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Leukemic blasts from patients with acute phase chronic myeloid leukemic and refractory acute myeloid leukemia are highly resistant to a number of cytotoxic drugs. To overcome multi-drug resistance, we engineered a diphtheria fusion protein by fusing human interleukin-3 (IL3) to a truncated form of diphtheria toxin (DT) with a (G 4 S) 2 linker (L), expressed and purified the recombinant protein, and tested the cytotoxicity of the DTLIL3 molecule on human leukemias and normal progenitors. The DTLIL3 construct was more cytotoxic to interleukin-3 receptor (IL3R) bearing human myeloid leukemia cell lines than receptor-negative cell lines based on assays of cytotoxicity using thymidine incorporation, growth in semi-solid medium and induction of apoptosis. Exposure of mononuclear cells to 680 pM DTLIL3 for 48 h in culture reduced the number of cells capable of forming colonies in semi-solid medium (colony-forming units leukemia) у10-fold in 4/11 (36%) patients with myeloid acute phase chronic myeloid leukemia (CML) and 3/9 (33%) patients with acute myeloid leukemia (AML). Normal myeloid progenitors (colony-forming unit granulocytemacrophage) from five different donors treated and assayed under identical conditions showed intermediate sensitivity with three-to five-fold reductions in colonies. The sensitivity to DTLIL3 of leukemic progenitors from a number of acute phase CML patients suggests that this agent could have therapeutic potential for some patients with this disease. Leukemia (2000) 14, 576-585.

Background: Options for bilateral autologous breast reconstruction in thin women are limited. The aim of this study was to introduce a novel approach to increase abdominal flap volume with the stacked hemiabdominal extended perforator (SHAEP) flap. The authors describe the surgical technique and analyze their results. Methods: A retrospective study was conducted of all SHAEP flap breast reconstructions performed since February of 2014. Patient demographics, operative details, complications, and flap reexplorations were recorded. The bipedicled hemiabdominal flap was designed as a combination of the deep inferior epigastric artery perforator (DIEP) and a second, more lateral pedicle: the deep or superficial circumflex iliac perforator vessels, the superficial inferior epigastric artery, or a lumbar artery or intercostal perforator. Results: A total of 90 SHAEP flap breast reconstructions were performed in 49 consecutive patients. Median operative time was 500 minutes (range, 405 to 797 minutes). Median hemiabdominal flap weight that was used for reconstruction was 598 g (range, 160 to 1389 g). No total flap losses were recorded. Recipient-site complications included partial flap loss (2.2 percent), hematoma (3.3 percent), fat necrosis (2.2 percent), and wound problems (4.4 percent). Minor donor-site complications occurred in five patients (10.2 percent). Most flaps were harvested on a combination of the DIEP and deep circumflex iliac artery vessels. Conclusions: This study demonstrated that the SHAEP flap is an excellent option for bilateral autologous breast reconstruction in women who require significant breast volume but have insufficient abdominal tissue for a bilateral DIEP flap. The bipedicled SHAEP flap allows for enhanced flap perfusion, increased volume, and abdominal contour improvement using a single abdominal donor site. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.