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J K Rees

Publications and source records attributed to J K Rees.

At least 37 records · Page 2Linked to original sources
PubMed1990

Effect of AML serum on normal human myeloid differentiation and hexamethylene bisacetamide-induced granulocytic differentiation of the human HL-60 promyelocytic leukaemic cell line.

The effect of serum from 32 AML patients on the normal human myeloid differentiation and the hexamethylene-bisacetamide induced granulocytic differentiation of HL-60 promyelocytic leukaemic cell line was studied. Nonadherent normal mononuclear marrow cells were cultured in vitro at a concentration of 5 x 10(5) cells/ml for 6 days with each of the 32 AML sera. Ten normal human AB sera were used as control. The results showed an inhibitory activity on both morphological and functional differentiation of normal human myeloid immature marrow cells by 29 out of the 32 AML sera tested. These 29 AML sera were added to cultures of HL-60 (2.5 x 10(5)/ml) leukaemia cell line which incorporated 2 mM hexamethylene-bisacetamide for 6 days. The results showed no significant inhibition of hexamethylene-bisacetamide induced granulocytic differentiation by any of the 29 AML sera. The efficacy of hexamethylene-bisacetamide in inducing differentiation in the presence of inhibitory factors suggests a possible role in the treatment of AML patients.

Acetamides↗
PubMed1990

The effect of monocytic involvement of hyperaldolasaemia in patients with acute myelogenous leukaemia.

Serum aldolase concentrations were determined in 78 patients with acute myelogenous leukaemia (AML). Mean serum aldolase concentration (+/- SD) at the time of diagnosis was 28.3 U/L (+19.4). 71.8% of AML patients had increased serum aldolase concentrations. The highest hyperaldolasaemia were observed in patients with acute myelomonocytic leukaemia and acute monoblastic leukaemia. The monocytic involvement in AML patients was significantly related to serum aldolasaemia. Human aldolase gene has been located on chromosome 16, whose structural aberrations are frequent in AML patients with monocytic involvement, explaining the link between serum hyperaldolasaemia and the monocytic involvement in AML patients.

Adult↗
PubMed1989

Effect of polar-planar compounds on the differentiation of normal human myeloid immature marrow cells.

Polar-planar compounds which are potent differentiating agents, have been reported to enhance the response of friend erythroleukaemic cells and other malignant cell lines to mitomycin C, cis-platinum and radiation. With the upcoming of phase II clinical trials of these polar compounds alone and in combination with cytotoxic agents, the effect of 3 polar compounds: dimethylsulphoxide, dimethylformamide and hexamethylene bisacetamide on the differentiation of normal human myeloid immature marrow cells was studied. The results showed that a long-term exposure to these polar compounds may lead to a premature senescence of these marrow progenitors.

Acetamides↗
PubMed1989

Low concentrations of cytosine arabinoside, 6-thioguanine, actinomycin-D and aclacinomycin A stimulates the differentiation of normal human marrow myeloid progenitor cells.

Myelosuppression is the major side effect of most anticancer cytotoxic drugs. Low concentrations of cytosine arabinoside (Ara-C), 6-thioguanine (6-Th), actinomycin-D (Act-D) and aclacinomycin A (ACM) have been reported to induce differentiation of leukaemic cell lines. With the proposed clinical trials of low-dosage of these four drugs, their effect on the differentiation of normal human myeloid progenitor marrow cells was studied. The four cytotoxic anticancer drugs at low concentrations stimulated normal human myeloid differentiation. Low dosage Ara-C has been used with great success in several clinical trials. The results suggest a similar therapeutic role for the other three anticancer drugs.

Aclarubicin↗
PubMed1989

Chemosensitivity testing of fresh leukaemia cells using the MTT colorimetric assay.

We have determined the feasibility of using the MTT colorimetric assay for measuring the sensitivity of fresh leukaemia cells to cytotoxic agents. A linear relationship was seen between the number of leukaemic cells plated and the resulting absorbance in the MTT assay at day 4. For 2 X 10(5) cells/well from CLL peripheral lymphocytes, the mean absorbance (measured at 540 nm) was 0.41. Similar curves were obtained with the assay carried out between days 3 and 7. ID50 values for CLL lymphocytes exposed to adriamycin (ADM) were in the range of 0.02-0.29 micrograms/ml, a similar range to that given by the DiSC dye exclusion assay. Sensitization of leukaemia cells to ADM by verapamil or cyclosporin A could be demonstrated in some patients but not in others. The lymphocytes from one patient with prolymphocytic leukaemia were abnormally resistant to ionizing radiation. These cells also showed resistance to melphalan and adriamycin but not to vincristine. The MTT assay appears to offer an attractive option for in vitro chemosensitivity testing in leukaemia, determination of cross-resistance profiles and studies of resistance modifiers.

