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Biomedical subjects

M G Whiteside

Publications and source records attributed to M G Whiteside.

At least 19 recordsLinked to original sources
PubMed1990

Etoposide in acute nonlymphocytic leukemia. Australian Leukemia Study Group.

Previously untreated patients with acute nonlymphocytic leukemia (ANLL) aged 15 to 70 years were randomized to either cytosine arabinoside 100 mg/m2/d continuous intravenous (IV) infusion days 1 through 7, daunorubicin 50 mg/m2/d IV days 1 through 3 (7-3), or the same drugs intensified with etoposide 75 mg/m2/d IV days 1 through 7 (7-3-7) as induction therapy. Patients achieving complete remission (CR) received two courses of consolidation therapy (5-2 or 5-2-5) followed by maintenance therapy. Of 264 eligible patients, CR occurred in 56% of 7-3 and 59% of 7-3-7 patients; 7-3-7 significantly improved remission duration (P = .01). The median remission duration was 12 months for 7-3 and 18 months for 7-3-7. Survival was similar when the two arms were compared overall. Subset analysis performed to identify patients with the most benefit showed that etoposide significantly prolonged remission duration in younger patients (less than 55 years) with a median of 12 months for 7-3 and 27 months for 7-3-7 (P = .01). Survival appeared to be prolonged with 7-3-7 in patients aged less than 55 years, with a median of 9 months for 7-3 as compared with 17 months for 7-3-7 (P = .03). In older patients (aged greater than or equal to 55 years), 7-3-7 was more toxic, with significantly more severe [World Health Organization (WHO) grade 3 or 4] stomatitis (P = .02) and no additional clinical benefit. Hematologic toxicity for induction courses was similar, with granulocytopenia less than 0.5 x 10(9)/L for a median of 16 days per course for 7-3 and 15 days for 7-3-7. Hematologic toxicity was more severe for 5-2-5 consolidation courses (P = .003). Induction and consolidation therapy intensified with etoposide resulted in significantly improved remission duration but not survival.

Adolescent↗
PubMed1988

Treatment of hairy cell leukemia with increasing doses of recombinant alpha A interferon.

Since July 1984, eight patients with advanced hairy cell leukemia have received treatment with recombinant alpha A interferon. At commencement of interferon, seven patients had progressive cytopenia, and one was in leukemic phase (greater than 20 x 10(9)/L circulating hairy cells). All patients had had previous splenectomy. Interferon was administered subcutaneously. The initial dose was 3 x 10(6) U/day, continued until peripheral counts stabilised. Subsequently, patients received 6 x 10(6) U/day, 9 x 10(6) U/day, and finally 12 x 10(6) U/day. The dose increases proceeded every 8-12 weeks, as tolerated. Seven patients had an objective response. There were four complete remissions, two partial remissions, and one minor response. Complete remission was documented only in patients on at least 6 x 10(6) U/day for 12 weeks. The median time to complete remission was 40 weeks (range 35-53). Normalisation of peripheral blood counts preceded histologic marrow improvement. The median times for response (platelets greater than or equal to 100 x 10(9)/L, hemaglobin greater than or equal to 12 gm/dL, neutrophils greater than or equal to 1.5 x 10(9)/L), were six to eight and 17 weeks, respectively. Toxicity included myelosuppression during the first four weeks of therapy. With increasing doses of interferon, myelosuppression did not recur. A transient, mild, flu-like syndrome affected all patients. Two patients developed asymptomatic transaminitis at doses greater than 6 X 10(6) U/day. This resolved with dose reduction. In one case impotence was reported during the first four weeks of each interferon level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Clinical factors influencing the efficacy of pooled platelet transfusions.

