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Biomedical subjects

H M Clink

Publications and source records attributed to H M Clink.

35 records · Page 2Linked to original sources
PubMed1979

The nature of remission in acute myeloblastic leukaemia.

15 patients with acute myeloblastic leukaemia (AML) in remission were given immunotherapy and 17 similar patients were given immunotherapy plus chemotherapy with the drugs used to induce remission. Median remission length was 245 days for both groups and median survival was 465 days for patients given chemoimmunotherapy and 476 days for patients given only immunotherapy. The failure of remission chemotherapy in AML cannot be attributed to induced resistance because the same drugs induced a second remission in 60% of the patients. From laboratory studies with human AML cells it is suggested that in AML the residual leukaemic cells mature after induction chemotherapy and are then refractory to further drug treatment. Relapse occurs when the leukaemic population proliferates and the environment permits dedifferentiation into frank blast cells.

Adolescent↗
PubMed1979

Marrow autotransplantation accelerates haematological recovery in patients with malignant melanoma treated with high-dose melphalan.

In a Phase I study, melphalan 140 mg/m2 was administered to 8 patients with disseminated malignant melanoma. Marrow was removed from the patients immediately before melphalan administration and returned i.v. 8 h later. Studies on marrow culture and melphalan pharmacokinetics predicted that this was a safe time to administer non-cryopreserved marrow. Four patients received lower doses of i.v. melphalan without autologous marrow. In the group receiving autologous marrow the time for recovery of peripheral-blood granulocytes to 800/mm2 or greater was significantly less (P = 0.01) than in those not receiving marrow. In 7 patients the tumour showed evidence of response to the drug and there was 1 complete remission. This treatment deserves investigation in patients with tumours more sensitive to drugs than melanoma.

Adult↗
PubMed1979

The recovery of iron uptake in erythropoietic bone marrow following large field radiotherapy.

Large X-ray fields, such as those used to irradiate major lymph-node areas in the treatment of lymphomas, often irradiate large areas of haemopoietic bone marrow. The absorbed doses received by the marrow are close to the tolerance level. Quantitative scanning of the bone marrow, using 52Fe and a digital whole-body scanner, has been carried out in a series of 22 patients treated by radiotherapy up to nine years previously in order to assess the extent and recovery of their erythropoietic marrow. The results showed large variations from patient to patient; in some patients the iron uptake in the marrow returned to near normal levels in two to three years, while in others the uptake remained suppressed after seven to eight years. The tolerance dose for the bone marrow appeared to be about 1100 ret. There was some evidence of a more rapid recovery of erythropoietic function in males than females, but no evidence to show that age of patient, type of disease or whether chemotherapy had been used influenced the results. Patients who showed a decreased iron uptake in an irradiated region of marrow generally showed a compensating increased uptake in unirradiated regions, which in some cases was associated with anaemia.

Adolescent↗
PubMed1977

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↗
PubMed1976

Distribution of granulopoietic activity in the human skeleton, studied by colony growth in agar diffusion chambers.

The colony forming ability of bone marrow cells from 110 haematologically normal patients was investigated by their growth in semi-solid agar in intraperitoneal diffusion chambers. Marrow aspirated from the sternum showed a consistently higher colony yield than that from the iliac crest. Study of site variation in the individual was possible in donors for bone marrow transplantation. In each of four cases, sternal marrow produced more colonies than any other site. Examination of smears made from the aspirated samples suggested that the difference in yield was not due to varying dilution by peripheral blood on aspiration from different sites. It is concluded, therefore, that the incidence of colony precursor cells is not uniform throughout the active marrow.

Agar↗
PubMed1974

Adult acute leukaemia.

