RESUMEN
Selecting the most suitable alternative donor becomes challenging in severe aplastic anemia (SAA) when a matched sibling donor (MSD) is unavailable. We compared outcomes in SAA patients undergoing SCT from matched unrelated donors (MUD, n=1106), mismatched unrelated donors (MMUD, n=340), and haploidentical donors (Haplo, n=206) registered in the EBMT database (2012-2021). For Haplo-SCT, only those receiving post-transplant cyclophosphamide (PT-Cy) for graft-versus-host disease (GVHD) prophylaxis were included. Median age was 20 years, and the median time from diagnosis to transplantation 8.7 months. Compared to MUD, MMUD (HR, 2.93; 95% CI, 1.52-5.6) and Haplo (HR, 5.15; 95% CI, 2.5-10.58) showed significantly higher risks of primary graft failure. MUD had lower rates of acute GVHD compared to MMUD and Haplo, grade II-IV (13%, 22%, and 19%, respectively, p<0.001) and III-IV (5%, 9%, and 7%, respectively, p=0.028). The 3-year non-relapse mortality was 14% for MUD, 19% for MMUD, and 27% for Haplo (p<0.001), while overall survival (OS) and GVHD and relapse-free survival (GRFS) were 81% and 73% for MUD, 74% and 65% for MMUD, and 63% and 54% for Haplo, respectively (p<0.001). In addition to donor type, multivariable analysis identified other factors like patient age, performance status, and interval between diagnosis and transplant associated with GRFS. For SAA patients lacking an MSD, our findings support MUD transplantation as the preferable alternative donor. However, selecting between a MMUD or Haplo donor remains uncertain and requires further exploration.
RESUMEN
Phencyclidine (PCP) has been suggested to induce symptoms of schizophrenia. However, animal models using PCP administration have produced ambiguous results thus far. It seems that acute effects are similar to symptoms of schizophrenia, however, it is not clear if PCP can induce permanent behavioral changes that reflect schizophrenic-like symptoms. Therefore, we assessed the ability of chronic PCP administration (3mg/kg, 14 days) to induce short or long lasting behavioral changes in rats. Social behavior, including ultrasonic vocalizations and motivation for social contact were investigated at different time points, up to 29-36 days, after cessation of PCP treatment. During a social separation test, performed at 5 and 36 days, PCP treated rats spent less time near the divider that separates them from their familiar cage mate compared with saline (SAL) treated rats. Further, at short term, PCP was able to induce a decrease in social behavior. In contrast, at long-term, PCP treated animals spent more time in contact when exposed to an unfamiliar partner as compared to SAL treated rats. But, this difference was not observed when exposed to a familiar partner. We did not find any difference in ultrasonic vocalizations at all time points. The results of our study indicate that PCP is unable to induce overt long term deficits in social interaction behavior. Rather, it seems that PCP diminishes motivation for social contact. The long-term consequences of chronic PCP administration on social behavior in rodent models remain complex, and future studies addressing this are still needed.
