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C. Paul,
U. Tidefelt,
G. Gahrton,
M. Björkholm,
M. Järnmark,
A. Killander,
E. Kimby,
J. Liliemark,
A. Lindeberg,
R. Lindquist, [......],
J. Palmblad,
C. Peterson,
B. Simonsson,
A.-M. Stalfelt,
C. Sundström, B. Wadman,
C. Wedelin,
A. M. Udén,
G. Öberg,
Å. öst
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ABSTRACT: 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.
06/2009; 3(5-6):355-364.
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ABSTRACT: 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.
Leukemia Research 11/1994; 18(10):783-90. · 2.92 Impact Factor
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ABSTRACT: 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.
Quality assurance in health care: the official journal of the International Society for Quality Assurance in Health Care / ISQA 10/1993; 5(3):201-11.
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A. Österborg,
A. Ahre,
M. Björkholm,
M. Björeman,
G. Brenning,
G. Gahrton,
H. Gyllenhammar,
B. Johansson,
G. Juliusson,
M. Järnmark, [......],
B. Simonsson,
A.-M. Stalfelt,
H. Strander,
B. Smedmyr,
E. Svedmyr,
A.-M. Udén, B. Wadman,
C. Wedelin,
Ph.D. H. Mellstedt M.D,
H. Mellstedt
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ABSTRACT: 86 previously untreated patients with multiple myeloma stage III entered a randomized trial comparing combination chemotherapy (VMCP/VBAP) (n = 42) with intermittent oral melphalan and prednisone (MP) treatment (n = 44). The treatment gropus were well comparable with regard to major prognostic factors. There was no statistically significant difference in the response rates, 52% (VMCP/VBAP) vs 61% (MP); in the response duration times, median 19 months vs 22 months, or in the survival times, median 24 months vs 28 months. However, survival of patients older than 65 years was significantly shorter in the VMCP/VBAP group (median 15 months) compared to the MP group (median 23 months) (p = 0.03). No significant difference in non-hematological or hematological toxicity was noted. The study further supports the notion that MP therapy should be used as primary standard treatment for patients with multiple myeloma.
European Journal Of Haematology 06/1989; 43(1):54 - 62. · 2.61 Impact Factor
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A Ahre,
M Björkholm,
H Mellstedt,
G Holm,
G Brenning,
L Engstedt,
G Gahrton,
J Hällen,
B Johansson,
S G Johansson,
L Karnström,
A Killander,
R Lerner,
D Lockner,
B Lönnqvist,
B Simonsson,
A M Stalfelt,
B Ternstedt, B Wadman
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ABSTRACT: 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.
European Journal of Cancer and Clinical Oncology 05/1983; 19(4):499-506.
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K Ideström,
E Kimby,
M Björkholm,
H Mellstedt,
L Engstedt,
G Gahrton,
B Johansson,
D Killander,
K H Robérts,
A M Stalfelt,
A M Udén, B Wadman,
S Wählby
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ABSTRACT: 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.
European Journal of Cancer and Clinical Oncology 12/1982; 18(11):1117-23.
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B Lönnqvist,
B Andersson,
M Björkholm,
L Engstedt,
G Gahrton,
R Hast,
G Holm,
A Killander,
B Lantz,
D Lockner,
H Mellstedt,
J Palmblad,
C Paul,
C Peterson,
B Simonsson,
A M Stalfelt,
A M Udén, B Wadman,
G Oberg
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ABSTRACT: 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.
Cancer Chemotherapy and Pharmacology 02/1982; 9(2):89-92. · 2.83 Impact Factor
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C Paul,
M Björkholm,
I Christenson,
L Engstedt,
G Gahrton,
R Hast,
G Holm,
A Killander,
B Lantz,
D Lockner,
B Lönnqvist,
H Mellstedt,
J Palmblad,
C Peterson,
B Simonsson,
A M Stalfelt,
A M Udén, B Wadman,
G Oberg
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ABSTRACT: 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.
