Advancements in Cord Blood Transplantation
By Kathy Loper

About 14,000 unrelated cord blood transplantation (UCBT) procedures have been performed worldwide in the past decade, based on estimates from the major registries in North America, Europe, Asia and elsewhere. The joint NMDP/AABB program “Clinical Advances in Hematopoietic Cell Transplantation” (9134-TC-CT) included three speakers providing the most recent information on clinical progress and future directions.

Product Types and Patient Outcomes

Vanderson Rocha MD, PhD, from Eurocord gave an update from the European perspective, reviewing hematopoietic stem cell transplant (HSCT) volumes by product type and patient outcomes. The focus continued on cord blood, which provides the convenience of a readily available donor source and rapid availability. Lower cell dose--leading to graft failure and delayed immune recovery--continued to be the major challenge.  As expected, engraftment is better in pediatric patients, with Eurocord reporting 78% two-year overall survival in children receiving UCBT with an HLA-identical or one-antigen mismatch graft. UCBT remains an alternative source of cells in the absence of an HLA-matched sibling donor for children with malignant and nonmalignant disorders. 

In reviewing adult UCBT data, Rocha described the major factors affecting outcomes. A detailed breakdown by product type, disease state, conditioning regimens and outcomes followed. Outcomes of single UCBT using a myeloablative regimen are comparable with results of 7/8 matched unrelated marrow grafts. The Eurocord presentation concluded with current recommendations including: Cell doses ≥ 2.5 x 10⁷ nucleated cells/kg and/or ≥ 1.5 x 10⁵ CD34+cells/kg.  The second factor for consideration is minimal mismatches (0-1 preferred) and Class I HLA mismatches preferred over Class II.

Haploidentical Transplantation

Gregory Hale, MD, from St. Jude’s Research Hospital, discussed “Haploidentical Transplantation for Childhood Malignancies.” In this setting, the donors are often parents or an older sibling and are, therefore, usually highly motivated and readily available to donate. These donor products have a potentially greater graft-vs.-leukemia effect including natural killer (NK) cell cytotoxicity, which may be helpful in refractory disease. 

 
The product selection approach at St. Jude’s focuses on most closely matched HLA types, followed by best mismatch for NK cell reactivity, and involves both positive and negative graft selection. Disease recurrence and relapse remain primary problems. Adult outcomes were then reviewed. When other donor sources are absent, haploidentical HSCT remains a feasible option for patients lacking a matched or unrelated donor. 

Reducing Toxicity

 A multidisciplinary approach and suggestions for reducing toxicity followed in a presentation by Kenneth Cooke, MD, from Case Medical Center. He suggested there might be a common thread linking the associated complications of HSCT--the role of the vascular endothelium as it suffers injury and transplant-related toxicities including graft-vs.-host disease, veno-occlusive disease, thrombotic microangiopathy, and infection. 

Functions of resting endothelial cells (ECs) and their roles in each of the most common transplant-related injuries were reviewed from a biological perspective. A novel therapeutic approach would ideally modulate EC injury without causing systemic bleeding or other toxicities, protect the recipient without compromising the anti-tumor effect, and preferably exhibit activity across the spectrum of vascular injury syndromes during HSCT.  In closing, Cooke reviewed various treatment modalities including a Phase III trial from the Cancer Trials Network. He concluded that while there has been a great deal of progress, there is also much yet to discover in the field of unrelated HSCT.