Long-term follow-up of patients >or=60 yr old with acute myeloid leukaemia treated with intensive chemotherapy.

It is still controversial how to treat elderly patients with acute myeloid leukaemia (AML), and results have been poor with most regimens. We report the long-term results of a randomised study performed by the Leukaemia Group of Middle Sweden during 1984-88 comparing two intensive chemotherapeutic drug combinations. Ninety patients >or=60-yr old with untreated AML were randomly allocated to treatment with daunorubicin, cytosine arabinoside (ara-C), and thioguanine (TAD) (43 patients) or a combination in which aclarubicin was substituted for daunorubicin (TAA) (47 patients). Forty-four patients (49%) entered complete remission (CR), 22/43 (51%) in the TAD group and 22/47 (47%) in the TAA group (ns). The CR rate in patients 70 yr 14/48 (29%) (P<0.0001). Early death within 30 d after treatment initiation was more often seen in patients >70 yr than in patients or=10 yr after inclusion of the last patient, 5/90 patients (one in the TAD group and four in the TAA group, respectively) were still alive, four in continuous complete remission and one in second complete remission. Thus, both treatment regimens appear to have similar efficacy, with a relatively high complete remission rate, and a reasonable survival as compared to other studies including some long-term survivors. However, early deaths are still numerous, particularly in patients above 70 yr of age, and the relapse rate is substantial.

The final phase in acute myeloid leukaemia (AML): a study of cause of death, place of death and type of care during the last week of life.

The aim of this study was to increase the knowledge of the final phase in acute myeloid leukaemia (AML), a period which entails many complex medical and psychosocial decisions. Data on cause and place of death were gathered through a retrospective review of medical and nursing records of 106 patients with AML who had died during 1995-1997. We focused on the actual phase of the disease and to what extent the patients were prescribed palliative care. With increased knowledge of the dying process in AML there are options to discuss which approach would be the most preferred final phase for an AML patient.

Quality of life in young patients with chronic myelocytic leukaemia during intensive treatment including interferon.

The aim of this study was to evaluate to what extent the quality of life (QOL) of young patients with chronic myelocytic leukemia (CML) was affected by treatment with interferon (IF) and intensive chemotherapy. In a main study performed by The Swedish CML Group, aiming at reduction of the malignant pH+ cell clone by treatment with hydroxyurea and IF followed by ABMT, QOL was evaluated with VAS scales and the Life Ingredient Profile in 44% of the patients. The intensive treatment did not lead to intolerable suffering or protracted reduction in QOL. However, 80% of the patients were on sick leave during the first year of treatment.

Cost analysis of different phases of acute myeloid leukaemia.

Priority lists have been formulated in several countries and cut-backs can be a threat to leukaemia treatment. We analysed the costs in different phases of disease for 54 conventionally treated patients with acute myeloid leukaemia. Thirty-two patients reached CR 1, seven patients are still alive as of May 1994. We found a cost per week and patient of 17,334 Swedish Crowns (SEK) (U.K. 1 pound = 10.57 and U.S. $1 = 5.91, 1990) in induction phase, 1854 in remission phase and 10,529 SEK in relapse phase. In the terminal phase 10% of the total cost was spent. The quality of life of the patients in relapse is discussed and palliative treatment is emphasized.

Costs over time in conventional treatment of acute myeloid leukaemia. A study exploring changes in treatment strategies over two decades.

OBJECTIVES: The aim was to analyse the consumption of different items in conventional treatment of acute myeloid leukaemia (AML) and their cost, in order to evaluate the economic consequences of new treatment strategies. DESIGN: Data on items of treatment were gathered retrospectively from case notes, including amount and date. Prices were gathered from price lists made up for internal billing/accounting. SETTING: The patients were all treated in a hospital with excellent treatment and service facilities. SUBJECTS: Seventy-three AML patients treated from 1973 to 1980, all since deceased, were compared with 54 patients treated from 1981 to 1988, of whom 14 were alive at the end of the observation period. INTERVENTIONS: The patients were treated according to randomized treatment protocols to achieve complete remission. Maintenance treatment or consolidation courses were given. In relapse, new induction treatment was given. MAIN OUTCOME MEASURES: Complete remission and survival were registered. The costs were divided into basic hospital costs and patient-specific costs. RESULTS: The mean total treatment cost for an AML patient in the 1970s was 211,138 SEK, and in 1980s 356,911 SEK. (UK 1 pound = 10.57 SEK, US$1 = 5.91 SEK 1990). All treatment costs increased between the periods: hospital costs by 20%, and patient-specific costs by 186%. Antibiotics, cytostatics and outpatient department costs had increased the most. The mean survival time almost doubled, and in the 1980s group there were several long-term survivors. CONCLUSIONS: The costs for AML treatment increased considerably from the 1970s to the 1980s. The effectiveness of these treatments increased as well, resulting in increased rate and duration of survival, and several patients were long-term survivors. It was not possible to identify the cost consequences of separate new technologies.