To determine the relative importance of clinical factors on the efficacy of platelet transfusions, 941 pooled platelet transfusions from HLA-unmatched donors were studied prospectively in 133 patients with bone marrow failure. Multiple linear regression analyses identified the major factors influencing one-hour-corrected increments (CI) as prior splenectomy, bone marrow transplantation, disseminated intravascular coagulation, concurrent intravenous amphotericin B, splenomegaly, and HLA antibody grade. The relative impact of these factors on CI has been quantitated by using a formula developed from these data. A linear relationship was demonstrated between increasing percentage of HLA antibody grade and decreasing CI. A number of other factors were less important in the linear regression model than the aforementioned major factors. These included platelet-specific antibodies, concurrent antibacterial antibiotics, clinical bleeding grade, and temperature. Factors that did not influence CI included the number of prior platelet transfusions, prior granulocyte transfusions, prior red cell transfusions, infection, age, blood group, diagnosis, sex, pretransfusion platelet count, prior pregnancies, and concurrent antineoplastic drugs. This study identified major clinical factors that significantly influenced CI and were major causes of refractoriness to pooled platelet transfusions.

Antibodies↗
PubMed1986

A phase I-II study of cytosine arabinoside, daunorubicin, and VP16-213 in adult patients with acute non-lymphocytic leukemia.

The combination cytosine arabinoside (ara-C), daunorubicin, and VP 16-213 was studied in 28 patients with acute non-lymphocytic leukemia to define the toxicity of the combination and assess its efficacy. Of 21 previously untreated patients, 16 (76%) achieved a complete response (CR) with the median remission duration not reached but exceeding 25 weeks. For CR patients, the median number of days with neutrophils less than 500/microliter was 19. The median survival for patients with CR is 60 weeks. Two of seven previously treated patients achieved CR for 11 weeks and in excess of 36 weeks, respectively. At the initial VP16-213 dose of 100 mg m-2 per day for seven days, severe stomatitis was seen in 38% of courses but was less with dose reduction to 75 mg m-2 per day for seven days. Other toxicity was similar to previous experience with ara-C and daunorubicin alone.

Acute Disease↗
PubMed1984

The biochemical and clinical consequences of 2'-deoxycoformycin in T cell chronic lymphocytic leukaemia.

The mechanisms for cell toxicity with adenosine deaminase inhibition by 2'-deoxycoformycin (dCF) in non replicating lymphoid cells include S-adenosylhomocysteine (SAH) hydrolase inactivation and reduction of cellular ATP content. These postulates were explored in a patient with T-CLL receiving dCF with a resultant fall in peripheral blood lymphocytes from 740 X 10(9)/1 to 90 X 10(9)/1 over 15 d. In red cells there was complete inhibition of adenosine deaminase and SAH hydrolase activities, progressive deoxyadenosine triphosphate (dATP) accumulation and ATP depletion but no significant alteration in adenosine monophosphate (AMP) deaminase activity or distribution in purine intermediates from radioactive adenosine. In T-CLL lymphocytes, there was incomplete lymphoid SAH hydrolase inactivation, reduced AMP deaminase activity and progressive dATP accumulation. The limited decrease in lymphocyte ATP content was related more to dCF administration than dATP accumulation, nor accompanied by significant changes in the distribution of purine intermediates from adenosine. These findings suggest that ATP depletion with dCF therapy does not reflect AMP deaminase activity modulation nor is of critical importance for cell toxicity. The exact role for elevated cellular dATP content and SAH hydrolase inactivation in this toxicity remains to be established.

AMP Deaminase↗
PubMed1983

Acyclovir therapy in patients with malignant disease and disseminated herpes zoster.

Acyclovir is a new antiviral agent which is active in vitro and in vivo against a variety of herpesviruses. Two cases are reported in which intravenous administration of acyclovir arrested the progress of disseminated herpes zoster within 24 to 48 hours after the beginning of therapy. There was no evidence of toxicity. Thus, acyclovir appears to be useful in the therapy of herpes zoster, but this requires evaluation.

Acyclovir↗
PubMed1982

Immunotherapy maintenance in acute non-lymphocytic leukaemia.

