Summary.
Background: One of the strongest predictive
factors for therapy outcome in childhood acute lymphoblastic leukaemia (ALL),
treated according to ALL-BFM protocols, is the response to initial prednisone
treatment. Prednisone response is characterized by the peripheral leukaemic
blast count. The threshold value for the characterisation as good or poor
prednisone response is 1000 blasts/μl on day eight of initial
prednisone treatment. It is frequently being discussed, whether patients with
ALL that initially present with < 1000 blasts/μl and still
show < 1000 blasts/μl by day eight of treatment, have the
same therapy outcome as prednisone good-responders with initially
≥ 1000 blasts/μl. Patients and methods: We
evaluated all patients included in the ALL-BFM 90 study showing good prednisone
response. This group included 660 patients presenting with
< 1000 blasts/μl at diagnosis. We compared these patients
with the prednisone good-responders that initially presented with
≥ 1000 blasts/μl. In addition we analysed all patients who
showed an increasing blast count within the threshold of
1000 blasts/μl by day eight of treatment. Results: Children presenting with ALL and
< 1000 blasts/μl at diagnosis showed a small but
significantly better outcome than prednisone good-responders with initially
≥ 1000 blasts/μl (5 year pEFS 0.86 vs. 0.81, P value
0.0064). If analyzed by treatment group, no significant differences were found.
Patients with < 1000 blasts/μl on day eight of treatment
but increasing blast count from diagnosis until day eight did not perform
worse. Conclusion: The prognostic value of the
prednisone response is not restricted to childhood ALL patients presenting with
≥ 1000 blasts/μl at diagnosis, but retains its strength as
a strong predictor of treatment outcome also in patients with < 1000
blasts/μl at diagnosis.
Hintergrund: In den ALL-BFM-Studien zur
Behandlung der akuten lymphoblastischen Leukämie (ALL) im Kindesalter hat
sich der Prednison-Response als einer der stärksten prognostischen
Faktoren für das Therapieergebnis erwiesen. Der Prednison-Response wird
durch die Anzahl der peripheren leukämischen Blasten am achten Tag der
Therapie charakterisiert. Zur Klassifizierung des Prednison-Response in
Good-Responder oder Poor-Responder wird die absolute leukämische
Blastenzahl benutzt (< 1000/μl oder ≥ 1000/μl am
Therapietag 8). Eine häufig diskutierte Frage betrifft die prognostische
Wertigkeit des Prednison-Response in den ALL-Patienten, die schon initial
< 1000 Blasten/μl im peripheren Blut zeigen und auch am achten
Therapietag < 1000 Blasten/μl aufweisen. Patienten und Methoden: Alle Patienten mit
Prednison-Good-Response aus der Therapiestudie ALL-BFM 90 wurden evaluiert.
Diese Gruppe beinhaltete 660 Patienten, die bereits bei Diagnosestellung
< 1000 periphere Blasten/μl aufwiesen. Solche Patienten wurden
bezüglich des Therapieergebnisses mit jenen verglichen, die einen
Prednison-Good-Response zeigten, jedoch initial mehr als ≥ 1000
periphere Blasten/μl hatten. Weiterhin analysierten wir die Patienten, die
innerhalb der ersten Therapiewoche einen Blastenanstieg zeigten, der jedoch die
Grenze von 1000 Blasten/μl am Therapietag 8 nicht überschritt.
Ergebnisse: ALL-Patienten mit < 1000
Blasten/μl bei Diagnosestellung zeigten ein geringfügig besseres
Therapieergebnis im Vergleich zu Prednison-Good-Respondern mit initial
≥ 1000 Blasten/μl (5-Jahres-pEFS 0,86 vs. 0,81, p=0,0064).
In einer stratifizierten Analyse innerhalb der Risikogruppen zeigte sich jedoch
kein Unterschied. Patienten, die innerhalb der ersten Therapiewoche einen
Blastenanstieg zeigten, der die Grenze von 1000 Blasten/μl am Therapietag 8
nicht überschritt, zeigten kein schlechteres Therapieergebnis als andere
Prednison Good-Responder. Schlussfolgerung: Der
prognostische Wert des Prednison-Response gilt auch für Patienten mit
einer initialen peripheren leukämischen Blastenzahl von
< 1000/μl.
Key words
Leukaemia - leukemia - ALL - childhood - prednisone response - prognosis - event free survival - treatment response
Schlüsselwörter
Leukämie - ALL - Prednison-Response - Prognose - ereignisfreies Überleben - Therapieansprechen
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Melchior Lauten, M. D.
Department of Paediatric Haematology and
Oncology Children's Hospital Hannover Medical
School
Carl-Neuberg-Strasse 1
30625 Hannover
Germany
Telefon: Tel. (+ 49)
5 11-5 32-90 12
Fax: Fax (+ 49)
5 11-5 32-92 49
eMail: E-mail: lauten.melchior@mh-hannover.de