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 Blood, 15 February 2006, Vol. 107, No. 4, pp. 1688-1695.
Prepublished online as a Blood First Edition Paper on August 30, 2005; DOI 10.1182/blood-2005-05-1897.

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TRANSPLANTATION

Factors associated with early molecular remission after T cell-depleted allogeneic stem cell transplantation for chronic myelogenous leukemia

Bipin N. Savani, Katayoun Rezvani, Stephan Mielke, Aldemar Montero, Roger Kurlander, Charles S. Carter, Susan Leitman, Elizabeth J. Read, Richard Childs, and A. John Barrett

From the Hematology Branch, National, Heart, Lung and Blood Institute; and the Departments of Laboratory Medicine and Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD.

Eighty patients with chronic myeloid leukemia (CML) underwent T cell-depleted stem cell transplantation from an HLA-identical sibling, with add-back of donor T cells on days 30 to 45 and days 60 to 100 in patients in whom grade 2 or greater acute graft-versus-host disease (GVHD) developed. The outcomes for 54 patients with chronic-phase (CP) and 26 with advanced-phase (AP) disease were as follows: overall survival, 85% ± 5% versus 36% ± 10%; transplantation-related mortality (TRM), 13% ± 5% versus 43% ± 11%; and current leukemia-free survival, 76% ± 6% versus 34% ± 9%. The day-30 lymphocyte count (LC30) was strongly associated with outcome. For patients in CP with counts greater than the median of 0.30 x 109/L, survival was 100% versus 70% ± 9% (P = .003); current LFS 100% versus 56% ± 9% (P = .002); and TRM 0% versus 26% ± 8% (P = .006). Higher-than-median LC30 correlated significantly with molecular remission (MR) at 3, 6, and 12 months and with higher CD34 doses. Lymphocyte subset analysis performed in 20 patients available for phenotyping showed that LC30 was highly correlated with absolute CD56+CD3- natural killer cell numbers (NK30), which also predicted for survival and MR. CD34 cell dose, LC30, and NK30, but not day-30 CD3+ cell count, were highly correlated and were significant predictors of transplantation outcome. These results suggest that transplanted CD34 cell doses greater than 5 x 106/kg may improve outcomes by increasing the early recovery of NK cells.


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