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Biomedical subjects

L Gandola

Publications and source records attributed to L Gandola.

At least 37 records · Page 2Linked to original sources

Long-term outcome of patients with monostotic Ewing's sarcoma treated with combined modality.

One hundred and twenty-one consecutive patients with monostotic Ewing's sarcoma (ES) were treated according to three consecutive combined modality programs from 1974 to 1986. Their 3-year progression free survival (PFS) rate from diagnosis of 59% was identical to the event free survival (EFS) rate, since all the 50 events occurring within 3 years from diagnosis were tumor recurrences. Primary tumor was treated with radiotherapy in 75 cases, surgical resection plus radiotherapy in 38, and radical surgery in 8. Chemotherapy was given to all patients and each program included adriamycin, vincristine, and cyclophosphamide +/- dactinomycin. Median follow-up was 12 years, ranging from 6 to 19 years. The PFS rate decreased to 49% at 6 years and plateaued at 46% after the 7th year from diagnosis, even though some relapses were observed as late as 14 years from diagnosis. Second malignancies developed in 7 patients free from progressive ES and were represented by osteogenic sarcoma in previously irradiated bone in 4 cases and by breast carcinoma in 3. No other event but tumor relapse or second malignancy occurred in this series. EFS rate was 47% at 6 years and 39% at 12 years, further decreasing in the following years because of a number of late events. A continuous PFS longer than 7 years may be consistent with cure in the majority of patients with monostotic ES. However, these patients should be followed indefinitely because of risk of second malignancies.

Adolescent↗

Histoplasmosis capsulati in Italy: autochthonous or imported?

Reports of a few apparently autochthonous cases of human histoplasmosis and results of epidemiological research suggested the autochthonous presence of the disease in Italy. Identifying two new histologically documented cases of Italian patients, who had never been abroad, and, the positive results of a histoplasmin reactivity survey carried out in the Province of Cremona, Italy confirmed this possibility.

Adolescent↗

Durability of hematopoiesis following autografting with peripheral blood hematopoietic progenitors.

BACKGROUND: It is still not known whether hematopoiesis reconstituted by autografting with the peripheral blood hematopoietic progenitors (CPCs) after myeloablative high dose radiotherapy and/or chemotherapy is durable and capable of coping with the increased demand imposed by boost radiotherapy, surgery, or infection. PATIENTS AND METHODS: The durability of hematopoiesis was evaluated in 34 consecutive cancer patients treated with myeloablative total body irradiation (n = 17, median follow-up 3 years, range 3-49 months) and/or alkylating-agent chemotherapy (n = 17, median follow-up 8 months, range 6-41 months) and autografted with CPCs because bone marrow autografting was contraindicated. CPCs (> or = 8 x 10(6) CD34 + cells/kg) had been collected during mobilization into the circulation in response to previous anticancer therapy and hematopoietic growth factor(s). RESULTS: Following brief temporary pancytopenia, all patients achieved normal and durable hematopoiesis. The newly reconstituted hematopoietic system was capable of reacting favorably to stressful and debilitating events such as surgery, radiotherapy, or varicella-zoster infection. No secondary irreversible failure of blood cell production occurred. CONCLUSIONS: The documentation of the durability of normal hematopoiesis following myeloablative cancer therapy and autografting with mobilized CPCs implies that the latter procedure, rather than being solely an alternative to bone marrow autografting, represents an advantageous tool of choice permitting substantial amelioration of the therapeutic index of high-dose cancer therapy.

Adult↗

Severe exacerbations of chronic obstructive pulmonary disease treated with BiPAP by nasal mask.

Bi-level pressure support ventilation via a nasal mask (NIPSV) was provided to 28 consecutive unselected patients with acute respiratory failure due to exacerbation of chronic obstructive pulmonary failure (COPD). If NIPSV improved gas exchange within 2 h, it was continued. Otherwise, patients would be promptly intubated. The patients median age was 68 years (minimum 56, maximum 82). The arterial blood gas drawn before initiating NIPSV showed (FiO2 21%) a mean PaO2 of 41.3 +/- 6 mm Hg, a mean PaCO2 of 66 +/- 15 mm Hg and a mean pH of 7.31. Upon admission the mean respiratory rate was 36 breaths/min and the median Apache II score was 20.5 (minimum 13, maximum 32). Despite oxygen administration all patients failed to improve their PaO2 and/or showed a consistent and dangerous hypercapnic response. NIPSV was performed with a median inspiratory positive airway pressure of 14 cm H2O (minimum 10, maximum 20) and a median expiratory positive airway pressure of 4 cm H2O (minimum 3, maximum 6). Eighteen patients (64%) were successfully ventilated with NIPSV, while in 10 (36%) NIPSV failed. A high Apache II score, but not admission blood gas exchange or respiratory rate, seems to be correlated with the failure to ventilate with NIPSV. The results of our preliminary experience suggest the use of NIPSV as an initial approach to acute respiratory failure due to exacerbation of COPD, particularly in patients with an Apache II score of less than 29.

