12th Congress of the European Hematology ... - Haematologica

12 th Congress of the European Hematology Association
Presidential Symposium: six best abstracts
0441
PRIMARY ALLOGENEIC STEM CELL TRANSPLANTATION VERSUS BEST AVAILABLE DRUG
TREATMENT IN CHRONIC MYELOID LEUKEMIA
R. Hehlmann, 1 T. Lahaye, 1 M. Pfirrmann, 2 A. Hochhaus, 1
M.C. Müller, 1 A. Reiter, 1 J. Hasford, 2 H.J. Kolb, 3 H. Heimpel, 4
D.K. Hossfeld, 5 A. Gratwohl, 6 Germany and the German CML Study
Group1 1 Medizinische Fakultät Mannheim, MANNHEIM, Germany; 2 IBE, LMU
München, MÜNCHEN, Germany; 3 Medizinische Klinik III, LMU München,
MÜNCHEN, Germany; 4 Universität Ulm, ULM, Germany; 5 Universität Hamburg,
HAMBURG, Germany; 6 Kantonsspital Basel, BASEL, Switzerland
Early allogeneic hematopoietic stem cell transplantation (HSCT) has
been proposed as primary treatment modality for patients (pts) with
chronic myeloid leukemia (CML). This concept has been challenged by
persisting transplantation mortality and improved drug therapy. In order
to verify retrospective results, a randomized controlled trial was
designed to compare primary HSCT and best available drug treatment
in a cohort of 621 newly diagnosed CML pts in chronic phase. Assignment
to treatment strategy was by eligibility for HSCT and genetic randomization
according to availability of a matched related donor. Evaluation
followed the intention to treat principle. 354 pts (62% male; median
age 40 years, range 11-59) were eligible and randomized. 135 pts
(38%) had a matched related donor of which 123 (91%) received a transplant
within a median of 10 months (range 2-106) from diagnosis. 4 pts
died before scheduled transplantation, 8 pts withdrew consent. 219 pts
(62%) had no related donor and received best available drug treatment.
Of these, 97 pts (44%) received a matched unrelated donor (MUD) transplant
in 1st chronic phase and were censored at the time of transplantation.
As 1st line treatment after randomization pts received interferon
alpha based therapy. In the course of the study a total of 197 pts
were switched to imatinib after failure of interferon alpha. Currently 31
(57%) of 54 living pts of the drug treatment group receive imatinib or
2nd generation tyrosine kinase inhibitors (dasatinib n=2, nilotinib n=1).
With a median observation time of 8.9 (4.2-11.2) years median survival
of all 621 pts was 8.1 years. During the first 8 years after diagnosis survival
curves of drug treated patients were superior to those of transplanted
patients reflecting transplant-related mortality. Beyond 8 years
survival curves were no longer distinct. 5 (10) year survival was 62%
(53%) for transplanted and 73% (52%) for drug treated pts, in the low
risk group 68% (59%) for transplanted and 85% (62%) for drug treated
pts, respectively. Survival was superior for drug treated pts up to the cutpoint
of survival curves at year 8 (p=0.041) and during the study period
up to 11 years from diagnosis (p=0.049), particularly so in low risk pts
(p=0.027 to cutpoint, p=0.032 overall). Significantly higher proportions
of complete cytogenetic remissions (91% vs 48%, p=0.002) and of major
molecular responses (ratio BCR-ABL/ABL