Recombinant interferon gamma in hairy cell leukemia, multiple myelome, and Waldestrom's macroglobulinemia
ABSTRACT Fifteen patients with multiple myeloma, five with hairy cell leukemia, and five with Waldenstrom's macroglobulinemia were treated with recombinant interferon gamma (rINF-gamma) to determine the antitumor activity of this agent. The rIFN-gamma was administered by daily intramuscular injection at doses ranging from 0.125 to 0.5 mg/m2. No responses were observed in patients with multiple myeloma, although in one patient the disease has remained stable for over 16 months. Minimal improvement in some hematologic indexes were observed in three of five patients with hairy cell leukemia. One partial remission and one minor response were documented in two of the five patients with Waldenstrom's macroglobulinemia. In five patients, an increase in normal serum immunoglobulins was observed. These results suggest that there is only minimal activity of rIFN-gamma as a single agent in neoplasms of B-cell origin.
- SourceAvailable from: Graziella Bellone
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- "e l s e v i e r . c o m / l o c a t e / i n t i m p IFN-γ as conventional chemotherapy against different types of tumor, including melanoma , glioma , small-cell lung , bladder , and breast  cancers, and in hematological , ovarian , renal , and gastrointestinal   malignancies, has had limited success, with severe dose-dependent toxicity. This suggests that invivo doses route, and/or administration schedule may be inappropriate in vivo. "
ABSTRACT: Natural killer (NK) cells are innate immune-system lymphocytes capable of killing tumor cells. They secrete cytokines, including interferon (IFN)-γ, which participate in shaping the initial inflammatory and downstream adaptive immune responses. Its potent immunoregulatory action means that IFN-γ might be beneficial in cases of tumor rejection, but its severe side-effects limit clinical applications. This pilot study compared low-dose IFN-γ prepared by sequential-kinetic-activation (SKA), with standard-dose recombinant (r) IFN-γ, in terms of ex-vivo cytotoxic activity of peripheral blood (PB)-NK cells from colorectal carcinoma (CRC) patients. This was tested against the NK-sensitive K562 cell line and the less-sensitive human CRC Caco-2 and HT-29 cell lines. Twenty primitive non-metastatic CRC patients, five metastatic CRC patients, and thirteen healthy donors were enrolled. PB lymphocytes (PBLs) were exposed to medium alone, SKA-IFN-γ (0.25fg/ml) or rIFN-γ (1ng/ml). NK cell cytolytic activity was examined via short-term (51)Cr-release. Pretreatment of PBL from non-metastatic patients with SKA-IFN-γ caused a significant increase in NK cell cytotoxicity, compared to those from normal donors, although less markedly than pretreatment with rIFN-γ against all three cell lines. In contrast, PBLs from metastatic CRC patients displayed significantly decreased NK-cell activity and responsiveness to both rIFN-γ and SKA-IFN-γ treatments. These results demonstrate in principle the immunomodulatory capacity of low-dose SKA-IFN-γ, and might open the door to the possibility of generating a novel, safe, and feasible approach to enhancing NK-cell antitumor activity in early-stage CRC patients.International immunopharmacology 12/2013; 19(1). DOI:10.1016/j.intimp.2013.12.011 · 2.71 Impact Factor
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- "DISCUSSION There is no standard salvage treatment for WM patients resistant to alkylator-based therapy. Doxorubicin (Claman et al, 1980), high-dose corticosteroids (Jane & Salem, 1988) and interferon (Quesada et al, 1988) have all been evaluated in patients with resistant WM. However, response rates are typically low and responses only brief. "
ABSTRACT: This phase II clinical trial evaluated bolus cladribine as a single agent in Waldenström macroglobulinaemia (WM).Cladribine was administered to 20 patients at a dose of 0.12 mg/kg/d by 2 h intravenous infusion for 5 consecutive days at monthly intervals for three courses. Partially responding patients were continued on therapy until maximal response and/or prohibitive toxicity, to a maximum of eight courses. Complete responders were treated with one additional course of cladribine.After a median of three courses of cladribine, all 20 patients were evaluable; one achieved a complete response (CR) (5%) and 10 achieved a partial response (PR) (50%). The median duration of response follow-up was 28 months (range 1–37 months). Four of 7 (57%) untreated and 7/13 (54%) previously treated patients responded. The major toxicity encountered was myelosuppression with 60% of patients demonstrating grade 3 or 4 neutropenia. Non-haematological toxicities included two patients with herpes zoster and two patients with non-melanoma skin cancers. At a median follow-up duration of 20 months, 17 patients remain alive and three have died.We confirm that bolus cladribine is an effective and safe method of drug delivery in WM patients. Recommendations regarding the equivalence of the continuous infusion and bolus methods in untreated patients requires further study. Bolus cladribine is more convenient and less costly than infusional cladribine since it obviates the need for central catheters and infusional devices.British Journal of Haematology 11/1998; 103(3):690 - 695. DOI:10.1046/j.1365-2141.1998.01069.x · 4.96 Impact Factor
Article: Waldenström’s Macroglobulinaemia[Show abstract] [Hide abstract]
ABSTRACT: Waldenström’s macroglobulinaemia is a rare B-cell malignancy. It is prevalent in the sixth and seventh decades, the median age at diagnosis being 63 years. Conventional treatment has involved alkylator therapy, especially chlorambucil given daily at a low dose or intermittently at a higher dose. Purine analogues, used initially as salvage therapy in refractory disease, are increasingly used for initial therapy. However, purine analogue therapy entails significant complications, including immunosuppression, pancytopenia and autoimmune haemolysis. Moreover, it is unclear whether purine analogues extend survival. All of these need to be considered before initiation of therapy. More recently, anti-CD20 monoclonal antibody and thalidomide have been used with a 30% response in treated patients. High-dose therapy with stem cell support achieves a partial response in a majority of patients receiving this modality of therapy. The median survival of 5 years has not improved considerably since the introduction of purine analogues. Complete response is still uncommon; using all available modalities of therapy may increase the complete response rate and improve survival. Great strides in understanding the malignant cell, the microenvironment and the potential interactions have identified potential targets for therapy in multiple myeloma. These agents may also be useful in Waldenström’s macroglobulinaemia. Since this is a rare malignancy, all patients should be treated with well-designed clinical protocols to achieve improvement in outcome.BioDrugs 16(3). DOI:10.2165/00063030-200216030-00004 · 2.12 Impact Factor