Comparison of busulphan, hydroxyurea and allogeneic bone marrow transplantation (BMT) in chronic myeloid leukaemia: BMT prolongs survival.
BACKGROUND
Whether busulphan-treated patients develop blastic transformation earlier than hydroxyurea treated has been a controversial issue. In a randomised prospective study, we examined the busulphan versus hydroxyurea influence on time to blast crisis and on survival. When we opened our study in 1984, the clinical benefit of allogeneic bone marrow transplantation (BMT) was not well known; to follow up the long-time outcome of this treatment was therefore of great interest.


METHODS
Previously untreated CML patients were randomly started on either hydroxyurea (30 mg/kg/day) or busulphan (0.1 mg/kg/day). The end points of the study were overall survival and time to blast crisis. A total of 26 patients subsequently underwent BMT.


RESULTS
A total of 179 patients were randomised, 90 of hydroxyurea, and 89 to busulphan treatment. There was no significant difference in survival between hydroxyurea- and busulphan-treated patients (P = 0.46); median survival was 3.5 and 3.2 years, respectively. In all, 85 of the patients were subsequently diagnosed with blast crisis, 41 in the busulphan and 44 in the hydroxyurea group. There was no significant difference between the two groups (P = 0.91). The 26 patients who were allotransplanted survived significantly longer than those who were not transplanted (P = 0.0001). The 5-year-survival rates were 50 and 22% and the 10-year-survival rates were 46 and 2%, respectively. The median survival was 4.7 years for the transplanted and 3.3 years for the nontransplanted patients.


CONCLUSIONS
We did not find any difference between hydroxyurea and busulphan treatment, either in overall survival or in blast crisis-free survival; transplanted patients survived significantly longer than nontransplanted patients.
Olsson-Strömberg
Ulla
U
Department of Medicine, University Hospital, Uppsala, Sweden. ulla.olsson.stromberg@medicin.uas.lul.se
Simonsson
Bengt
B
Ahlgren
Tomas
T
Björkholm
Magnus
M
Carlsson
Karin
K
Gahrton
Gösta
G
Hast
Robert
R
Löfvenberg
Eva
E
Linder
Olle
O
Ljungman
Per
P
Malm
Claes
C
Paul
Christer
C
Rödjer
Stig
S
Turesson
Ingemar
I
Udén
Ann-Mari
AM
Wahlin
Anders
A
Killander
Andreas
A
Wadman
Bengt
B
Westin
Jan
J
Vikrot
Olle
O
Zettervall
Olle
O
Oberg
Gunnar
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D002066:Busulfan; D006918:Hydroxyurea