In vitro selective effect of melphalan on human T-cell populations

Ben-Efraim, Shlomo; Komlos, L.; Notmann, J.; Hart, Jacob; Halbrecht, I

doi:10.1007/bf00199312

Cited by 10 publications

(4 citation statements)

References 14 publications

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“…The effects of anticancer drugs on human lymphocyte subsets have been reported by several investigators [3,4]. Previously, we found that the distribution of T cell subsets in PBM from cancer patients after Adriamycin administration showed a significant increase of CD8 + cells, while no significant difference was observed in the CD4 + populations [2].…”

Section: Discussionmentioning

confidence: 90%

Augmentation of the generation of lymphokine-activated killer cells after a single dose of mitomycin C in cancer patients

Nakamura

Arinaga

Akiyoshi

1989

Cancer Immunol Immunother

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The effect of mitomycin C administration on the generation of cytotoxic cells, induced by in vitro activation of peripheral blood mononuclear cells (PBM) with interleukin-2, was studied in patients with various carcinomas. The ability of PBM to generate lymphokine-activated killer (LAK) cell activity against Raji cell targets was significantly augmented 5 and 7 days after a single intravenous dose of 12 mg/m2 mitomycin C, when compared to that of PBM obtained before mitomycin C injection. Further, LAK cell activity against autologous tumor cells was also significantly increased after the drug administration. The distribution of lymphocyte subsets exhibited a significant increase in the percentage of CD3+ cells after injection, with the elevation of the CD4/CD8 ratio. Furthermore, the proportion of the CD4+ Leu8+ subpopulation, which identifies inducers of suppression, was significantly reduced. Thus, the decrease in the proportion of suppressor-inducer subsets of PBM might be at least partially, responsible for the augmented generation of LAK cells after mitomycin C administration.

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Section: Discussionmentioning

confidence: 90%

Augmentation of the generation of lymphokine-activated killer cells after a single dose of mitomycin C in cancer patients

Nakamura

Arinaga

Akiyoshi

1989

Cancer Immunol Immunother

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“…In addition, the use of newer chemotherapeutic agents as a part of the conditioning regimen likely has a greater impact on CMVspecific T cell immunity than the use of melphalan CMV viremia associated with fever, n (%) 2 (50.0) 5 (45.5) 5 (55.6) 5 (62.5) 3 (37.5) Biopsy-proven invasive CMV disease, n (%) 0 (0.0) 0 (0.0) 1 (11.1) 0 (0.0) 0 (0.0) CMV treatment, n (%) 8 No alone. In terms of chemotherapeutic effects, melphalan is associated with bone marrow suppression, including neutropenia [19], and decreased numbers of T lymphocytes, including CD4 1 T cells [20]. Along with causing neutropenia, bortezomib diminishes the proliferation and function of CD8 1 T lymphocytes as well as NK cells [21].…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus Reactivation Following Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma in the Era of Novel Chemotherapeutics and Tandem Transplantation

Goulston

Sanders

Lampas

et al. 2012

Biology of Blood and Marrow Transplantation

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Cytomegalovirus (CMV) is an important pathogen after allogeneic transplantation. However, few studies have examined CMV reactivation after autologous peripheral blood stem cell transplantation (APBSCT) to treat multiple myeloma (MM), especially in the setting of the newer chemotherapeutic agents and/or 2 sequential APBSCTs (ie, tandem transplantation). A retrospective chart review of patients with MM who underwent either single APBSCTor tandem transplantation was conducted to evaluate the incidence, risk factors, and outcomes of CMV infection at a single institution. A total of 104 patients with MM underwent transplantation during the study period, including 66 patients who received tandem transplantation. The majority of patients (66 of 104; 63.5%) were CMV-seropositive, and CMV viremia was frequently detected in this subgroup (32 of 66; 48.5%). No primary CMV infections were identified. CMV reactivation was more common in recipients of tandem transplantation than in recipients of single APBSCT (P \.001). In addition, patients who developed CMV viremia were more likely to have received conditioning therapy with melphalan, bortezomib, dexamethasone, and thalidomide compared with those without CMV reactivation (P 5 .015). However, on multiple logistic regression analysis, only receipt of tandem transplantation was significantly associated with CMV reactivation (odds ratio, 5.112; 95% confidence interval, 1.27-20.60; P 5 .022). Febrile episodes of CMV viremia were observed in 17 patients (17 of 32; 53.1%), and invasive CMV disease was diagnosed in 1 patient. Our data suggest that CMV reactivation after APBSCT for MM is relatively common, and that viremia is often associated with fever. CMV surveillance should be considered, especially when tandem transplantation is performed using combination chemotherapy with high-dose melphalan.

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“…Arguments in favor of extrapolation from experimental animal tumor models to human neoplasia are based on the similarity between the immune system pattern and function of immunocompetent cells and of their soluble products as well as on the similarity between certain induced animal tumors and corresponding human tumors. Moreover, certain anticancer reagents like alkylating drugs reveal similar activity against murine and human cells: Thus, CY and L-PAM act selectively, both against murine suppressor T cells [66] and against human suppressor T cells [67]. On the other hand, the dissimilarities between human cancer and experimental tumor mod-7 els render extrapolation extremely difficult.…”

Section: Human Tumor Xenografts In Immunodeficient Micementioning

confidence: 99%

One Hundred Years of Cancer Immunotherapy: A Critical Appraisal

Ben-Efraim

1999

Tumor Biology

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First attempts of cancer immunotherapy were made approximately 100 years ago on the assumption that tumor cells are recognized as ‘foreign’ by the immune system. Later on, a whole series of experimental animal tumor models were developed. They included the use of syngeneic tumors, spontaneously arising tumors and human tumor xenografts in immunodeficient mice. The experimental data contributed to our understanding of the interaction between immunocompetent cells and their products on the one hand and tumor cells on the other. On this basis, various immunotherapeutic protocols have been devised which included the use of ‘nonspecific’ components such as bacterial adjuvants, cytokines, NK cells and macrophages and attempts were made to raise specific T and B cell responses against tumor cells. Many human tumor-associated antigens have been characterized, and various ways of increasing the immunogenicity of human tumor cells have been described. Moreover, more insight has been achieved in defining ‘high risk’ populations on the basis of genetic background, the role of environmental factors and the characterization of ‘precancerous’ cells. Some cancer vaccines have been used in clinical trials which have resulted in partially beneficial therapeutic effects but have not provided a full solution for a rational use of immunotherapy against human neoplasia.

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In vitro selective effect of melphalan on human T-cell populations

Cited by 10 publications

References 14 publications

Augmentation of the generation of lymphokine-activated killer cells after a single dose of mitomycin C in cancer patients

Augmentation of the generation of lymphokine-activated killer cells after a single dose of mitomycin C in cancer patients

Cytomegalovirus Reactivation Following Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma in the Era of Novel Chemotherapeutics and Tandem Transplantation

One Hundred Years of Cancer Immunotherapy: A Critical Appraisal

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