Early hematopoietic recovery after single unit unrelated cord blood transplantation in adults supported by co-infusion of mobilized stem cells from a third party donor

Abstract

BACKGROUND AND OBJECTIVES: Our objective was to improve the outcome of cord blood (CB) transplantation in adults, by overcoming the limitations imposed by the low number of stem cells present in CB units. DESIGN AND METHODS: We combined single CB units and co-infusion of third party donor (TPD)-derived peripheral blood mobilized hematopoietic stem cells (MHSC) following myeloablative conditioning with reduced extra-hematologic toxicity. RESULTS: Twenty-seven eligible patients with high-risk hematologic malignancies (age 16-60 years, median 29, weight 43-78 Kg, median 67) received CB units (median nucleated cell count 2.37x10(7)/Kg, median CD34+ cells 0.11x10(6)/Kg) co-infused with TPD-derived MHSC (2.30x10(6)/Kg CD34+ cells; <1x10(4)/Kg CD3+ cells). Neutrophil engraftment (>0.5x10(9)/L) occurred 10 days (9-36) post-transplant and was initially of TPD-origin in all patients except for four who received maternal MHSC, and then became of stable CB-origin. Median times to CB-derived neutrophil count >0.5x10(9)/L and full CB-chimerism were 22 and 55 days, respectively. The maximum cumulative incidence for engraftment, CB-engraftment and full CB-chimerism was 0.93 (95%CI: 0.83-1.00). The median time to reach unsupported platelet counts >20x10(9)/L was 33 days, with a maximum cumulative incidence of 0.74 (95%CI: 0.59-0.93). Transplant-related morbidity was associated primarily with non-neutropenic phase infections. Co-infusion of TPD-cells was well tolerated, with only 14.8% of recipients developing acute graft-versus-host disease (grade III-IV) and 20% developing a chronic (limited) form. The predicted 4-year overall survival was 69% for the whole group and 77% for the 23 patients receiving non-maternal TPD. INTERPRETATION AND CONCLUSIONS: Our strategy offers prompt engraftment with a low rate of complications in a feasible alternative protocol that overcomes the current limitations of a single CB-transplant in adults.