Biomedical subjects

Luisa Ponchio

Publications and source records attributed to Luisa Ponchio.

5 recordsLinked to original sources

PubMed2005

Peripheral blood progenitor cell collection in chronic myeloid leukemia patients with complete cytogenetic response after treatment with imatinib mesylate.

BACKGROUND: Imatinib mesylate (IM) was introduced in chronic myeloid leukemia (CML) treatment in the late 1990s and substantially changed the therapeutic approach to the disease, by inducing complete cytogenetic response (CCR) in approximately 60 percent of cases. Nevertheless, some concerns exist about the duration of response to treatment and the onset of resistance to IM. STUDY DESIGN AND METHODS: Twenty-five chronic-phase CML patients in stable CCR (>6 months) treated for at least 1 year with IM at the standard dose (400 mg/day) were mobilized with recombinant human granulocyte-colony-stimulating factor (Filgrastim) at 10 microg per kg for 4 to 6 days, with the aim of collecting at least 2 x 10(6) CD34+ cells per kg. Standard cytogenetic analysis and first-round and/or nested polymerase chain reaction were performed in basal and postmobilization samples to examine the presence of bcr-abl transcripts. RESULTS: CD34+ cells collection was successful in 16 patients, yielding a median of 3.01 x 10(6) +/- 1.09 x 10(6) CD34+ cells per kg at the first attempt, and in 4 of the 9 remaining patients who were remobilized after a temporary withdrawal of IM, yielding a median of 2.65 x 10(6) +/- 0.7 x 10(6) CD34+ cells per kg, with an overall 80 percent success rate. No correlation between mobilization and duration of the disease, length of IM treatment, or previous interferon-alpha and/or hydroxyurea treatment was found. CONCLUSIONS: Autologous CD34+ cells may be mobilized and collected in most CML patients who achieve CCR after IM treatment, with a view to possible use in the event that resistance to IM occurs in patients not eligible for allogeneic peripheral blood progenitor cell transplantation or those lacking an HLA-matched donor.

Antigens, CD34↗

PubMed2004

Pilot study of the mechanism of action of preoperative trastuzumab in patients with primary operable breast tumors overexpressing HER2.

PURPOSE: To elucidate the mechanism by which trastuzumab, a humanized monoclonal antibody against HER2 with proven survival benefit in women with HER2-positive metastatic breast cancer, mediates its antitumor activity. EXPERIMENTAL DESIGN: A pilot study including 11 patients with HER2-positive tumors treated in a neo-adjuvant setting with trastuzumab was performed. Trastuzumab was administered i.v. at a dose of 4 mg/kg followed by three weekly i.v. doses of 2 mg/kg. The primary tumor was surgically removed 7 days after the last treatment. Surgical samples, tumor biopsies, and lymphocytes from these patients were collected for biological studies. RESULT: Clinical data indicated one complete pathological remission and four partial remissions using RECIST (Response Evaluation Criteria in Solid Tumors). Trastuzumab was well tolerated and neither serious adverse events nor changes in cardiac function were observed during this short-term treatment and after surgery. The biological data showed that, independent of response, (a) all patients showed high levels of circulating trastuzumab; (b) saturating level of trastuzumab was present in all of the tumors; (c) no down-modulation of HER2 was observed in any tumors; (d) no changes in vessel diameter was observed in any tumors; (e) no changes in proliferation was observed in any tumors; and (f) a strong infiltration by lymphoid cells was observed in all cases. Patients with complete remission or partial remission were found to have a higher in situ infiltration of leukocytes and a higher capability to mediate in vitro antibody-dependent cellular cytotoxicity activity. CONCLUSIONS: The results of this pilot study argue against trastuzumab activity in patients through down-modulation of HER2 but in favor of antibody-dependent cellular cytotoxicity guiding efforts to optimize the use of trastuzumab in breast cancer patients.

Antibodies, Monoclonal↗

PubMed2002

T-cell dynamics after high-dose chemotherapy in adults: elucidation of the elusive CD8+ subset reveals multiple homeostatic T-cell compartments with distinct implications for immune competence.

