Recovery of humoral immunity after cessation of chemotherapy for childhood acute lymphoblastic leukemia (ALL) was investigated by determining blood leukocyte, lymphocyte and B‐lymphocyte, and serum immunoglobulin (Ig) levels and IgG subclasses at 0, 1, 3, 6, 9, and 12 months after cessation of chemotherapy for ALL in 14 patients. Blood B‐lymphocytes were analyzed with the use of flow cytometry and monoclonal CD20 antibody. At cessation of chemotherapy, the amount of blood B‐lymphocytes was subnormal in most patients but increased to normal levels in 1 month after therapy was discontinued. The recovery of serum Ig, which reflect B‐cell function, was slower, but occurred by 6 months after therapy was discontinued in most patients. The authors conclude that by 6 months after cessation of chemotherapy for ALL, a sufficiently functioning immune system by these parameters is established and that prophylactic antibiotics can be withdrawn and immunizations started. Cancer 1992; 69:1481‐1486.

undiagnosed vitamin B12 deficiency is remarkably common in the aged, but no specific risk group for screening can be identified. Thus, biochemical screening of unselected aged population is justified. General practitioners play a key role in diagnosing early vitamin B12 deficiency.

Early response after induction is a prognostic factor for disease outcome in childhood acute myeloid leukaemia (AML). Residual disease (RD) detection by multiparameter flow cytometry (MFC) was performed at day 15 and before consolidation therapy in 101 patients enrolled in the Nordic Society of Paediatric Haemato-Oncology AML 2004 study. A multicentre laboratory approach to RD analysis was used. Event-free survival (EFS) and overall survival (OS) was significantly different in patients with and without RD at both time points, using a 0·1% RD cut-off level. RD-negative and -positive patients after first induction showed a 5-year EFS of 65 ± 7% and 22 ± 7%, respectively (P < 0·001) and an OS of 77 ± 6% (P = 0·025) and 51 ± 8%. RD-negative and -positive patients at start of consolidation therapy had a 5-year EFS of 57 ± 7% and 11 ± 7%, respectively (P < 0·001) and an OS of 78 ± 6% and 28 ± 11%) (P < 0·001). In multivariate analysis only RD was significantly correlated with survival. RD before consolidation therapy was the strongest independent prognostic factor for EFS [hazard ratio (HR):5·0; 95% confidence interval (CI):1·9-13·3] and OS (HR:7·0; 95%CI:2·0-24·5). In conclusion, RD before consolidation therapy identifies patients at high risk of relapse in need of intensified treatment. In addition, RD detection can be performed in a multicentre setting and can be implemented in future trials.

Interleukin-6 (IL-6) is a major growth factor for the clonal malignant plasma cells in multiple myeloma (MM). The effect of IL-6 may be enhanced by soluble IL-6 receptor (sIL-6R). As there is a clinical need for improved stratification of MM patients at diagnosis, we have studied the role of sIL-6R as a prognostic marker in 207 newly diagnosed MM patients. Serum sIL-6R concentration was above the upper reference limit in 47% of the patients at diagnosis. The concentrations of sIL-6R and two other prognostic factors, IL-6 and beta-2 microglobulin (beta 2M), were all significantly higher in the patients who died within 3 years compared with those who survived. However, serum sIL-6R did not show linear correlation with IL-6 or beta 2M levels. In univariate logistic regression analysis sIL-6R was a significant predictor of 3-year mortality. Kaplan-Meier analysis showed that raised levels of sIL-6r were associated with shorter survival. When the patients were stratified into four groups according to their serum IL-6 and sIL-6R levels the patients with normal serum levels of both parameters had clear survival benefit. As beta 2M was the most powerful prognostic factor in the multivariate analysis, the patients were also stratified according to their serum beta 2M and sIL-6R levels. The patients with raised levels of both beta 2M and sIL-6R had shorter survival than the patients in the other three groups. Thus, measurement of these parameters at diagnosis would help to stratify MM patients.

Results:The intra-and between-assay imprecision (CV) for the holoTC RIA were 4 -7% and 6 -8%, respectively. A 95% central reference interval for serum holoTC was 37-171 pmol/L. All participants (n ‫؍‬ 16) with probable Cbl deficiency, 86% of those with possible, and 30% of those with potential Cbl deficiency had holoTC below the reference limit (<37 pmol/L). The holoTC correlated

Recovery of cell-mediated immunity after cessation of chemotherapy for childhood acute lymphoblastic leukemia (ALL) was investigated in 14 children to monitor the duration of immune deficiency. The numbers of blood T cells and their subsets were analyzed at 0, 1, 3, 6, 9 and 12 months after discontinuation of therapy with monoclonal antibodies and flow cytometry. The total T-cell count was low at cessation but normalized at 1 to 3 months, whereas the T-cell subsets CD4+, CD8+, CD4+Leu8-, and CD4+CD45RA+ recovered differently. In children ages 3 to 6 years, the numbers of CD4+ cells and their subsets were normal at cessation, whereas in children ages 7 to 18 years, CD4+ and CD4+Leu8+ cell counts normalized only at 6 months. The numbers of CD8+ cells or activated T cells were not increased and the CD4+/CD8+ ratio was not inverted, unlike recovery after bone marrow transplantation. Although the groups showed a mean reversion to normal values by 6 months, there were individual patients who continued to have subnormal values for 1 year after therapy, some of whom exhibited increased susceptibility to infections.

SUMMARYWe have examined the expression of the IgG Fc receptors (FcRI, FcRII, FcRIII) and complement receptors (CR1, CR3) in neutrophils from 42 patients with febrile bacterial infection, 20 patients with febrile viral infection and 69 non-febrile healthy individuals. Using receptor-specific MoAbs and immunofluorescence flow cytometry the relative fluorescence intensity (as a measure of receptor number) and the proportion of receptor-positive cells were determined in peripheral blood neutrophils exposed to minimal processing, consisting only of erythrolysis. Both the percentage of FcRI-positive neutrophils and FcRI number per neutrophil were significantly (P < 0 . 001 and P < 0 . 0001) increased in bacterial infected patients compared with controls, whereas in viral infected patients only the FcRI percentage was markedly elevated (P < 0 . 05). In addition, both FcRII and CR1 levels were significantly higher in the bacterial infection group than in the viral infection and control groups (bacterial versus control P < 0 . 001, bacterial versus viral P < 0 . 0001). No changes in expression of FcRIII or CR3 were found in the patient groups. The kinetic analysis of receptor expression in bacterial infection patients revealed a shift in the percentage of FcRI-bearing neutrophils towards normal values already on day 2 after the first analysis. On the other hand, the levels of FcRI, FcRII and CR1 remained clearly elevated in these patients during 1 week's follow-up period. We conclude that febrile infection may cause systemic activation of the entire pool of circulating neutrophils, resulting in alterations in cell surface receptor expression, some of which are characteristic of the nature of the infectious agent.

Serum bioactive but not immunoreactive interleukin-6 (IL-6), and serum C-reactive protein (CRP), have been reported to be of prognostic significance in multiple myeloma (MM). We measured serum immunoreactive IL-6 by a sensitive enzyme-linked immunosorbent assay in 30 MM patients at diagnosis. In 30% of the patients serum immunoreactive IL-6 exceeded the upper reference limit. The concentrations of CRP and IL-6 showed a linear association. Logarithmically transformed IL-6, CRP and beta 2-microglobulin were significant variables by univariate survival analysis; by multivariate analysis CRP was a slightly stronger prognostic factor than IL-6 and the only one of independent prognostic significance.