 years) and 51 patients entered complete remission (79.7%). Thirty-two patients completed consolidation and were randomised between maintenance therapy (n = 16) and no treatment (n = 16). 21 patients have relapsed with neither remission duration nor relapse rate being affected by maintenance therapy.

Adult↗
PubMed1987

Restoration of active haemopoiesis in a patient with myelofibrosis and subsequent termination in acute myeloblastic leukaemia: case report and review of the literature.

A patient with polycythaemia vera developed typical myelofibrosis after 15 yr. After a further 8 months, during which time she was pancytopenic and transfusion-dependent, a slow spontaneous recovery in haemopoiesis occurred and the full blood count became normal. 6 months later pancytopenia recurred and soon afterwards the patient developed acute myeloblastic leukaemia from which she died. The evolution of bone marrow morphology and isotopic studies. Only 2 previous reports of this kind of transformation exist in the literature, although restoration of normal or polycythaemic haemopoiesis has been reported in 8 patients with myelofibrosis. It is likely that these transformations occur because of alterations in stem cell behaviour rather than as a result of therapy.

Acute Disease↗
PubMed1987

Prospective comparison of laser nephelometry with standard agglutination techniques for detection of rheumatoid factor.

IgM rheumatoid factor was assayed by three routine methods: latex fixation; haemagglutination; and end point laser nephelometry in 69 patients with definite or classical rheumatoid arthritis and 58 patients with other non-rheumatoid arthropathies, selected prospectively according to the American Rheumatism Association clinical criteria. The operators of the assays were unaware of the clinical diagnoses. In the group with rheumatoid arthritis 75.4% were positive by latex fixation, 73.9% by haemagglutination, and 55.1% by nephelometry. In the group with non-rheumatoid arthropathies 10.4% were positive by latex fixation, 8.6% by haemagglutination, and 10.4% by nephelometry. Thus the simple and inexpensive latex fixation test was as good as the haemagglutination test, and both were significantly better than nephelometry in the laboratory confirmation of the clinical diagnosis of definite or classic rheumatoid arthritis (chi 2 = 5.40 and 4.56, and p less than 0.025 and less than 0.05, respectively). None of these tests was significantly better or worse than the others in producing positive results in the group with non-rheumatoid arthropathies.

Adolescent↗
PubMed1986

Pulmonary aspergillosis in immunosuppressed patients with haematological malignancies.

Invasive pulmonary aspergillosis as a cause of mortality and morbidity in patients with haematological malignancies is becoming more common. Predisposing factors are powerful immunosuppressive chemotherapy, neutropenia and synergistic combinations of antibiotics of great potency and wide spectrum of activity. Clinical and radiological signs are heterogeneous, sometimes misleading and often absent. Treatment is often empirical on suspicion alone. Amphotericin B is the only effective drug but it has marked toxicity, mainly renal. Infection is usually fatal without adequate treatment. This paper describes eight cases of invasive pulmonary aspergillosis seen in one centre in two years, reviews the literature and assesses associated problems.

Adolescent↗
PubMed1983

Meningeal relapse in Ph1-positive acute lymphoblastic and lymphoid blast crisis of chronic granulocytic leukemia. Is CNS-prophylaxis indicated?

Two cases of Ph1-positive acute lymphoblastic leukemia (ALL) and one case of lymphoid blast crisis (LyBc) of chronic granulocytic leukemia (CGL) treated with standard chemotherapy for ALL are presented. Hematologic remissions lasting 6, 12, and 15 months were achieved in all cases. Meningeal relapse occurred in all three, terminating remission in two cases and occurring immediately after systemic relapse in the third. No CNS-prophylaxis was given to the patient who relapsed at six months. Methotrexate (MTX) alone or combined with cranial irradiation formed the prophylaxis given in the other cases. Experience of these patients together with an analysis of reported cases of Ph1 ALL and CGL-LyBc suggests CNS-prophylaxis may prolong first remission. A large scale trial of this appears indicated.

Adult↗
PubMed1982

Acute myelogenous leukaemia following cytotoxic therapy: five cases and a review.