Cancer Chemotherapy and Pharmacology 02/1981; 6(1):65-73. · 2.83 Impact Factor
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G Gahrton,
M Björkholm,
G Brenning,
I Christenson,
L Engstedt,
S Franzén,
B Gullbring,
G Holm,
C Högman,
P Hörnsten, [......],
H Mellstedt,
J Palmblad,
C Paul,
C Pauli,
C Peterson,
P Reizenstein,
B Simonsson,
K O Skårberg,
A M Udén, B Wadman
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ABSTRACT: Forty-four adult patients under 60 years of age with acute nonlymphoblastic leukemia were randomized for induction treatment with one of the following three regimens: R 1 = courses of daunorubicin on day 1 + ARA-C on days 1--5; R 2 = courses of daunorubicin on days 1 and 2 + ARA-C on days 4--8; R 3 = courses of daunorubicin-DNA complex on days 1--2 + ARA-C on days 4--8. Out of 14 patients, 9 went into remission on R 1, 6 out of 14 on R 2, and 8 out of 16 on R 3. The preliminary results suggest that daunorubicin-DNA complex has the same efficacy for inducing remission as daunorubicin alone, if the same time intervals and dosages are used.
Cancer Chemotherapy and Pharmacology 02/1979; 2(1):73-6. · 2.83 Impact Factor
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ABSTRACT: In order to study the effect of oxymetholone therapy in advanced myelofibrosis, 11 patients (4 females, 7 males) were given, 3--5 mg per kg body weight, long-term oxymetholone treatment in a prospective multicenter study. Five cases had previously had a diagnosis of polycythemia vera. All patients had anemia initially, 4 leukocytopenia and 10 thrombocytopenia in addition. Hepato-splenomegaly was present in all cases but in varying degree. Five patients required regular blood transfusions before treatment. In 9 of the 15 courses given, there was normalization of the peripheral blood or substantial improvement (better than 3 g hemoglobin/dl or 50 X 10(9) platelets/1) after androgens. Significant effects were noted both on hemoglobin values and platelet counts. The need for blood transfusions ceased completely in all 5 cases. When oxymetholone treatment was reduced or interrupted 4 patients relapsed; 2 of them responded to a renewed course. The red cell counts returned to previous polycythemic values in one patient and another died from acute leukemia. The results of this study suggest that androgens might be of value in advanced cases of myelofibrosis with transfusion-requiring anemia or severe thrombocytopenia.
Blut 08/1978; 37(1):19-26.
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Ch. S-n Lindemalm,
A. Killander,
M. Björkholm,
G. Brenning,
L. Engstedt,
S. Franzén,
G. Gahrton,
B. Gullbring,
G. Holm,
S. Höglund, [......],
B. Lönnqvist,
H. Mellstedt,
J. Palmblad,
C. Pauli,
P. Reizenstein,
B. Simonsson,
K. -O. Skårberg,
A. -M. Udén,
F. Vanky, B. Wadman
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ABSTRACT: Of 112 patients (maximum age 70 years) with acute nonlymphocytic leukemia, 62 (55%) went into remission on an induction therapy of cytosine arabinoside and daunorubicin. 20 patients were randomized for maintenance treatment consisting of chemotherapy only and 22 patients for combined chemo-immunotherapy. The chemotherapy consisted in 5-day courses of daunorubicin and cytosine arabinoside and of thioguanine and cytosine arabinoside, alternating every month. The chemo-immunotherapy group also received weekly intracutaneous injections of 109 allogeneic nonirradiated leukemic myeloblasts and 106 BCG organisms (Glaxo) by Heaf gun.The median duration of the first remission was 164 days for the chemotherapy group and 464 days for the chemo-immunotherapy group. The corresponding median times of survival were 344 days for the first group and 734 days for the second group. The difference concerning median duration of survival is statistically significant. Thus immunotherapy seems to prolong survival.
Cancer Immunology and Immunotherapy 07/1978; 4(3):179-183. · 3.70 Impact Factor
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ABSTRACT: This is a prospective multi-center study in which patients with aregenerative anaemia were treated with a standardized high dosage regime of an anabolic steroid (oxymetholone, Anasteron). 53 patients were included and divided into two groups according to bone marrow cellularity. Furthermore the hypocellular group was subdivided in order to make comparison with earlier studies possible. In the hypocellular group, the frequency of remission was 56% and the 2-year-survival from the onset of symptoms was 75%. This is longer than in some earlier studies, perhaps because of possible differences in etiology and/or because of the effect of systematic high dosage, long term androgen therapy. Patient selection was minimized and was not considered to be of major importance. Patients with hypercellular marrows, on the other hand, responded poorly to androgens. In this group 63% died of acute leukaemia, which confirms earlier suggestions that this form of aregenerative anaemia, frequently is of a preleukaemic nature.
