E. Capochiani

Hepatitis C virus infection in patients with non-Hodgkin's lymphoma

Summary. Hepatitis C virus (HCV), which is both a hepatotropic and a lymphotropic virus, has been proposed as a possible causative agent of mixed cryoglobulinaemia. This ‘benign’ lymphoproliferative disorder can switch over to a malignant B‐cell non‐Hodgkins lymphoma (NHL). Therefore HCV infection has been investigated in a series of 50 unselected Italian patients with B‐cell NHL. Antibodies against HCV were found in 30% of NHL and HCV viraemia in 32% of cases. HCV‐related markers were detected in 34% (17/50) of our NHL patients; this prevalence is particularly significant when compared with HCV seropositivity in Hodgkins lymphoma (3%) and healthy controls (1.3%).

Motility of rhG‐CSF‐induced neutrophils in patients undergoing chemotherapy: evidence for inhibition detected by image analysis

The motility of circulating neutrophils from seven patients affected by intermediate and high‐grade non‐Hodgkins lymphoma was investigated before and after rhG‐CSF administration (5μg/kg/d for 5 d subcutaneously) in the course of chemotherapy. Random motility and bacterial lipopolysaccharide‐induced chemotaxis were studied by the micropore filter technique in a Boyden chamber. These functions were evaluated by a very sensitive technique, based on a computer‐assisted image processing system, capable of giving several parameters about the kinetics of cell migration. Along with a significant increase in neutrophil number, a significant decrease both in random and stimulated motility was found. The kinetics of cell migration showed that the cells maintained the typical gaussian pattern of random motility. On the contrary, neutrophils were found to have lost the typical stimulated migration peak. These findings are consistent with a rhG‐CSF‐induced impairment of the directional movement, rather than of the ability of moving at random. These effects were found in patients who, in the same experimental conditions, had displayed an enhanced phagocytosis and phagocytosis‐associated chemiluminescence along with an enhanced CD32 expression, not due to an aspecific cell manipulation. Two hypotheses may be taken into account: (i) an increased adhesiveness due to a direct or an indirect activity of the cytokine; (ii) an abnormality in the cytoskeleton maturation and/or rearrangement during the accelerated bone marrow transit of myeloid cells. These findings emphasize that rh‐GCSF administration can modulate several functions which play an important role in host defence, and suggest the utility of carrying out further studies to investigate the optimum dosage both to correct neutrophil number and preserve neutrophil functional activities.

Third Generation Chemotherapy with P-VABEC for Aggressive Non-Hodgkin's Lymphomas of the Elderly

Between July 1990 and March 1992, 23 elderly patients with intermediate or high-grade non-Hodgkins lymphomas (NHL) received a combination chemotherapy (P-VABEC: Etoposide, Adriamycin and Cyclophosphamide on days 1, 15, 29, 43, Vincristine and Bleomycin on days 8, 22, 36, 50 and Prednisolone on weeks 1-9). The regimen was administered on an outpatient basis. The median age of the patients was 67 years (range 60-78); 15 were previously untreated, 8 were on second line therapy; 6 patients (44%) had stage IV disease, 19 (83%) B symptoms, 15 (65%) had bulky disease, and (26%) bone marrow involvement. The complete remission (CR) rate was 57%, and the partial remission (PR) rate 43%, with an overall response rate of (100%). No difference in response rate was observed between previously untreated patients and patients treated with P-VABEC as second-line therapy while hematological and clinical toxicity were very mild.

Consolidation Therapy with Idarubicin, Cisplatin and Prednisone (CIP) After P-VABEC Regimen in the Treatment of Intermediate and High Grade Non-Hodgkin's Lymphoma of the Elderly

Aggressive treatments in elderly patients with NHL are often responsible for acute complications and increased mortality. The present study confirms that P-VABEC is able to induce a high CR rate (71%), with an overall response rate of 92%. The 4-year actuarial OS was 45%, and the FFS was 38%. Despite these good results 57% of CRs relapsed in a relatively short time (median 9.5 months; range 2-47). Because of this we decided to evaluate the role of a consolidation schedule (CIP), including idarubicin and cisplatin. The toxicity of P-VABEC/CIP regimen was comparable to that of P-VABEC alone. After a median follow-up of 20 months (range 8-49), 93% of CR patients treated with P-VABEC-CIP were still in complete remission. The 4-year actuarial overall survival was 92%, and the failure-free survival in CR patients was 72%. The difference in OS and FFS between the two groups was statistically significant. These results suggest that a short course of additional therapy is feasible in elderly patients treated with P-VABEC and may increase the OS and FFS, without adding toxicity.

A new effective treatment for indolent lymphoma: a pilot study with fludarabine, idarubicin and prednisone combination (FLIDA)

The management of indolent lymphomas is still controversial. Intensive therapies may improve remission rate but in association with toxicity. Fludarabine and idarubicin are very active drugs in indolent lymphomas. This pilot trial was designed to evaluate the efficacy of a regimen comprising fludarabine, idarubicin and prednisone (FLIDA) in the treatment of low‐grade non‐Hodgkins lymphoma at diagnosis. We have assessed the response of 16 adult patients (median age 57 years, range 45–71 years) treated on an outpatient basis: the overall response rate was 93.8 per cent (CR 43.8 per cent, PR ≥50 per cent). The toxicity of this regimen was very low, with no relevant hematological and infectious complications.