Papers by Giulia Marzocchi
Cancer Genetics and Cytogenetics, 2010
Additional chromosome abnormalities (ACAs) occur in less than 10% of cases at diagnosis of Philad... more Additional chromosome abnormalities (ACAs) occur in less than 10% of cases at diagnosis of Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). In some cases, on the basis of the persistence of the ACAs in Ph-negative cells after response to imatinib, a secondary origin of the Ph chromosome has been demonstrated. In this study, the possible prognostic value of this phenomenon was evaluated. Thirty-six Ph-positive CML patients were included in the study. In six patients, ACAs persisted after the disappearance of the Ph. A complete cytogenetic response (CCR) was obtained in five of these six patients, and five of six also had a high Sokal score. In all the other cases, ACAs disappeared together (in cases of response to therapy with imatinib) or persisted with the Ph (in cases of no response to imatinib). In the former cases, the primary origin of the Ph was demonstrated. CCR was obtained in 22 cases (17 with low to intermediate Sokal scores), while no response was observed in 8 patients (5 with a high Sokal score). Sokal score seems to maintain its prognostic value for patients in whom the Ph occurs as a primary event, but not in those in whom it occurs as a secondary one. Ó
Oncotarget, Jan 9, 2015
The prime focus of the current therapeutic strategy for Multiple Myeloma (MM) is to obtain an ear... more The prime focus of the current therapeutic strategy for Multiple Myeloma (MM) is to obtain an early and deep tumour burden reduction, up to the level of complete response (CR). To date, no description of the characteristics of the plasma cells (PC) prone to achieve CR has been reported. This study aimed at the molecular characterization of PC obtained at baseline from MM patients in CR after bortezomib-thalidomide-dexamethasone (VTD) first line therapy.One hundred and eighteen MM primary tumours obtained from homogeneously treated patients were profiled both for gene expression and for single nucleotide polymorphism genotype. Genomic results were used to obtain a predictor of sensitivity to VTD induction therapy, as well as to describe both the transcription and the genomic profile of PC derived from MM with subsequent optimal response to primary induction therapy.By analysing the gene profiles of CR patients, we identified a 5-gene signature predicting CR with an overall median acc...
Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 15, 2015
Purpose To evaluate the role of 18F-FDG PET/CT in 282 symptomatic MM pts treated up-front between... more Purpose To evaluate the role of 18F-FDG PET/CT in 282 symptomatic MM pts treated up-front between 2002 and 2012. Experimental design All pts were studied by PET/CT at baseline, during post-treatment follow-up and at the time of relapse. Their median duration of follow-up was 67 months. Results Forty-two percent of the pts at diagnosis had > 3 FLs and in 50% SUVmax was > 4.2; EMD was present in 5%. On multivariate analysis, ISS 3, SUVmax > 4.2 and failure to achieve best CR were the leading factors independently associated with shorter PFS and OS. These 3 variables were used to construct a prognostic scoring system based on the number of risk factors. After treatment, PET/CT negativity (PET-neg) was observed in 70% of pts, while conventionally-defined CR was achieved in 53%. Attainment of PET-neg favourably influenced PFS and OS. PET-neg was an independent predictor of prolonged PFS and OS for patients with conventionally-defined CR. Sixty-three percent of pts experienced re...
American Journal of Hematology, 2015
Multiple myeloma (MM) is often associated with renal insufficiency (RI) which adversely influence... more Multiple myeloma (MM) is often associated with renal insufficiency (RI) which adversely influences the prognosis. Several studies demonstrated that bortezomib can improve both renal function and outcome. We prospectively evaluated 21 newly diagnosed MM patients with severe renal impairment secondary to tubularinterstitial damage, most of them due to myeloma kidney, who were primarily treated with bortezomib-based therapy combined with high cut-off hemodialysis (HCOD). The median serum creatinine level at baseline was 6.44 mg dL 21 and calculated median estimated glomerular filtration rate (eGFR), according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, was 8 mL/min/1.73 m 2 . Serum free light chain (sFLC) median concentration was 6,040 mg L 21 . Post induction and best stringent complete response rates were 19 and 38%, respectively. Responses were fast, occurring within a median of 1.4 months. The combination of bortezomib and HCOD led to a prompt and remarkable (>90%) decrease in sFLC levels. Sixteen patients (76%) became dialysis independent within a median of 32 days. With a median follow up of 17.2 months, the 3-year PFS and OS were 76 and 67%, respectively. No early deaths were observed. This study demonstrates that incorporation of bortezomib into induction therapy combined with HCOD is a highly effective strategy in rescuing renal function and improving outcomes in patients with MM and RI.
