HLA-HAPLOIDENTICAL UMBILICAL-CORD BLOOD STEM-CELL TRANSPLANTATION IN A CHILD WITH ADVANCED LEUKEMIA - CLINICAL OUTCOME AND ANALYSIS OF HEMATOPOIETIC RECOVERY

Growing attention has been focused on cord blood as a source of transp lantable hematopoietic stem cells. However, clinical experience is rat her limited. In this study we describe a child with advanced acute lym phoblastic leukemia who received an HLA-haploidentical cord blood tran splant. The patient was transplanted in third complete remission after conditioning with fractionated total body irradiation, thiotepa and c yclophosphamide. Forty-one milliliters of cryopreserved umbilical cord blood, containing 0.15 x 10(8) nucleated cells/kg and 0.25 x 10(4) CF U-GM/kg, were infused. Cyclosporine and prednisone were administered f or graft-versus-host disease (GVHD) prophylaxis. The patient received G-CSF from day +1 to day +35, but no improvement in granulocyte counts was observed. Therefore, administration of GM-CSF was started on day +36 to day +59, which resulted in a significant increase in white bloo d cells and granulocyte counts. Sustained myeloid engraftment was evid enced by a granulocyte count >0.5 x 10(9)/1 by day +41. The presence o f donor-derived cells could be documented in the peripheral blood and bone marrow of the patient by cytogenetic analysis, HCA phenotyping an d DNA studies. Forty-one days after transplant, clonogenic bone marrow assays showed the presence of low frequencies of primitive hematopoie tic progenitor cells (BFU-E = 19/10(5) and CFU-GM = 8/10(5)). The chim erism was complete and no host-derived cells could be detected. Howeve r, the engraftment was restricted to the myeloid lineage whereas lymph oid and megakaryocytic engraftments were inadequate. The immunophenoty pe of the patient's peripheral blood showed the presence of T lymphocy tes expressing an immature phenotype (CD2+ CD3-) at day +21. Among the subset of T cells expressing the CD3 antigen, the majority were CD45R O+ memory cells and a significant proportion was positive for the acti vation markers CD25, CD69 and HLA-DR, suggesting that these T cells ha d been activated in vivo. On day +41, a mild cutaneous rash consistent with grade I acute GVHD resolved with steroid treatment. Unfortunatel y, the patient died of hepatic insufficiency and renal failure 84 days after transplantation. Autopsy showed a multiorgan failure with hepat ic veno-occlusive disease (VOD). Overall, this study shows that (1) co rd blood transplantation from an HLA-mismatched donor can be performed with a low risk of acute GVHD, and (2) a small volume of cord blood c ontaining a reduced number of CFU-GM is sufficient to achieve engraftm ent.