The adjusted International Prognostic Index and beta-2-microglobulin predict the outcome after autologous stem cell transplantation in relapsing/refractory peripheral T-cell lymphoma.

BACKGROUND AND OBJECTIVES: Preliminary data on the use of autologous stem cell transplantation (ASCT) as a salvage therapy for peripheral T-cell lymphoma (PTCL) indicate that the results are similar to those obtained in aggressive B-cell lymphomas. The aim of our study was to analyze outcomes of a large series of patients with PTCL with a prolonged follow-up who received ASCT as salvage therapy. DESIGN AND METHODS: Between 1990 and 2004, 123 patients in this situation were registered in the GELTAMO database. The median age at transplantation was 43.5 years; in 91% of patients the disease was chemosensitive. RESULTS: Seventy-three percent of the patients achieved complete remission, 11% partial remission and the procedure failed in 16%. At a median follow-up of 61 months, the 5-year overall and progression-free survival rates were 45% and 34%, respectively. The presence of more than one factor of the adjusted International Prognostic Index (a-IPI) and a high beta2-microglobulin at transplantation were identified as adverse prognostic factors for both overall and progression-free survival and allowed the population to be stratified into three distinct risk groups. INTERPRETATION AND CONCLUSIONS: Our data show that approximately one third of patients with PTCL in the salvage setting may enjoy prolonged survival following ASCT, provided they are transplanted in a chemosensitive disease state. The a-IPI and beta2-microglobulin level predict the outcome after ASCT in relapsing/refractory PTCL.

Hla-DPB1 mismatch in HLA-A-B-DRB1 identical sibling donor stem cell transplantation and acute graft-versus-host disease.

BACKGROUND: The role of human leukocyte antigen (HLA)-DPB1 as a transplantation antigen is controversial. A higher incidence of acute graft-versus-host disease (aGVHD) has been described after unrelated donor bone marrow transplant when both HLA-DPB1 alleles were mismatched. METHODS: We investigated the impact of a single HLA-DPB1 mismatch after HLA-A-B-DRB1 identical sibling donor transplantation on aGVHD. We analyzed 627 adult patient-donor pairs and identified 30 pairs without HLA-DPB1 identity (4.78%). In 17 cases, the patient had an allele that was not shared by the donor. RESULTS: The cumulative incidence of grades II-IV aGVHD was higher in the HLA-DPB1 mismatched group (66.7% vs. 35.7%, p=0.012). The HLA-DPB1 mismatch was identified by multivariate analysis as an independent risk factor for aGVHD (p=0.020, RR=2.68, 95% CI: 1.73-3.62). CONCLUSIONS: HLA-DPB1 can mediate alloreactive responses. A single HLA-DPB1 mismatch increases the risk of aGVHD after sibling donor stem cell transplantation.

High dose chemotherapy and autologous stem cell transplantation in patients with peripheral T-cell lymphoma not achieving complete response after induction chemotherapy. The GEL-TAMO experience.

BACKGROUND AND OBJECTIVES: Patients with aggressive non-Hodgkin's lymphomas (NHL) who do not obtain a complete response (CR) after induction chemotherapy have a poor prognosis. However, provided they are sensitive to the first regimen of chemotherapy, 25-40% of them with a B-cell phenotype may achieve long-term survival when treated with high dose chemotherapy and autologous stem cell transplantation (HDC/ASCT). The aim of this study was to analyze the efficacy of this therapy in the corresponding patients with peripheral T-cell lymphoma (PTCL). DESIGN AND METHODS: We retrospectively evaluated the efficacy of ASCT in 35 patients with PTCL from the GEL-TAMO registry, who did not achieve a CR to standard induction chemotherapy regimens for aggressive NHL. Thirty-one patients underwent transplantation after achieving a partial response (PR) and 4 patients were non-responders. RESULTS: Following HDC/ASCT, 23 (66%) of the patients achieved a CR, 4 (11%) a PR and in 7 (20%) cases the transplant failed. One patient was not evaluated because of early toxic death. With a median follow-up of the survivors of 37.5 months, 18 patients (51%) are alive and 15 patients (43%) are free of disease. Transplant-related mortality rate at 100 days was 11% and at 5 years the probabilities of survival, freedom from progression and disease-free survival for complete responders were 37%, 36% and 55% respectively. Pre-transplant lactate-dehydrogenase level, age-adjusted International Prognostic Index (aa-IPI) and tumor score correlated with survival. INTERPRETATION AND CONCLUSIONS: One third of the patients with PTCL who fail to achieve CR to the first chemotherapeutic regimen can be rescued with HDC/ASCT. Pre-transplant values of IPI and tumor score risk systems for aggressive lymphomas were useful to predict subsequent survival.

Positive selection for CD34+ reduces the incidence and severity of veno-occlusive disease of the liver after HLA-identical sibling allogeneic peripheral blood stem cell transplantation.

OBJECTIVE: T-cell depletion (TCD), primarily developed to prevent graft-vs-host disease (GVHD), might reduce early liver dysfunction after allogeneic hematopoietic stem cell transplantation. However, no comparative studies have been performed to investigate this. We analyzed the influence of selection for CD34(+) cells on the incidence and severity of hepatic veno-occlusive disease (VOD). PATIENTS AND METHODS: Five hundred and one patients who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from HLA-identical siblings were included in the present study. Two hundred and ninety patients (59%) were grafted with CD34+ positively selected grafts and 211 (41%) with nonmanipulated grafts. Their mean age was 38 years (range 17-63). All patients had hematological malignancies and 96% were conditioned with combinations either of cyclophosphamide plus total-body irradiation or of cyclophosphamide plus busulphan. Most of the patients received GVHD prophylaxis with methotrexate (MTX) or cyclosporin A. RESULTS: Fifty-two patients (10.4%) developed VOD. VOD was more frequent in patients receiving nonmanipulated grafts (16.1% vs 6.2%; p<0.0009), in those with a Karnofsky score less than 90 (17.5% vs 7.8%; p=0.001), and with the use of MTX for GVHD prophylaxis (14.8% vs 7%; p=0.005). In multivariate analyses, only CD34+ positive selection (p=0.0007) and Karnofsky score (p=0.004) emerged as independent risk factors for VOD. The same effect was observed in the subset of patients with severe VOD. CONCLUSION: These findings show that CD34+ selection not only decreases the incidence of GVHD but also prevents VOD after HLA-identical sibling PBSCT.

Risk factors for acute graft-versus-host disease in patients undergoing transplantation with CD34+ selected blood cells from HLA-identical siblings.

A study on 315 patients undergoing transplantation with CD34+ selected blood cells from HLA-identical siblings was performed to determine risk factors for acute GVHD (aGVHD). Recipients of a dose of CD34+ cells (x 10(6)/kg) of 2 or less, more than 2 to 4, and more than 4 had a cumulative incidence of aGVHD grades I-IV of 21%, 35%, and 43%, respectively (log-rank P =.01); similarly, recipients of a dose of CD3+ cells (x 10(6)/kg) of 0.05 or less, more than 0.05 to 0.1, and more than 0.1 had a cumulative incidence of aGVHD grades I-IV of 18%, 35%, and 44%, respectively (log-rank P =.007). Using a Cox regression model, 4 independent factors for aGVHD I-IV were identified: increased CD34+ cell dose (P =.02), increased CD3+ cell dose (P =.02), female patients (P =.01), and higher patient age (> 42 years) (P =.007). This study shows, for the first time in T-cell-depleted transplantations, a positive correlation between the number of CD34+ cells and aGVHD and, also, that the number of CD3+ cells necessary to initiate aGVHD is lower than previously reported.