PubMed Health⌕ Search

Biomedical subjects

M Aapro

Publications and source records attributed to M Aapro.

64 records · Page 4Linked to original sources

[Super intensive treatment followed by bone marrow autograft in cases of hematologic neoplasms and solid tumors].

Thirty-one patients underwent autologous bone marrow transplantation (ABMT) after intensive radio and/or chemotherapy. On 18 occasions, bone marrows were treated in vitro with either Asta-Z 7557, Asta-Z 7654 or the rat monoclonal antibody Campath-1M and complement. Sixteen patients were transplanted for acute leukemia: 6 patients were in first complete remission (CR), 5 in CR greater than 1 and 5 in relapse. Twelve out of fourteen evaluable patients have relapsed. Two patients transplanted in CR 2 and CR 1 remain in CR after 9.5 and 12 months respectively. Nine patients were transplanted for aggressive lymphoma: four patients were in CR 1, 2 in CR greater than 1, 1 in first relapse and 2 refractory to best available second line chemotherapy. All 3 achieved CR after ABMT. Nine patients are evaluable: 4 relapsed and 5 remain in CR at 5, 6.5, 21, 25 and 39 months, this last patient transplanted in a refractory state, the others in CR 1. Four patients were transplanted for refractory Hodgkin's disease: 3 patients are evaluable. One patient achieved complete remission which lasted 9 months. Two patients were transplanted for relapsed solid tumors and achieved a partial response. In conclusion, the response rate is encouraging for patients transplanted during active and sometimes refractory phases of the diseases (8/13 evaluable patients achieved CR). However, for the whole group of patients, including those transplanted for acute leukemia in CR 1, the relapse rate was high. Durable remissions were achieved for patients with aggressive lymphoma who were transplanted early in the disease.

Acute Disease↗

Cell cultures and detection of minimal residual disease: significance and limitations.

This introductory article puts into perspective the usefulness of cell cultures in the area of detection of minimal residual disease. We stress the role of single cell cultures in selective media as a means to increase the number of residual tumor cells, thereby facilitating their detection by other methods. Prior treatment may affect the growth potential of cells for a very long time. Quantitation of the event to be detected is thus highly dependent on the characteristics of the cells which are also influenced by their growth environment. This environment may be optimized by the judicious use of growth factors in defined media.

Antineoplastic Agents↗

[Quantitative detection and elimination of neuroblastoma cells in vitro. Comparative study of the efficacy of an immunomagnetic method and lymphokine-activated killer cells].

Much effort is devoted to eliminating residual tumor cells - which escape detection by conventional methods - from remission bone marrow harvested for autologous transplantation. The quantitative determination of the efficacy of these purging methods is generally difficult. This report describes an in vitro reproducible tumor model. Normal mononuclear blood cells were deliberately contaminated with cells from the human neuroblastoma cell line SK-N-AS. The frequency of clonogenic SK-N-AS cells was determined in limiting dilution culture before and after treatment. Two methods of purging these tumor cells from the mixed cell suspension were compared, 1) an immunomagnetic method taking advantage of the existence of a monoclonal antibody (mAb) specific for 90-95% of the tumor cells, and 2) a method based on cell mediated cytotoxicity testing the activity of previously lymphokine activated killer (LAK) cells. Immunomagnetic purging eliminated 90% (1 log) of all SK-N-AS cells and 99% (2 log) of the mAb-binding clonogenic tumor cells. In contrast, LAK cell treatment removed only between 0.1 to 0.3 log (23-50%) of the clonogenic SK-N-AS cells.

Antibodies, Monoclonal↗

Quantity and nature of residual bone marrow T cells after treatment of the marrow with Campath-1.

Precise characterization of T-cell depletion in marrows used for transplantation is necessary for the evaluation of their potential contribution to engraftment and to graft-versus-host disease. A limiting dilution culture method that allows the determination of small numbers of bone marrow T cells is described. It can detect less than one T cell in 10(4) cells. Bone marrow T-cell depletion with the rat monoclonal antibody Campath-1 and fresh human complement results in a median decrease of 1.7 log (range, 1.6-2.1 log) of marrow T cells. A 2.7 to 3.3-log reduction is obtained when peripheral blood T cells are treated. A second incubation with fresh complement removes additional T cells from peripheral blood and from marrow samples, indicating the importance of bystander marrow cells to complement activity. The assay system described also allows the phenotypic study of responding cells growing in culture. These studies demonstrate that, after treatment with Campath-1 plus complement, no T-subset imbalance occurs. Furthermore, the T cells in these cultures are derived from mature T cells contained in the samples.

