André Bosly

A quantitative study of peripheral blood stem cell contamination in diffuse large-cell non-Hodgkin's lymphoma: one-half of patients significantly mobilize malignant cells.

Autologous transplantation using peripheral blood stem cells (PBSCs) collected after chemotherapy, followed by growth factor administration (ASCT), is increasingly used in the treatment of non‐Hodgkins lymphoma (NHL). However, quantitative data regarding contaminating malignant cells in the harvests are still scarce. We prospectively investigated 37 diffuse large‐cell lymphomas (DLCLs) in complete remission (CR) that were treated according to multicentric protocols at our centre. DNA was extracted from the diagnostic lymph node. The complementarity‐determining region (CDR) III was sequenced and a patient‐specific oligomer synthesized. Contamination was evaluated semiquantitatively by polymerase chain reaction (PCR) and was confirmed by a limiting dilution analysis. PBSCs collected at regeneration after administration of granulocyte colony‐stimulating factor (G‐CSF), steady‐state bone marrow (BM) and peripheral blood samples at CR were compared. DNA was available in 37 patients, from which 22 rearrangements could be sequenced. Patients (nu2003=u200315) who had both the required follow‐up samples and a suitable clonal marker were investigated. In two cases, the patient‐specific PCR assay set up at diagnosis later gave false‐negative results in samples in which clonal DNA was still detectable by other sets of primers. PBSC contamination was highly variable: 7 out of 15 patients showed a PBSC/BM ratio of NHL cells greater than 1 log, whereas 8 out of 15 patients showed no difference and could vary from one apheresis to another. Eight ASCTs were performed, five of which used highly contaminated PBSCs: four patients relapsed early, three with disseminated lymphoma. Thus, 50% of DLCLs in CR seem to mobilize significantly malignant cells at regeneration under G‐CSF. Considering the higher numbers of cells reinfused, this translates into a much higher number of lymphoma cells reinfused when compared with autologous bone marrow transplantation (ABMT). However, their clonogenic potential remains unknown and, despite concerning observations in certain cases, it is still unclear whether this has an impact upon the outcome of ASCT.

Translocation t(8;16)(p11;p13) in Acute Non-Lymphocytic Leukemia: Report on Two New Cases and Review of the Literature

Two new cases of t(8;16)(p11;p13) in acute nonlymphocytic leukemia (ANLL) are described. These two patients in addition to the 34 previously described, showed a striking association with myelomonocytic (M4) or monocytic (M5) leukemia, extramedullary infiltration, erythrophagocytosis and disseminated intravascular coagulation. One of our patients showed a TCRbeta gene rearrangement. Alltogether 36 cases of t(8;16) ANLL have been documented until today. We here review their clinical and cytogenetic features.

From health locus of control to immune control: internal locus of control has a buffering effect on natural killer cell activity decrease in major depression.

Decreased immunity in depressive as compared with control subjects has been well documented, although some depressed patients have severe alterations whereas others have milder ones or not at all. Since for equal severities of depression, there may be individual differences in the degree of perceived control over ones condition, we investigated the interaction of perceived control with immunological variations. Immune function (T and B lymphocytes, lymphocyte proliferation and natural killer cell activity (NKCA)) were evaluated in 34 adult major depressives and in 18 healthy controls. Lymphocyte proliferation did not differ between the two groups, but NKCA was significantly lower in the depressed patient group. Among the depressed subjects, those who experienced less subjective control also showed significantly lower NKCA. An internal locus of control appears to act as a buffer against the decrease in cellular immunity observed in major depression. Further studies should focus on methods of coping and on degree of perceived control rather than on diagnostic and nosographic variables alone.

A Phase-i Study of Vinblastine Tryptophan Ester

SummaryVinblastine tryptophan ester (VTrpE) is a new vinca alkaloid derivative that achieves antitumor activity in a large variety of animal models. In this phase I study the drug was given as an i. v. injection over 5 min, once a week or once every 2 weeks. Twenty patients with advanced cancer were entered in this trial. The doses ranged from 2.5 mg/m2 to 35 mg/m2. Myelosuppression is the dose-limiting toxicity, with the risk of leukopenia being more serious than that of thrombocytopenia, but the myelosuppression is always reversible. Neurotoxicity, well documented when other vinca alkaloid derivatives are used, is insignificant. Two cases of disease stabilization have been observed in patients with non-small cell lung cancer. For VTrpE, a dose schedule of 30 mg/m2 per week may be recommended for phase II studies in non-small cell lung cancer.

Blunted rise in intracellular calcium in CD4+ T cells in response to mitogen following autologous bone marrow transplantation.

Summary. Following autologous bone marrow transplantation (ABMT), both impaired T cell activation and defective production of the principal T cell growth factor, interleukin‐2 (IL‐2), has been observed. These processes are dependent on a rise of intracellular calcium ([Ca2±]i), a step which follows binding of T cell receptor (TCR) and transduction of signal via the generation of cytoplasmic second messengers. In order to better understand the nature of defective cellular immunity in ABMT, in the present study we investigated the rise of [Ca2±]i in T cells of recipients of ABMT. By concomitant labelling lymphocytes with anti‐CD4 antibody and addition of fluo‐3 as fluorescent calcium indicator, we have selected for the T cell subset which is the principal source of IL‐2. Short‐term (less than 1 year post‐transplantation) recipients of ABMT show a statistically significant blunted rise in [Ca2±]i in response to concanavalin A as compared to normal controls not accounted for solely by a decreased percentage of CD4± cells in these patients. The [Ca2±]i response of CD4± cells from long‐term (greater than 1 year post‐transplant) recipients was lower than that of the normal group although not to a statistically significant level. These findings suggest that following ABMT is a defect in the early stages of T cell activation involving either T cell receptor binding or early signal transduction ultimately resulting in depressed transcription of IL‐2 mRNA. These defects are analogous to findings in both allogeneic transplantation where factors of histoincompatability and graft‐versus‐host disease (GVHD) come into play, as well as in the defective T cell activation of the normal ageing process.

Management of Non-Hodgkin’s Lymphomas: Conclusions of the First Intercity Meeting, 1986

On 15 December 1986 in Strasbourg (France) the first Intercity Meeting of the European School of Oncology was held with a survey of the current status of non-Hodgkin’s lymphoma (NHL) management. The conclusions of this meeting are presented here. The Working Formulation for clinical use [1] (Table 1) is used throughout this paper.