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Granulocyte-macrophage–colony stimulating factor (GM-CSF) administration stimulates the proliferation of hemopoietic progenitors. Shortly (48–96 hours) after its discontinuation, feedback phenomena occur and the progenitor proliferation rate drops below baseline levels. As the quiescence of hyperplastic bone marrow suggests that hemopoietic cells may be refractory to the toxic effects of cytostatic drugs, the decision was made to test the hypothesis that GM-CSF given before chemotherapy may be myeloprotective. Fifty-six patients with newly diagnosed Stage II–IV Hodgkin disease, ages 18–77 years, were randomized to receive GM-CSF (5 μg/kg subcutaneously) or placebo from Day 7 to Day 4 before each chemotherapy administration (6 cycles of a hybrid of mechlorethamine, vincristine, procarbazine, and prednisone with doxorubicin, bleomycin, vinblastine, and dacarbazine). The treatment was considered a success if the delivery rate of chemotherapy was >90% after 3 cycles and >80% after 6 cycles. Thirty patients received GM-CSF and 26 placebo. The dose intensity (85.2% vs. 79.6%) and the overall success in terms of delivery rate (56.7% vs. 50%) were higher in the GM-CSF group, although these differences were not statistically significant. The neutrophil nadirs were higher in the GM-CSF group during the first three cycles and subsequently similar in both groups. No significant differences in terms of myelotoxicity or drug delivery were observed between the two treatment arms. Although the myeloprotective effect of the prechemotherapy administration of GM-CSF seems to be minimal, the data indicate a safe timing between GM-CSF discontinuation and further chemotherapy. Because cumulative myelotoxicity has been observed with other growth factors, given in the interval between the chemotherapy cycles, this may be relevant to the planning of rapid cycling. Cancer 2000;88:454–60. © 2000 American Cancer Society.

Until now, literature data support the fact that the CHOP regimen represents the standard first line treatment for patients with advanced intermediate-grade non-Hcdgkin's lymphoma. Recently, idarubicin has been introduced in clinical trials because of its favourable preclinical profile: it is more active than daunorubicin and doxorubicin against a number of experimental tumour systems and is significantly less cardiotoxic in animal models. From March 1991 to June 1993, 115 previously untreated patients with stage II to IV intermediate-grade non-Hodgkin's lymphoma, according to the Kiel classification, were enrolled in a phase III comparative trial. The objectives of the study were to compare the efficacy and safety of using idarubicin instead of doxorubicin in the polychemother-apeutic regimen CHOP (cyclophosphamide, doxorubicin, vincristine, and dexamethasone). Of the 115 patients registered for the trial, 103 were cvaluable: 52 received CH(doxorubicin)OP and 51 received CI(Idaruhicin)OP. Known prognostic factors were equally distributed among the two groups. There were no significant differences between the 2 groups in the rates of partial and complete response. The overall response rate was 87%. with complete response in 62%: 638 in the CHOP group, and 59% in the CIOP group. At 30 months (median 20 months), 868 of all CR patients were alive without disease in the CHOP group and 85% in the CIOP group. Patients treated with CHOP experienced Severe alopecia more frequently (P = .004). Only three patients in the CIOP group showed cardiac adverse event (I moderate and 2 mild), while in the CHOP group 4 mild, 2 moderate and I severe were recorded. LVEF monitoring was carried out in 31 patients of the CHOP group and in 27 of the CIOP group. A median drop of 8.3% of the LVEF was observed in patients treated with CHOP regimen as compared to 4.8% in patients with CIOP regimen (P = .OOO1). In this trial, the "idarubicin arm" (CIOP regimen) was found to have an equivalent therapeutic efficacy and, slightly, reduccd clinical toxicity in comparison to the standarddoxorubicin-containing CHOP rcgimen in patients with intcrmediate-grade non-Hodgkin's lymphoma.

