No abstract

The medium-risk B cell precursor acute lymphoblastic leukemia (ALL) accounts for 50-60% of total childhood ALL and comprises the largest number of relapses still unpredictable with diagnostic criteria. To evaluate the prognostic impact of minimal residual disease (MRD) in this specific group, a case control study was performed in patients classified and treated as medium (or intermediate)-risk according to the criteria of national studies (ALL-BFM 90, DCLSG protocol ALL-8, AIEOP-ALL 91), which includes a good day 7 treatment response. Standardized polymerase chain reaction (PCR) analysis of patient-specific immunoglobulin and T cell receptor gene (TCR) rearrangements were used as targets for semiquantitative estimation of MRD levels: у10 −2 , 10 −3 , р10 −4 . Twenty-nine relapsing ALL patients were matched with the same number of controls by using white blood cell count (WBC), age, sex, and time in first complete remission, as matching factors. MRD was evaluated at time-point 1 (end of protocol Ia of induction treatment, ie 6 weeks from diagnosis) and time-point 2 (before consolidation treatment, ie 3 months from diagnosis). MRD-based high risk patients (у10 −3 at both time-points) were more frequently present in the relapsed cases than in controls (14 vs 2), while MRD-based low risk patients (MRD negative at both time-points) (1 vs 18) showed the opposite distribution. MRD-based high risk cases experienced a significantly higher relapse rate than all other patients, according to the estimated seven-fold increase in the odds of failure, and a much higher rate than MRD-based low risk patients (OR = 35.7; P = 0.003). Using the Cox model, the prediction of the relapse-free interval at 4 years was 44.7%, 76.4% and 97.7% according to the different MRD categories. MRD-based risk group classification demonstrate their clinical relevance within the medium-risk B cell precursor ALL which account for the largest number of unpredictable relapses, despite the current knowledge about clinical and biological characteristics at diagnosis. Therefore, MRD detection during the first 3 months of follow-up can provide the tools to target more intensive therapy to those patients at true risk of relapse. Leukemia (2000) 14, 1939-1943.

No abstract

Summary. The standard therapy for patients with fever and chemotherapy-related neutropenia is hospitalization and infusion of broad-spectrum antibiotics. Early discharge of a de®ned group of patients at low risk for septicaemia would be of great advantage for these patients. In this study plasma interleukin-8 (IL-8) and interleukin-6 (IL-6) levels measured at start of fever (n 72) could de®ne a low-risk group of febrile patients with neutropenia due to chemotherapy. For this purpose we collected and analysed data on 72 fever episodes from 53 patients with chemotherapy-related neutropenia, aged between 1 and 66 years. Of the 72 episodes, 18 were classi®ed as bacteraemia and/or clinical sepsis (sepsis group). The IL-6 and IL-8 plasma concentration were signi®cantly increased in patients with chemotherapy-related neutropenia and fever due to bacteraemia versus fever of non-bacterial origin (P 0´043 and P 0´022 respectively). Logistic regression analysis, with sepsis as the outcome variable, revealed signi®cant effects of age combined with either IL-6 or IL-8. Sepsis occurrence was lowest for patients <16 years and highest in patients between 16 and 50 years, and was higher in patients with increased IL-6 (P 0´032) or IL-8 (P 0´049). No signi®cant effect of leucocyte count, C-reactive protein, sex or underlying malignancy at presentation was detected. The plasma IL-6 and IL-8 levels were fairly strongly correlated (Pearson r 0´62). Using a cut-off value with 100% sensitivity, both IL-8 and IL-6 could de®ne a low-risk group of neutropenic patients of 28% (CI 15±40%) at the start of the febrile period. Intervention studies are warranted to con®rm this result and to investigate whether an early discharge based on IL-8 or IL-6 measurement is safe, increases the quality of life, and results in cost savings.

Langerhans' cell histiocytosis (LCH) is characterized by an accumulation and/or proliferation of cells with a Langerhans' cell (LC) phenotype. The aetiology and pathogenesis of LCH are unknown; it is suggested that LCH is caused by an immunological dysregulation. Production of cytokines is a central feature of immunological regulation. LCH lesions and normal LCs were studied for the presence of cytokines known to influence the functioning of LCs: IL‐1α, IL‐1β, IL‐4, GM‐CSF, IFN‐γ, TGF‐α, TGF‐β, bFGF, and TNF‐α. Cytokines were abundantly present within LCH lesions; LCH cells stained for IL‐1α, IL‐1β, IL‐4, GM‐CSF, TGF‐α, TGF‐β, TNF‐α, and IFN‐γ. Macrophages, lymphocytes, eosinophil granulocytes, and, surprisingly, multinucleated giant cells were also sources of cytokines. These results suggest that cytokines play a prominent role in the pathogenesis of LCH and may explain phenomena that often occur in LCH, such as osteolysis and fibrosis and the recruitment of typical inflammatory infiltrates. The results also suggest that a ‘down‐regulatory’ signal is lacking in LCH, resulting in an accumulation and/or proliferation of abnormal LCs.