Abstract

Adjustment of immune reaction, balancing between graft-versus-tumor (GVT) effect and graft-versus-host disease (GVHD), is of primary importance for improved therapeutic outcome after allogeneic hematopoietic cell transplantation (HCT). We retrospectively reviewed the medical records of 315 patients with hematologic malignancies who underwent allogeneic HCT at our center between 2000 and 2004. The median age of the patients was 46 (range, 1–68) years. The diagnoses included acute myeloid leukemia or myelodysplastic syndrome (n=153), chronic myelogeneous leukemia (n=30), acute lymphoblastic leukemia (n=36), lymphoma (n=90), and other hematologic malignancies (n=6). Seventy-two patients had low-risk and 243 had high-risk disease. Patients were conditioned with fludarabine-based reduced-intensity (n=160) or conventional myeloablative regimen (n=155). Donors included HLA-matched (n=120) or mismatched (n=53) relatives and unrelated volunteers (n=142). Stem cell source was G-CSF-mobilized peripheral blood stem cell (n=169), bone marrow (n=117), or cord blood (n=29). Of the 187 patients with measurable disease before HCT, 139 (75%) achieved complete remission. In a multivariate analysis, myeloid disease and the development of acute or chronic extensive GVHD were associated with a higher probability of achieving complete remission. Currently, 155 patients (49%) are alive with a median follow-up of 931 (range, 88–1968) days. Multivariate analyses revealed that a higher HCT-specific comorbidity index (HCT-CI) score, disease risk, graft rejection, and transplant from donors other than HLA-matched relatives were associated with increased risks of poor overall survival (OS) and progression-free survival (PFS). A higher HCT-CI score, greater patient age, graft rejection, and transplant from donors other than HLA-matched relatives were associated with an increased risk for non-relapse mortality (NRM). Patients with high-risk disease were associated with an increased risk of relapse or progressive disease (PD). After adjusting for these significant variables, grade III–IV acute GVHD was associated with increased risks of high NRM and poor OS and PFS. Chronic extensive GVHD was associated with an increased risk of NRM, without any significance for PD, OS, and PFS. In a subset analysis of 160 patients who received reduced-intensity conditioning, chronic extensive GVHD was associated with a decreased risk of PD. In conclusion, marginally intensified GVT effect with severe acute or chronic extensive GVHD appears to be offset by increased toxicities and mortality. Future study should focus on identification of narrow window for better control of immune reaction to induce tolerable GVHD with clinically significant GVT effect.

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