Francesco Buccisano | "Tor Vergata" University of Rome (original) (raw)

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Papers by Francesco Buccisano

Research paper thumbnail of Standard dose and prolonged administration of azacitidine are associated with improved efficacy in a real-world group of patients with myelodysplastic syndrome or low-blast count acute myeloid leukemia

European Journal of Haematology, 2015

Azacitidine is the standard of care for higher-risk myelodysplastic syndromes (MDS). We evaluated... more Azacitidine is the standard of care for higher-risk myelodysplastic syndromes (MDS). We evaluated factors affecting the outcome of azacitidine treatment in 196 "real world" patients, retrospectively collected by two Italian cooperative groups. The study included 184 MDS and 12 low-blast count acute myeloid leukemia (AML). Azacitidine was administered at the standard dose of 75 mg/m(2) /day for 7 days (StD) in 163 patients, and 100 mg/day for 5-7 days in 33 patients. After a median of 4.5 azacitidine cycles (range 7-15 cycles), 182 patients were evaluable for response. Nineteen % achieved complete remission (CR), 17% partial remission (PR), and 21% hematological improvement (HI). The disease was stable or progressive in 29% and 14% of patients, respectively. The probability of response was significantly higher in patients who received the 75 mg/m(2) /7 day compared to 100 mg through 5-7 days dose (CR/PR/HI: 63 vs 37%, p=0.0005). Median overall survival was 17.1 months. Low MDS-CI and achievement of CR/PR/HI were significant predictors of survival in the multivariable analysis. Our data show that maximal azacitidine efficacy is associated to the standard dose and to prolonged treatment, beyond 4-6 cycles, with the goal of also improving "quality" of response. Lower MDS-CI and IPSS-R scores, hematologic response and disease stability, are associated to longer survival. The risk of febrile events is highest during the first treatment cycles, and is associated to active disease. This article is protected by copyright. All rights reserved.

Research paper thumbnail of A Leukemia-Associated CD34/CD123/CD25/CD99-positive Immunophenotype Identifies FLT3-mutated Clones in Acute Myeloid Leukemia

Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 8, 2015

Purpose We evaluated leukemia-associated immunophenotypes (LAIP) and their correlation with fms-l... more Purpose We evaluated leukemia-associated immunophenotypes (LAIP) and their correlation with fms-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1) gene mutational status in order to contribute a better identification of patients at highest risk of relapse in AML. Bone marrow samples from 132 patients with acute myeloid leukemia (AML) were analyzed by 9-color multiparametric flow cytometry (MPFC). We confirmed the presence of the mutation in diagnostic samples and in sorted cells by conventional RT-PCR and by patient-specific RQ-PCR. Within the CD34+ve cell fraction we identified a discrete population expressing high levels of the IL-3 receptor alpha-chain (CD123) and MIC-2 (CD99) in combination with the IL-2 receptor alpha-chain (CD25). The presence of this population positively correlated with the internal tandem duplications (ITD) mutation in the FLT3 gene (r = 0.71). Receiver operating characteristics (ROC) showed that, within the CD34+ve cell fraction a percentage of CD123/C...

Research paper thumbnail of Cord blood transplantation in adults with acute myeloid leukaemia

Best practice & research. Clinical haematology, 2010

Allogeneic haematopoietic stem cell transplantation represents a potential life-saving procedure ... more Allogeneic haematopoietic stem cell transplantation represents a potential life-saving procedure for many patients affected by acute myeloid leukaemia. However, in the past its application has been limited by the availability of a HLA matched sibling. To date, an allogeneic transplant from alternative haematopoietic stem cell sources (volunteer unrelated donor, umbilical cord blood, haploidentical family donor) should be considered for all patients with high-risk disease defined by integration of clinical and biological prognosticators. In this context, following the preliminary, encouraging results, the transplant of unrelated umbilical cord blood has been progressively increased because of its prompt availability and a more permissive HLA incompatibility between donor and recipient. Furthermore, the decreased risk of GVHD, the use of reduced intensity conditionings and the graft of double cord blood units permit to extend cord blood transplant to a higher proportion of adult patie...

