Effects of Recipients’ Body Weight and Total Nucleated Cell Dose on Outcomes of Unrelated Bone Marrow Transplantation: Analysis of Clinical Data of 3,114 Leukemia Patients from the Database of the Japan Marrow Donor Program

In allogeneic bone marrow transplantation (BMT) from unrelated donor of Japan Marrow Donor Program (JMDP), the standard bone marrow nucleated cell dose for transplantation is regulated as 3.0×10E8 total nucleated cells (TNC)/recipient’s body weight (RBW) (kg). RBW are also used to estimate the target harvest volume of bone marrow from the donor. So RBW determine the dose of harvested TNC, and these factors will influence the outcomes of BMT. We retrospectively analyzed the clinical data of 3,114 adult transplant patients (median age 33, range 16–70) from extracted the database of JMDP. The diagnosis of these patients were AML (n=1257), ALL (n=927) and CML (n=930). Five years overall survival (OAS) of all cases was estimated as 47.6%. Possible factors that could influence on survival and hematological recovery were analyzed by using proportional hazards analysis. In univariate analysis, TNC>=3.0×10E8/RBW was one of the significant factors to improve OAS (p=0.022). TNC/recipients’ ideal body weight (IBW) whose body mass index (BMI) was over 22 could be also a significant favorable factor for OAS (p=0.014). In multivariate analysis, variables correlated with improving OAS were TNC>=2.0×10E8/IBW (p=0.011), using tacrolimus for GVHD prophylaxis (p=0.011), younger recipient’s age (p=0.013). TNC>=2.0×10E8/IBW were also powerful variables correlated with the recovery of neutrophils, reticulocytes and platelets. These findings suggest that TNC/IBW can substitute for TNC/RBW to evaluate infused cell dose. And in our data set, use of IBW to estimate the harvest volume from the donor brought 10.7% reduction of target bone marrow volume compared with use of RBW. JMDP sets up the upper limit of harvested bone marrow volume based on the donor’s BW, but heavyweight recipients often require larger volume of bone marrow from the donors. Appropriate evaluation of TNC for transplantation and recipients’ BW by using BMI may be one of the useful methods to improve outcomes of unrelated BMT and avoid excess risk and stress of unrelated donors.