Quality of life of patients with acute myeloid leukaemia.

In a prospective study of 27 patients with acute myeloid leukaemia (AML) quality of life was studied using three different instruments, Life Ingredient Profile, Karnofsky Performance Scale and Vitagram. The course of the disease was followed during the induction period, remission, relapse and in the terminal phase. We found that induction treatment entailed physical and psychological distress with decreased quality of life but with continued ability to enjoy various leisure activities. Patients who survived experienced a change of attitude with regard to what was important in their lives. They reverted to their earlier lifestyle within 2 years.

Quality of life during induction treatment of acute myeloid leukaemia. A comparison of three intensive chemotherapy regimens using three instruments for quality of life assessment.

From a main study describing quality of life in patients with acute myeloid leukaemia (AML) over time, 22 patients who had received induction treatment with POCAL (prednisone, vincristine, doxorubicin, Ara-C, thioguanine), MEA (mitoxantrone, etoposide, Ara-C) or TAD (daunorubicin, Ara-C, thioguanine) chemotherapy regimens were selected. Their quality of life was assessed with Karnofsky performance scale (KPS) and Vitagram as well as with life ingredient profile (LIP), a new instrument for assessing quality of life during chemotherapy treatment. The patients' quality of life was found to be affected for short periods during induction treatment. The POCAL regimen seemed to lead to the least deterioration in quality of life, whereas the MEA treatment had more pronounced effects in this respect. In patients treated according to the TAD regimen gastrointestinal side-effects were mild compared to those of the other regimens. However, to show significant differences between treatment regimens larger multicentre studies are needed. The LIP instrument appeared to display a superior capacity for evaluating the distress of patients compared with the other instruments.

Assessing quality of life in leukemia: presentation of an instrument for assessing quality of life in patients with blood malignancies.

The Life Ingredient Profile (LIP)--a new instrument for iterated quality of life assessments in patients with haematological malignancies--is presented. It is intended to reflect the patient's estimation of the symptoms of disease as well as the side-effects of treatment and is designed for comparing different regimens of chemotherapy. In a pilot study of 35 patients with myeloma, lymphoma and acute leukaemia, the LIP showed good validity, reliability and sensitivity to change. It was easy to apply and the structured interviews took only 10-20 min. LIP appears to assess important dimensions of quality of life without being a burden to the patient or the nursing staff.

Treating acute leukaemias--a venture into economic uncertainty? A method for estimating the cost of treating patients with acute myelocytic leukaemia.

The objective of this paper is to report a method for estimating the cost of treating acute myelocytic leukaemia (AML). It is based on individual data from 54 patients treated with aggressive induction courses of chemotherapy. The study records the cost of the entire survival period for 40 patients and of at least 16 months' survival for the remaining 14 patients. All treatment activities were registered from the patient records and the price of each activity was estimated. As far as possible the principle of opportunity cost was used. The median survival time was 50 weeks and the average cost per patient was c. 300,000 SEK (= c. USD 50,000) in 1988 prices. A young man who achieved three remissions and lived for five years had the highest cost, c. 1 million SEK (= USD 155,000). The costs for AML treatment was higher in the 1980s than in the 1970s but led to longer survival for patients who survived the initial period.

A Randomized Comparison of Doxorubicin and Doxorubicin-DNA in the Treatment of Acute NonLymphoblastic Leukemia.

In the light of previous findings that treatment of leukemia patients with DNA-linked doxorubicin gave higher doxorubicin concentrations in leukemic cells than treatment with doxorubicin alone, the Leukemia Group of Middle Sweden performed a randomized clinical trial to compare the effects of doxorubicin and doxorubicin-DNA in patients with acute non-lymphoblastic leukemia. One hundred and twenty consecutive patients within the age range 15 to 60 years were randomized to one of three treatment groups. In two of these, remission induction treatment was performed with prednisolone, vincristine, ara-C and thioguanine combined with either doxorubicin or doxorubicin-DNA. Patients entering a complete remission received intensive consolidation during 16 months with 4 courses each of doxorubicin (+/ - DNA)/ara-C, doxorubicin (+/ - DNA)/azacytidine, ara-C and amsacrine. The third treatment group followed a protocol from a previous study with daunorubicin and ara-C for induction therapy and a less intensive maintenance therapy. No further patients were assigned to this "control" group after 3 years or to the two other groups after 6 years. This report is based on a follow-up 31 months thereafter. The overall rate of complete remission was 67% and the mean time to complete remission was 71 days, with no differences between the treatment groups. Patients treated with the doxorubicin-DNA conjugate had a significantly longer survival [median for all patients 27.2 months (p < 0.01) and for patients in CR 47.0 months (p < 0.025)] and longer duration of first remission (median 23.6 months, p < 0.025) than the other groups. There were significantly fewer reports of cardiotoxicity (p < 0.05) and severe intestinal toxicity (p < 0.02) in patients treated with the doxorubicin-DNA conjugate and there was a tendency towards less hepatic (p < 0.08) and renal toxicity (p < 0.08). The frequency of myelosuppression, fever and infectious complications was similar in all three groups. Complex binding to DNA appears to increase the therapeutic effects and reduce some toxic effects of doxorubicin in patients with ANLL.

