Kanti R. Rai

The frequency of long‐term remission in patients with acute myelogenous leukaemia treated with conventional maintenance chemotherapy: a study of 760 patients with a minimal follow‐up time of 6 years

Summary Remission duration associated with the administration of conventional maintenance chemotherapy to patients with acute myelogenous leukaemia was evaluated. The records of 760 patients who entered remission between 1974 and 1979 were reviewed. The median duration of remission was 1.1 years with 16% of patients remaining in remission at 8 years. The relapse curve was biphasic with a high rate of relapse during the first 2½ years of remission followed by a much lower relapse rate thereafter. Leukaemic relapses were noted through 8 years of remission. A plateau phase indicating freedom from the risk of leukaemic recurrence is not clearly apparent yet but may exist after the eighth year of remission.

Combination chemotherapy and radiotherapy for acute lymphocytic leukemia in adults: results of CALGB protocol 7113.

Abstract One hundred and forty-nine adult patients with acute lymphocytic leukemia (ALL) were treated with protocol defined combination chemotherapy-radiotherapy by 25 member institutions of the Cancer and Leukemia Group B. Induction of remission was attempted with vincristine (V), prednisone (P), L-asparaginase (A), with or without intrathecal methotrexate (IT-MTX) and followed by daunorubicin (D) in those patients not in complete remission after 4 weeks. The overall complete remission (CR) rate was 72%; daunorubicin was needed to achieve CR in 20 of the 107 remitting patients. The administration of IT-MTX during remission induction, especially when given simultaneously with A, was found to increase toxicity without therapeutic benefit. Remissions were maintained with either parenteral courses of 6-mercaptopurine (6-MP), and methotrexate (MTX), plus intermittent doses of V, P, and bis-β-chloroethylnitrosourea(BCNU) or with daily oral 6-MP, weekly oral MTX, and periodic VP reinforcements. All patients remaining in remission for 3 months or longer received CNS chemoradiotherapy. Median remission duration was 15 months. Continuous oral maintenance proved at least equivalent to intermittent parenteral remission therapy. Median survival was 17 months for all patients and 29 months for qualified patients achieving CR. Frequency and duration of response, and duration of survival were independent of age between ages 30 and 60. Above age 60 the prognosis is significantly less good. Thirty-two percent of the responders (life table estimate) remain in continuous first remission at 5 y. Toxicity was acceptable, except for an excessive frequency and severity of infections: (1) when V, P. A, and IT-MTX were given simultaneously; and (2) early in remission when full doses of maintenance chemotherapy were employed prior to complete recovery of normal bone marrow function. Results of treatment of ALL in adults have improved markedly during the last decade but lag behind those observed in children for reasons as yet unexplained.

Prediction of response of patients with acute nonlymphocytic leukaemia to remission induction therapy: use of clinical measurements

Two hundred patients with acute nonlymphocytic leukaemia received remission induction therapy consisting of cytosine arabinoside and an anthracycline antibiotic. Analysis of the pretherapy characteristics of the patients demonstrated that patient age was the most important factor in determining whether or not the patient would survive remission induction therapy. Assessment of the characteristics of the bone marrow after 6 d of therapy permitted the recognition of patients who were likely to fail to enter remission because of persistent leukaemia. Taken together, these observations demonstrate that it is possible to identify patients for whom conventional chemotherapy is not likely to be of benefit either because it is too intensive or because it is not intensive enough to produce a complete remission.

Changes in body composition of cancer patients following combined nutritional support

The effects of combined nutritional support (parenteral, enteral, and oral) were measured in cancer patients unable to maintain normal alimentation. Changes in body composition were quantified by measurement of total body levels of nitrogen, potassium, water, and fat. The protein-calorie intake of the patients was also evaluated by dietary survey (4-day recall). Standard anthropometric and biochemical measurements for nutritional assessment were obtained for comparison. The dietary evaluation indicated that the dietary supplementation for all patients was more than adequate to meet their energy requirements. Almost all patients gained weight on the combined nutritional support regimens. Determination of body composition indicated that change in body weight was equal to the sum of the changes in body protein, total body water, and total body fat. The findings from the anthropometric nutrition indices (arm muscle circumference and triceps skinfold) were consistent with the results of the body composition study. Information on the nature of the tissue gained was obtained by comparison of body composition data with the ratio of protein:water:lean body mass for normal tissue. The mean gain of protein in the cancer patients was quite small (0.3-0.6 kg). The main change in body weight appeared to be the result of gains in body water and body fat. The total body nitrogen to potassium ratio served to define the extent of tissue anabolism following hyperalimentation. The ratio dropped in the cancer patients following hyperalimentation toward the value of the control subjects on ad libidum diets. The body compartment techniques described have demonstrated their usefulness in determining the effects of hyperalimentation on cancer patients.

Mediastinal irradiation for chronic lymphocytic leukemia

Thirty-one patients with chronic lymphocytic leukemia were treated with mediastinal radiation. In none of the patients was complete remission achieved; either partial remission or clinical improvement was achieved in 52 per cent, but the duration of response was short. The response rate was 77 per cent for the patients receiving a total radiation dose greater than 3,000 rads and 45 per cent for those receiving less than 3,000 rads. Severe life-threatening toxicity was noted in 11 patients and seven of these patients died; two patients died with progressive disease. Severe toxicity was manifested by one or more of the following: bone marrow aplasia, pancytopenia, gram-negative sepsis, generalized herpes zoster and severe esophagitis. Neither the total dose of radiation nor the dose per week correlated withe the severity of reaction or death.

Inhibition of DNA synthesis by cytosine arabinoside: Relation to response of acute non-lymphocytic leukemia to remission induction therapy and to stage of the disease

The sensitivity of leukemic marrow cell DNA synthesis to cytosine arabinoside (araC) exposure in vitro was studied in specimens obtained from patients with acute non-lymphocytic leukemia. Cells from patients who had been treated with araC in the past were more likely to be resistant to the effect of araC on DNA synthesis than cells obtained from patients who had not been so-treated previously. Resistance to the effects of araC on DNA synthesis was associated with the failure of high-dose araC therapy to induce remissions in relapsed patients, whereas remission induction failure in previously untreated patients was not associated with araC resistance.