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Also see under the heading: VII. CORD BLOOD TRANSPLANTATION IN CHILDREN, i. Malignant Disorders, Citation 13, Michel et al, 2003.
- Relapse risk after umbilical cord blood transplantation: enhanced graft-versus-leukemia effect in recipients of 2 units. Verneris MR, Brunstein CG, Barker J, MacMillan ML, DeFor T, McKenna DH, Burke MJ, Blazar BR, Miller JS, McGlave PB, Weisdorf DJ, Wagner JE. Blood. 2009;114:4293-9.
This analysis was performed to identify risk factors associated with leukemia relapse following myeloablative umbilical cord blood (UCB) transplantation. Acute leukemia patients (n = 177; 88 with acute lymphoblastic leukemia and 89 with acute myeloid leukemia) were treated at a single center. Patients received a UCB graft composed of either 1 (47%) or 2 (53%) partially human leukocyte antigen (HLA)-matched unit(s). Conditioning was with cyclophosphamide and total body irradiation with or without fludarabine
The incidence of relapse was 26% (95% confidence interval [CI], 19%-33%). In multivariate analysis, relapse was higher in advanced disease patients (> or = third complete remission [CR3]; relative risk [RR], 3.6; P < .01), with a trend toward less relapse in recipients of 2 UCB units (RR = 0.6; P = .07). However, relapse was lower for CR1-2 patients who received 2 UCB units (RR 0.5; P < .03). Leukemia-free survival was 40% (95% CI, 30%-51%) and 51% (95% CI, 41%-62%) for single- and double-unit recipients, respectively (P = .35). Although it is known that transplantation in CR1 and CR2 is associated with less relapse risk, this analysis reveals an enhanced graft-versus-leukemia effect in acute leukemia patients after transplantation with 2 partially HLA-matched UCB units.
Despite the lower rate of relapse in double-unit recipients, the increase in overall and disease-free survival was not statistically significant, likely reflecting the limited sample size.
Notably, a recent retrospective registry analysis in adults with chronic lymphoid malignancies also demonstrated lower relapse risk in those who received a transplant of 2 UCB units. Taken together these data suggest that the use of 2 UCB units is associated with an enhanced GVL effect.
Additional comments gleaned from the article: Identification of suitable bone marrow donors remains a challenge. Important advantages of umbilical cord blood include (1) rapid donor identification and availability and (2) a low incidence of graft-versus-host disease despite a high degree of HLA mismatch.
Until recently the limited cell dose in a single UCB unit has been the principal obstacle to the widespread use of UCB as an HSC source, especially for patients who are older and weigh more. UCB transplantation with 2 partially HLA-matched UCB units appears to overcome this limitation.
Although an ongoing prospective, randomized study in children with acute leukemia will definitively address the question about the relative risk of relapse in recipients of 1 or 2 units, it is already clear that the use of 2 UCB units has markedly opened up the option of UCB transplantation to nearly all adults, with few being disqualified on the basis of an inadequate cell dose.
- Umbilical cord blood transplantation: where do we stand? Wadlow RC, Porter DL. Biol Blood Marrow Transplant 2002; 8:637-647
Because there appears to be less GVHD with cord blood transplants, there is concern that graft-versus-leukemia activity may be diminished, leading to an increased rate of relapse. Some observations suggest that graft-versus-leukemia activity following cord blood transplantation is similar to that of conventional bone marrow transplants. In one study, only 8% of 48 patients with chronic myelogenous leukemia suffered relapse after cord blood transplantation. In comparison, relapse rates after syngeneic or T-cell-depleted matched-sibling transplantation, which results in loss of graft versus-leukemia activity, may be more than 50%. Nevertheless, the authors cautioned that further data will be important before definitive conclusions can be reached.
- Unrelated donor hematopoietic cell transplantation: marrow or umbilical cord blood? Grewal SS, Barker JN, Davies SM, Wagner JE. Blood 2003; 101:4233-4244.
Overall, there is no evidence thus far to suggest a higher risk of leukemia relapse after umbilical cord blood transplantation. However, prospective studies comparing similar patient populations receiving cord blood or marrow grafts are needed for reliable conclusions. The authors state that it remains to be seen if such studies will be feasible or ever performed. Randomization will be difficult as cord blood grafts are available much faster than unrelated donor marrow. Hence high-risk patients (e.g., leukemia in tenuous remission) may be more likely to receive cord blood transplants. Strict control of patient risk factors will be critical for any reliable comparison between cord blood and marrow transplantations.
- Graft-versus-leukemia-induced complete remission following unrelated umbilical cord blood transplantation for acute leukemia. Howrey RP, Martin PL, Driscoll T, Szabolcs P, Kelly T, Shpall EJ, et al. Bone Marrow Transplant 2000; 26:1251-1254.
A 15-year-old female received an unrelated three of six HLA antigen matched umbilical cord blood (UCB) transplant for refractory, relapsed T-cell ALL. She engrafted and a day 34 bone marrow aspirate showed 100% donor cells and no evidence of leukemia. One hundred and ninety days after transplantation the patient developed pancytopenia and was subsequently found to have a leukemic relapse. Immunosuppression was discontinued and she was started on G-CSF and erythropoietin. Moderate skin and gut GVHD developed which was treated with both topical and low-dose oral steroids. Over the next few weeks she became transfusion independent and a follow-up bone marrow aspirate showed complete remission. She continued in complete remission for 4 months, at which time localized leukemic relapse was found in a soft tissue breast mass in spite of continued bone marrow remission. While the patient ultimately died of progressive disease, this case demonstrates that mismatched UCB in conjunction with G-CSF is capable of generating a GVL effect that can induce a complete remission.