Research paper thumbnail of Deferasirox chelation therapy in patients with transfusion-dependent MDS: a ‘real-world’ report from two regional Italian registries: Gruppo Romano Mielodisplasie and Registro Basilicata

European Journal of Haematology, 2015

Research paper thumbnail of Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia

Research paper thumbnail of An increase in hemoglobin, platelets and white blood cells levels by iron chelation as single treatment in multitransfused patients with myelodysplastic syndromes: clinical evidences and possible biological mechanisms

Annals of Hematology, 2015

Iron chelation therapy can improve hematopoiesis in myelodysplastic syndromes. Only few studies s... more Iron chelation therapy can improve hematopoiesis in myelodysplastic syndromes. Only few studies showed hematologic improvement with deferoxamine, and the erythroid responses were correlated with good compliance to long-term treatment. Indeed, single-case reports and data from clinical trials testing the efficacy of deferasirox reported hematologic improvements with varying rates of response in different lineages. Overall, about 760 myelodysplastic syndrome (MDS) patients with iron overload receiving deferasirox were included in six different studies, and an increase in hemoglobin level was reported to range from 6 to 44.5 %, an increase in platelet count from 13 to 61 %, and in neutrophil count from 3 to 76 %. In all the published studies, hematologic improvements were not related to serum ferritin or to non-total binding iron changes; indeed, other pathways were indicated as possible pathogenetic mechanisms, such as decreased NF-kB activity, modulation of mTOR signalling, and reduced reactive oxygen species. The aims of this review are to provide all available information relating clinical and hematologic changes after chelation therapy and to discuss potential mechanisms involved in such responses.

Research paper thumbnail of All-trans retinoic acid and low-dose cytosine arabinoside for the treatment of 'poor prognosis' acute myeloid leukemia

Leukemia, 1995

Thirty-three patients with 'poor prognosis' acute myeloid leukemia, no longer suitable fo... more Thirty-three patients with 'poor prognosis' acute myeloid leukemia, no longer suitable for aggressive chemotherapy, were treated with daily oral all-trans retinoic acid (45 mg/m2) daily and subcutaneous cytosine arabinoside (20 mg standard dose twice a day, day 1 to 10, every 4 weeks). Seventeen patients were males and 16 females, the median age was 67 (range 39-82 years). Eleven patients were at onset of disease, 15 were refractory to previous conventional therapies, three were in first relapse and three in second relapse and one patient had a secondary AML. Seventeen patients had a bone marrow blast infiltration < 50% and 16 > or = 50%. A total of 16 (48%) patients entered complete remission; the rate of complete remission increased to 88% in those patients (n = 17) with < 50% blast infiltration at the time of entering the study. Seventeen patients (52%) were resistant. The difference in response to therapy, according to bone marrow blast percentage (< or > ...

Research paper thumbnail of Clinical relevance of P-glycoprotein expression in de novo acute myeloid leukemia

Blood, 1996

Cytofluorimetric detection of the multidrug resistance (MDR)-associated membrane protein (P-170) ... more Cytofluorimetric detection of the multidrug resistance (MDR)-associated membrane protein (P-170) was performed at the time of diagnosis in 158 patients with acute myeloid leukemia using the C219 monoclonal antibody (MoAb). In 108 of these cases the JSB1 MoAb was also tested. An improved histogram subtraction analysis, based on curve fitting and statistical test was applied to distinguish antigen-positive from antigen-negative cells. A marker was considered positive when more than 20% of the cells were stained. At onset, P-170 was detected in 43% of cases with C219 and in 73% of cases with JSB1. There was a strict correlation between C219 and JSB1 positivity, as all C219+ cases were also positive for JSB1 MoAb (P < .001). No relationship was found between sex, age, organomegaly, and MDR phenotype. Significant correlation was found between CD7 and both C219 and JSB1 expression (P < .001 and .001, respectively). C219-negative phenotype was more often associated with a normal kary...

