A randomized trial of three novel regimens for recurrent acute myeloid leukemia demonstrates the continuing challenge of treating this difficult disease.

To improve the outcome of relapsed/refractory acute myeloid leukemia (AML), a randomized phase II trial of three novel regimens was conducted. Ninety patients were enrolled and were in first relapse or were refractory to induction/re-induction chemotherapy. They were randomized to the following regimens: carboplatin-topotecan (CT), each by continuous infusion for 5 days; alvocidib (formerly flavopiridol), cytarabine, and mitoxantrone (FLAM) in a timed sequential regimen; or sirolimus combined with mitoxantrone, etoposide, and cytarabine (S-MEC). The primary objective was attainment of a complete remission (CR). A Simon two-stage design was used for each of the three arms. The median age of the patients in the FLAM arm was older at 62 years compared with 55 years for the CT arm and the S-MEC arm. The overall response was 14% in the CT arm (5/35, 90% CI 7%-35%), 28% in the FLAM arm (10/36, 90% CI, 16%-43%), and 16% in the S-MEC arm (3/19, 90% CI, 4%-36%). There were nine treatment-related deaths, seven of which occurred in the FLAM arm with four of these in elderly patients. We conclude that the FLAM regimen had an encouraging response rate and should be considered for further clinical development but should be used with caution in elderly patients.

Organ-Derived Decellularized Extracellular Matrix: A Game Changer for Bioink Manufacturing?

The extracellular matrix (ECM) comprises a complex milieu of proteins and other growth factors that provide mechanical, biophysical, and biochemical cues to cells. The ECM is organ specific, and its detailed composition varies across organs. Bioinks are material formulations and biological molecules or cells processed during a bioprinting process. Organ-derived decellularized ECM (dECM) bioinks have emerged as arguably the most biomimetic bioinks. Here, we review bioinks derived from different decellularized organs, the techniques used to obtain these bioinks, and the characterization methods used to evaluate their quality. We emphasize that obtaining a good-quality bioink depends on the choice of organ, animal, and decellularization method. Finally, we explore potential large-scale applications of bioinks and challenges in manufacturing such bioinks.