Between January 1975 and December 1977, 264 adult patients with acute non-lymphocytic leukaemia entered the Australian National Leukaemia Trial. Of 251 evaluable patients, three induction regimens achieved similar complete response (CR) rates. CROP (cytosine arabinoside, daunorubicin, vincristine, prednisolone) produced CR in 41% of patients, 7 and 3 (cytosine arabinoside, daunorubicin) in 42% and 7 and 3 plus hydroxyurea in 52%. Remission duration and survival were similar when induction regimens were compared. Forty-five patients reaching maintenance therapy were randomised to either chemo-immunotherapy (BCG plus intradermal leukaemic blast cells) or chemotherapy alone. The duration of CR in these two groups was almost identical, though patients receiving chemotherapy alone had prolonged survival (median 161 weeks) when compared to the chemo-immunotherapy group (84 weeks, p = 0 . 07). Institutions with less developed supportive facilities reported lower CR rates (p = 0 . 04). Leucocytosis (greater than 100 X 10(9)/1) and older age (greater than 50 years) were associated with shortened survival. The Trial has failed to show any advantage for this form of immunotherapy.

Acute Disease↗
PubMed1979

Erythroleukemia following drug induced hypoplastic anemia.

Three patients with drug-induced hypoplastic anemia terminating 2 to 6 years after presentation with erythroleukemia are described. All were treated for prolonged periods with androgen and corticosteroid and two of the patients showed apparent dependence on this therapy for optimal hematologic status. The leukemic phase was heralded by loss of this dependence and development of sideroblastic dyserythropoiesis with progression to bizarre erythroid hyperplasia and fatal cytopenia. The exact relationship between androgen and corticosteroid therapy and the erythroleukemia remains speculative.

Adrenal Cortex Hormones↗
PubMed1979

The leukaemias.

The leukaemias comprise a group of blood disorders which differ widely in regard to prognosis, the need for treatment and the intensity of treatment. A detailed understanding of them is necessary to decide which cases require treatment, and where the treatment is to be carried out. Such an understanding is also needed in counselling and advising patients, proper communication being a very important part of management. Acute leukaemia (with some exceptions) requires intensive and difficult treatment appropriate only in properly staffed hospital units. Chances of control range from reasonable to very good, especially in children, and significant prolongation of survival is seen in those who achieve remission. Future prospects for cure are promising. Chronic lymphatic leukaemia may be a very benign disease, though risk of infection increases as time passes. Chronic myeloid leukaemia, though initially benign, is less chronic than is generally believed and commonly the disease transforms to an acute pattern which cannot for long be controlled.

Adolescent↗
PubMed1977

Filtration leukopheresis granulocyte support for infected neutropenic patients.

A pilot study of granulocyte support for neutropenic infected patients by means of white cells collected from the Aminco Celltrifuge at the Peter MacCallum Clinic showed acceptable side effects in donor and recipients, and an encouraging recovery occurred in two out of four patients treated. White cell filtration leukopheresis was introduced at the Alfred Hospital Haematology and Medical Oncology Unit in November, 1975, for supportive therapy of all patients with white cell counts below 500/mm3 who had sustained febrile episodes (temperatures greater than 38 degrees C for more than 48 hours) while receiving appropriate or empiric parenteral antibiotic therapy. A minimum of four or more daily transfusions was given from group and cross-matched compatible donors until fever lysis, recovery of the neutrophil count to over 500/mm3 or death. Of 13 patients given white cell support, 12 survived and were discharged from hospital. One patient died having received only one transfusion when he was moribund. We believe that white cell filtration leukopheresis cell support is useful when used with parenteral antibiotic therapy for infected neutropenic patients, and it has resulted in a high rate of recovery from life-threatening infection in patients at risk.

Agranulocytosis↗
PubMed1977

The management of febrile episodes in-neutropenic cancer.

