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Biomedical subjects

H E Kay

Publications and source records attributed to H E Kay.

At least 55 records · Page 3Linked to original sources

Acid-phosphatase reaction in acute lymphoblastic leukaemia.

The diagnostic value of the acid-phosphatase reaction was assessed double-blind in 148 cases of acute lymphoblastic leukaemia (A.L.L.) classified by surface-membrane markers and entered into the M.R.C. U.K. A.L.L. trials. 90% of cases of T-A.L.L. showed a positive reaction in the majority of blast cells, while only 2% of common-A.L.L. and 10% of null-A.L.L. were positive. This cytochemical reaction distinguished the more aggressive form of A.L.L. any may aid the choice of therapy.

Acid Phosphatase↗

Analysis of treatment in childhood leukemia. IV. The critical association between dose fractionation and immunosuppression induced by cranial irradiation.

The degree of long term lymphopenia induced by cranial irradiation is shown to be dependent upon the number of fractions into which the standard cranial dose of 2400 rads is divided. The mean lymphocyte count of patients three months after receiving this dose in five fractions was 1.84 X 10(9)/1; in twelve fractions it was 1.12 X 10(9)/1 and in twenty fractions it was 0.64 X 10(9)/1. An explanation for this finding is offered which is based upon marked radiosensitivity of certain lymphocytes and the pattern of recirculation and redistribution of these cells.

Brain↗

Early deaths in acute myelogenous leukemia.

In a series of 84 patients with acute myelogenous leukemia, 24 died within 6 weeks of starting treatment. Twenty of the 24 patients had failed to achieve remission at the time of death. Death was due to infection in 20 patients and in 17 of these to septicemia; but whereas severe local infection with septicemia accounted for 12 deaths, only five patients died of septicemia without local infection. Bleeding was the direct cause of death in only four patients and an associated terminal event in another three; of these four patients three had disseminated intravascular coagulopathy. Surprisingly, in this group of patients age and overall clinical status at the time of admission were of no prognostic value in the first 6-week period. The importance of drug resistent disease associated with intractable local infection as a major cause of early death is emphasized.

Adult↗

Analysis of treatment of childhood leukaemia. V. Advantage of reduced chemotherapy during and immediately after cranial irradiation.

This paper compares anti-leukaemic efficiency with toxicity to the patient of chemotherapy during and immediately after central nervous system irradiation. The drug regimen consisted of daily mercaptopurine (MP) and weekly methotrexate (MTX) at the maximum tolerated dose. Of 140 patients with acute lymphoblastic leukaemia allocated to receive this drug regimen during and after cranial irradiation, 8 died in complete remission within 6 months of the end of irradiation. Details of the nature of these deaths are given. This result led the Working Party to modify the chemotherapy scheduled for this stage in treatment. The modified chemotherapy consisted of MP at reduced dosage before and during cranial irradiation and omission of MP and MTX for 3 weeks after irradiation, during which time daily prednisolone with 2 doses of vincristine were substituted. Following that, the treatment reverted to the original schedule of daily MP and weekly MTX at maximum tolerated dose. Of 109 patients allocated to this modified regimen only one died in remission within 24 weeks after cranial irradiation. Analysis of the anti-leukaemic effect of the modified regimen showed that up to 600 days it was at least as effective as the original more intensive regimen. We conclude that there is a definite advantage in keeping chemotherapy to a minimum during and immediately following cranial prophylactic irradiation.

Brain↗

Analysis of treatment in childhood leukaemia. III. Independence of lymphopenia induced by irradiation and by chemotherapy.

Lymphopenia induced by treatment for acute lymphoblastic leukaemia is analysed and discussed in relation to the type and incidence of infection occurring in those patients during complete remission. Blood lymphocytes can be placed into three largely independent groups: (1) those lymphocytes susceptible to long-term depletion following irradiation; (2) those lost from the blood during and for a short period after maintenance chemotherapy with methotrexate and 6-mercaptopurine; and (3) the remainder which are not depleted by irradiation or maintenance chemotherapy. The number of cells in each compartment varies from child to child and probably with age but on average is about 1.2 x 10(9)/1. for group 1, 0.7 x 10(9)/1. for group 2 and 0.4 x 10(9)/1. for group 3. Conventional lymphocyte typing crosses these barriers in that: Group 1 consists mainly of E-rosetting cells and cells which show a mitotic response to phytohaemagglutinin; Group 2 also contains E-rosetting cells but contains a major proportion of blood lymphocytes with surface immunoglobulin and essentially all antibody dependent cytotoxic lymphocyte (K-cell) activity; Group 3 comprises E-rosetting cells and a few immunoglobulin-staining cells.

