Potential diagnostic and prognostic significance of the transformation-enhancing factor(s) in the plasma cryoprecipitate of tumor patients

A biological activity which enhances cell transformation (TEF) in Rous sarcoma virus temperature-sensitive mutant-infected cultures has been evidenced in the plasma cryoprecipitate from patients affected with different types of neoplastic disease. In the present paper we report data on the analysis of TEF activity in the plasma cryoprecipitates from leukemic and tumor patients tested either before or during specific antineoplastic treatments. The screening of 57 cases of different neoplastic diseases and of 57 controls, healthy subjects or patients affected with other non-neoplastic diseases indicates that TEF activity is generally related to the presence of neoplasia. Furthermore, a follow-up of patients from the onset of the disease through its evolution during therapy suggests that variations of TEF activity in the plasma cryoprecipitate correlate well with the clinical and pathological conditions, thus indicating the TEF as a potential marker for monitoring cancer patients.     

Ageing of rabbit red cells in vitro: membrane modifications and their possible role in red cell survival in vivo

In vitro incubation induces, in rabbit red cell membranes, significant modifications consisting mainly in a decrease of sialic acid and galactose. In vivo the life span of incubated erythrocytes seems to be correlated to the degree of surface alterations and ATP depletion: larger surface modifications and energy charge reduction induce shorter survival time. It can therefore be postulated that incubation of red cell in vitro can cause an ageing process similar to that occurring physiologically in vivo.     

Severe platelet dysfunction in a patient with autoantibodies against membrane glycoproteins IIb-IIIa

A young women affected by Hodgkin's disease developed chronic autoimmune thrombocytopenic purpura. Splenectomy induced normalization of her platelet count, but hemorrhagic symptoms did not disappear. The patient's platelets did not aggregate in response to collagen and ADP and the IgG fraction of the patient's plasma induced the same defect in normal platelets. The women's IgG recognized glycoproteins IIb and IIIa of normal platelet membranes. Prednisone therapy induced the disappearance of bleeding symptoms and the normalization of platelet aggregation.     

Clinical and biological effects of treatment with amifostine in myelodysplastic syndromes

We treated six patients with primary myelodysplastic syndrome (MDS) with amifostine (200 mg/m(2) i.v./three times a week for three consecutive weeks). Neutrophil counts were more frequently increased than platelet and reticulocyte counts, but no reduction of the transfusion requirement was observed. Significant reduction of the marrow blasts was observed in one case of refractory anaemia with excess of blasts. In vitro stimulation of haematopoiesis was observed in five cases. The apoptotic rate of marrow cells was significantly diminished even after the first course. Our findings show fairly good clinical and biological response to amifostine in MDS.     

The east–west advancement flap (horizontal advancement flap) to repair a defect on the nose ala

Background The repair of an alar nasal defect is a frequent challenge for dermatologic surgeons for reasons of the high rate of non‐melanoma cancers in the area. Objective Our aim was to describe the use of an east–west cheek‐based flap (horizontal advancement flap) to repair a surgical defect on the nose ala. Methods Benefits and limits of this surgical procedure are evaluated. Result The resulting S‐shaped scar was well‐camouflaged among the natural skin lines (melolabial fold and melonasal junction). No architectural distortion of the nose resulted from the procedure. Conclusion In selected patients with small‐to‐medium‐size defects of the nasal ala, the horizontal advancement flap is a simple, reliable and aesthetic reconstruction option.     

ProMECE-CytaBOM vs MACOP-B in Advanced Aggressive Non-Hodgkin's Lymphoma: Long Term Results of a Multicenter Study of the Italian Lymphoma Study Group (GISL)

A randomized trial was designed in order to compare the efficacy and feasibility of ProMECE-CytaBOM (P-C) and MACOP-B (M-B) in patients with advanced, aggressive non Hodgkin's lymphoma (NHL). P-C and M-B were chosen due to their association with a very high complete remission rate when compared to other published protocols. The study was conducted on 210 patients with intermediate or high-grade NHL in stage I bulky, or stages II-IV, randomized to receive either 6 courses of P-C delivered every 28 days (106 patients), or 12 weeks of M-B chemotherapy (104 patients). In both regimens doxorubicin was replaced by a 20% higher dose of epidoxorubicin (i.e. 30 mg/m² of the analog). At the end of induction therapy patients could receive additional radiotherapy to residual masses or to sites of previous bulky disease. The two groups of patients were compared for response rates, number and severity of therapy related side effects, overall survival, disease-free survival, and time to treatment failure.

Sixty-five patients (62%) treated with P-C and 69 patients (67%) treated with M-B achieved a complete remission, with no significant differences between the two treatment arms (P = 0.13). The overall objective response rate (complete + partial remission) was 74% for patients treated with P-C, and 81% for patients treated with M-B, respectively. The 4-year relapse-free survival rate was 59% for P-C and 69% for M-B, respectively (P = 0.11). We observed an eventual total of 120 treatment failures, 64 (61%) in the group treated with P-C and 56 (54%) among those treated with M-B (P = 0.29). Patients alive without disease at four years were estimated to be 42% in the P-C arm and 49% in the M-B arm (P = 0.27). The estimated 4-year overall survival was 54% for P-C and 61 % for M-B, and the differences were also not significant (P = 0.29). Patients treated with M-B experienced more and more severe side effects, including mucositis, infections, neurologic, pulmonary and cardiac abnormalities. Patients treated with P-C had a 1.3 g mean decrease of hemoglobin over the induction therapy, while patients treated with M-B experienced a 2.2 g mean decrease (P = 0.01).