Cell Line↗
PubMed1989

AML associated with previous cytotoxic therapy, MDS or myeloproliferative disorders: results from the MRC's 9th AML trial.

The outcome of treatment with standard first line therapy of 66 patients with acute myeloid leukaemia (AML) secondary to preceding chemotherapy (Group 1), a myelodysplastic state (Group 2) or a myeloproliferative disorder (Group 3) was analysed in relation to the preceding disorder, the cytogenetic pattern where available, and the cytology and cytochemistry of blood and bone marrow. The complete remission (CR) rate for the secondary AMLs was 36% (24/66), with 24% (16/66) dying in the induction period and 39% (26/66) having resistant disease. The CR rate was 25% (5/20) for Group 1, 42% (15/36) for Group 2, and 40% (4/10) for Group 3. Even after allowance for the generally older age of the secondary AML patients, they still had a significantly poorer CR rate than the de novo AMLs (P = 0.0004). The lower CR rate was chiefly due to resistant disease. Despite this, overall survival was not significantly worse for the secondary AML patients (P = 0.15). For the 36% that achieved remission, remission duration appeared similar to that of de novo cases. Of 62 cases with adequate cytology, 38 (61%) had evidence of erythroid and/or megakaryocytic dysplasia with a CR rate of 32% (12/38). The CR rate of these multineage leukaemias was not significantly different from that of the 24 (39%) who showed granulocyte/monocyte precursor involvement only, 42% (10) of whom achieved CR. The presence of features of differentiation within blast cells such as Auer rods or sudanophilia (greater than 50% positive blasts) was associated with a higher remission rate 47% (18/38) than that of poorly differentiated cases 17% (3/18) (P = 0.04) and thus appeared to be a more important determinant of CR achievement than was lineage involvement. Cases with a normal karyotype had a 33% (7/21) CR rate, while those with chromosomal abnormalities had a 37% (9/24) CR rate. Only 12 of the 45 cases with adequate cytogenetic analysis showed deletions or monosomies involving chromosomes 5 or 7, and seven of these were in Group 1.

Adolescent↗
PubMed1989

The effect of human recombinant granulocyte-macrophage colony stimulating factor on the proliferation and differentiation of myeloid progenitors in congenital agranulocytosis marrow cells.

Congenital agranulocytosis is a rare and frequently fatal infantile disease characterized by recurrent bacterial infections, persistent absence of neutrophils in the peripheral blood and an arrest of myeloid maturation at the promyelocyte/myelocyte stage. The effect of human recombinant Granulocyte-Macrophage colony stimulating factor (GM-CSF) alone and in combination with retinoic acid, dimethylsulphoxide or actinomycin-D on the proliferation and differentiation of bone marrow cells from a child with congenital agranulocytosis was studied. Cells were treated at a concentration of 1 x 10(5) per ml in in-vitro culture with GM-CSF alone and in combination with retinoic acid, dimethylsulphoxide or actinomycin-D for 7 days at 37 degrees C in humidified incubator containing 5% CO2 in air. GM-CSF showed a profound stimulatory effect on the proliferation of myeloid progenitors from the child bone marrow and restored colony numbers in the retinoic acid-, dimethylsulphoxide- and actinomycin-D-inhibited cultures.

Agranulocytosis↗
PubMed1988

Translocation 5;21 and interstitial deletion of chromosome 7 in a case of chronic myelomonocytic leukemia.

We report a case of chronic myelomonocytic leukemia with a translocation involving chromosome 5 and 21, namely, t(5;21)(q35.3;q22.1), and an interstitial deletion of the long arm of chromosome 7. High-resolution analysis at the 900-band stage has shown that the lesion in chromosome 7 is an interstitial deletion involving loss of the segments q22-q35 of the long arm of chromosome 7 and retaining the telomere.

Aged↗
PubMed1988

Terminal deoxynucleotidyl transferase and HLA-DR expression appear unrelated to prognosis of acute myeloid leukaemia.

Mononuclear cells from peripheral blood or bone marrow from 314 patients with acute myeloid leukaemia were examined for the presence of nuclear terminal deoxynucleotidyl transferase (304 patients), surface membrane expression of HLA-DR (314 patients) and the common acute lymphoblastic leukaemia antigen (281 patients). All patients were treated with identical remission induction chemotherapy, and morphological diagnosis was carried out in a central laboratory. The overall complete remission rate was 70%. There were no significant correlations between the immunological markers and complete remission rate, duration of remission, or survival.

Adolescent↗
PubMed1987

Comparison of 1 + 5 DAT and 3 + 10 DAT followed by COAP or MAZE consolidation therapy in the treatment of acute myeloid leukemia: MRC ninth AML trial.