Antimetabolites, Antineoplastic↗

Analysis of treatment in childhood leukaemia. II. Timing and the toxicity of combined 6-mercaptopurine and methotrexate maintenance therapy.

The first and second Medical Research Council UKALL trials have shown that alteration in the timing of methotrexate and 6-mercaptopurine maintenance therapy for the treatment of acute lymphoblastic leukaemia can markedly change drug induced toxicity. Maintenance chemotherapy in both trials used a similar total dosage of these drugs but the timing of their administration was different in the two schedules.

Child↗

Development of CNS leukaemia in acute myeloid leukaemia in childhood.

In 130 cases of acute myeloid leukaemia in children below the age of 14 years in Great Britain, there were 21 cases in which the central nervous system was involved. The incidence and timing is similar to that of acute lymphoblastic leukaemia; in a small number of patients who received prophylactic treatment, involvement of the central nervous system was prevented.

Adolescent↗

Meningeal leukemia after blastic transformation of chronic myeloid leukemia.

In two patients with blastic transformation of chronic myeloid leukemia complete remission was induced, but meningeal leukemia subsequently developed. The recognition of blast cell crisis as the presenting feature of chronic myeloid leukemia is discussed, together with treatment of this condition and its rare complication, meningeal leukemia. The development of meningeal leukemia in this disease is almost certainly due to the increased survival that has been produced by advances in therapy for blastic transformation.

Adult↗

Studies of parents of children with acute leukemia.

In a case-control study, 70 mothers and 24 fathers of children with acute leukemia (AL) were compared with 70 mothers and 24 fathers of normal children. Three significant differences (p smaller than 0.05) were found when 35 factors were compared among the mother pairs and one difference among the father pairs. Mothers of children with AL, though alike in most respects to their matched controls, had a significantly lower number of monocytes than their controls. This was a new observation. The mothers of the children with AL also had higher levels of gamma-globulin, IgA, and IgG (Philadelphia only), which confirmed previous observations. The fathers and mothers had higher levels of basophils. These findings direct attention to the immune systems, particularly the mononuclear cells, of the parents of children with AL, as a focus for further studies on the etiology and pathogenesis of childhood leukemia.

Acute Disease↗

Chromosome banding studies in acute leukaemia at diagnosis.

Cytogenetic study by a chromosome banding technique has been attempted in 93 cases of acute leukaemia at diagnosis. Banding patterns were difficult to visualise in the bone-marrow chromosomes of patients with acute leukaemia because of the fuzzy appearance of the fixed metaphases. The proportion of patients with abnormal chromosomes was higher in acute lymphoblastic (ALL) than in acute myeloid (AML) leukaemia. Abnormalities were present in all cases of other cytological types. Hyperdiploidy was the most commonly found numerical error in both ALL and AML but a larger proportion of patients with ALL had hyperdiploidy in more than 30% of the cells. In ALL it was generally found that the higher the frequency of hyperdiploidy the greater was the number of chromosomes per cell. Hypodiploidy not attributable to random losses was found in only 6 patients. Clones identified by rearranged or marker chromosomes were found in all types of leukaemia. Clones marked by a 7q-chromosome, in which the break point was the same, were identified in 1 adult with ALL and 2 children with AML. The high frequency of randomly disturbed chromosomal breakage found in the bone-marrow chromosomes of a high proportion of the patients may be related to the disease process.

Adolescent↗

Safe method of collecting leukaemia cells from patients with acute leukaemia for use as immunotherapy.

Leukaemia cells were collected from the blood of 72 untreated patients using a continuous-flow blood cell separator. The yield of cells was proportional to the number circulating in the patient, and up to 1 x 10(12) could be obtained in three hours. Complications of the procedure were mild, consisting of chills and shivering in 18% of patients. Leucopheresis at the time of diagnosis is an essential part of setting up a specific immunotherapy programme for patients with acute myelogenous leukaemia, and the lack of harmful side effects makes the collection of these cells ethically justified. The need for a centralized service to provide cells for this form of therapy is emphasized.

Adolescent↗