Scandinavian journal of haematology 03/1976; 16(2):90-100.
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D Killander,
A Dohlwitz,
L Engstedt,
S Franzén,
G Gahrton,
B Gullbring,
G Holm,
A Holmgren,
S Höglund,
A Killander, [......],
H Mellstedt,
P J Moe,
J Palmblad,
P Reizenstein,
K O Skårberg,
B Swedberg,
A M Udén, B Wadman,
L Wide,
L Ahström
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ABSTRACT: One hundred and fourteen patients with acute leukemia, 57 children (10 AML and 47 ALL) and 57 adults (37 AML and 20 ALL) were treated with L-asparaginase (Asnase) 200 or 1000 IU/kg daily for 30 days unless withdrawn on account of side effects. Combinations with other cytotoxic drugs were used in all but eight patients. Hypersensitive reactions, decrease in Asnase activity in plasma, and bivalent antibodies to Asnase appeared more frequently in adults (28%, 46%, and 79%, respectively) than in children (16%, 17%, and 25% respectively). There was a clear association between these three parameters. Thus hypersensitive reactions generally developed at the time of or after the decrease in plasma Asnase activity. Antibodies were detected only where Asnase activity had disappeared from the plasma. This time sequence, and in vitro experiments, suggest the formation of antigen-antibody complexes which might be responsible for inactivation of Asnase and for the development of hypersensitive reactions. However in many cases antibodies were found without concomitant enzyme inactivation or hypersensitive reactions. Antibodies to Asnase of IgE type (reagins) were found in only 10 children and 6 adults. There was no correlation between hypersensitive reactions, decrease in Asnase activity, and IgE antibodies. The frequency of remission among patients developing bivalent antibodies to Asnase was 68% (13/19) in contrast to 27% (3/11) among patients whose sera contained no detectable antibodies to Asnase, but the difference was not statistically significant.
Cancer 02/1976; 37(1):220-8. · 4.77 Impact Factor
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A M Udén,
G Brenning,
L Engstedt,
S Franzén,
G Gahrton,
B Gullbring,
G Holm,
S Höglund,
S Jameson,
A Killander,
D Killander,
D Lockner,
H Mellstedt,
J Palmblad,
P Reizenstein,
K O Skårberg,
B Swedberg, B Wadman,
L Wide
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ABSTRACT: 77 unselected adult patients with acute myeloblastic leukaemia (AML), including practically all AML patients from an area with 1.9 million inhabitants, were randomized for either (1) 5 days pretreatment with 1-asparaginase and prednisolone followed by a combination of rubidomycin and cytosine arabinoside (ARAP), or (2) treatment with a combination of rubidomycin, cytosine arabinoside and prednisolone without 1-asparaginase pretreatment (RAP). Complete remission was induced with ARAP in 12 patients (31%) and with RAP in 13 patients (34%). Thus pretreatment with 1-asparaginase did not improve the therapeutic response. The overall remission frequency was significantly higher below the age of 60; 50% compared to 13% above this age. Side-effects such as liver dysfunction, nausea and vomiting were more common in patients pretreated with 1-asparaginase. Sterilization of the gut did not improve the remission frequency with either regime.
Scandinavian journal of haematology 09/1975; 15(1):72-80.
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Acta Haematologica 02/1973; 49(6):321-30. · 1.35 Impact Factor
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Blut 09/1971; 23(2):61-8.
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Nordisk medicin 08/1971; 86(27):835.
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ABSTRACT: 45 patients with hypoproliferative or aregenerative anaemia were treated with oxymetholone, steroid an anabolic, androgenic steroid. Minimum treatment time accepted for entrance into the study was 3 months. Therapeutic effect was assessed by effect on bone marrow cellularity, haemoglobin concentration and granulocyte and platelet counts. Patients with a hypocellular marrow responded best. Of 18 cases, a partial remission was seen in 8 and a complete remission in 5. A complete remission was only seen in patients who did not have pancytopenia. Of the 7 patients with myelofibrosis, 4 had thrombocytopenia at the outset. Improvement after treatment was seen in all 4. The only serious side-effect that necessitated withdrawal of treatment was jaundice.
Acta Haematologica. 08/1970; 49(6):321-330.