The management of 33 febrile episodes in neutropenic patients suffering from acute leukaemia and other cancers is described. In 32 out of 33 episodes, the fever subsided. One patient died of cerebral haemorrhage while infected. The most common clinical sites of infection were, in order of frequency, the chest, the throat and the skin. Positive cultures were obtained in about half the episodes, the most common site being the throat followed by blood and sputum. The most common organisms isolated were Gram negative. Eighty-four per cent of febrile episodes occurred with neutrophil counts of less than 500/mm3, and in the majority of these, less than 100 neutrophils per cubic millmetre. All patients were reverse barrier nursed and on becoming febrile were given 48 hours of parenteral antibiotic therapy. The most common antibiotic combination used was gentamicin and cephalothin. At 48 hours, granulocyte transfusion and a third antibiotic were added to the regimen of patients not responding. The percentage response to antibiotics alone, in this series, at 58% was similar to that of other series, but the mortality experienced was lower.

Agranulocytosis↗
PubMed1976

Immunotherapy with chemotherapy in the maintenance of remission in acute myeloblastic leukaemia.

Thirteen patients with acute myeloblastic leukaemia or one of its variants in remission have been given maintenance treatment with a combination of chemotherapy and immunotherapy. Chemotherapy was given for one week in four, and immunotherapy was given during the intervening three weeks. The immunotherapy consisted of BCG vaccine given by Heaf gun, and snap-frozen pooled allogeneic irradiated leukaemic cells. The median duration of survival was 147 weeks, and the median duration of the first complete remission was 76 weeks. It is difficult to compare these results with other figures reported, but they add to the evidence which suggests that immunotherapy is of value in the maintenance treatment of patients with this disease. Further controlled trials are necessary.

Acute Disease↗
PubMed1976

Chemoimmunotherapy for maintenance in acute myeloblastic leukemia.

Of 30 adult patients with acute myeloblastic leukemia, 14 achieved complete remission. Eight of these were given chemoimmunotherapy for maintenance. The immunotherapy consisted of intradermal pooled allogeneic leukemic cells (snap-frozen irradiated) and BCG vaccine given by Heaf gun, given twice in 4 weeks. The chemotherapy was given for 1 week in 4 weeks. The median duration of remission in these eight patients was 115+ weeks and the median duration of survival was 147+ weeks. The other six patients who were given chemotherapy only for maintenance had a median duration of remission of 15 weeks and a median survival of 52 weeks. The two groups cannot be compared properly, however, as allocation of patients was not random, and the chemotherapy differed significantly.

Adolescent↗
PubMed1975

The detection of glucose-6-phosphate dehydrogenase deficiency in mediterraneans by comparative quantitative enzyme electrophoresis.

Glucose-6-phosphate dehydrogenase (G6PD) can be easily isolated from haemolysates by cellulose acetate electrophoresis, and heterozygous (as well as hemizygous and homozygous) G6PD deficiency can be readily detected if the activity of the enzyme is determined densitometrically after electrophoresis and expressed as a ratio of the activity of a second enzyme, 6-phosphogluconate dehydrogenase (6PGD), which is isolated at the same time and whose activity is similarly determined. A method is presented here, together with the results of a recent survey in which 400 babies of Greek origin were tested for G6PD deficiency by the method. An overall incidence of 4-3% was found in the group; 2-9% of the males were completely G6PD deficient and 5-2% of the females were heterozygous for the deficiency.

Australia↗
PubMed1975

Non-specific immunological function in acute myeloblastic leukaemia.

Immunological function was investigated in patients with acute myeloblastic leukaemia, both in the untreated stage of the disease and in remission. IgM concentrations were found to be raised in 7 out of 29 patients during the untreated stage. There were only minimal changes in 1gG, 1gA and C' concentrations, and in the incidence of auto-antibodies to normal tissue components. Reactions to standard skin tests were considerably impaired--only 2 out of 10 leukaemic patients in remission responded to 2 or more of these tests. Furthermore the response in leukaemic patients was much weaker than in the corresponding controls. PHA stimulation of lymphocytes from patients in remission showed considerable variation from near normal to gross impairment but a response below 40% of normal was associated with a short remission period, suggesting that PHA stimulation may be a useful indication of the likelihood of relapse.

Acute Disease↗