Intermittent high-dose melphalan/prednisone vs continuous low-dose melphalan treatment in multiple myeloma.

Patients with newly diagnosed multiple myeloma were randomly allotted to an intermittent high-dose melphalan/prednisone (MP) treatment (120 patients) or a continuous low-dose melphalan (M) regimen (99 patients). The median observation time was 59 months (range 33-84). Response to therapy was obtained in 45% of the MP group and 31% of the M group (P less than 0.05). No significant difference in response with regard to clinical stage was noted. Median survival was 36 months in the MP group and 29 months in the M group. Survival was longer in stage I and II myeloma than in the stage III cases, at least in the MP group. The median and 5-yr survival rates in stages I and II were significantly better in the MP than in the M group. Response to therapy was associated with length of survival, median survival being 62 months in responding patients and 20 months in non-responders. The MP and M groups did not differ in this respect.

Treatment of chronic lymphocytic leukaemia and well-differentiated lymphocytic lymphoma with continuous low- or intermittent high-dose prednimustine versus chlorambucil/prednisolone.

Prednimustine, a new antitumour drug, is a chlorambucil ester of prednisolone. The present prospective randomized study compares the effect of continuous low-dose (B) and intermittent high-dose (C) prednimustine in previously untreated patients with progressive CLL and WDLL. The control group received continuous chlorambucil/prednisolone therapy (A). One hundred and eighteen patients, 88 CLL and 30 WDLL, were evaluable. Response to therapy (greater than 50% improvement) was noted in 61, 55 and 57% in groups A, B and C respectively. The difference was not statistically significant. Time to response, response duration and survival did not show any differences between the groups. Responding patients survived longer than patients with stationary and progressive disease. Median survival time was 72 months from diagnosis and 52 months from start of therapy, with no differences between the treatment groups. Toxicity of prednimustine was usually mild and similar to that of the two constituents. Treatment schedule C showed a slight advantage with regard to frequency of side effects. In conclusion, in this study the therapeutic effect of prednimustine was equal to that of its constituents administrated separately.

Prednimustine and vincristine compared with cytosine arabinoside and thioguanine for treatment of elderly patients with acute nonlymphoblastic leukemia.

Sixty-seven patients with acute nonlymphoblastic leukemia (ANLL) and above the age of 60 years were randomly allocated to treatment with either prednimustine + vincristine or cycles with cytosine arabinoside and thioguanine. Of the 67 patients, 13 (19%) entered a complete remission and four a partial remission. Of 33 patients randomized to prednimustine and vincristine (15 adequately treated), three entered a complete remission and one a partial remission. Four further patients went into complete remission after a switch to other treatment modalities. Of 34 patients randomized to cycles of ARA-C and thioguanine (22 adequately treated), four entered a complete remission and three a partial remission with the correct program. One patient entered a remission with intermittent cytosine arabinoside + thioguanine (wrong program) and one further patient entered a complete remission after a switch to prednimustine and vincristine. Prednimustine + vincristine did not appear to be superior to treatment with cytosine arabinoside thioguanine cycles for elderly patients with ANLL.

Comparison of daunorubicin and daunorubicin-DNA complex in the treatment of acute nonlymphoblastic leukemia.

Sixty consecutive patients, 15-60 years old, with ANLL were divided randomly into three groups for induction treatment with one of the following regimens: R1, daunorubicin (DNR) 1.5 mg/kg on day 1 + ARA-C 2 mg/kg body weight on days 1-5; R2, DNR 1.5 mg/kg on days 1 and 2 + ARA-C 2 mg/kg on days 4-8; R3, DNR-DNA complex 1.5 mg/kg on days 1 and 2 + ARA-C 2 mg/kg on days 4-8. Maintenance treatment consisted of monthly courses of DNR 1.5 mg/kg (R1, R2) or DNR-DNA 1.5 mg/kg (R3) combined with ARA-C 1 mg/kg on days 1-5, alternating with thioguanine 2 mg/kg PO on days 1-5 combined with ARA-C 1 mg/kg IV on days 1-5. Fourteen patients of 20 went into complete remission with R1, 13 or 18 with R2, and 15 of 22 with R3. The overall remission frequency was 70% and there was no significant difference between the different groups. The median time in first remission and the median survival time were 300 and 510 days, respectively, with R1; 335 and 495 days with R2; and 295 and 677 days with R3. There was no statistically significant difference between the groups treated according to the different regimens concerning the time in first remission. Survival was slightly better with R3 than with R1. Treatment with the DNR-DNA complex caused less pronounced thrombocytopenia and fewer 'minor' cardiac abnormalities than treatment with free DNR in the same dosage schedule.