Research paper thumbnail of Biological pattern of AML-M0 versus AML-M1: response

Research paper thumbnail of P-glycoprotein expression in de novo acute myeloid leukemia

Leukemia & lymphoma, 1997

Detection of the multidrug resistance P-glycoprotein (PGP) phenotype was performed at the time of... more Detection of the multidrug resistance P-glycoprotein (PGP) phenotype was performed at the time of diagnosis in 223 patients with acute myeloid leukemia (AML) by flow cytometry using C219 Monoclonal Antibody (MoAb). On the other hand, JSB1 MoAb was tested in 173 of these samples. At onset, PGP was detected in 57.4% of cases with C219 and 75.9% of cases with JSB1. There was no correlation between PGP expression and sex, age, marrow blast percentage or extramedullary disease. On the contrary, strict correlations were noted either between C219 negativity and FAB M3 subtype or between C219 positivity and FAB M5 group (P = 0.003). Significant correlation was found between PGP phenotype and CD7, as 143 of 223 samples had similar patterns of staining with C219 (P < 0.0001). Finally, there was a close relationship between C219 and JSB1 positivity: all the C219+ cases were positive for JSB1 (P < 0.0001). Concerning the karyotype, most patients with monosomy or del (7) were MDR positive;...

Research paper thumbnail of Biological features of acute myeloid leukemia in the elderly

Research paper thumbnail of Multiparametric analysis for the enumeration of CD34+ cells from bone marrow and stimulated peripheral blood

International journal of molecular medicine, 1998

Determination of CD34+ cells was performed in bone marrow and G-CSF mobilised peripheral blood sa... more Determination of CD34+ cells was performed in bone marrow and G-CSF mobilised peripheral blood samples. We adopted three different protocols of analysis: the Milan/Mulhouse protocol, the ISHAGE guidelines for CD34+ cell determination and our own protocol based upon the use of PAINT-A-GATEPRO software analysis program. An excellent correlation was demonstrated between the three methods (r2 0.98); however the analysis of variance showed a statistically significant difference between the results generated with the three methods (P=0.001). The differences between the three procedures are discussed with a special focus on the value of CD34+dim cells and the role of CD45 in the setting of a double staining. We have in fact identified a minor subset (CD34+CD38+CD45-) which would go unrecognised based upon its CD45 negativity.

Research paper thumbnail of Quantitative analysis of Fas and bcl-2 expression in hematopoietic precursors

Haematologica, 2001

We investigated the expression of bcl-2 and CD95 (Apo1-/Fas) on CD34+ cells obtained from bone ma... more We investigated the expression of bcl-2 and CD95 (Apo1-/Fas) on CD34+ cells obtained from bone marrow (BM), mobilized peripheral blood (MPB), and umbilical cord blood (UCB) samples. The expression of bcl-2 and Fas was then compared with that of other markers usually associated with immaturity; functional tests using the agonistic antibody anti- Fas CH11 were also carried out. The analysis was performed by flow cytometry on purified CD34+ cells in a three (CD95 PE, CD34 APC and CD71 FITC) and in a four (CD38 PE, HLA-DR PerCP, CD34 APC and bcl-2 FITC) fluorescence assay. The results were expressed as mean fluorescence index (MFI); bcl-2 expression was significantly higher (p < 0.001) in BM (3.73 +/- 0.63) than in MPB (2.47 +/- 0.39) and UCB (2.38 +/- 0.58); Fas was significantly less expressed (p < 0.001) in UCB (1.27 +/- 0.78) than in MBP (3.63 +/- 2.19) and BM (4.56 +/- 1.69). CD34 expression was significantly (p < 0.001) brighter in UCB compared to in MBP and BM, while CD3...