Acute Disease↗

High-dose sequential chemoradiotherapy, a widely applicable regimen, confers survival benefit to patients with high-risk multiple myeloma.

PURPOSE: To assess the toxicity, efficacy, and applicability of high-dose therapy with bone marrow and/or peripheral-blood autotransplantation in high-risk, previously untreated patients with multiple myeloma. PATIENTS AND METHODS: Thirteen consecutive patients with high-labeling index (LI) multiple myeloma received a novel high-dose sequential (HDS) regimen consisting in the high-dose administration of cyclophosphamide (7 g/m2) followed by vincristine (1.4 mg/m2) plus methotrexate (8 g/m2 with leucovorin rescue), etoposide (2 g/m2) and, finally, total-body irradiation (TBI; 10 Gy) plus melphalan (120 mg/m2) with autografting of peripheral-blood hematopoietic progenitor cells. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 5 micrograms/kg/d) was continuously infused after cyclophosphamide and etoposide both to accelerate hematopoietic recovery and to expand/mobilize the hematopoietic progenitor-cell pool. RESULTS: Among 13 patients, 12 completed the program; 10 (or 77%) achieved a complete response and five are alive and disease-free after a median follow-up duration of 36 months (range, 24 to 52). The durations of both freedom from progression (FFP; median, 38 months) and overall survival (OS; median, 41 months) were significantly superior in the 13 HDS-treated patients as compared with 19 well-matched historical controls. CONCLUSION: HDS emerges as a highly effective, well-tolerated, and widely accessible regimen capable of imparting a survival benefit to patients with high-LI multiple myeloma. Larger studies using this or similar programs in standard-risk myeloma are clearly warranted.

Adult↗

Histoplasmin sensitivity among a student population in Crema, Po Valley, Italy.

Histoplasmin skin tests were conducted on a student population in Crema, Po Valley, Italy. In this geographical area two autochtonal cases of disseminated histoplasmosis occurred in HIV-negative men. In the last year we tested 776 senior high school students, mean age 18 years, 335 males and 441 females. Histopalsmin skin sensitivity was 1.23%, with a mean area of induration of 5.78 mm. All subjects but one had never been abroad. This preliminary survey confirms the possibility of autochtonal histoplasmal infection in the Po Valley, Italy.

Adolescent↗

Non specific immunity in aged healthy subjects and in patients with chronic bronchitis.

We investigated the effects of aging on some functional activities (chemotaxis, phagocytosis, nitroblue tetrazolium reduction and candidacidal activity) of peripheral polymorphonuclear and mononuclear phagocytes in 96 healthy subjects and 89 patients with chronic bronchitis, aged 40 to 100 years. The subjects were divided according to age into younger (40-65 years) and older (66-100 years) individuals. No subject was taking any drug known to affect phagocytic functions. A few abnormalities in PMN and monocyte functions were observed in aged healthy subjects, in comparison to the younger ones; in fact, only the chemotactic response to complement-derived chemotactic factors was significantly impaired in elderly healthy individuals. On the contrary, multiple alterations of phagocyte activities, i.e., chemotaxis, phagocytosis, and candidacidal activity were observed in aged subjects with chronic bronchitis, compared to healthy adults. However, the results obtained in older and younger patients with chronic bronchitis were superimposable. The present data suggest that the decline in functional activities of phagocytes in the aged could depend on the effect of the underlying chronic bronchitis on the cellular components of the non-specific host defense system, rather than a direct effect of the aging process.

Adult↗

High-dose sequential chemo-radiotherapy with peripheral blood progenitor cell support for relapsed or refractory Hodgkin's disease--a 6-year update.

