D. Grinblatt

Does younger donor age affect the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies beneficially?

Sixty three patients aged 27–66 years (median 52) were allografted from HLA-matched sibling (n=47), 10 of 10 allele-matched unrelated (n=19), or one-antigen/allele-mismatched (n=7) donors aged 24–69 years (median 46) after a conditioning regimen comprising 100u2009mg/m2 melphalan. Cyclophosphamide (50u2009mg/kg) was also administered to patients who had not been autografted previously. Cyclosporine or tacrolimus, and mycophenolate mofetil were administered to prevent graft-versus-host disease (GVHD). The 2-year cumulative incidences of relapse and TRM were 55 and 24% respectively, and 2-year probabilities of overall survival (OS) and disease-free survival (DFS) were 36 and 21%, respectively. Poor performance status, donor age >45 years and elevated lactate dehydrogenase (LDH) increased the risk of treatment-related mortality (TRM), refractory disease and donor age >45 years increased the risk of relapse, and OS and DFS were adversely influenced by refractory disease, poor performance status, increased LDH, and donor age >45 years. Our data suggest that younger donor age is associated with better outcome after sub-myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) for hematologic malignancies due to lower TRM and relapse. This finding raises the question of whether a young 10-allele-matched unrelated donor is superior to an older matched sibling donor in patients where the clinical situation permits a choice between such donors.

Optimizing the CD34 + cell dose for reduced-intensity allogeneic hematopoietic stem cell transplantation

Low CD34 + cell doses increase allograft-related mortality and very high doses increase the risk of graft-versus-host disease. The optimum CD34 + cell dose remains undefined. The effect of the CD34 + cell dose based on ideal weight was analyzed in 130 patients with hematologic malignancies undergoing reduced-intensity allogeneic blood cell transplantation in the context of factors known to affect the outcome: chemosensitivity, donor age, lactate dehydrogenase (LDH), human leukocyte antigen (HLA) match, performance status, and platelet count. The survival of patients receiving >8 × 106/kg CD34 + cells was not significantly different from those receiving <6. The outcome of those receiving 6–8 × 106/kg CD34 + cells was significantly better than the rest. This superiority was confirmed in multivariable analysis. Among patients receiving ≤8 × 106/kg CD34 + cells, an increasing number of infused cells was associated with higher overall survival in a continuous fashion (Risk ratio (RR) 0.8759; p = 0.045). Cell dose based on actual weight did not correlate with survival. The number of CD34 + cells infused, a potentially modifiable factor, affects survival after reduced-intensity allogeneic transplantation. We recommend a CD34 + cell dose of 6–8 × 106 per kg ideal body weight to optimize outcome. The possible adverse effect of higher cell doses (>8) needs further confirmation.

Ideal rather than actual body weight should be used to calculate cell dose in allogeneic hematopoietic stem cell transplantation

Whether the CD34+ and CD3+ cell doses in allogeneic HSCT should be estimated using actual (ABW) or ideal (IBW) body weight has never been definitively determined. We have shown that CD34+ cell doses based upon IBW are better predictive of engraftment after autologous and allogeneic HSCT. Sixty-three patients undergoing reduced-intensity HSCT after a uniform preparative regimen were evaluated to determine the effect of cell dose. ABW and IBW were 45–147u2009kg (median 79) and 52–85u2009kg (median 67) respectively. The ABW-IBW difference was −24% to +133% (median +16%); nine patients were >5% underweight and 41 were >5% overweight. The CD34+ cell dose (106/kg) was 1.4–11.8 (median 5) by IBW and 1.2–9.3 (median 4.5) by ABW. The CD3+ cell dose (108/kg) was 0.9–14.9 (median 3) by IBW and 0.7–19.7 (median 2.7) by ABW. While CD34+ and CD3+ cell doses based upon IBW were found to affect transplant-related mortality, and disease-free and overall survival significantly, those based on ABW were either not predictive of outcome or the differences were of borderline significance. We suggest using IBW rather than ABW to calculate cell doses for HSCT; for statistical analyses and for clinical practice if a specific cell dose is being targeted.

Erratum: Ideal rather than actual body weight should be used to calculate cell dose in allogeneic hematopoietic stem cell transplantation (Bone Marrow Transplantation (2006) vol. 37 (553-557) 10.1038/sj.bmt.1705282)

Correction to: Bone Marrow Transplantation (2006) 37, 553–557. doi:10.1038/sj.bmt.1705282; published online 30 January 2006 Due to a typesetting error the figure legends of Figures 3 and 4 were published incorrectly. The figures with corrected legends are shown below.