Research paper thumbnail of Clinical significance of soluble p53 protein in B-cell chronic lymphocytic leukemia

Haematologica, 2004

p53 status and CD38 antigen are biological factors influencing response to therapy and clinical c... more p53 status and CD38 antigen are biological factors influencing response to therapy and clinical course in B-cell chronic lymphocytic leukemia (B-CLL). This study tests the hypothesis that soluble p53 alone and in association with CD38 can enucleate B-CLL subsets at worse prognosis. Wild and mutant forms of p53 protein were evaluated in 197 B-CLL patients at diagnosis or before progression by an immunoenzymatic method in plasma using an anti-p53 monoclonal antibody. CD38 expression was analyzed by a multicolor flow cytometric assay. Higher levels of both soluble p53 (sp53) and CD38 were significantly correlated with intermediate and high Rai stages, with higher beta2-microglobulin and soluble CD23 values, determined at diagnosis. Shorter overall survival (OS) and progression-free survival (PFS) were both observed in sp53+ and CD38+ patients (p<0.0001). Simultaneous positivity or negativity for sp53 and CD38 identified two subsets of patients, the former with a worse prognosis and ...

Research paper thumbnail of Quantitative analysis of P-glycoprotein, bcl-2 and transferrin receptor allows the stratification of acute myeloid leukemia patients within different prognostic risk classes

Research paper thumbnail of Overexpression of BCL-2 as a possible mechanism of chemoresistance in immature acute myeloid leukemia

Research paper thumbnail of Dose-intensive, Ara-C/mitoxantrone-based chemotherapy followed by hematopoietic stem cell transplantation for adult acute lymphoblastic leukemia

Research paper thumbnail of The amount of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia

Research paper thumbnail of CD38 antigen expression, and soluble p53 levels predict outcome in B-chronic lymphocytic leukemia

Research paper thumbnail of Optimal post-remission therapy for flow-cytometry minimal residual disease positive adult patients with acute myeloid leukemia

Research paper thumbnail of Standard dose and prolonged administration of azacitidine are associated with improved efficacy in a real-world group of patients with myelodysplastic syndrome or low-blast count acute myeloid leukemia

European Journal of Haematology, 2015

Azacitidine is the standard of care for higher-risk myelodysplastic syndromes (MDS). We evaluated... more Azacitidine is the standard of care for higher-risk myelodysplastic syndromes (MDS). We evaluated factors affecting the outcome of azacitidine treatment in 196 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;real world&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; patients, retrospectively collected by two Italian cooperative groups. The study included 184 MDS and 12 low-blast count acute myeloid leukemia (AML). Azacitidine was administered at the standard dose of 75 mg/m(2) /day for 7 days (StD) in 163 patients, and 100 mg/day for 5-7 days in 33 patients. After a median of 4.5 azacitidine cycles (range 7-15 cycles), 182 patients were evaluable for response. Nineteen % achieved complete remission (CR), 17% partial remission (PR), and 21% hematological improvement (HI). The disease was stable or progressive in 29% and 14% of patients, respectively. The probability of response was significantly higher in patients who received the 75 mg/m(2) /7 day compared to 100 mg through 5-7 days dose (CR/PR/HI: 63 vs 37%, p=0.0005). Median overall survival was 17.1 months. Low MDS-CI and achievement of CR/PR/HI were significant predictors of survival in the multivariable analysis. Our data show that maximal azacitidine efficacy is associated to the standard dose and to prolonged treatment, beyond 4-6 cycles, with the goal of also improving &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;quality&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; of response. Lower MDS-CI and IPSS-R scores, hematologic response and disease stability, are associated to longer survival. The risk of febrile events is highest during the first treatment cycles, and is associated to active disease. This article is protected by copyright. All rights reserved.

