Trisomy 20q13 --> 20qter in a girl with multiple congenital malformations and a recombinant chromosome 20 inherited from a paternal inversion (20)(p13q13.1): clinical report and review of the trisomy 20q phenotype

We report on a patient with a rec(20)dup(20q) chromosome abnormality derived from a paternal chromosome 20 inversion [inv(20)(p13q13.1)]. The rearrangement results in a duplication of 20q13.1 to 20qter and a deletion of 20p13 to 20pter. The patient is a girl with craniofacial features and multiple congenital malformations that overlap with the abnormalities previously described in trisomy 20q syndrome. To our knowledge this is the first report of a patient with rec(20)dup 20q.     

Urgent desensitization in patients bridged to heart transplantation under extracorporeal membrane oxygenation support: A preliminary experience

Antihuman leukocyte antigen (HLA) antibodies restrict the access to cardiac allografts. Desensitization therapy is a major challenge in patients with cardiogenic shock waiting for urgent heart transplantation (HT). We retrospectively reviewed six patients (mean age of 37.5 years [16–70]) who underwent plasmapheresis (PP) under extracorporeal membrane oxygenation (ECMO) before transplant between January 2017 and September 2018. The average duration of follow‐up was 25 months [20–32]. Mean fluorescence intensity (MFI) of HLA‐specific antibodies was reported as follows: score 4 for MFI < 1000, score 6 for 1000 < MFI < 3000 and score 8 for MFI > 3000. The mean duration of ECMO support was 29 days [1–74] and 6.8 [1–29] PP sessions were performed per patient before transplant. The mean number of HLA‐specific antibodies before HT was 9.6 for score 6 [4–13] and 5.8 for score 8 [1–12]. Four patients had major complications after transplantation (2 hemorrhagic shocks, 5 infectious events). Mean MFI reduction rate was 94% [79–100] for Class I and 44.2% for Class II [0–83]. Hospital survival was 100%, and early antibody‐mediated rejection was diagnosed in one patient at 7 days after HT. Plasmapheresis under ECMO support was associated with favorable early outcomes in highly sensitized candidates for urgent heart transplantation.     

Approval summary: Docetaxel in combination with prednisone for the treatment of androgen-independent hormone-refractory prostate cancer.

PURPOSE: Docetaxel, a taxane previously approved for the treatment of breast cancer and non-small cell lung cancer, was approved by the United States Food and Drug Administration on May 19, 2004 for use in combination with prednisone for the treatment of metastatic androgen-independent (hormone-refractory) prostate cancer. The purpose of this summary is to review the database supporting this approval. EXPERIMENTAL DESIGN: In a randomized, global study enrolling 1,006 patients, two schedules of docetaxel were compared with mitoxantrone + prednisone as follows: MTZ q 3w, mitoxantrone 12 mg/m2 every 21 days + prednisone 5 mg twice a day for a total of 10 cycles; TXT q 3w, docetaxel 75 mg/m2 every 21 days + prednisone 5 mg twice a day for a total of 10 cycles; and TXT qw, docetaxel 30 mg/m2 days 1, 8, 15, 22, and 29 every 6 weeks + prednisone 5 mg twice a day for a total of 5 cycles. RESULTS: There was a statistically significant overall survival advantage shown for the TXT q 3w arm over MTZ q 3w (median survival 18.9 months versus 16.5 months, P = 0.0094). No overall survival advantage was shown for TXT qw compared with MTZ q 3w. The most commonly occurring adverse events included anemia, neutropenia, infection, nausea, sensory neuropathy, fluid retention, alopecia, nail changes, diarrhea, and fatigue. CONCLUSIONS: This report describes the Food and Drug Administration review supporting this first approval of a combination therapy for hormone-refractory prostate cancer based on demonstration of a survival benefit.     

Preclinical evaluation of 2-[4-(7-chloro-2-quinoxalinyloxy)phenoxy]-propionic acid as a modulator of etoposide in human Waldenstrom's macroglobulinemia xenograft model.

We have previously reported that XK469 (2-[4-(7-chloro-2-quinoxalinyloxyphenoxy]-propionic acid) enhances topo IIalpha expression in WSU-WM cells in vitro [E. Mensah-Osman et al., Mol. Cancer Ther., 1: 1321-1326, 2002]. To test the hypothesis that XK469-induced expression of topo IIalpha sensitizes WSU-WM cells to the topo IIalpha inhibitor etoposide (VP-16), we investigated the antitumor effects of XK469 and VP-16 in vivo, using the WSU-WM SCID xenograft model. Individual dosages of XK469 at 20-60 mg/kg/injection i.v. for a maximum-tolerated dose of 240 mg/kg were achievable in SCID mice. Simultaneous administration of a subtherapeutic dose of XK469 (20 mg/kg) and VP-16 at its maximum-tolerated dose of 15 mg/kg proved to be highly toxic and lethal. However, daily sequential treatment of XK469 given i.v. via tail vein at 20 mg/kg for a total of 120 mg/kg, followed 7 h later by VP-16 i.p. at 15 mg/kg for a total of 90 mg/kg, had no significant toxicity in SCID mice. The sequential treatment was associated with enhanced antitumor activity. Tumor growth inhibition T/C, tumor growth delay T-C, and log(10) kill for XK469 alone were 61%, 3 days and 0.46; VP-16 alone 6%, 12 days and 1.83, respectively; whereas the sequential administration of both agents gave a T/C value of 0%, T-C value of 23 days and a log(10) kill of 3.5. On the basis of these animal results, we conclude that the sequential treatment of WSU-WM tumors with XK469 and VP-16 was highly active. The study supports our in vitro observation that XK469 potentiates VP-16 activity. The sequential use of both agents resulted in clinically significant antitumor activity in the WM model.