In vivo response to remission induction poly-chemotherapy in NOD/SCID/huALL reflects patient risk and outcome

V Münch; N Hasan; M Schirmer; S Mirjam Eckhoff; KM Debatin; LH Meyer

doi:10.1055/s-0034-1374834

Klinische Pädiatrie, Inhaltsverzeichnis

In vivo response to remission induction poly-chemotherapy in NOD/SCID/huALL reflects patient risk and outcome

V Münch ¹, N Hasan ¹, M Schirmer ¹, S Mirjam Eckhoff ¹, KM Debatin ¹, LH Meyer ¹

¹Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany

Abstract

As novel therapeutics are urgently needed for treating acute lymphoblastic leukemia (ALL) we established a poly-agent chemotherapy regimen in our NOD/SCID/huALL xenograft model investigating its effectivity on different patient-derived xenograft (pdx) ALL samples, which further can be used to evaluate novel substances in combination modalities.

ALL carrying recipients receiving multi-agent chemotherapy showed a significant delay of post-treatment leukemia reoccurrence compared to vehicle-treated controls in 6 pdx ALL samples and even induced long-term remission in one sample within 30 weeks of monitoring.

Previously, we associated a short/long time to leukemia engraftment (TTL^short/TTL^long) of diagnostic ALL cells with early/late relapse. VDA treated TTL^short pdx ALLs also displayed a significantly shorter time to leukemia reoccurrence compared to TTL^long pdx ALL samples.

In summary, our xenograft model can be used for applying an effective remission induction therapy protocol thereby combining the evaluation of novel substances in a preclinical setting, which links in vivo treatment response of pdx ALL samples to patient outcome, tightly reflecting ALL characteristics in our model.