Research paper thumbnail of A Leukemia-Associated CD34/CD123/CD25/CD99-positive Immunophenotype Identifies FLT3-mutated Clones in Acute Myeloid Leukemia

Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 8, 2015

Purpose We evaluated leukemia-associated immunophenotypes (LAIP) and their correlation with fms-l... more Purpose We evaluated leukemia-associated immunophenotypes (LAIP) and their correlation with fms-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1) gene mutational status in order to contribute a better identification of patients at highest risk of relapse in AML. Bone marrow samples from 132 patients with acute myeloid leukemia (AML) were analyzed by 9-color multiparametric flow cytometry (MPFC). We confirmed the presence of the mutation in diagnostic samples and in sorted cells by conventional RT-PCR and by patient-specific RQ-PCR. Within the CD34+ve cell fraction we identified a discrete population expressing high levels of the IL-3 receptor alpha-chain (CD123) and MIC-2 (CD99) in combination with the IL-2 receptor alpha-chain (CD25). The presence of this population positively correlated with the internal tandem duplications (ITD) mutation in the FLT3 gene (r = 0.71). Receiver operating characteristics (ROC) showed that, within the CD34+ve cell fraction a percentage of CD123/C...

Research paper thumbnail of Cord blood transplantation in adults with acute myeloid leukaemia

Best practice & research. Clinical haematology, 2010

Allogeneic haematopoietic stem cell transplantation represents a potential life-saving procedure ... more Allogeneic haematopoietic stem cell transplantation represents a potential life-saving procedure for many patients affected by acute myeloid leukaemia. However, in the past its application has been limited by the availability of a HLA matched sibling. To date, an allogeneic transplant from alternative haematopoietic stem cell sources (volunteer unrelated donor, umbilical cord blood, haploidentical family donor) should be considered for all patients with high-risk disease defined by integration of clinical and biological prognosticators. In this context, following the preliminary, encouraging results, the transplant of unrelated umbilical cord blood has been progressively increased because of its prompt availability and a more permissive HLA incompatibility between donor and recipient. Furthermore, the decreased risk of GVHD, the use of reduced intensity conditionings and the graft of double cord blood units permit to extend cord blood transplant to a higher proportion of adult patie...

Research paper thumbnail of Deferasirox chelation therapy in patients with transfusion-dependent MDS: a ‘real-world’ report from two regional Italian registries: Gruppo Romano Mielodisplasie and Registro Basilicata

European Journal of Haematology, 2015

Research paper thumbnail of Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia

Research paper thumbnail of An increase in hemoglobin, platelets and white blood cells levels by iron chelation as single treatment in multitransfused patients with myelodysplastic syndromes: clinical evidences and possible biological mechanisms

Annals of Hematology, 2015

Iron chelation therapy can improve hematopoiesis in myelodysplastic syndromes. Only few studies s... more Iron chelation therapy can improve hematopoiesis in myelodysplastic syndromes. Only few studies showed hematologic improvement with deferoxamine, and the erythroid responses were correlated with good compliance to long-term treatment. Indeed, single-case reports and data from clinical trials testing the efficacy of deferasirox reported hematologic improvements with varying rates of response in different lineages. Overall, about 760 myelodysplastic syndrome (MDS) patients with iron overload receiving deferasirox were included in six different studies, and an increase in hemoglobin level was reported to range from 6 to 44.5 %, an increase in platelet count from 13 to 61 %, and in neutrophil count from 3 to 76 %. In all the published studies, hematologic improvements were not related to serum ferritin or to non-total binding iron changes; indeed, other pathways were indicated as possible pathogenetic mechanisms, such as decreased NF-kB activity, modulation of mTOR signalling, and reduced reactive oxygen species. The aims of this review are to provide all available information relating clinical and hematologic changes after chelation therapy and to discuss potential mechanisms involved in such responses.

