Lymphocyte recovery is a major determinant of outcome after matched unrelated myeloablative transplantation for myelogenous malignancies

Abstract

A higher absolute lymphocyte count 1 month (LC30) after allogeneic hematopoietic stem cell transplantation (HSCT) is associated with better outcome in patients transplanted from a matched sibling. We studied 102 SCT patients with unrelated donor and matched unrelated donors and the relationship between LC30 and outcome in patients with myelogenous leukemia. Conditioning was myeloablative using cyclophosphamide (Cy) with busulfan (Bu; n=61) or total body irradiation (TBI; n=41). LC30 was low (<0.2x10(9)/L) in 18 patients, intermediate (0.2-1.0x10(9)L) in 67, and high (>1.0x10(9)/L) in 17 patients. In multivariate analysis, independent factors associated with high relapse-free survival (RFS) were high LC30, high CD34 cell-dose, and absence of acute graft-versus-host disease (aGVHD) grades II-IV. When analyzed as a continuous variable in multivariate analysis, a higher LC30 was associated with a lower transplant-related mortality (TRM; relative hazard [RH]=0.87, P < .05), higher relapse-free survival (RH=3.42, P=.036), and improved survival (RH=4.53, P=.016, excluding GVHD). In patients with high, intermediate, and low LC30, overall survival (OS) was 91% versus 60%, versus 36% (P=.02 and .001, respectively). This significant relationship was maintained in patients who did not develop GVHD by day 30. Significant risk factors to develop low LC30 was chronic myelogenous leukemia (CML; hazard ratio [HR] 0.73, P=.001), prophylaxis with granulocyte colony-stimulating factor (G-CSF; HR 0.81, P=.02) and aGVHD (HR 0.84, P=.05). These results indicate that LC30 is an independent prognostic factor for transplant outcome in matched unrelated SCT for myelogenous malignancies.

Figure 1

Distribution of absolute lymphocyte counts at day 30 after unrelated donor HSCT. Figures are given as ×10⁹/L.

Figure 2

(a) Cumulative incidence of treatment-related mortality (TRM), (b) Actuarial relapse free survival (RFS) for all patients, (c) Cumulative incidence of aGVHD grades II-IV of patients with an absolute lymphocyte count on day +30 (LC30) <0.2 × 10⁹ (solid line), 0.2-1.0 × 10⁹ (dotted line) and ≥1.0 × 10⁹ (dashed line). (d) Actuarial RFS for 77 patients who did not develop aGvHD before day 30.