Klin Padiatr 2014; 226 - A13
DOI: 10.1055/s-0034-1374834

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

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 (TTLshort/TTLlong) of diagnostic ALL cells with early/late relapse. VDA treated TTLshort pdx ALLs also displayed a significantly shorter time to leukemia reoccurrence compared to TTLlong 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.