This trial, which will probably accrue over 1,000 patients before it closes, has already demonstrated that high remission rates are attainable in large multicenter studies using 'conventional' doses of ara-C. The results in the group aged less than 40 are comparable with many single-center studies. There is, at the moment, only a borderline difference in the remission rates between the two forms of induction therapy but the more intensive regimen of DAT 3 + 10 achieves remission more quickly and requires less supportive care. Analysis of the reasons for failure to enter remission continues to show that inadequate supportive care remains an important reason why the remission rates are not higher. Drug-related deaths in remission, though decreasing gradually in this study, are a disturbing consequence of increasing the intensity of consolidation treatment.

Adolescent↗
PubMed1986

Principal results of the Medical Research Council's 8th acute myeloid leukaemia trial.

Between 1978 and 1983, 1127 patients with de-novo acute myeloid leukaemia (AML) were entered into the Medical Research Council (MRC)'s 8th AML trial. All received the same induction therapy consisting of daunorubicin, cytarabine, and 6-thioguanine--DAT (1 + 5). The 67% who entered complete remission were randomised to consolidation with two or six further courses of DAT. Adults under the age of 55 were randomised for central nervous system (CNS) prophylaxis with intrathecal cytarabine and methotrexate. Finally, those still in remission after 1 year of cytarabine and 6-thioguanine (AT) maintenance were randomised to receive either late intensification with cyclophosphamide, vincristine, cytarabine, and prednisolone (COAP) or continued AT. The median survival for the whole group was 12 months; the median duration of first remission was 15 months, with relapse-free survival at 5 years estimated at 18%. The factors most strongly associated with poor survival were performance status and age at presentation, but even among those over 60 years of age, half went into remission. Six courses of DAT consolidation gave a small advantage over two courses in reducing the number of late relapses but no significant survival advantage. Late intensification showed a marginally significant advantage over continued AT maintenance. The incidence of CNS relapse was low and unaffected by prophylaxis. The second remission rate varied from 10% when the first remission was shorter than 6 months to 61% when it had continued for more than 2 years. 40 patients received histocompatible allogeneic bone-marrow transplants in first remission. There was a high procedure-related death rate, particularly among patients over 30 years of age. Thus, initially at least, the transplanted group had shorter survival than a comparable group of chemotherapy-treated patients. Treatment specifications remained unchanged throughout the trial but those enrolled in the later half of the trial had a better (p = 0.003) survival.

Adolescent↗
PubMed1986

Features affecting outcome during remission induction of acute myeloid leukaemia in 619 adult patients.

Six hundred and nineteen patients with de novo acute myeloid leukaemia, entered into the Medical Research Council's eighth trial of therapy have been studied. All patients were treated with the same remission induction regimen. Pretreatment variables comprising age, clinical status, haematological status and a detailed marrow cytology and cytochemistry score have been analysed. Poorer remission rates have been found in older patients, in those with lower Karnofsky scores and in patients with a platelet count of less than 25 X 10(9)/l. Leukaemias showing evidence of cytoplasmic maturation along the granulocyte and monocyte lines, as evidenced by granules, Auer rods, a high percentage of Sudan black positive blast cells and morphological and cytochemical abnormalities of neutrophils were associated with a higher remission rate. Marrow eosinophilia was a good prognostic feature. Nuclear features of immaturity, i.e. increasing numbers and prominence of nucleoli were associated with a low remission rate. Abnormalities of the erythroid series, notably Periodic acid-Schiff positivity which was present in 133 cases (22% of the total), was associated with a low remission rate. Patient age and pretreatment Karnofsky score were the most useful predictors of treatment outcome.

Adolescent↗
PubMed1984

8;21 translocation in acute granulocytic leukaemia: cytological, cytochemical and clinical features.

Thirty patients with the 8;21 translocation and three with closely related variants have been studied. Ages ranged from 3 to 64 years (mean 28.3). Thirty-one were entered into the MRC's 8th Acute Myeloid Leukaemia Trial. Twenty-nine (88%) achieved complete remission. Marrow smears from most patients showed granulocytic maturation (M2, FAB classification) with characteristic abnormalities, but at least six showed predominantly myeloblastic (M1) morphology. The blast cells were markedly heterogeneous with regard to size and nuclear cytoplasmic ratio. Typical staining patterns were observed in the blast cells using Sudan black B and diaminobenzidine peroxidase stains, and to a lesser extent with periodic acid-Schiff and chloroacetate esterase. Butyrate esterase was negative in all cases. Auer rods were present in the granulocyte precursors in 31 cases and in eosinophil precursors in two cases. In most cases the existence of the translocation was predicted from the cytological and cytochemical findings. Seven patients developed solid leukaemic deposits, principally in the mastoid cavities, orbital cavities or thoracic spine (extradural).

Adolescent↗