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Correspondence

Creation of a Double Chimera after the Transplantation of Umbilical-Cord Blood from Two Partially Matched Unrelated Donors

N Engl J Med 2001; 344:1870-1871June 14, 2001

Article

To the Editor:

Despite promising outcomes in the transplantation into pediatric recipients of umbilical-cord blood from unrelated donors, the low cell dose adversely affects both the rate of hematopoietic recovery and the probability of survival.1-3 The cell dose is a major limitation of the procedure, particularly in adults. An alternative to the ex vivo expansion of cells, which has yet to be shown to be efficacious, is the transplantation of 2 closely HLA-matched units of umbilical-cord blood.

We transplanted 2 units of umbilical-cord blood from male infant donors into a 53-year-old, 84-kg woman with accelerated-phase chronic myelogenous leukemia and no bone marrow donor. The units were mismatched with the patient at both HLA-DRB1 alleles and mismatched with each other at one HLA-DRB1 allele. The infused doses of cells were 0.7×107 (Donor 1) and 0.9×107 (Donor 2) nucleated cells per kilogram of the recipient's body weight. Conditioning consisted of cyclophosphamide (120 mg per kilogram), fractionated total-body irradiation (1320 cGy), and antithymocyte globulin, with prophylaxis against graft-versus-host disease consisting of cyclosporine and methylprednisolone as previously described.4 Granulocyte colony-stimulating factor (5 μg per kilogram) was given daily from day 0 until neutrophil engraftment occurred. Neutrophil recovery (as defined by an absolute neutrophil count of more than 5×108 per liter) occurred on day 25. Bone marrow biopsies on days 21 and 55 revealed 97 percent and 98 percent donor cells, respectively, each with 20 of 20 cells in metaphase of male origin. The contribution of each graft to hematopoiesis after transplantation was assayed by analysis of restriction-fragment–length polymorphisms (Table 1Table 1Contribution of the Two Umbilical-Cord Blood Grafts to Hematopoiesis after Transplantation.).

Transplantation with two immunologically distinct units of umbilical-cord blood can be associated with engraftment, with each unit contributing to hematopoiesis for at least 60 days after transplantation. Consistent with the data in preimmune sheep,5 these findings suggest that crossed immunologic rejection between the units of umbilical-cord blood may not occur.

Our results contrast with those of previous studies in which the cells from only one of multiple donors of bone marrow6 or umbilical-cord blood7 engrafted. Unlike those studies, our study used units that were relatively closely matched.

Unfortunately, despite a normal neutrophil count and the absence of graft-versus-host disease, disseminated aspergillus infection developed in the patient, who died 68 days after transplantation. Nonetheless, our findings should prompt further investigation of the transplantation of umbilical-cord blood from two partially HLA-matched donors as a method of increasing the dose of cells, particularly for adult recipients. Furthermore, in the future, this approach may facilitate the evaluation of the efficacy of culture for ex vivo expansion in which 1 of 2 units of umbilical-cord blood is expanded.

J.N. Barker, M.B., B.S.
D.J. Weisdorf, M.D.
J.E. Wagner, M.D.
University of Minnesota, Minneapolis, MN 55455

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