Antibodies, Monoclonal↗

[Effect of T-cell depletion of the graft on graft survival and graft vs host disease].

A limiting dilution culture method has been developed which allows the detection of small numbers of residual marrow T cells following their depletion with the monoclonal antibody Campath-I and autologous complement. In seven consecutive patients the degree of T cell depletion obtained was 1.82 (1.27-2.82) log. The number of nucleated cells per kg decreased by 50% and the number of CFU-GM per kg decreased by 60%. In all except one case marrow cellularity was found to be satisfactory 3 weeks after the transplant. Peripheral engraftment of granulocytes (greater than 500/mm3 on day 20, greater than 1000/mm3 on day 27), lymphocytes (greater than 500 on day 39, greater than 1000 on day 66), platelets (greater than 20,000 and self-sustained after day 24) and red blood cells (day to last infusion = 19) indicated a delay in recovery of lymphocytes and possibly granulocytes, but not platelets or red blood cells, compared to the engraftment seen in non-T depleted patients. No correlation between nucleated cells infused, GFU-GM and engraftment was found. However, the extent of T cell depletion apparently affects lymphocyte, and possibly granulocyte, recovery. The delay in lymphoid engraftment is also reflected by nonresponsiveness to alloantigens during the first 6-9 months following marrow grafting in the absence of graft vs. host disease.

Graft Survival↗

An effective five-drug antiemetic combination for prevention of chemotherapy-related nausea and vomiting. Experience in eighty-four patients.

Antiemetics of known efficacy have been shown to block mainly one of three neurotransmitter receptors in the brain. A combination of antiemetics, designed specifically for outpatient use and consisting of metoclopramide, thiethylperazine, diphenhydramine, dexamethasone, and diazepam, is capable of blocking multiple sites in the emesis pathway. Eighty-four patients receiving highly emetic chemotherapy (85% received cisplatin) completed 200 trials of this five-drug combination using two similar regimens. Complete control (i.e., no nausea or vomiting) was achieved in 45% and two or fewer episodes of vomiting was experienced in 72% of these 200 trials. The mean number of vomiting episodes was 1.65, the median 1.0, and the range 0-15. Sedation was nearly universal, although no serious toxicity was encountered. Thus, this antiemetic combination designed for outpatient use proved highly effective in controlling nausea and vomiting associated with highly emetic anticancer treatment.

Adolescent↗

Clinical efficacy of cancer subcutaneous immunotherapy with interleukin-2 in relation to the pretreatment levels of tumor growth factor insulin-like growth factor-1.

AIMS AND BACKGROUND: IGF-1 has been proven to be one of the most important growth factors for normal and neoplastic cells. Abnormally high levels of IGF-1 have been observed in cancer patients. Since it has been demonstrated that some growth factors may counteract the action of antitumor cytokines, the presence of increased IGF-1 concentrations could reduce the efficacy of cancer biotherapies with cytokines, such as IL-2. The present study was performed to evaluate the efficacy of IL-2 immunotherapy in relation to the pretreatment levels of IGF-1 in advanced cancer patients. METHODS: The study included 20 consecutive patients with metastatic renal cell cancer who were treated subcutaneously with IL-2 at 6 million IU/day for 5 days/week for 6 weeks. IGF-1 serum levels were measured by RIA on venous blood samples collected before the immunotherapy, after 3 weeks, and at the end of IL-2 injection. RESULTS: Objective tumor regressions were obtained in 5/20 patients, consisting of 1 complete response (CR) and 4 partial responses (PR). Nine patients had stable disease and the last 6 patients progressed. Abnormally high pretreatment levels of IGF-1 were seen in 13/20 patients. The percent of clinical responses (CR + PR) was significantly higher in patients with normal pretreatment concentrations of IGF-1 than in those with elevated levels (4/7 vs 1/13, P < 0.01). No significant changes in mean IGF-1 levels occurred during IL-2 therapy. However, mean IGF-1 levels increased in progressing patients and decreased in those with a response or stable disease, even though none of the differences was statistically significant. CONCLUSIONS: The study showed that high pretreatment levels of IGF-1 are associated with a reduced efficacy of IL-2 immunotherapy of renal cancer. Further studies are required to establish whether IGF-1 levels simply reflect the extension of disease, or whether they may influence per se the action of IL-2.

Analysis of Variance↗