In conclusion, both P-C and M-B resulted in effective treatment for patients with aggressive NHL, and provided similar activity. However P-C was more manageable in an outpatient setting and produced less acute toxic effects.     

Cell kinetics of CD34-positive hematopoietic cells following chemotherapy plus colony-stimulating factors in advanced breast cancer

Bone-marrow (BM) hematopoietic precursors are recruited into proliferative activity when colony-stimulating factors (CSF) are sequenced with chemotherapy (CT). Previous studies suggested that further CT can be safely administered only when the increased proliferative activity of these cells has subsided, because most cytostatic drugs selectively damage cycling cells. The safest interval between CSF discontinuation and the start of the next CT course needs to be ascertained in vivo. Thirty patients with advanced breast cancer were treated with an intensified FEC regimen, planned at 21-day intervals, sequenced with granulocyte-macrophage (GM)-CSF (15 patients) or granulocyte (G)-CSF (15 patients). Using flow cytometry (FCM) we evaluated the proliferation kinetics of CD34⁺ BM hematopoietic progenitors before CT + CSF and at different times after CSF administration was stopped. FEC + GM- and FEC + G-CSF sequences both induced a rapid and sustained increase in the percentage of BM myeloid precursors (BMMP%) and in the cycling status of CD34+ BM cells. However, while the BMMP% remained elevated in both cases after CSF were stopped, the enhanced proliferative activity of CD34+ cells decreased more rapidly after GM- than after G-CSF. Using FCM, CD34⁺ BM-derived hematopoietic presursor cell kinetics is readily evaluated in the clinical setting. The administration of CSF following CT increases both the proliferative activity of CD34+ BM cells and the BMMP%. After CSF were discontinued a kinetic refractoriness of hematopoietic progenitors was more evident after GM-CSF than after G-CSF. These data may be of value in designing clinical trials to avoid cytostatic damage to the BM hematopoietic stem-cell compartment. © 1995 Wiley-Liss, Inc.     

A prognostic index for multiple myeloma.

The current prognostic systems have failed to identify multiple myeloma (MM) patients who require aggressive therapy. These staging systems do not reliably distinguish patients with different prognoses. This paper explores the possibility of improving the prognostic forecast in MM by considering some clinical characteristics at diagnosis together with response to first-line chemotherapy. A total of 231 patients were prospectively randomised in a multicentre trial to no therapy vs melphalan + prednisone (MP) for stage I, MP in stage II, and MP vs peptichemio, vincristine and prednisone for stage III. The clinical features of these groups were evaluated for prognostic variables predictive of overall survival by means of univariate and multivariate analysis. The independently significant variables were incorporated into a model that identified three groups of patients with different risks of death and different overall survival. Three variables retained statistical significance: the staging system proposed by the British Medical Research Council, a composite parameter integrating the percentage of bone marrow plasma cells with cytological features of the infiltrating elements (plasma cell vs plasmablast), and response to 6 months of first-line chemotherapy. These three variables led the proposal of a scoring system able to identify three different risk classes (with median overall survival of 52, 28 and 13 months respectively) and to estimate individual patient prognosis more flexibly. The proposed risk classes, drawn from both diagnostic and therapeutic parameters, are thought to be a clinical and investigational instrument for separating MM patients into comparable groups, for selecting the best available therapy and for evaluating response with respect to the disease of each new patient.     

Cell cycle status and apoptosis of hematopoietic progenitor cells released into the peripheral blood after taxanes and granulocyte colony-stimulating factor in breast cancer patients

Paclitaxel and its analogue docetaxel show a significant antitumor activity, particularly evident in breast cancer. Paclitaxel has also been proved to be effective as a peripheral blood progenitor cell (CPC) mobilizing agent. To optimize the use of active, disease-specific drugs as CPC priming, we have evaluated the effects of either paclitaxel or docetaxel both at standard dosages and followed by granulocyte colony-stimulating factor (G-CSF), on circulating CPC release and function in 18 patients with advanced breast cancer who had failed previous anthracycline-based regimens. The reported differences in biological behaviour between bone marrow and blood-derived hematopoietic progenitor cells and the ability of both paclitaxel and docetaxel to induce apoptosis, prompted us to simultaneously evaluate the cell cycle perturbations induced on CD34+ cells. Median CD34+ peaks were 24 microl (range: 10-58) in the paclitaxel-treated patients and 39 microl (range: 17-91), respectively, in the patients who received docetaxel. After paclitaxel, the percentage of CD34+ cells in S-phase was low (bromodeoxyuridine, BrdU, labelling index = 3.4+/-2%) with a concomitant presence of early apoptotic cells (8.1+/-3%). On the contrary, after docetaxel, the percentage of CD34+ cells in S-phase was higher (BrdU labelling index = 14.5+/-4%, p<0.05 vs. paclitaxel), while early apoptotic cells were detected at a similar rate (8. 6+/-3%, p = n.s. vs. paclitaxel). In conclusion, when used at standard dosages, with respect to paclitaxel + G-CSF, docetaxel + G-CSF is a more satisfactory tool to mobilize CPC and to induce them into the cell cycle. These data should be taken into account when combinations of docetaxel with other agents are explored as CPC mobilizing regimens for autografting.