The two-step approach to allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) provides the only potentially curative option for multiple hematological conditions. However, allogeneic HSCT outcomes rely on an optimal balance of effective immune recovery, minimal graft-versus-host disease (GVHD), and lasting control of disease. The quest to attain this balance has proven challenging over the past few decades. The two-step approach to HSCT was conceptualized and pioneered at Thomas Jefferson University in 2005 and remains the main platform for allografting at our institution. Following administration of the transplant conditioning regimen, patients receive a fixed dose of donor CD3+ cells (HSCT step one-DLI) as the lymphoid portion of the graft on day -6 with the aim of optimizing and controlling T cell dosing. Cyclophosphamide (CY) is administered after the DLI (days -3 and -2) to induce donor-recipient bidirectional tolerance. On day 0, a CD34-selected stem cell graft is given as the myeloid portion of the graft (step two). In this two-step approach, the stem cell graft is infused after CY tolerization, which avoids exposure of the stem cells to an alkylating agent, allowing rapid count recovery. Here, the two-step platform is described with a focus on key results from studies over the past two decades. Finally, this review details lessons learned and current strategies to optimize the graft-versus-tumor effect and limit transplant-related toxicities.

Knowledge and Attitudes About Genetic Testing Among Black and White Women with Breast Cancer.

Prior to embarking on a large descriptive evaluation of genetic/racial variations in symptom phenotype, we sought foundational information to determine racial differences in (1) feasibility (consent) and acceptability of collecting genomic samples, (2) genetic literacy, and (3) concerns of genomic research during breast cancer (BC) chemotherapy. Women with early-stage BC undergoing chemotherapy were recruited from an academic, urban breast care center. Information was collected for consent to participate, genetic literacy, and concerns about genetic testing in Black and White women with BC. Fifty-six women were eligible, and 48 were consented (24 Black, 24 White). All participants consented to blood testing. This highly educated sample's mean age was 52.5 + 12.05 (years). Education (years) and genetic knowledge were positively correlated (p = .038). Genetic scores were high, and only one question significantly differed by race. On interview, most participants thought conducting genetic research helped to better understand hereditary disease and/or identify genes that cause disease and stated that they participated in the research to help other people. The majority of participants responded that friends/family would participate in genetic research without concerns, though three Black participants cited mistrust as a possible concern. Overall, there were high levels of genetic knowledge, slightly different between Black and White women. There were no high levels of personal concern regarding genetic testing. Black women reported more concern than White women that friends/family would have hesitations about participating in genetic research. There was general acceptability of blood collection for genetic testing among women with early-stage BC without racial difference.