Clinical Lymphoma Myeloma and Leukemia, 2014
Stem Cells, 2006
However, the early response of human BM-derived stem cells (SC) to liver injury is still unknown.... more However, the early response of human BM-derived stem cells (SC) to liver injury is still unknown. Here, we studied 24 patients undergoing orthotopic liver transplantation (OLT) for end-stage liver disease or hepatocellularcarcinoma, and 13 patients submitted to liver resection. The concentration of circulating BM-derived SC was determined by phenotypic analysis and clonogenic assays. Moreover, we assessed the serum level of inflammatory and tissue-specific cytokines. Reverse transcriptase-polymerase chain reaction and fluorescence-in situ hybridization were also used to characterize mobilized SC. At baseline, patients showed a significant lower concentration of circulating CD133 ؉ , CD34 ؉ SC and clonogenic progenitors (colony-forming unit cells) than healthy controls. However, the time-course evaluation of peripheral blood cells after OLT demonstrated the significant early mobilization of multiple subsets of hematopoietic and endothelial stem/progenitor cells. Cytogenetic and molecular analyses of CD34 ؉ cells showed the host origin of mobilized SC and the expression of transcripts for GATA-4, cytokeratin 19, and ␣-fetoprotein hepatocyte markers. In contrast with OLT, only total circulating CD34 ؉ cells significantly increased after liver resection. Mobilization of BM cells after OLT or liver surgery was associated with increased serum levels of granulocyte-colony stimulating factor, interleukin-6, stem cell factor, hepatocyte growth factor, and vascular endothelial growth factor. In summary, we demonstrate that tissue damage after OLT and liver resection induces increased serum levels of multiple cytokines but only ischemia/reperfusion injury associated with OLT results in the remarkable mobilization of BM stem/progenitor cells. STEM
Leukemia Research, 2011
We investigated whether low-level Bcr-Abl kinase domain mutations can be detected in patients who... more We investigated whether low-level Bcr-Abl kinase domain mutations can be detected in patients who have stable responses to first-line nilotinib-like it is known to happen in patients receiving imatinib. We screened for mutations twelve such patients by cloning and sequencing. Only one case was found to harbor mutations at low levels (including a T315I). However, major molecular response (MMR) was maintained and it even improved to complete molecular response. Our results suggest that a) Bcr-Abl mutations, even at low level, seem to be very rare in patients in MMR on first-line nilotinib; b) low-level mutations do not always predict for subsequent relapse.
Leukemia & Lymphoma, 2009
Journal of Hepatology, 2006
Journal of Clinical Oncology, 2010
Deletions of the derivative chromosome 9 [der(9)] have been associated with a poor prognosis in c... more Deletions of the derivative chromosome 9 [der(9)] have been associated with a poor prognosis in chronic myeloid leukemia (CML) across different treatment modalities. In the imatinib era, the prognostic impact of der(9) deletions has been evaluated mainly in patients with late chronic-phase (CP) CML, giving partially conflicting results. Few data are available in the early CP setting. For this reason, in 2006, the European LeukemiaNet recommendations still considered der(9) deletions as a candidate adverse prognostic factor and required a careful monitoring of the patient. To investigate the prognostic value of der(9) deletions in early CP CML, we performed an analysis of three prospective imatinib trials of the Italian Group for Hematological Malignancies of the Adult (GIMEMA) CML Working Party. A fluorescent in situ hybridization (FISH) analysis of bone marrow cells was performed at diagnosis; der(9) deletions were detected in 60 (12%) of 521 evaluable patients. At 60 months, the cumulative incidence of complete cytogenetic response and major molecular response-and the probability of event-free survival, failure-free survival, progression-free survival, and overall survival-in patients with and without deletions were not statistically different. Our data strongly support the notion that, when investigated by FISH, der(9) deletions are not a poor prognostic factor in patients with early CP CML treated with imatinib.
Journal of Clinical Oncology, 2006
other than (or in addition to) the F317L might have intervened, nor can we exclude the possibilit... more other than (or in addition to) the F317L might have intervened, nor can we exclude the possibility that the concomitant M351T or L387M mutations in the third and fifth patients might have contributed to resistance. However, our experience suggests that the F317L mutation might be problematic at least in some advanced-phase patients treated with second-line dasatinib.
Haematologica, 2008
Imatinib mesylate is the first line treatment for chronic myeloid leukemia. In patients with adva... more Imatinib mesylate is the first line treatment for chronic myeloid leukemia. In patients with advanced phase of the disease, the advent of imatinib significantly increased survival. However, few long-term data, based on large, prospective and controlled trials are available on the outcome of these patients.
Haematologica, 2007
The emergence of resistance to the Bcr-Abl inhibitor imatinib mesylate in patients with Philadelp... more The emergence of resistance to the Bcr-Abl inhibitor imatinib mesylate in patients with Philadelphia chromosome-positive (Ph+) leukemia has prompted the development of second-generation compounds active against several imatinib-insensitive mutant forms of Bcr-Abl, including dasatinib (BMS-354825; Bristol-Myers Squibb). In order to assess which pre-existent or emerging kinase domain mutations are associated with decreased clinical efficacy of desatinib, we analyzed BCR-ABL kinase sequences before and during treatment in 21 Ph+ patients who failed to respond to or relapsed during dasatinib therapy. In all patients but one, resistance to dasatinib was invariably found to be associated with mutations at residue 315 and/or at residue 317.
Cancer Genetics and Cytogenetics, 2010
Additional chromosome abnormalities (ACAs) occur in less than 10% of cases at diagnosis of Philad... more Additional chromosome abnormalities (ACAs) occur in less than 10% of cases at diagnosis of Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). In some cases, on the basis of the persistence of the ACAs in Ph-negative cells after response to imatinib, a secondary origin of the Ph chromosome has been demonstrated. In this study, the possible prognostic value of this phenomenon was evaluated. Thirty-six Ph-positive CML patients were included in the study. In six patients, ACAs persisted after the disappearance of the Ph. A complete cytogenetic response (CCR) was obtained in five of these six patients, and five of six also had a high Sokal score. In all the other cases, ACAs disappeared together (in cases of response to therapy with imatinib) or persisted with the Ph (in cases of no response to imatinib). In the former cases, the primary origin of the Ph was demonstrated. CCR was obtained in 22 cases (17 with low to intermediate Sokal scores), while no response was observed in 8 patients (5 with a high Sokal score). Sokal score seems to maintain its prognostic value for patients in whom the Ph occurs as a primary event, but not in those in whom it occurs as a secondary one. Ó
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Papers by Giulia Marzocchi