Spontaneous autologous graft-versus-host disease in plasma cell myeloma autograft recipients: flow cytometric analysis of hematopoietic progenitor cell grafts.

Nine plasma cell myeloma patients spontaneously developed histologically proven autologous graft-versus-host disease (GVHD) limited predominantly to the gastrointestinal tract within 1 month of initial autologous hematopoietic cell transplantation (AHCT) using high-dose melphalan conditioning. All recipients responded promptly to systemic and nonabsorbable oral corticosteroid therapy. All patients previously received systemic therapy with thalidomide, lenalidomide, or bortezomib before AHCT. Using enzymatic amplification staining-enhanced flow cytometry, we evaluated expression of selected transcription regulators, pathway molecules, and surface receptors on samples of the infused hematopoietic cell grafts. We demonstrated significantly enhanced expression of GATA-2, CD130, and CXCR4 on CD34(+) hematopoietic progenitor cells of affected patients compared with 42 unaffected AHCT controls. These 3 overexpressed markers have not been previously implicated in autologous GVHD. Although we did not specifically evaluate T cells, we postulate that exposure over time to the various immunomodulating therapies used for induction treatment affected not only the CD34(+) cells but also T cells or relevant T cell subpopulations capable of mediating GVHD. After infusion, the affected hematopoietic progenitor cells then encounter a host that has been further altered by the high-dose melphalan preparative regimen; such a situation leads to the syndrome. These surface markers could be used to develop a model to predict development of this syndrome. Autologous GVHD potentially is a serious complication of AHCT and should be considered in plasma cell myeloma patients with otherwise unexplained gastrointestinal symptoms in the immediate post-AHCT period. Prompt recognition of this condition and protracted treatment with nonabsorbable or systemic corticosteroids or the combination may lead to resolution.

Outcome of patients with stage II and III nonseminomatous germ cell tumors: results of a single center.

BACKGROUND: The prognostic factors in nonseminomatous germ cell tumors have been mainly derived from the analysis of stage I tumors. AIMS: The aim of this study was to evaluate some prognostic factors and the outcome of patients with stage II and III nonseminomatous germ cell tumors according to risk groups treated between 1993 and 2002. SETTINGS AND DESIGN: Patients were retrospectively classified as good, intermediate and poor risk groups according to International Germ Cell Cancer Consensus Group. MATERIALS AND METHODS: Biopsy specimens of 58 patients with stage II and III nonseminomatous germ cell tumors were analyzed by means of tumor histopathology, primary localization site of the tumor, relapse sites, initial serum tumor marker levels, the presence of persistent serum tumor marker elevation and the patients' outcome. STATISTICAL ANALYSIS: Kruskall Wallis test and Mann-Whitney U test were used to determine the differences between the groups. Kaplan-Meier method was used for survival analysis and log rank test was used to compare the survival probabilities of groups. Cox proportional hazard analysis was used to determine the prognostic factors in univariate and multivariate analysis. RESULTS: Five-year overall and disease-free survival rates were calculated as 85% and 75% in stage II; 44% and 29% in stage III cases, respectively. Fifty-seven percent of patients were classified in good risk, 9% in intermediate risk and 27% in poor risk groups. Five-year overall survival rates were 97%, 75% and 7% (P<0.001) and disease-free survival rates were 83%, 34% and 7% (P<0.001) in good, intermediate and poor risk groups, respectively. Analysis of the prognostic factors revealed that the localization site of the primary tumor (P<0.001), the initial beta-HCG level (p:0.0048), the presence of yolk sac and choriocarcinoma components in tumor (p:0.003 and p:0.004), relapse sites of tumor (lung versus other than lung) (p:0.003), persistent elevation of serum tumor markers (P<0.001) were significant prognostic factors in univariate analysis. However, in multivariate analysis, only the localization site of tumor (p:0.049) and the relapse site (p:0.003) were found statistically significant. CONCLUSIONS: This retrospective study revealed that in advanced stage of nonseminomatous germ cell tumors, the outcome is essentially related with the localization site of the tumor and the relapse site.