Non-Hodgkin lymphomas (NHL) of the Central Nervous System (CNS) are rare but they nonetheless consistute a clinical, biological and therapeutic problem of great interest. Primary lymphomas of the CNS account for 2% of all malignant lymphomas and for 0.3–1.5% of all intracranial tumors. Surgery and radiotherapy afford only poor control of the disease. The most satisfactory results have been achieved with combination therapy, surgery+radiotherapy+chemiotherapy, but the optimal combination has still to be devised. Secondary neuromeningeal involvement affects a fair number of patients with systemic NHL. The symptoms are broadly the same as in CNS NHL and the treatment as problematic. There have recently been suggestions that the onset of CNS NHL may be exacerbated by immunodeficiency states such as occur in patients who have undergone organ transplantation, in autoimmune disease and, still more recently, in the acquired immunodeficiency syndrome (AIDS). The frequency of these tumors is anyway on the increase and a better insight into the disease in essential.

Abstract:  Conventional cytogenetics is considered the gold standard for evaluating CML during interferon (IFN) treatment. Drawbacks to this approach are the small number of metaphases available during IFN therapy and the impossibility of scoring interphase cells. We applied, besides cytogenetics, double-color FISH (dc-FISH) detection of BCR-ABL gene fusion to monitor 20 CML patients on IFN. dc-FISH easily detected 200 cells per specimen, while with cytogenetic examination a mean of 16.1 mitoses per sample were scored. Though the correlation of dc-FISH and cytogenetic data was good (r=0.77, p<0.001), the discrepancy between the two methods as regards the proportion of leukemic cells in the marrow was often important. dc-FISH detected a relevant proportion of BCR-ABL+ cells in three patients classified as complete cytogenetic responders and showed that, after 9–12 months of IFN treatment, a significant reduction of BCR-ABL+ cells was present in all the 20 patients tested. This might suggest that all CML patients are potentially responsive to IFN. Though more data are required, we think that dc-FISH is more informative than cytogenetic analysis for CML monitoring. Notably because of the simplicity of the procedure, this method could be easily standardized among different laboratories, thus permitting cross-comparison in therapeutic trials.

A prospective randomized study on aggressive non-Hodgkin's lymphomas was conducted by investigators at several Italian institutions with the intent of comparing two third-generation conceptually different regimens: the regimen containing methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B), a short-term continuous twelve-week therapy, and F-MACHOP (5-fluorouracil, methotrexate with leucovorin rescue, cytarabine, cyclophosphamide, doxorubicin, vincristine, and prednisone), a monthly intensive cyclic treatment combining prednisone with six active non-cross-resistant cytotoxic drugs. The goals of this study were the response rate, relapse-free survival, and incidence of hematologic and nonhematologic toxicities.Two hundred-eighty-six patients included between 15 and 60 years fulfilled the criteria for entry to the study; 140 patients were treated with MACOP-B and 146 with F-MACHOP. The minimum follow-up was 24 months. Clinical characteristics of all patients were similar and known prognostic factors were equally distributed between the two groups. Complete remission (CR) was achieved by 61% and 67% of the patients treated with MACOP-B and F-MACHOP, respectively; 4% and 6% were primarily resistant, 2% and 5%, respectively, died of causes directly related to therapy. At 50 months, 74% of all CR patients were alive without disease and there were no significant differences in relapse-free survival between the two groups: 75% in the F-MACHOP group and 73% in the MACOP-B group at 50 months. There was a higher incidence of mucositis among patients treated with MACOP-B than among those given F-MACHOP (11% vs 3.5%). Higher incidences of severe cytopenia (51% vs 21%) and of fatal sepsis (5% vs 2%) were recorded among patients treated with F-MACHOP than with MACOP-B.The third-generation regimens, F-MACHOP and MACOP-B, are as effective as other regimens. A prognostic analysis taking into account the principal covariates (age, symptoms, stage, serum lactate dehydrogenase, mediastinum involvement, bulky disease, histology, therapy, and dose intensity) was assessed for their impact on complete response rate incidence and on relapse rate from complete response by multivariate analysis. The linear logistic model showed that symptoms, advanced stage, mediastinum involvement, and bulky disease are prognostic factors that increase the risk of a lower rate of complete response. These data confirm the important role of a pretreatment selection for the poor-risk patients and, on the basis of these parameters, it will probably be possible to consider these patients for high-dose therapy with autologous bone marrow transplantation or autologous hematopoietic stem-cell support.