BACKGROUND: Very few studies using high-dose therapy and autologous bone marrow transplantation have a long (i.e., > 3 years) follow-up. We report here the 6-year update of a study employing high-dose sequential chemo-radiotherapy in 25 patients with poor-risk Hodgkin's disease. PATIENTS AND METHODS: All patients were either refractory (7 patients) or partial responders (9 patients) or early relapses (9 patients) following induction chemotherapy consisting of MOPP/ABVD in 20 patients and MOPP/ABVD followed by salvage CEP for the remaining 5 patients. The high-dose chemo-radiotherapy regimen employed consisted in the rapid sequential administration of high-doses of cyclophosphamide, methotrexate, etoposide and total body irradiation plus melphalan. RESULTS: As compared to 4-year results, the 6-year probabilities of relapse-free survival, freedom from progression and overall survival were almost superimposable. In fact, during the two additional years elapsed since prior survey, only one event occurred (fatal cerebral hemorrhage) that was unrelated to Hodgkin's disease. In particular, the proportion of patients remaining event-free was 78% for those with short initial complete response and 31% for patients who had failed initial MOPP/ABVD. According to previous experience, both groups have a very low or no chance of long-term event-free survival when treated with standard-dose salvage chemotherapy. CONCLUSIONS: The very favorable long-term results of the high-dose sequential regimen together with its excellent tolerability and lack of early or late fatal toxicities, will assist clinicians in defining optimal timing for high-dose therapy in the management of Hodgkin's disease. According to a revised cost/benefit analysis, it would appear that, at present, the best timing of high-dose sequential therapy in patients failing MOPP/ABVD is at first early relapse.

Actuarial Analysis↗

Hypofractionated accelerated radiotherapy in osteogenic sarcoma.

A method of hypofractionated accelerated radiotherapy (3 weekly fractions of 6 Gy over 2 weeks to a total tumor dose of 36 Gy) was used as single modality in 14 patients with osteogenic sarcoma for palliative treatment of the primary tumor site (six cases) or skeletal metastases (15 sites). A durable response, radiologically assessed, was obtained in 17 of the 21 (81%) irradiated sites. When this irradiation modality was combined with chemotherapy, to treat patients presenting with synchronous metastases (eight cases) or refusing amputation (five cases), a radiologically assessed response was observed in 12 of 13 (92%). In no case did a local recurrence occur before surgery or death because of progressive disease elsewhere. Of the seven patients who later had to undergo ablative surgery, a 100% and 95% tumor necrosis was observed in 6 and 1, respectively. Because of intralesional resection of primary osteogenic sarcoma after preoperative chemotherapy, seven additional patients were irradiated. None recurred at the level of the primary site. Although effective in inducing remission of osteogenic sarcoma, this irradiation method produced severe damages to normal tissues in a high proportion of patients.

Adolescent↗

Flow cytometry for clinical estimation of circulating hematopoietic progenitors for autologous transplantation in cancer patients.

Optimum methods of harvesting circulating hematopoietic progenitors for autologous transplantation to support myeloablative cancer therapy are still uncertain, mostly because of the lack of an assay for marrow-repopulating stem cells. The CFU-GM assay, the commonly used indirect indicator of the quality of the graft, is poorly standardized and provides results evaluable only retrospectively. Based on the knowledge that hematopoietic progenitors express CD34 and CD33 differentiation antigens, we developed a dual-color direct immunofluorescence flow cytometry assay with the aim of replacing the CFU-GM assay advantageously. For this purpose, we applied both assays to 157 blood samples obtained daily throughout 20 different recoveries from pancytopenia induced by high-dose cyclophosphamide or etoposide cancer therapy with or without recombinant human GM colony-stimulating factor (rhGM-CSF). The appearance of CD34+ cells in the circulation indicated that hematopoietic progenitors had increased to more than 500 CFU-GM/mL, a level clinically adequate for large-scale harvest by leukapheresis. Total CD34+ cells correlated well with CFU-GM (r = .89), and data could be fitted by a linear regression line described by the equation y = 388.3 + 64.0x, where y = CFU-GM/mL and x = CD34+ cells per microliter. Moreover, in a series of six patients treated with myeloablative chemoradiotherapy, early hematopoietic recovery of marrow functions was predicted more accurately by the number of transplanted CD34+/CD33+ cells than by either total nucleated cells, CFU-GM, CD34+/CD33- cells, or CD34-/CD33+ cells. Data presented in this article favor clinical use of the CD34/CD33 flow cytometry assay to guide harvesting of circulating hematopoietic progenitors for autologous transplantation and contribute to better understanding of the role played by circulating hematopoietic progenitor cell subsets in marrow recovery after myeloablative cancer therapy.

Antigens, CD↗

Prolonged disease-free survival after high-dose sequential chemo-radiotherapy and haemopoietic autologous transplantation in poor prognosis Hodgkin's disease.