Research paper thumbnail of All-trans retinoic acid and low-dose cytosine arabinoside for the treatment of 'poor prognosis' acute myeloid leukemia

Leukemia, 1995

Thirty-three patients with 'poor prognosis' acute myeloid leukemia, no longer suitable fo... more Thirty-three patients with 'poor prognosis' acute myeloid leukemia, no longer suitable for aggressive chemotherapy, were treated with daily oral all-trans retinoic acid (45 mg/m2) daily and subcutaneous cytosine arabinoside (20 mg standard dose twice a day, day 1 to 10, every 4 weeks). Seventeen patients were males and 16 females, the median age was 67 (range 39-82 years). Eleven patients were at onset of disease, 15 were refractory to previous conventional therapies, three were in first relapse and three in second relapse and one patient had a secondary AML. Seventeen patients had a bone marrow blast infiltration < 50% and 16 > or = 50%. A total of 16 (48%) patients entered complete remission; the rate of complete remission increased to 88% in those patients (n = 17) with < 50% blast infiltration at the time of entering the study. Seventeen patients (52%) were resistant. The difference in response to therapy, according to bone marrow blast percentage (< or > ...

Research paper thumbnail of Clinical relevance of P-glycoprotein expression in de novo acute myeloid leukemia

Blood, 1996

Cytofluorimetric detection of the multidrug resistance (MDR)-associated membrane protein (P-170) ... more Cytofluorimetric detection of the multidrug resistance (MDR)-associated membrane protein (P-170) was performed at the time of diagnosis in 158 patients with acute myeloid leukemia using the C219 monoclonal antibody (MoAb). In 108 of these cases the JSB1 MoAb was also tested. An improved histogram subtraction analysis, based on curve fitting and statistical test was applied to distinguish antigen-positive from antigen-negative cells. A marker was considered positive when more than 20% of the cells were stained. At onset, P-170 was detected in 43% of cases with C219 and in 73% of cases with JSB1. There was a strict correlation between C219 and JSB1 positivity, as all C219+ cases were also positive for JSB1 MoAb (P < .001). No relationship was found between sex, age, organomegaly, and MDR phenotype. Significant correlation was found between CD7 and both C219 and JSB1 expression (P < .001 and .001, respectively). C219-negative phenotype was more often associated with a normal kary...

Research paper thumbnail of Biological pattern of AML-M0 versus AML-M1: response

Research paper thumbnail of P-glycoprotein expression in de novo acute myeloid leukemia

Leukemia & lymphoma, 1997

Detection of the multidrug resistance P-glycoprotein (PGP) phenotype was performed at the time of... more Detection of the multidrug resistance P-glycoprotein (PGP) phenotype was performed at the time of diagnosis in 223 patients with acute myeloid leukemia (AML) by flow cytometry using C219 Monoclonal Antibody (MoAb). On the other hand, JSB1 MoAb was tested in 173 of these samples. At onset, PGP was detected in 57.4% of cases with C219 and 75.9% of cases with JSB1. There was no correlation between PGP expression and sex, age, marrow blast percentage or extramedullary disease. On the contrary, strict correlations were noted either between C219 negativity and FAB M3 subtype or between C219 positivity and FAB M5 group (P = 0.003). Significant correlation was found between PGP phenotype and CD7, as 143 of 223 samples had similar patterns of staining with C219 (P < 0.0001). Finally, there was a close relationship between C219 and JSB1 positivity: all the C219+ cases were positive for JSB1 (P < 0.0001). Concerning the karyotype, most patients with monosomy or del (7) were MDR positive;...

