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Biomedical subjects

G Rosti

Publications and source records attributed to G Rosti.

At least 127 records · Page 7Linked to original sources

Mitoxantrone (M) and vinblastine (V) in the treatment of advanced breast cancer.

Twenty-four patients with metastatic breast cancer, all but 1 pretreated with one or more chemotherapeutic regimens, were entered in a pilot study to assess toxicity and efficacy of the combination mitoxantrone and vinblastine. Dominant sites of metastases were viscera in 9 patients, bone in 10 and soft tissues in 5. All patients received mitoxantrone 10 mg/m2 i.v. on day 1 and vinblastine 1.7 mg/m2 by 4 hour infusion on days 3, 4 and 5, every 3-4 weeks. Objective responses (1 CR, 7 PR) were observed in 8 (38%) of the 21 evaluable patients. Median duration of response was 10.5 months. Of 12 patients pretreated with an anthracycline containing regimen, 4 responded (1 CR and 3 PR). Major toxicity was myelosuppression, grade 4 in 2 cases and grade 3 in 2 others. No evident alopecia was observed and only 1 case of grade 1 cardiac toxicity. In conclusion, mitoxantrone followed by vinblastine is an effective regimen in metastatic breast cancer also in pretreated patients, and previous anthracycline administration does not seem to reduce the percentage of response. Moreover, toxicity is generally mild.

Adult↗

Cytogenetic and molecular studies in patients with chronic myeloid leukemia and variant Philadelphia translocations.

Out of 105 Philadelphia (Ph) positive chronic myeloid leukemia patients analyzed, six (5.7%) carried a variant Ph translocation, namely t(6;9;9;10;22)(q24;p13;q34;p15;q11); t(9;13;22)(q34;q21;q11);der(2)(2pter----2q31::9q21---- 9q34::22q11----22qter) and der(9)t(2;9) (9pter----9q21::2q31----2qter);t(7;9;22)(q11;q34 ;q11), 14q + ;t(7;9;22)(q35;q34;q11), and t(9;11;22) (q34;q13;q11), respectively. Five of these patients were analyzed with Southern blotting. Three of them showed an atypical molecular pattern; namely, the patient with t(9;13;22) showed no rearrangement in the breakpoint cluster region (bcr), the patient with t(7;9;22)(q35;q34;q11) showed a 3' deletion, and the patient with t(7;9;22), 14q + showed a bcr rearrangement 3' to the exon 4 of the M-BCR. Chromosome in situ hybridization studies demonstrated that in patient one, a two-step translocation occurred: the first step moved the 3' bcr from chromosome 22 to chromosome 9, and the second moved the terminal part of 22q, carrying the c-sis protooncogene, to 10p. Variant Ph translocations appear to be associated with atypical molecular breakpoints.

Chromosome Banding↗

Depression and abnormal illness behavior in cancer patients.

Evaluation of the incidence of depression among cancer patients has been the object of a number of studies. Recent reports of medically ill patients have indicated that depression is related to several dimensions of abnormal illness behavior (e.g., hypochondriasis, irritability, denial, disease conviction). To investigate the relationship between depression and abnormal illness behavior in cancer patients, a study was conducted of 196 patients with a recent diagnosis of cancer and with a good performance status (Karnofsky score greater than 80). The Hamilton Depression Rating Scale (HDRS) and the Illness Behavior Questionnaire (IBQ) were administered in their validated Italian forms. A cutoff point of 17 on the HDRS revealed 38.26% of the patients as having symptoms of depression, whereas a more conservative cutoff point of 21 indicated a depressive state in 23.97% of the patients. Depressed patients had higher scores on all the IBQ dimensions except that of psychologic versus somatic perception of illness. The results were confirmed by the correlation between the parameters. Higher levels of denial were reported by females and by patients receiving adjuvant or palliative chemotherapy, who had, however, lower levels of dysphoria than patients not receiving treatment. Higher levels of irritability were shown in hospitalized patients. No relationship was found between medical status variables (Karnofsky score, tumor status, and disease extent) and psychologic measures, except for denial. The findings seem to confirm the importance of assessment of depression and illness behavior in cancer patients and suggest the need for more thorough investigation of the psychosocial variables associated with them.

Adult↗

Autologous bone marrow transplantation with immunotoxin-purged marrow for advanced multiple myeloma.

A system to purge the bone marrow of myeloma cells has been developed in our laboratories with the aim of treating with myeloablative radiochemotherapy patients suffering from advanced multiple myeloma. This system is based on the ex vivo incubation of the marrow with an immunotoxin composed of the 8A monoclonal antibody--that recognizes plasma cells and B-cell precursors--and the ribosome-inactivating protein momordin. 8 patients have so far been treated. 4 are surviving from 4 to 18 months after ABMT, whereas 4 died after 1 to 6 months, 2 from infections, 1 from relapsing disease and 1 from veno-occlusive disease. A marked tumour reduction was observed in all evaluable patients; however, none has achieved complete disappearance of the disease. The haemopoietic reconstitution was significantly delayed in 3 patients. These preliminary results show the feasibility of this approach in advanced MM patients with heavily infiltrated marrow. The place of ABMT in the treatment of MM remains to be determined; the selection of patients with still responding and less advanced disease would probably produce better results.

Adult↗

High-dose chemoradiotherapy and allogenic bone marrow transplantation in multiple myeloma.

