Abstract
Abstract 516
Early lymphocyte recovery is an important determinant of hematopoietic stem cell transplant (SCT) outcome. We found that robust day 30 lymphocyte counts are associated with a decreased incidence of relapse, decreased rates of both acute and chronic graft-versus-host disease (a-GvHD, c-GvHD), and increased survival. Natural killer (NK) cells contribute to lymphocyte recovery and may be associated with a strong graft-versus-leukemia and anti-GvHD effect. However, the contribution of the recovery of specific T cell subsets to transplant outcome has not been fully explored. We studied 43 patients undergoing a myeloablative matched-sibling T-cell depleted or selectively depleted SCT for a variety of hematological malignancies including AML, ALL, CML, and MDS. Median age was 43 years (range, 13–68), and median CD34 cell dose was 6.1×106/kg (range, 3.1-10.1). Thirty-one patients developed a-GvHD (12 grade I, 18 grade II, 1 grade II). Twelve patients had c-GvHD (7 limited, 5 extensive). On day 30 after SCT a peripheral blood sample was collected on all patients and cryopreserved. In preparation for analysis, mononuclear cells from these samples were thawed and rested overnight. Flow cytometry was then performed on a BD FACS CantoII flow cytometer with multicolor fluorochrome antibodies to CD3, CD4, CD8, CD27, and CD45RO. Subsets were defined as follows: Naive (N) CD27+CD45RO-, Central Memory (CM) CD27+CD45RO+, Effector Memory (EM) CD27-CD45RO+, and Effectors (E) CD27-CD45RO-. Data was analyzed by BD FACSDiva software, and Kaplan-Meier survival statistical analysis was performed on the readouts. Median subset frequencies were CD3+: 254 /μL (range, 75-2085), CD4+ : 132 /μL (range, 3-501), CD8+ :101 /μL (range, 9-1361), CD4+ EM 49/μL (range, 2-252), CD4+CM 60/μL (range, 1-253), CD8+ EM: 50 cells/μL (range 2-977), CD8+ CM 28 /μL (range, 2-401), Naïve and Effector cells were minimally or non-detected in both CD4+ and CD8+ compartments. When T cell subset recovery was correlated with transplant outcomes (a-GVHD, c-GVHD, relapse and survival) one significant association was identified: low CD4+ CM counts correlated with a higher incidence of c-GvHD. Patients that had less than the median value of 60 CD4+ CM cells/μL had a significantly higher likelihood of developing c-GvHD (HR 4.28, p=0.039, see figure). Additionally, when considering degree of disease, low CD4+ CM counts were associated with the severest manifestations of c-GvHD (p=0.021). As a result, we conclude that low absolute concentrations of CD4+ CM cells on day 30 after SCT reflects a deficiency in regulatory mechanisms important in the control of alloreactivity, and may be used as a surrogate marker for individuals at risk of developing c-GvHD.
No relevant conflicts of interest to declare.
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