VEPEMB in elderly Hodgkin's lymphoma patients. Results from an Intergruppo Italiano Linfomi (IIL) study.

BACKGROUND: In advanced age the prognosis of Hodgkin's lymphoma (HL) is poor, but, as a consequence of the low incidence of HL in the elderly, prospective studies are lacking and the best treatment strategy is difficult to define. PATIENTS AND METHODS: One-hundred and five HL patients over 65 years of age were treated homogeneously with an original reduced-intensity regimen designed for HL in the elderly containing vinblastine, cyclophosphamide, procarbazine, etoposide, mitoxantrone and bleomycin (VEPEMB). Forty-eight early stage (IA-IIA) patients received three courses of VEPEMB followed by involved field irradiation. Fifty-seven advanced stage (IIB-IV) patients received six courses followed by radiotherapy limited to the areas of bulky disease. RESULTS: Mean age was 71 years (range 66-83). Co-morbidities were present in 39 patients (37%). A treatment plan modification for poor tolerance or toxicity was needed in 18 patients. Results were satisfactory, even if they were better in early rather than in advanced stage disease: complete response rate 98% versus 58% (P <0.01); 5-year failure-free survival 79% versus 34% (P <0.01). The results were affected by advanced stage, systemic symptoms and co-morbidity but they were not influenced by age itself. CONCLUSIONS: VEPEMB is an effective and low toxic regimen for HL in the elderly. Co-morbidity is a prognostic factor more important than age itself.

Naturally occurring and therapy-induced antibodies to human granulocyte colony-stimulating factor (G-CSF) in human serum.

Sera were obtained from two groups of patients. Group A included 7 patients with low-grade non-Hodgkin's lymphoma treated with three or more cycles of standard-dose chemotherapy and recombinant human granulocyte-colony stimulating factor (rhG-CSF). The cytokine was administered to half the patients after the first chemotherapy cycle and to the other half after the second according to a randomized design and then to all patients from the third chemotherapy cycle on, until documented hemopoietic reconstitution. Group B included 3 patients with high-grade non-Hodgkin's lymphoma, 1 patient with resistant Hodgkin's disease, and 1 patient with multiple myeloma who received high-dose chemotherapy and rhG-CSF. Anti-G-CSF antibodies were detected in the sera of 4 patients. Both immunoglobulin IgM and IgG antibodies were detected at low levels in pretreatment sera from one group A patient. IgG antibody titers increased markedly during the first and second periods of G-CSF administration. IgG class antibodies developed in 3 groups B patients during the first course of rhG-CSF administration. Circulating anti-G-CSF antibodies did not seem to affect hematological recovery. Low levels of anti-G-CSF antibodies were also detected in sera (15/135) from different healthy adults and in sera (5/40) from umbilical cord blood. Saturable antibody binding and competition enzyme-linked immunosorbent assay (ELISA) and immunoblotting confirmed antibody specificity.

Natural and therapy-induced anti-GM-CSF and anti-G-CSF antibodies in human serum.

Serum samples were obtained from patients with lymphoid and plasma cell malignancies who received after chemotherapy human recombinant GM-CSF or G-CSF. Sera from some patients revealed the presence of anti-cytokine antibodies, particularly after repetitive cytokine injections. Antibody Fab binding in a saturable manner by ELISA and Western immuno-blotting confirmed antibody specificity. Anti-cytokine antibodies were detected before the exogenous cytokine injections in some patients, but increasing antibody levels were found after one or subsequent treatments. Low levels of anti-GM-CSF and anti-G-CSF antibodies were also detected in a relatively large proportion (about 10-30%) of normal sera from different adult healthy volunteers who had never been treated before with exologous cytokines as well as from cord blood. EBV-immortalized cord blood derived B-cell cultures were also found to produce anti GM-CSF and/or anti-G-CSF antibodies with high frequency.