17 patients with multiple myeloma (MM) received marrow transplants from their HLA-matched, MLC-negative sibling donors. 9 patients had progressive disease not responding to conventional treatments, while the other 8 patients were rated as responders. The most frequently used conditioning regimen consisted of total body irradiation and high-dose, multi-agent chemotherapy with cyclophosphamide plus either oral melphalan (5 cases) or BCNU (1 case) on both these drugs (7 cases). 12 patients were evaluable for response to BTM: 7 of them (6 responders and 1 with advanced refractory MM) entered complete remission, while 5 had a sustained decrease in tumor mass that ranged between 72% and 93%. 11 patients died of transplant-related causes, 1 of them with signs of progressive disease. The remaining 6 patients are alive and 5 of them maintain a complete remission status 4 to 67 (median 36) months after BMT. It is concluded that therapeutic benefits of transplantation in MM are still offset by the high mortality related to the procedure. A more accurate selection of patients who would most benefit from BMT and performing transplant at an earlier phase of the disease are warranted before major advances can be made in the cure of these patients.

Adult↗

High-dose etoposide and autologous bone marrow transplantation as intensification treatment in small cell lung cancer: a pilot study.

A pilot study was conducted in which 15 patients with small cell lung cancer (SCLC) with limited or extended disease were treated with high dose etoposide (600 mg/m2 daily for 3 consecutive days) followed by autologous bone marrow transplantation (ABMT). Twelve patients underwent a double graft. All had achieved complete or partial remission with conventional induction chemotherapy (adriamycin and etoposide, plus cisplatin in five cases). After ABMT six of the 15 patients did not receive radiotherapy to the chest; all but four patients received prophylactic brain irradiation. No toxic deaths were recorded during the period of aplasia. Eleven patients relapsed and died after ABMT. The median time to death was 18 months. One other patient died at 13 months of unknown cause. At the present time three patients are alive and free of disease at 54, 51 and 47 months respectively. This pilot study shows that high dose etoposide and ABMT is well tolerated as late intensification for responsive SCLC. Definite conclusions about its precise role in therapy cannot yet be drawn.

Adult↗

Allogeneic bone marrow transplantation for multiple myeloma.

Seventeen patients received marrow transplants from their HLA-matched, MLC-negative, sibling donors. Nine patients had progressive disease not responding to conventional treatments, while the other 8 patients were rated as responders. The most frequently used conditioning regimen consisted of total body irradiation and high-dose multi-agent chemotherapy with cyclophosphamide plus either oral melphalan (5 cases) or BCNU (1 case) on both these drugs (7 cases). Twelve patients were valuable for response to BTM: 7 of them (6 responders and 1 with advanced refractory MM) entered complete remission, while 5 had sustained decrease in tumor mass that ranged between 72% and 93%. Eleven patients died of transplant-related causes, 1 of them with signs of progressive disease. The remaining 6 patients are alive and 5 of them maintain a complete remission status 4 to 67 (median 36) months after BMT.

Adult↗

Relapse after allogeneic bone marrow transplantation for Philadelphia chromosome positive chronic myeloid leukemia: cytogenetic analysis of 24 patients.

One hundred patients with chronic myeloid leukemia (CML) submitted to bone marrow transplantation (BMT) were included in a cooperative cytogenetic study. Relapse (defined on the basis of hematological and cytogenetic findings) occurred in 24 (24%) patients at different intervals after BMT. In 18 of these patients (studied on average 3.3 times between BMT and relapse) no Ph-positive metaphases were detected before relapse. Sixteen (75%) of the patients relapsed with the same chromosomal pattern as that seen before BMT; eight patients, of whom five relapsed in blast crisis, showed additional chromosomal abnormalities resembling those seen in non-transplanted patients. One of these patients relapsed in cells of donor origin. After recognition of relapse, various hematological and cytogenetic patterns were observed. Four patients showed spontaneous reversion to normal (donor-type) chromosomes and hematology. Two other patients were followed for prolonged periods with hypercellular marrows with more than 50% Ph-positive cells but with normal peripheral blood values. The majority of patients proceeded to clinical relapse and required treatment with chemotherapy. We conclude that the isolated finding of a minority of Ph-positive metaphases after BMT should not be classified as relapse; for patients who do relapse, the sequence of cytogenetic and hematological events thereafter is variable.

Adolescent↗

Metastases to the submaxillary gland from breast cancer: case report.

A case of metastases to the submaxillary gland from breast carcinoma is reported. The patient, a 68-year-old female, had been operated for a stage II N+ breast carcinoma 4 years before. She then received six courses of CMF adjuvant program. A literature review is presented concerning the 8 well-documented cases reported.

Aged↗

Cyclophosphamide, methotrexate,5-fluorouracil, alternating with adriamycin and mitomycin C in metastatic breast cancer: a pilot study.

To explore the clinical applicability of the Goldie and Coldman hypothesis, we treated 28 patients with metastatic breast cancer with alternating non-cross-resistant chemotherapy. The patients received cyclophosphamide, 600 mg/m2, 5-fluorouracil, 600 mg/m2, methotrexate, 40 mg/m2, alternated every three weeks with adriamycin, 60 mg/m2, and mitomycin C, 10 mg/m2. Only one patient had previously received palliative chemotherapy. Six patients had received adjuvant CMF, and 17 patients had been pretreated with endocrine therapy (13 for advanced disease, 4 as adjuvant). Fourteen patients had bone involvement, and 10 had visceral metastases. A mean of 12 cycles was given to 24 evaluable patients. The objective response rate was 67%: 11 patients (46%) achieved complete and 5 (21%) partial remission. Response rate in soft tissues was 83.3%, in bone 50%, in liver 100%, and in lung 80%. The median duration of response was 14 months, with 7 patients still in remission. No life-threatening toxicity was observed. Our preliminary results support the validity of this approach and the efficacy of this combination chemotherapy. A large-scale randomized study is warranted.

Adult↗