Surgical Outcomes in Patients With Preoperative Anemia Undergoing Colectomy for Colon Cancer.

INTRODUCTION: Preoperative anemia is relatively common in colon cancer patients; however, its impact on short-term surgical outcomes is not well established. The aim of our study was to evaluate short-term surgical outcomes in colon cancer patients with preoperative anemia undergoing colectomy. METHODS: We performed a 4-year analysis of the ACS-NSQIP and included all adult patients who underwent colectomy for colon cancer. Patients were stratified into two groups based on preoperative anemia (Preop Anemia, No Preop Anemia). Our outcome measures were 30-day complications, 30-day unplanned readmissions, and 30-day mortality. RESULTS: A total of 35,243 colon cancer patients who underwent colectomy were included in the analysis, of whom 50.4% had preoperative anemia. The mean age was 65 ± 13 years and the mean hemoglobin level was 12 ± 2 g/dL. Patients in the anemia group were more likely to be African American, have higher ASA class ≥3, and were more likely to receive at least 1 unit of packed red blood cells preoperatively (7.1% versus 0.3%, P < 0.01). Patients in the anemia group had higher rates of 30-day complications (34.5% versus 16.6%, P < 0.01), 30-day readmission related to the principal procedure (11.7% versus 8.7%, P < 0.01), and 30-day mortality (3.1% versus 1%, P < 0.01). On regression analysis, preoperative anemia was independently associated with higher odds of 30-day complications (P < 0.01), but not 30-day readmission, or 30-day mortality (P = 0.464 and P = 0.362 respectively). CONCLUSIONS: Preoperative anemia appears to be associated with postoperative complications. Preoperatively optimizing hemoglobin levels may lead to improved outcomes.

Engraftment kinetics after transplantation of double unit cord blood grafts combined with haplo-identical CD34+ cells without antithymocyte globulin.

Double unit cord blood (dCB) transplantation (dCBT) is associated with high engraftment rates but delayed myeloid recovery. We investigated adding haplo-identical CD34+ cells to dCB grafts to facilitate early haplo-identical donor-derived neutrophil recovery (optimal bridging) prior to CB engraftment. Seventy-eight adults underwent myeloablation with cyclosporine-A/mycophenolate mofetil immunoprophylaxis (no antithymocyte globulin, ATG). CB units (median CD34+ dose 1.1 × 105/kg/unit) had a median 5/8 unit-recipient human leukocyte antigen (HLA)-match. Haplo-identical grafts had a median CD34+ dose of 5.2 × 106/kg. Of 77 evaluable patients, 75 had sustained CB engraftment that was mediated by a dominant unit and heralded by dominant unit-derived T cells. Optimal haplo-identical donor-derived myeloid bridging was observed in 34/77 (44%) patients (median recovery 12 days). Other engrafting patients had transient bridging with second nadir preceding CB engraftment (20/77 (26%), median first recovery 12 and second 26.5 days) or no bridge (21/77 (27%), median recovery 25 days). The 2 (3%) remaining patients had graft failure. Higher haplo-CD34+ dose and better dominant unit-haplo-CD34+ HLA-match significantly improved the likelihood of optimal bridging. Optimally bridged patients were discharged earlier (median 28 versus 36 days). ATG-free haplo-dCBT can speed neutrophil recovery but successful bridging is not guaranteed due to rapid haplo-identical graft rejection.

Evaluation of Cord Blood Total Nucleated and CD34+ Cell Content, Cell Dose, and 8-Allele HLA Match by Patient Ancestry.

How cord blood (CB) CD34+ cell content and dose and 8-allele HLA match vary by patient ancestry is unknown. We analyzed cell content, dose, and high-resolution HLA-match of units selected for CB transplantation (CBT) by recipient ancestry. Of 544 units (286 infused, 258 next-best backups) chosen for 144 racially diverse adult patients (median weight, 81 kg), the median total nucleated cell (TNC) and CD34+cell +contents were higher for Europeans than for non-Europeans: 216 × 107versus 197 × 107 (P = .002) and 160 × 105 versus 132 × 105 (P = .007), respectively. There were marked cell content disparities among ancestry groups, with units selected for Africans having the lowest TNC (189 × 107) and CD34+ cell (122 × 105) contents. Units for non-Europeans were also more HLA-mismatched (P = .017). When only the 286 transplanted units were analyzed, the adverse effect of reduced cell content was exacerbated by the higher weights in some groups. For example, northwestern Europeans (high patient weight, high unit cell content) had the best-dosed units, and Africans (high weight, low unit cell content) had the lowest. In Asians, low cell content was partially compensated for by lower weight. Marked differences in 8-allele HLA-match distribution were also observed by ancestry group; for example, 23% of units for northwestern Europeans were 3/8 to 4/8 HLA-matched, compared with 40% for southern Europeans, 46% for white Hispanics, and 51% for Africans. During the study period, 20 additional patients (17 non-Europeans; median weight, 98 kg) did not undergo CBT owing to the lack of a suitable graft. CB extends transplantation access to most patients, but racial disparities exist in cell content, dose, and HLA match.