Acute myelogenous leukaemia (AML) following cytotoxic chemotherapy has been reported increasingly. Five new cases are presented including the first described following treatment for immune thrombocytopaenia. A review of the literature has revealed 226 case reports of treatment-linked AML with sufficient detail to permit further study. Of the total of 231 patients, 76 (33 per cent) followed Hodgkin's disease, 59 (25.5 per cent) multiple myeloma, 22 (9.5 per cent) non-Hodgkin's lymphoma, 32 (14 per cent) other solid tumours and 42 (18 per cent) non-malignant diseases. The time interval from the start of chemotherapy to the diagnosis of AML was similar in all disease groups whether the patients had received radiotherapy or not. Differences emerged when the duration of exposure to chemotherapy was analysed in the individual disease groups; exposure was shorter in those patients treated for Hodgkin's disease and solid tumours than with the others suggesting that the pattern of administration of chemotherapy may be important. The effects of radiotherapy in addition to chemotherapy could not be defined precisely, but the study highlights the particular risk that appears to arise from alkylating agents, and the need to define optimal methods of administration of chemotherapy with minimal risk of inducing leukaemia.

Adolescent↗
PubMed1981

Terminal deoxynucleotidyl transferase expression in acute non-lymphoid leukaemia: an analysis by immunofluorescence.

Indirect immunofluorescence for terminal transferase enzyme (TdT) was used to study the blasts of 64 patients with acute non-lymphoid leukaemia (ANLL). In 32 patients no TdT positive cells were seen. In 19 cases a small subpopulation of cells expressing TdT was detected; these constituted up to 5% of total nucleated cells, and it was not clear whether these TdT positive cells were part of the leukaemic process or represented residual normal bone marrow lymphoid cells. The remaining 13 patients had TdT positive cells accounting for 7-90% of the total. In two of these cases TdT was expressed on blasts with myeloid features, representing an aberrant expression of TdT by myeloid cells; in contrast, in three cases mixed populations of TdT positive lymphoid blasts and TdT negative myeloid blasts were observed. In the remaining cases it was not possible to determine whether the TdT positive cells had definite lymphoid or myeloid features. Cytogenetic analysis showed no evidence of the Philadelphia chromosome. Response to treatment was assessed in 11 of the 13 patients. Only one patient remitted with the initial choice of therapy (DAT); four failed to respond to initial regimes of vincristine and prednisone (V & P) while the other five patients did not respond to myelotoxic combinations (DAT). Only one patient subsequently entered complete remission on second line therapy (V & P). This group of patients with TdT+ ANLL had a particularly bad prognosis, and appeared to differ from cases of TdT positive acute undifferentiated leukaemia, which often respond to V & P therapy.

Acute Disease↗
PubMed1981

Terminal transferase expression in relapsed acute myeloid leukaemia.

In three cases of acute myeloid leukaemia marked increases in expression of the nuclear enzyme, terminal deoxynucleotidyl transferase (TdT), were observed during disease relapse. The first case was heterogeneous at diagnosis, consisting of subpopulations of large TdT- myeloblasts and small TDT+ blasts; however, at relapse there was complete replacement by TdT+ lymphoblasts. The other cases at diagnosis were both typical acute myeloid leukaemia, TdT-; at relapse, one showed a mixture of TdT- myeloblasts and TdT+ lymphoblasts, while in the other, TdT was demonstrated on a subpopulation of myeloblasts. No chromosomal abnormalities were found. It is suggested that in the first two cases these phenomena may have been due to leukaemic involvement of a pluripotential stem cell, or that sub-clones with different properties may have coexisted. In the third case at relapse, TdT was expressed aberrantly by malignant myeloid cells.

Aged↗
PubMed1980

Mixed lymphoblastic-myelomonoblastic leukemia in treated Hodgkin's disease.

In a case of acute leukemia occurring 5.5 yr after diagnosis of Hodgkin's disease, a mixture of lymphoid and myelomonocytoid blasts was identified by morphological, cytochemical, and immunologic methods. The majority of blasts were characterised as lymphoid by their strong expression of nuclear terminal transferase (TdT) enzyme. In contrast, a minor blast population was identified as myelomonocytoid by the strong nonspecific esterase positivity and lack of TdT. The two distinct blast cell populations showed different sensitivity to the various chemotherapeutic protocols used.

Adolescent↗
PubMed1979

Fatal retroperitoneal haemorrhage complicating anticoagulant therapy.

Eight cases are reported of extensive retroperitoneal haemorrhage in patients receiving anticoagulant therapy who subsequently died and underwent postmortem examination. No patient had an obvious source of bleeding, and in 5 cases no other cause for death was apparent. Three patients had had vascular surgical procedures: the other 5 were given anticoagulants for suspected venous thrombo-embolism. Six cases presented as unexpected circulatory collapse with rapid demise. Four patients had in addition gastro-intestinal bleeding of varying degree, with no obvious source. This acute massive type of retroperitoneal bleeding contrasts with the commoner presentations of pain, swelling, bruising and compression neuropathy: a high index of suspicion and urgent treatment are required if mortality is to be reduced.

Adult↗