Immunotherapy with CD25/CD71-allodepleted T cells to improve T-cell reconstitution after matched unrelated donor hematopoietic stem cell transplant: a randomized trial.

BACKGROUND AIMS: Delayed immune reconstitution is a major challenge after matched unrelated donor (MUD) stem cell transplant (SCT). In this randomized phase 2 multi-center trial, Adoptive Immunotherapy with CD25/71 allodepleted donor T cells to improve immunity after unrelated donor stem cell transplant (NCT01827579), the authors tested whether allodepleted donor T cells (ADTs) can safely be used to improve immune reconstitution after alemtuzumab-based MUD SCT for hematological malignancies. METHODS: Patients received standard of care or up to three escalating doses of ADTs generated through CD25+/CD71+ immunomagnetic depletion. The primary endpoint of the study was circulating CD3+ T-cell count at 4 months post-SCT. Twenty-one patients were treated, 13 in the ADT arm and eight in the control arm. RESULTS: The authors observed a trend toward improved CD3+ T-cell count at 4 months in the ADT arm versus the control arm (230/µL versus 145/µL, P = 0.18), and three ADT patients achieved normal CD3+ T-cell count at 4 months (>700/µL). The rates of significant graft-versus-host disease (GVHD) were comparable in both cohorts, with grade ≥2 acute GVHD in seven of 13 and four of eight patients and chronic GVHD in three of 13 and three of eight patients in the ADT and control arms, respectively. CONCLUSIONS: These data suggest that adoptive transfer of ADTs is safe, but that in the MUD setting the benefit in terms of T-cell reconstitution is limited. This approach may be of more use in the context of more rigorous T-cell depletion.

Relationship between physician supply and breast cancer survival: a geographic approach.

Breast cancer is the most common cancer in women, accounting for nearly 30% of all female cancers. Breast cancer is the second leading cause of cancer mortality in women in the US. During the last two decades, the benefits of early detection, early intervention, and postoperative treatment have resulted in decreased breast cancer mortality in the US general population. However, the distribution of breast cancer mortality varies among geographic regions of the US. The reasons for this variation remain largely unknown. We choose to look for a possible association between the numbers of physicians in each city within the State of Florida and breast cancer survival among women aged 40+ residing in that particular city. Using Cox Proportionate Hazard Modeling, we found a direct association between the number of physicians practicing in a particular city and breast cancer survival in that particular city (P=0.0153), while controlling for other known risk factors affecting survival. To our knowledge, this is the first study to report an association between physician supply and cancer survival within defined geographic areas. This association shows as physician density consistently dropped in a defined geographic area so did time of survival among women with breast cancer.