Therapeutic Monoclonal Antibodies Targeting Immune Checkpoints for the Treatment of Solid Tumors.

Recently, modulation of immune checkpoints has risen to prominence as a means to treat a number of solid malignancies, given the durable response seen in many patients and improved side effect profile compared to conventional chemotherapeutic agents. Several classes of immune checkpoint modulators have been developed. Here, we review current monoclonal antibodies directed against immune checkpoints that are employed in practice today. We discuss the history, mechanism, indications, and clinical data for each class of therapies. Furthermore, we review the challenges to durable tumor responses that are seen in some patients and discuss possible interventions to circumvent these barriers.

Racial disparities in access to HLA-matched unrelated donor transplants: a prospective 1312-patient analysis.

Availability of 8/8 HLA-allele matched unrelated donors (URDs) is a barrier for ethnic and racial minorities. We prospectively evaluated receipt of 8/8 HLA-allele matched URD or either 7/8 URD or cord blood (CB) transplants by patient ancestry from 2005 to 2017. Matched URDs were given priority if they were available. Of 1312 patients, 723 (55%) received 8/8 URD, 219 (17%) 7/8 URD, 319 (24%) CB, and 51 (4%) had no 7/8 or 8/8 URD or CB graft. Europeans were more likely to receive an 8/8 URD transplant than non-Europeans (67% vs 33%) and less likely to have no URD or CB graft (1% vs 9%). Southern Europeans received 8/8 URD transplants (41%) at rates similar to those of Asians (34%) and white Hispanics (35%); Africans were the least likely (18%) to undergo 8/8 URD transplantation. CB and 7/8 URDs extended transplant access to all groups. In 742 recent patients, marked racial disparity in 8/8 URD access between groups observed in earlier years persisted with only a modest increase in the percentage of 8/8 URD transplants. Of 78 recent African patients, 46% received a CB transplant and 14% had no 7/8 or 8/8 URD or CB graft. Increasing registry size has not resolved the racial disparity in URD access, which emphasizes the importance of alternative graft sources.

Prospective Evaluation of Unrelated Donor Cord Blood and Haploidentical Donor Access Reveals Graft Availability Varies by Patient Ancestry: Practical Implications for Donor Selection.

The availability of cord blood (CB) and haploidentical (haplo) donors in all patient populations is not established. We have investigated the addition of haplo-CD34+ cells to CB grafts (haplo-CBT) to speed myeloid engraftment. Thus, we have prospectively assessed CB and haplo donor availability in adult patients without 8/8 HLA-allele matched unrelated donors (URDs). Analysis of 89 patients eligible for haplo-CBT revealed 4 distinct patient groups. First, 6 patients (7% of total, 33% non-European) underwent CBT only as they had no suitable family members to type. In group 2, 49 patients (45% non-European) received haplo-CBT using the first haplo donor chosen. Group 3 (n = 21, 76% non-European) underwent CBT with/without haplo. In this group, the first haplo donor chosen failed clearance in 20 patients and transplantation was too urgent to permit donor evaluation in 1. Fifty-three haplo donors were evaluated (2 to 6 per patient) for 21 group 3 patients, and 43 of 53 (81%) haplos failed clearance for predominantly medical and/or psychosocial reasons. Group 4, (n = 13, 85% non-European with a high median weight of 96 kilograms) had no CB grafts with/without no haplo donors. Overall, African patients had the worst donor availability with only 65% having a suitable CB graft and only 44% having a suitable haplo donor. Additionally, in non-European patients, a greater number of haplos required evaluation/patient to secure a suitable haplo graft. Although these data should be confirmed in a larger study, it suggests that there are barriers to the availability of both CB and haplo grafts in adult patients without 8/8 URDs, especially in those with African ancestry, and has multiple practical implications for patient management.