Simultaneous Transplantation of Three Cord Blood Units in Adults with High Risk Acute Leukemia.

Abstract

Adult patients with high risk acute leukemia have allogeneic hematopoietic transplantation as the only therapeutic option with some curative potential. Those who lack related or unrelated marrow donor are deprived of this possibility. Patients of smaller size may benefit from the transplantation of single cord blood unit, but for heavier patients two units may be required as reported by Barker et al. (Blood 2005; 105:1343). For very heavy patients even more units would be necessary to approximate the preferred threshold of 37 millions of cells per kilo. Moreover, cord blood units have variable size and it is always a risk that the only HLA-matched units for given patients would be small and two units would not provide adequate number of cells even for patients of moderate size. This is yet another argument to attempt transplantation of more than two units. Three patients have so far been included. Patient No 1 was 24 yrs old male (body weight 87 kg) with resistant AML transplanted with 3 units (two matched at 4/6 HLA antigens, one matched at 3/6 HLA antigens) on March 29, 2004 following conditioning with standard BuCy4 + ATG regimen. This patient died d. +42 of Gram negative sepsis without hematopoietic reconstitution. Patient No 2 is 22 yrs old male (body weight 100 kg) with Ph+ ALL in complete remission, who was transplanted on October 11, 2004 with 3 units (two matched at 4/6 HLA antigens, one matched at 3/6 antigens) following conditioning with TBI, etoposide and ATG. This patient had neutrophil recovery d. +27, and platelet recovery d. +49. He is alive and well 9 months after the transplant fully chimeric with progeny of only one of transplanted units. Patient No 3 is 31 yrs old male (body weight of 100 kg) with ALL relapsed after autologous BMT with multiple cytogenetic abnormalities. He was transplanted May 24, 2005 with 3 units (one matched at 5/6 HLA antigens, two matched at 4/6 HLA antigens) following conditioning with treosulfan, cyclophosphamide, melphalan and ATG (he earlier received TBI prior auto-BMT). Patient obtained neutrophil recovery d. +36 and as of d.+60 still has low platelets. No data on chimerism are yet available. These data confirm that transplantation of more than two cord blood units is feasible and may provide therapeutic option for patients with high risk leukemia who lack marrow donor and for whom two cord blood units do not provide sufficient number of cells. As in the case of the transplantation of two units patients seem to be reconstituted with progeny of only one “winning” unit.