Although effective in achieving durable remission in selected tumors incurable by conventional-dose chemotherapy, high-dose regimens requiring bone marrow transplantation remain too toxic for widespread use. With the aim to improve the therapeutic index of high-dose therapy, we have developed a novel program whereby several non-cross-resistant agents (including total body irradiation at myeloablative dose) were delivered sequentially rather than concurrently. The regimen has been tested in 25 patients with Hodgkin's disease refractory to primary chemotherapy (MOPP and ABVD) or relapsed within 12 months after first complete remission. The efficacy of the sequential regimen (72% complete response rate, 49% event-free survival and freedom from progression at four years, with a median observation of 3.5 years for patients remaining alive) compares favorably with the activity so far reported for the most effective high-dose regimens. Toxicity was low; no toxic deaths occurred and only three life-threatening adverse events were documented after autografting. The excellent tolerability of the final myeloablative course most likely reflects the speed and completeness of haematologic recovery that followed the use of peripheral blood progenitors as the sole or additional source of myeloid stem cells. The reduction of haematologic toxicity was further emphasized when rhG-CSF was employed to both shorten post-chemotherapy neutropenic intervals and to collect large amounts of peripheral blood stem cells. We expect that the use of growth factors will have a major impact on the therapeutic index of high-dose regimens. This, in turn, will confirm their safety as primary treatment in selected high-risk subsets.

Adult↗

Comparative efficacy of ceftriaxone versus ceftazidime in the treatment of nosocomial lower respiratory tract infections.

Seventy-two hospitalized patients with pneumonia or bacteremia were randomly allocated to receive ceftriaxone 2 g once daily i.v. or ceftazidime 2 g twice a day i.v. At the end of the study 60 patients were evaluable, 31 in the ceftazidime group and 29 in the ceftriaxone group. Thirty-four patients (ceftazidime = 15, ceftriaxone = 19) yielded one or more pathogens, of which 64% were gram-negative bacilli. Clinical cure or improvement was observed in 90% of patients in both groups. All 3 cases of bacteremia were cured. Three patients in each group failed to respond to the administered drug. Eradication of the pathogen(s) was observed in 82% of the ceftazidime group and in 86% of the ceftriaxone group. Two episodes of superinfection due to Pseudomonas aeruginosa were recorded in the ceftriaxone group, while Candida spp. was isolated from the sputum in 2 patients in the ceftazidime group. Three strains of P. aeruginosa (2 in the ceftazidime group, 1 in the ceftriaxone group) persisted despite the treatment. No side effects were seen except for skin rash in 2 patients receiving ceftazidime. Compliance was good in both groups, particularly with the once daily administration of ceftriaxone. Overall ceftriaxone and ceftazidime appear to be equally effective in the treatment of nosocomial pneumonia, with the exception of P. aeruginosa infection.

Adolescent↗

Total body irradiation and high-dose melphalan with bone marrow transplantation at Istituto Nazionale Tumori, Milan, Italy.

The technique of total body irradiation (TBI) developed at Istituto Nazionale Tumori, Milan, Italy, is described. This technique consists of i) administration of 12.5 Gy and 14.85 Gy TBI for autologous and allogeneic bone marrow transplantation respectively; ii) in all cases in vivo dosimetry of absorbed TBI dose; and iii) radiation doses to lungs higher than previously described. As of June 1988, seventeen patients with Hodgkin's disease and four with lymphoblastic lymphoma received TBI and 120-180 mg/m2 melphalan. Respiratory function was prospectively evaluated demonstrating moderate and transient reduction of pulmonary function.

Adolescent↗

Prospective evaluation of pulmonary function in cancer patients treated with total body irradiation, high-dose melphalan, and autologous hematopoietic stem cell transplantation.

Pulmonary function tests (standard vital capacity, SVC; total lung capacity, TLC; forced expiratory volume in 1 second-forced vital capacity ratio, FEV1/FVC; carbon monoxide transfer factor, DLCO) were prospectively evaluated in patients (median age 25 years, 13-52 years; median follow-up 20 months, 6-51 months) with Hodgkin's disease (15 patients), non-Hodgkin's lymphoma (9 patients), and inflammatory breast cancer (3 patients) treated with sequential high-dose therapy comprising the following phases over approximately 2 months: a) cyclophosphamide (7 g/m2); b) vincristine (1.4 mg/m2), methotrexate (8 g/m2), and cisplatinum (120 mg/m2) or etoposide (2 g/m2); c) total body irradiation (TBI; 12.5 gy, 5 fractions over 48 hours), intravenous melphalan (120-180 mg/m2), and transplantation of autologous peripheral blood and/or bone marrow hematopoietic stem cells. Within 2 months after transplantation, 12 patients also received 25 Gy radiotherapy boost to mediastinum and clavicular regions. In vivo dosimetry evaluations of fractionated TBI treatments showed that mean radiation dose absorbed by lungs was 12.18 Gy (97.4% of TBI dose). Despite such a high radiation dose, we observed only transient and subclinical decrease of SVC, TLC, and DLCO. The decrease of SVC, TLC, and DLCO was more evident and prolonged in patients receiving radiotherapy boost. All parameters progressively recovered to normal values within 2 years after transplantation. In contrast, FEV1/FVC remained within normal limits in all patients, thus demonstrating the absence of obstructive ventilatory changes. In addition, no interstitial pneumonia was observed.

