Leukocyte recovery and early treatment-related mortality after bone marrow transplantation.

To the Editor: hypocellular marrow. Detailed information on the mode of death, disease status at death, and principal and contributory causes of death was extracted from a prospective database to ensure the In a study of considerable practical relevance, Offner et al have exclusion of patients dying of infections or hemorrhage secondary shown that from 15 days after autologous or allogeneic bone marrow to acute GVHD because the latter were classified as dying primarily transplantation (BMT), the risk of mortality due to any cause within of GVHD. the first 100 days becomes progressively greater in patients whose Serial total leukocyte counts obtained by automated counters on absolute neutrophil count is õ0.1 1 10/L. This observation could 712 consecutive patients receiving marrow allografts for hematobe of clinical significance in the third and fourth week after translogic malignancies were analyzed to see if the leukocyte count on plantation, when additional therapeutic interventions may be applied days 2-22 after BMT was predictive of death (as defined) or death/ to patients with neutrophil counts of õ0.1 1 10/L to decrease early second infusion. For each of these posttransplant days, patients were mortality. grouped on the basis of the leukocyte counts (10/L) in three ways There are some limitations to the study: although the investigators (°0.1 v ú0.1, °0.2 v ú0.2, and °0.3 v ú0.3), and actuarial probamention that causes of death such as relapse and regimen-related bilities of death and death/second infusion calculated. The log-rank toxicity could diminish the relative importance of the degree of test was used to compare the differences. The following factors were neutropenia in autograft recipients, these causes of death as well as analyzed in multivariate fashion to see their effect on the probability fatal acute graft-versus-host disease (GVHD), which account for a of death or death/second infusion: age, sex, diagnosis, conditioning significant number of deaths in the first 100 days after allogeneic regimen, type of donor, GVHD prophylaxis, nucleated cell dose, BMT, could decrease the impact of neutropenia after allogeneic prophylactic administration of a growth factor within 2 weeks of transplantation as well. Secondly, although neutropenia is the most BMT, and the total leukocyte count on day 16 after BMT. important risk factor for death due to bacterial or fungal infections, Fifty-two patients fulfilled the definition of death, and 99 the the use of the absolute neutrophil count may ignore the contribution definition of death/second infusion. The leukocyte counts on days of monocytes to recovery from infections. Also, in our experience, 2-10 did not affect the specified outcomes significantly. However, the absolute neutrophil count is somewhat unreliable and prone to from day 12 onward, the lower leukocyte count for each of the considerable variation when the total leukocyte count is low. three comparisons on each day was associated with a significantly Because there is no universally accepted definition of delayed increased risk of death and death/second infusion. Figures 1 and 2 engraftment after BMT, and prolongation of pancytopenia is associshow the high significance. ated with an increasing probability of serious infections and bleeding, In multivariate analysis, a leukocyte count °0.2 1 10/L on day we have tried to arrive at an operational definition of graft failure 16 was the strongest factor predicting subsequent death (25 of 114 after allogeneic BMT. To specifically identify patients who could patients v 23 of 546 patients with leukocytes ú0.2 1 10/L, relative benefit from early intervention in the third week posttransplant, we risk 4.5, P õ .0001) and death/second infusion (48 of 114 v 47 of limited the events studied to (1) death primarily as a result of infec546, relative risk 5.5, P õ .0001). The findings were similar in tion, hemorrhage, or graft failure within 3 months; and (2) second recipients of non–T-cell depleted marrow from HLA-identical sibinfusion of allogeneic or autologous marrow as therapy for primary lings (relative risks 4.5 and 7.6, P Å .0001 and õ.0001), and after failure of engraftment within 2 months of the first infusion. Primary substitution of the day 16 leukocyte counts with day 14 and day 17; failure of engraftment was usually diagnosed on the basis of an absolute neutrophil count ofõ0.11 10/L on day 21 with a markedly with the leukocyte count being the strongest factor in all analyses.