Seventy-eight adult patients with acute leukaemia were classified cytologically into 3 categories: acute lymphoblastic leukaemia (ALL), acute myelogenous leukaemia (AML) or acute undifferentiated leukaemia (AUL). The periodic acid-Schiff stain was of little value in differentiating the 3 groups. The treatment response in each group was different: 94% of patients with ALL (16/17) achieved complete remission with prednisone, vincristine and other drugs in standard use in childhood ALL; 59% of patients with AML (27/46) achieved complete remission with cytosine arabinoside and daunorubicin (22 patients), or 6-thioguanine and cyclophosphamide (2 patients), 6-thioguanine, cyclophosphamide and Adriamycin (1 patient), and cytosine and Adriamycin (1 patient); only 2 out of 14 patients (14%) with acute undifferentiated leukaemia achieved complete remission using cytosine and daunorubicin after an initial trial of prednisone and vincristine had failed. Prednisone and vincristine would seem to be of no value in acute undifferentiated leukaemia. It would seem also that no benefit is obtained by classifying all patients with acute leukaemia over 20 years of age as "adult acute leukaemia" and treating them with the same polypharmaceutical regimen. The problems posed by each disease are different and such a policy serves only to obscure them.

Acute Disease↗
PubMedDate not supplied

Bone marrow transplantation in acute myeloid leukaemia.

It is apparent from the accompanying Table 9 and Figure 5, that transplantation offers an improved survival in AML. The use of CSA has made possible the technique of a mis-matched transplant, but as yet an unrelated donor has not been used. It may be that tolerance is more easily established with a one haplotype mis-match than with a completely unrelated person who may, nevertheless, be HLA identical. Clearly this would be an exciting project for the future, provided that all problems concerning relapse of disease and GvHD are overcome, and will also probably depend upon improvements in tissue typing techniques. (table; see text) Certainly we would now recommend this form of treatment to all patients under 40 years of age, in first remission from AML. Patients above this age, have responded less well and have been prone to more complications. We do not as yet know whether a complete remission is essential prior to embarking on a graft; certainly a few patients have been in early relapse, and this does not seem to have necessarily produced a poor outcome. Florid relapse at the present time is a definite contra-indication and no patients have been grafted in this situation. It will be noted that results for acute lymphoblastic leukaemia and chronic granulocytic leukaemia are bad. The first group were grafted early in the programme, but the number of relapses was extremely high and was accompanied in many circumstances by interstitial pneumonitis. Transplantation in chronic granulocytic leukaemia, a disease in which the prognosis has not improved for the past 20 years, has also not been successful except in one syngeneic graft. Two of the three deaths were in previously treated patients, one in blast transformation, but the third was virtually untreated and GvHD was a very serious problem indeed. Other reports of grafting for CGL have been discouraging except in twins. All these deaths occurred early. Whether this therapeutic approach will remain a treatment of choice remains to be seen, but we are very encouraged by our progress so far, although much work remains to be done.

Bone Marrow Transplantation↗
PubMedDate not supplied

Toxicity and immunosuppressive activity of binary combinations of 2'-deoxycoformycin and 2'-deoxyadenosine.

Treatment of mice with 2'-deoxycoformycin (dCf) for 5 days produced inhibition of spleen and lymph node adenosine deaminase (E. C. 3.5.4.4) activity but no hematologic toxicity or weight loss. A 64-fold elevation of erythrocyte dATP was observed. However, if mice were injected with 2'-deoxyadenosine (AdR) in combination with dCf, weight loss, hematologic toxicity, and liver cell necrosis occurred. These mice had a severe blood coagulation defect and a 73-fold elevation of plasma alanine transaminase activity, plasma prealbumin became undetectable, and erythrocyte dATP levels were elevated 1500-fold. Death during treatment appeared to be from acute liver failure since bone marrow toxicity was only detected following termination of treatment. These effects were not seen in mice receiving adenosine in combination with dCf. dCf, either alone or in combination with AdR, inhibited the contact sensitization to oxazalone in mice. The inhibition was associated with signs of systemic toxicity which were more pronounced in the combination-treated groups. If dATP is the toxic metabolic accumulated in the malignant cells of patients treated with dCf, we propose that AdR supplementation of treatment should be considered with extreme caution since severe damage to normal tissues might result.

Adenosine Deaminase↗