Lineage Classification of Childhood Acute Lymphoblastic Leukemia according to the EGIL Recommendations: Results of the ALL-BFM 2000 Trial

 

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Abstract

Background:

Flow cytometry immunophenotyping (FCM) is an undispensable tool for the diagnosis and for the treatment stratification of childhood acute lymphoblastic leukemia. The correlation of the EGIL-classification with prognostically relevant parameters like age, prednisone response and risk group is analyzed.

Patients:

Between March 2000 and June 2009 12 patients less than 1 year of age, 1 836 patients with 1 to less than 6 years, 620 patients with 6 to less than 10 years, 615 patients with 10 to less than 15 years and 275 patients with 15 to less than 19 years were analyzed with a comprehensive 4-color antibody panel and classified according to the EGIL recommendations.

Methods:

Bone marrow or peripheral blood mononuclear cells were isolated by ficoll gradient centrifugation, washed and stained with fluorochrome-conjugated antigen-specific monoclonal antibodies. Cell preparations were acquired and analyzed on a flow cytometer.

Results:

Centralized FCM was performed for 2 775 patients (82.6%) with B-cell precursor acute lymphoblastic leukemia, 493 patients (14.7%) with T-cell acute lymphoblastic leukemia and 90 patients (2,7%) with biphenotypic acute leukemia. There was a slight overall predominance of male (56.1%) over female (43.9%) patients. Patients with B-cell precursor ALL had a slightly more favourable outcome with a 10y pEFS of 78±1.0%, compared to patients with a T-ALL or BAL (biphenotypic acute leukemia) phenotype with a 10y pEFS of 74±1.8% (n.s.) or 69±9.0% (p<0.009), respectively.

Conclusions:

FCM according to the EGIL recommendations not only provides diagnostic lineage determination and subclassification but also enables an initial prognostic orientation before MRD (minimal residual disease)-based risk stratification becomes available.

Zusammenfassung

Die Immunphänotypisierung mittels Durchflusszytometrie ist für die Diagnose und Risiko­stratifizierung ein unverzichtbarer Bestandteil der initialen Diagnostik bei akuten Leukämien. Die Korrelation der von der EGIL vorgeschlagenen Linienzuordnung und Subklassifizierung von akuten lymphatischen Leukämien mit dem Geschlecht, dem Alter, der Prednison-Antwort und der Risikozuordnung wurde analysiert. Zwischen März 2000 und Juni 2009 wurden 12 Patienten im ersten Lebensjahr, 1 836 Patienten im Alter von 1 bis 6 Jahren, 620 Patienten zwischen 6 und 10 Jahren, 615 Patienten zwischen 10 und 15 Jahren und 275 Patienten im Alter zwischen 15 und 18 Jahren zum Zeitpunkt der Diagnose untersucht. Die mononukleären Zellen dieser Patienten wurden mittels Ficoll-Gradientenzentrifugation isoliert, gewaschen und mit antigenspezifischen, Fluorochrom-konjugierten monoklonalen Antikörpern markiert und an einem Durchflusszytometer gemessen und analysiert. Die zentrale Durchflusszytometrie ergab bei 2 775 Patienten die Diagnose einer BCP-ALL (82.6%), bei 493 Patienten die Diagnose einer T-ALL (14.7%) und bei 90 Patienten die einer biphänotypischen akuten Leukämie (2.7%). Der Anteil männlicher Patienten war mit 56.1% etwas größer als der der weiblichen Patientinnen. Patienten mit BCP-ALL hatten die größte Wahrscheinlichkeit eines ereignisfreien-Überlebens nach 10 Jahren (pEFS) mit 78±1,0%, im Vergleich zu Patienten mit T-ALL (74±1,8%; n.s.) oder BAL (69±9,0%; p<0.009).

Schlussfolgerung:

Die EGIL – Klassifikation stellt nicht nur eine zuverlässige Linienzuordnung und Subklassifizierung akuter lymphatischer Leukämien sicher, sondern gibt auch eine prognostische Zuordnung bevor die MRD-basierte Risikostratifizierung im weiteren Erkrankungsverlauf möglich wird.

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