G. Pizzolo

Estimated 6-year event-free survival of 55% in 60 consecutive adult acute lymphoblastic leukemia patients treated with an intensive phase II protocol based on high induction dose of daunorubicin

On the basis of a previous experience suggesting that daunorubicin dose in induction was an independent prognostic factor in adult ALL, we designed a chemotherapeutic regimen (ALLVR589) characterized by high doses of daunorubicin (270u2009mg/m2) in induction and by high-dose Ara-C in post-remission. The protocol was otherwise conventional: induction and post-remission therapy were followed by chemo-radio prophylaxis of the central nervous system (CNS) and periodical reinductions over a 3-year maintenance period. Sixty consecutive patients (male 42, female 18, median age 34 years, range 14–71; B-lineage, 35; T-lineage, 25; Ph′ and bcr/abl positive, 7) recruited between 1989 and 1996, were evaluated for treatment outcome. Complete remissions were 56 (93%), one patient had refractory disease, early deaths were five (8%); 19/56 (34%) patients relapsed, five of whom were Ph′+. Median time to relapse was 11 months (range 3–47); 68% of relapses occurred within 12 months from CR. No CNS relapses were observed. After a median follow-up of 44 months (1–100), 33/60 (55%) patients remain event-free; 23/60 (38%) are off-therapy in continuous CR (median follow-up from diagnosis: 63 months; range 38–100). These results suggest that increasing DNM dosage in induction is one of the possible approaches to improve the outcome of adult ALL by decreasing the relapse occurrence.

ICAM‐1 tissue overexpression associated with increased serum levels of its soluble form in Hodgkin's disease

Summary. We investigated ICAM‐1/CD54 tissue immunoreactivity and serum levels of its soluble form (sICAM‐1) in patients with Hodgkins disease (HD) at diagnosis. ICAM‐1 was strongly expressed in involved tissues, and sICAM‐1 serum levels were higher in HD (79 patients) than in controls (P < 0 · 01), and in patients with more advanced or more active disease (stages III ± IV vI ± II: P= 0 · 002; stage ‘B’v‘A’: P <0 · 0001; ‘bulky’disease v non‐‘bulky’: P= 0 · 042). We suggest that tissue ICAM‐1 overexpression leading to increase of circulating sICAM‐1 may interfere with the lymphocyte adhesion machinary thus contributing to the well‐known immune derangement of HD.

Detection of a soluble form of the receptor for interleukin 2 in the serum of patients with hairy cell leukaemia.

The sera of patients with hairy cell leukaemia (HCL) contain a factor which inhibits the binding of anti-IL-2R antibody to its target (activated T lymphocytes). The presence of this factor, which probably corresponds to the soluble form of IL-2R (sIL-2R), can be easily detected using a simple immunocytochemical inhibition assay. In a series of patients with chronic lymphoproliferative diseases the presence of sIL-2R appeared to be specific for HCL, using the sensitivity of our test, since it could not be detected in sera from normal subjects and patients with B-cell lymphocytic leukaemia or Hodgkins disease. Thus it might be used as an additional tool for characterizing HCL patients.

Immuno-histological analysis of bone marrow involvement in lymphoproliferative disorders

Summary. Cryostat sections from bone marrow biopsies submerged in gum‐sucrose solution and snap‐frozen can be stained with various antisera to detect both the membrane and cytoplasmic antigens on normal and malignant populations in their tissue environments. This technique seems to be the method of choice to analyse the degree of BM involvement in cases of non‐Hodgkins lymphoma where conventional histology provides equivocal results. The uniform expression of only one type of light chain in B lymphoma and the analysis of the T cell infiltrate in T‐CLL using monoclonal antibodies is demonstrated.

Serum levels of soluble interleukin‐2 receptor in hairy cell leukaemia: a reliable marker of neoplastic bulk

In hairy cell leukaemia (HCL), the strong membrane expression of the Tac antigen, corresponding to the p55 chain of the interleukin‐2 receptor (IL‐2R), is associated with the presence in the serum of high levels of a soluble form of the same molecule (sIL‐2R). Previous observations that therapy‐induced clinical and haematologic improvement in HCL is accompanied by a progressive decrease of sIL‐2R suggest a possible correlation between sIL‐2R levels and tumour burden. To verify this hypothesis, we monitored the variation of sIL‐2R values in 13 non‐splenectomized HCL patients admitted for treatment with recombinant interferon alpha‐2. The data were correlated with the estimated weight of bone marrow (BM) and spleen infiltrations, which in these patients almost entirely account for the tumour mass. The regression analysis test showed a direct correlation between sIL‐2R values and both BM neoplastic involvement (r= 0.63) and spleen tumour mass (r= 0.76). In addition, the correlation was further improved (r= 0.86) when sIL‐2R values were correlated with the total neoplastic mass, as calculated by the sum of spleen and BM neoplastic tissue weight. These data indicate that the detection of sIL‐2R in HCL is a reliable non‐invasive marker of tumour burden, which can be regarded as an additional useful tool for monitoring treatment response.

The diagnostic value of serum copper levels and other hematochemical parameters in malignancies.

An increase in the serum copper (Cu++) level has been described as a sensitive index of disease activity in several hematologic and nonhematologic malignancies. In order to explore the diagnostic value of Cu++ compared to other hematochemical parameters frequently abnormal in malignancies, Cu++, serum α2 globulin (α2), plasmatic fibrinogen (Fibr), the erythrocyte sedimentation rate (ESR), and serum iron (Fe++) have been detected and evaluated in 267 patients affected with the following diseases: Hodgkins lymphoma (HL), non-Hodgkins Lymphomas (NHL), Acute Leukemias (AL), Chronic Myeloid Leukemia (CML), Chronic Lymphocytic Leukemia (CLL), Myeloma (MM), and Breast Cancer (BC). The best correlation between Cu++ increase and disease activity has been found in HL, NHL, AL, and BC. In these diseases, when the considered parameters were compared, Cu++ and ESR showed a similar pattern, i.e., a high frequency of abnormalities in active disease. It is concluded that Cu++ represents a good complement to some other aspecific parameters in evaluating the activity and diffusion of neoplasias and the therapeutic results, particulary in HL, NHL, AL and BC.

Acute Lymphoblastic Leukaemia after Radiotherapy and Adjuvant Chemotherapy (CMF) for Breast Cancer

Acute lymphoblastic leukaemia, defined by immunological markers as a non-T, non-B, which occurred in a patient with breast cancer 2 years after the end of radiotherapy and CMF adjuvant chemotherapy, i