High-dose CHOP plus etoposide (MegaCHOEP) in T-cell lymphoma: a comparative analysis of patients treated within trials of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL).

BACKGROUND: T-cell lymphomas (T-NHL) generally carry a poor prognosis. High-dose therapy (HDT) and autologous stem cell transplantation (ASCT) are increasingly used to treat younger patients. DESIGN AND METHODS: We treated patients <61 years with high-risk aggressive lymphoma with four to six courses of dose-escalated CHOP plus etoposide (MegaCHOEP) necessitating repeated ASCT. Outcomes of patients with mature T-NHL (excluding anaplastic lymphoma kinase-positive anaplastic large cell lymphoma) and aggressive B-NHL were compared using multivariate Cox regression analysis. RESULTS: Compared with 84.4% of B-NHL patients, 66.7% of T-NHL patients were able to receive all treatments; the rates of progressive disease were 27.3% in T-NHL and 16.3% in B-NHL patients. At 3 years, event-free survival (EFS) and overall survival were significantly worse for T-NHL [25.9% confidence interval (CI) 10.4% to 41.4% and 44.5% CI 26.5% to 62.5%) than for B-NHL patients (60.1% CI 52.1% to 68.1%; P < 0.001 and 63.4% CI 55.4% to 71.4%; P = 0.016). In multivariate analysis, T-NHL was a strongly significant adverse risk factor for EFS (relative risk 2.2, P = 0.001). CONCLUSIONS: MegaCHOEP for T-NHL patients was no better than other high-dose regimens and was unable to address the major problems of HDT/ASCT: neither early progressions nor early relapses were reduced. This study sheds some doubt on expectations that HDT/ASCT will significantly improve outcomes for patients with T-NHL.

Lissencephaly, abnormal lymph nodes, and T-cell deficiency in one patient.

We report on a child with lissencephaly type I, abnormal lymph nodes, and immunodeficiency, associated with recurrent infections, autoimmune disease, spastic tetraplegia, and psychomotor retardation. Diagnostic measures included cranial computer tomography (CT) and magnetic resonance imaging (MRI) scanning, several in vivo and in vitro immunological tests, and histology of skin, lymph nodes, and liver including electron microscopy and immunohistology. Despite medical supervision, the child died at age 4 years. A common pathogenetic mechanism of defective migration of neurons and the dysmaturation of lymph nodes is most probable. The T-cell deficiency may represent a common defect of the development of both neuronal and lymphatic tissue, as the six-layered cerebral cortex and the B-cell areas in lymph nodes develop at about the same gestational age. A common defect could also be assumed involving genetically determined cell surface proteins.

Erdheim-Chester disease: evidence for a disease entity different from Langerhans cell histiocytosis? Three cases with detailed radiological and immunohistochemical analysis.

Erdheim-Chester (EC) disease is a rare pathological entity with a highly specific and characteristic pattern of radiographic bone changes. Histologically it resembles Langerhans cell histiocytosis (LCH), and it is still a matter of discussion whether EC disease is a distinct entity or a type of LCH. In this study, 3 cases of Erdheim-Chester disease were followed up over years and examined in detail both radiologically and immunohistochemically. All 3 cases showed the pathognomonic skeletal features for EC disease as well as an identical immunohistochemical phenotype quite different from LCH. Macrophages and Touton cells reacted strongly positive with the histiocytic marker CD 68, whereas staining with S100 and CD1a, markers for Langerhans cells, were negative. Both the immunohistochemical phenotype and the bone changes were clearly distinct from LCH.

Purification and characterization of human bone marrow lymphocyte subpopulations: evidence for the existence of an alloreactive immature T cell.

This study was conducted in order to clarify further the role of bone marrow lymphocyte (BML) subsets in graft-versus-host disease (GVHD) after clinical BM transplantation. Human BML separated by velocity sedimentation through a continuous sucrose gradient were found to consist of 38% T, 21% B and 41% null cells. T cells were purified from BML or peripheral blood lymphocytes (PBL) by rosette formation with sheep red blood cells (SRBC) and subsequent gradient centrifugation. Mitogenic stimulation of BML, PBL and the respective T cell subsets revealed the well-known reactivity of mature T lymphocytes, whereas non-T lymphocytes comprising T cell precursors showed only a weak response. In allogeneic stimulation kinetics, however, non-T-BML disclosed a delayed but marked responsiveness as compared to BML and T-BML suggesting that a T cell precursor matures under culture conditions. This cell type could be involved in GVHD in addition to mature T cells after clinical bone marrow transplantation.

Interleukin-9 expression in human malignant lymphomas: unique association with Hodgkin's disease and large cell anaplastic lymphoma.

To test the possibility that interleukin-9 (IL-9), the human homologue of the mouse T-cell growth factor P40, may be involved in the pathogenesis of human lymphomas, we examined IL-9 expression in a variety of tumors both by Northern blot analysis and by in situ hybridization. Of 18 B-cell non-Hodgkin's lymphomas and 11 peripheral T-cell lymphomas, none expressed IL-9 message. By contrast, IL-9 message was found in two of six cases of large cell anaplastic lymphoma (LCAL) and in 6 of 13 cases of Hodgkin's disease (HD). In HD the strongest signals were observed in Hodgkin (H) and Sternberg-Reed (SR) cells, but IL-9 mRNA was also detected in small lymphocytic cells. A search for IL-9 message in a panel of 20 cell lines derived both from hematopoietic and nonhematopoietic tumors confirmed the unique association of IL-9 expression with HD and LCAL in as much as the only two cell lines with IL-9 message were derived from cases of HD and LCAL. These results suggest that IL-9 is not involved as an autocrine growth factor in the pathogenesis of most B- and T-cell lymphomas, but that it may play a role in HD and LCAL.