Adolescent↗

Questionable role of CNS radioprophylaxis in the therapeutic management of childhood rhabdomyosarcoma with meningeal extension.

A series of 15 consecutive children with head and neck nonorbital rhabdomyosarcoma (RMSA) with meningeal extension were prospectively treated with chemotherapy consisting of Adriamycin (doxorubicin; Adria Laboratory, Columbus, OH) (ADM), vincristine (VCR), cyclophosphamide (CPM), and dactinomycin (DACT) followed by radiotherapy (60 Gy) to the primary tumor volume, along with intrathecal methotrexate (IT MTX). Thirteen of 15 responded to preradiation chemotherapy. Four of 13 relapsed. Relapse occurred at the level of the primary tumor in three of four. The 3-year progression-free survival (PFS) was 59%, similar to that achieved in a previous series treated with a comparable therapeutic approach that also included whole-brain radiotherapy as a prophylaxis of possible occult meningeal seeding. It is concluded that CNS prophylaxis with radiotherapy is questionable in the management of childhood RMSA with meningeal extension.

Adolescent↗

Recombinant human granulocyte-macrophage colony-stimulating factor reduces hematologic toxicity and widens clinical applicability of high-dose cyclophosphamide treatment in breast cancer and non-Hodgkin's lymphoma.

High-dose administration of anticancer agents is attractive both on theoretic and clinical grounds. Yet, high-dose regimens are usually used as salvage treatments, mainly as a consequence of their considerable hematologic toxicity. One pertinent example is represented by cyclophosphamide, an alkylating agent with a wide spectrum of marked antitumor activity. When used at doses up to 7 g/m2 (190 to 200 mg/kg) this drug does not cause myeloablation, but induces a severe, albeit transient, myelosuppression, which requires platelet transfusions in approximately 50% of treated patients, and is frequently complicated by infectious episodes, occasionally lethal. To accelerate hematopoietic recovery, we continuously infused for 14 consecutive days 5.5 micrograms/kg/d of the glycosylated human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) into 15 patients with breast cancer and non-Hodgkin's lymphoma treated with 7 g/m2 cyclophosphamide. This schedule was chosen having obtained the fastest hematopoietic recovery among four different options during an initial schedule-finding phase on 12 overall patients. Twenty-one comparable subjects with solid tumors served as controls. We report here that this relatively low, well-tolerated dose of rhGM-CSF reduces from 20 to 14 (median) and from 24 to 14, the number of days required to recover circulating granulocyte counts over 1,000 and 2,500/microL, respectively. The stimulatory effect was associated with a remarkable clinical benefit. In fact, treated patients experienced less infectious complications (7% v 24%) were eligible to receive chemotherapy earlier (median, by day +14 v day +20 for controls), and fewer required prophylactic platelet transfusions (13% v 43%). Our results show that even very high doses of cyclophosphamide can be administered with improved hematologic toxicity, tolerable morbidity, and reduced supportive care requirements. The increase in the therapeutic index made possible by rhGM-CSF infusion prompts the use of high-dose cyclophosphamide, and possibly of other agents with similar myelotoxic activity, early in the clinical course of chemotherapy-sensitive tumors.

Adolescent↗

[Clinico-laboratory evaluation a new sustained-release preparation of anhydrous theophylline].

The clinical effectiveness and the pharmacokinetic parameters of a once-a-day sustained release preparation of anhydrous theophylline were studied in a trial carried out on 10 adult patients affected by bronchial asthma or chronic obstructive lung disease. Treatment with this new theophylline preparation allowed us to obtain mean serum concentrations within the therapeutic range (5-20 mcg/ml) which remained quite constant during 24 hours. All patients evidenced improvement of dyspnea and of the signs of bronchospasm. Tolerability was very good.

Adult↗