UNRELATED CORD BLOOD TRANSPLANT EXPERIENCE BY THE PEDIATRIC BLOOD AND MARROW TRANSPLANT CONSORTIUM

Abstract

Cord blood (CB) has emerged as a potential source of hematopoietic stem cells for patients who are in need of hematopoietic stem cell transplant (HSCT). The authors analyzed the Pediatric Blood and Marrow Transplant Consortium's (PBMTC) data of consecutive unrelated CB transplants performed during the initial 2 years of using placental blood grafts. From January 1995 to December 1996 PBMTC performed a total of 44 unrelated CB transplant for a variety of diseases consisting of acute leukemias (n = 29), congenital conditions (n = 9), and bone marrow failure (n = 6). There were 15 females and 29 males with median age of 5 years (range 0.4-20.6 years) and median weight of 18.2 kg (range 6.3-70 kg). The median volume of CB units was 80 mL (range 44.5-215 mL) and the median cell dose given was 4.3 x 10(7)/kg of recipient weight (range 1.1-23 x 10(7)/kg). Techniques used for human leukocyte antigen (HLA) matching were serologic typing for class I HLA antigens and high-resolution molecular typing for HLA-DRB1 alleles. HLA disparities were as follows: 4 were 6/6 matches, 21 were 5/6, 15 were 4/6, and 4 were 3/6. Twenty-nine (66%) of CB units were DRB1 matched with recipients. Conditioning regimens consisted of either total body irradiation containing (n = 31) or chemotherapy only (n = 11) regimens. All but 3 patients receive cyclosporine as part of graft vs. host disease (GvHD) prophylaxis in combination with either methotrexate (MTX) or methylprednisolone (Pred). The other 3 patients had FK506 and MTX for GvHD prophylaxis. Myeloid engraftment (absolute neutrophil count > or = 500) occurred at a median of 21 days (range 10-43 days) and platelet > or = 50,000/mm3 was noted at a median of 44 days (range 16-102 days). Eight patients died too early (< day + 28) for evaluation of engraftment (5 for infection, 2 for multiorgan failure, 1 for toxic epidermolysis). The probability of having grade II-IV acute GvHD for all patients was 44 +/- 0.7%. The incidence of a GvHD is similar for 4/6 and 5/6 antigen when DRB1 matched, at 47 and 52%, respectively. Chronic GvHD was noted in 28% of patients surviving > 90 days. The Kaplan-Meier estimate of 4-year event-free survival was 43%. A Cox model for analysis of factors associated with survival was DRB1 matching, p = .001; cell dose, p = .009; and younger age, p = .03. In conclusion, CB transplant offers a good alternative to bone marrow transplant Although GvHD occurs, it is usually of low severity despite the high frequency of multiple HLA antigen mismatches. It also appears that a 4/6 is as good as a 5/6 matched antigen CB unit when DRB1 matched especially in the pediatric setting.