Number of nucleated cells infused during allogeneic and autologous bone marrow transplantation: an important modifiable factor influencing outcome.

To the Editor: have represented a group of patients with compromised marrow reserve due to either high-risk disease or previous chemotherapy who subsequently had problems during the transplant. Although variables relating to disease biology and patient characHowever, in a study of factors affecting hematologic recovery after teristics are strong determinants of outcome after bone marrow transunpurged autologous blood or marrow transplantation in 240 patients plantation (BMT), the identification of these nonmodifiable factors with acute leukemia (which included the previous 74 patients), a nucleis often of limited practical use. On the other hand, treatmentand ated cell dose ofõ2 1 10/kg was independently associated with slower transplant-related factors, which are modifiable, can potentially be recovery to 0.5 1 10/L neutrophils, and with slower and incomplete manipulated in clinical practice to improve the results of transplantarecovery to 501 10/L platelets. There was a strong correlation between tion. The number of nucleated cells infused during transplantation neutrophil recovery and five increasing nucleated cell dose levels (õ1.5, is a variable which is usually controllable. Therefore, it is encourag1.5-2, ú2-2.5, ú2.5-3.5, and ú3.5 1 10/kg). ing to see that increasing this number as much as possible improves Long-term follow-up of 85 first-remission AML patients allosurvival by reducing transplant-related mortality in patients allografted from HLA-identical siblings after cyclophosphamide and grafted from unrelated donors. single-fraction TBI with cyclosporine for graft-versus-host disease We have also found in a number of different studies that the (GVHD) prophylaxis showed that infusion of a lower nucleated cell nucleated cell dose significantly affects transplant-related mortaldose (°2.6 1 10/kg) was independently predictive of increased ity, survival, and the speed as well as completeness of hematotransplant-related mortality (relative risk 2.69, PÅ .002). The higher logic reconstitution after autologous and allogeneic transplantacell dose was associated with better disease-free survival (relative tion for hematologic malignancies. risk 2.01, P Å .045) in multivariate analysis. Figure 1 shows the Among 74 patients with acute myeloid leukemia (AML) autoeffect of the cell dose in this group of patients. grafted in first remission after melphalan and single-fraction totalSimilarly, in a study of transplant-related mortality in 138 acute body irradiation (TBI), 7 of 21 patients receiving °2 1 10 nucleleukemia patients allografted after melphalan and TBI with ated cells/kg body weight and 7 of 53 patients receiving ú2 1 10 cyclosporine { methotrexate, a high infused marrow cell dose nucleated cells/kg body weight died of treatment-related toxicity (P (¢2.5 1 10 total nucleated cells/kg or ¢0.6 1 10 mononuclear Å .047, x test). In multivariate analysis, patients receiving the cells/kg) protected against fatal interstitial pneumonitis compared higher cell dose had a significantly better disease-free survival (relawith lower cell doses (risk ratio 0.47, P Å .023). tive risk 2.17, P Å .045). The higher toxic death rate and poorer After allogeneic transplantation in 712 patients with hematologic disease-free survival in patients receiving °2 1 10 nucleated cells/ malignancies, a low total leukocyte count in the third week was kg was only partially due to incomplete or delayed hematopoietic found to be the most significant predictor of death due to infections, reconstitution with resultant increase in bleeding or infections behemorrhage, or graft failure within the first 3 months. A low nuclecause the cell dose did not affect the probability or rapidity of ated cell dose (õ2.5 1 10/kg) was independently associated with engraftment significantly in this group of 74 patients. Because 2 1 increased risk of death due to these causes (relative risk 2.2, P Å 10/kg cells is our usual target for collection during an autologous marrow harvest, those receiving °2 1 10/kg nucleated cells may .025).