Recovery of total T cell numbers after in vivo T-cell depletion in humans is accompanied by complex perturbation within the CD8+ subset. We aimed to elucidate the reconstitution of CD8+ T cells by separate analysis of putative naïve CD95- CD28+, memory CD95+ CD28+ and CD28- T cell compartments after acute maximal depletion by high-dose chemotherapy (HD-ChT) in women with high-risk breast cancer. We found that recovery of putative naïve CD8+ CD95- CD28+ and CD4+ CD95- CD28+ T cells, was compatible with a thymus-dependent regenerative pathway since their recovery was slow and time-dependent, their values were tightly related to each other, and their reconstitution patterns were inversely related to age. By analysing non-naïve T cells, a striking diversion between putative memory T cells and CD28- T cells was found. These latter increased early well beyond normal values, thus playing a pivotal role in total T-cell homeostasis, and contributed to reduce the CD4 : CD8 ratio. In contrast, putative memory T cells returned to values not significantly different from those seen in patients at diagnosis, indicating that this compartment may recover after HD-ChT. At 3-5 years after treatment, naïve T cells persisted at low levels, with expansion of CD28- T cells, suggesting that such alterations may extend further. These findings indicate that CD28- T cells were responsible for 'blind' T-cell homeostasis, but support the notion that memory and naïve T cells are regulated separately. Given their distinct dynamics, quantitative evaluation of T-cell pools in patients undergoing chemotherapy should take into account separate analysis of naïve, memory and CD28- T cells.

Adult↗

PubMedDate not supplied

Retrorectal tumours: a case report.

The authors describe a case of retrorectal tumour in a 48-year-old female. Retrorectal tumours are rare, and their diagnosis is notoriously difficult and late. In this case the first-step diagnosis was made on the basis of clinical findings and radiological investigations such as abdominal ultrasonography. The second step included pelvic CT scans and MR imaging which yielded more precise anatomical details and information for the best surgical approach. We opted for a posterior approach with complete, easy removal of the tumour mass which, after pathological examination, turned out to be an epidermoid cyst. The postoperative course was uneventful and, one year after operation, the patient complains only of mild, irregular perineal pain with completely negative radiological investigations (US and CT scan).

Epidermal Cyst↗

PubMedDate not supplied

Evaluation of infectious complications and immune recovery following high-dose chemotherapy (HDC) and autologous peripheral blood progenitor cell transplantation (PBPC-T) in 148 breast cancer patients.

BACKGROUND AND OBJECTIVES: High-dose chemotherapy (HDC) with autologous PBPC-T has been reported to be effective in hematological and in selected solid malignancies. In this setting, infectious complications represent a relevant cause of morbidity. PATIENTS AND METHODS: To ascertain the incidence, types and factors influencing the development of early and late infections, we retrospectively analyzed 148 consecutive breast cancer (BC) patients receiving HDC and PBPC-T, both for primary high-risk BC (pBC) and metastatic disease (mBC). RESULTS: Early infection strongly associated with the occurrence of grade 4 mucositis (p < 0.001), was documented in 28 patients (19%). Late re-activation of varicella zoster virus (VZV) occurred in 14 patients (9%); an inverse correlation between the VZV re-activation and the total amount of T-cells transferred with the graft was observed. Evaluation of immune reconstitution, carried out in 10 out of 148 patients, showed a long-lasting CD+ T-cells depression (> 2 year), mainly involving the naive CD4+ T-cell subset. Conversely, the analysis of the frequency of proliferating T-lymphocyte precursors, specific for antigens expressed by 3 different widespread pathogens, demonstrated that, notwithstanding the delayed recovery of CD4+ cells, many T-lymphocyte functions were within normal range 1 year after PBPC-T. CONCLUSION: Altogether these results show that severe mucositis is associated with early bacterial infections and the infusion of large numbers of T-cells plays a role in controlling late VZV reactivation.

Adult↗