Research paper thumbnail of Biological features of acute myeloid leukemia in the elderly

Research paper thumbnail of Multiparametric analysis for the enumeration of CD34+ cells from bone marrow and stimulated peripheral blood

International journal of molecular medicine, 1998

Determination of CD34+ cells was performed in bone marrow and G-CSF mobilised peripheral blood sa... more Determination of CD34+ cells was performed in bone marrow and G-CSF mobilised peripheral blood samples. We adopted three different protocols of analysis: the Milan/Mulhouse protocol, the ISHAGE guidelines for CD34+ cell determination and our own protocol based upon the use of PAINT-A-GATEPRO software analysis program. An excellent correlation was demonstrated between the three methods (r2 0.98); however the analysis of variance showed a statistically significant difference between the results generated with the three methods (P=0.001). The differences between the three procedures are discussed with a special focus on the value of CD34+dim cells and the role of CD45 in the setting of a double staining. We have in fact identified a minor subset (CD34+CD38+CD45-) which would go unrecognised based upon its CD45 negativity.

Research paper thumbnail of Quantitative analysis of Fas and bcl-2 expression in hematopoietic precursors

Haematologica, 2001

We investigated the expression of bcl-2 and CD95 (Apo1-/Fas) on CD34+ cells obtained from bone ma... more We investigated the expression of bcl-2 and CD95 (Apo1-/Fas) on CD34+ cells obtained from bone marrow (BM), mobilized peripheral blood (MPB), and umbilical cord blood (UCB) samples. The expression of bcl-2 and Fas was then compared with that of other markers usually associated with immaturity; functional tests using the agonistic antibody anti- Fas CH11 were also carried out. The analysis was performed by flow cytometry on purified CD34+ cells in a three (CD95 PE, CD34 APC and CD71 FITC) and in a four (CD38 PE, HLA-DR PerCP, CD34 APC and bcl-2 FITC) fluorescence assay. The results were expressed as mean fluorescence index (MFI); bcl-2 expression was significantly higher (p < 0.001) in BM (3.73 +/- 0.63) than in MPB (2.47 +/- 0.39) and UCB (2.38 +/- 0.58); Fas was significantly less expressed (p < 0.001) in UCB (1.27 +/- 0.78) than in MBP (3.63 +/- 2.19) and BM (4.56 +/- 1.69). CD34 expression was significantly (p < 0.001) brighter in UCB compared to in MBP and BM, while CD3...

Research paper thumbnail of Clinical significance of soluble p53 protein in B-cell chronic lymphocytic leukemia

Haematologica, 2004

p53 status and CD38 antigen are biological factors influencing response to therapy and clinical c... more p53 status and CD38 antigen are biological factors influencing response to therapy and clinical course in B-cell chronic lymphocytic leukemia (B-CLL). This study tests the hypothesis that soluble p53 alone and in association with CD38 can enucleate B-CLL subsets at worse prognosis. Wild and mutant forms of p53 protein were evaluated in 197 B-CLL patients at diagnosis or before progression by an immunoenzymatic method in plasma using an anti-p53 monoclonal antibody. CD38 expression was analyzed by a multicolor flow cytometric assay. Higher levels of both soluble p53 (sp53) and CD38 were significantly correlated with intermediate and high Rai stages, with higher beta2-microglobulin and soluble CD23 values, determined at diagnosis. Shorter overall survival (OS) and progression-free survival (PFS) were both observed in sp53+ and CD38+ patients (p<0.0001). Simultaneous positivity or negativity for sp53 and CD38 identified two subsets of patients, the former with a worse prognosis and ...

Research paper thumbnail of Quantitative analysis of P-glycoprotein, bcl-2 and transferrin receptor allows the stratification of acute myeloid leukemia patients within different prognostic risk classes

Research paper thumbnail of Overexpression of BCL-2 as a possible mechanism of chemoresistance in immature acute myeloid leukemia

Research paper thumbnail of Dose-intensive, Ara-C/mitoxantrone-based chemotherapy followed by hematopoietic stem cell transplantation for adult acute lymphoblastic leukemia

Research paper thumbnail of The amount of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia

Research paper thumbnail of CD38 antigen expression, and soluble p53 levels predict outcome in B-chronic lymphocytic leukemia

Research paper thumbnail of Optimal post-remission therapy for flow-cytometry minimal residual disease positive adult patients with acute myeloid leukemia