M. Defina - Academia.edu (original) (raw)

Papers by M. Defina

British Journal of Haematology, 2010

Effect of a p210 multipeptide vaccine associated with imatinib or interferon in patients with chr... more Effect of a p210 multipeptide vaccine associated with imatinib or interferon in patients with chronic myeloid leukaemia and persistent residual disease: a multicentre observational trial. Lancet, 365, 657-662. Fig 1. BCR-ABL1/ABL1 molecular monitoring by RQ-PCR in two patients treated with imatinib and p210 vaccine.

International Journal of Hematology, 2014

Journal of biological regulators and homeostatic agents, 2016

T-cell Acute Lymphoblastic Leukemia (T-cell ALL) is a rare haematological neoplasia, that affects... more T-cell Acute Lymphoblastic Leukemia (T-cell ALL) is a rare haematological neoplasia, that affects children and less commonly adults. Female genital tract and particularly uterus involvement in acute ALL is rare. This report presents the CT features of a 64-year-old woman with uterine relapse of T-cell ALL, occurring 11 months after the diagnosis, as a second, unique relapse of disease. The patient was asymptomatic when a CT examination showed a homogenous thickness of the uterine wall in comparison with the previous CT examination. Histology from biopsy specimens, obtained through hysteroscopy, confirmed T-cell ALL localisation (TdT+, CD10+, CD3c+ and CD2+). The uterus could be a site of relapse in patients suffering from ALL. Even though an MRI examination could better demonstrate the disease in cases of suspected female genital tract involvement by ALL, the comparison of differences between a present and a previous CT examination is sufficient to suspect the diagnosis.

Anti-Cancer Agents in Medicinal Chemistry, 2016

In recent years there has been a great improvement in molecular characterization of acute myeloid... more In recent years there has been a great improvement in molecular characterization of acute myeloid leukemia (AML) allowing the stratification of patients in different rate of risk. Patients with FLT3 mutated AML have poor prognosis because of resistance to induction chemotherapy or early relapse. Several first and second generation molecules, able to inhibit FLT3 signaling have been developed and many single agent or combination studies are ongoing. Of these, quizartinib seems to have the best clinical activity. Unfortunately, resistance to FLT3 inhibitors has been observed and many scientists are currently investigating new strategy to restore sensitivity to FLT3 inhibitors.

Journal of the Siena Academy of Sciences, 2009

Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 2015

The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the cha... more The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0 cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kin...

Journal of the Siena Academy of Sciences, 2009

Journal of the Siena Academy of Sciences, 2009

The patogenesis of MDS is complex and remain elusive. shows a hypothetical model. The proposed mo... more The patogenesis of MDS is complex and remain elusive. shows a hypothetical model. The proposed models agree that a multistep process occurs through which a hematopoietic stem cell is mutated and attains a growth advantage. This may occur as a result of environmental damage or inherited predisposition. The mutated clone is associated with morphological dysplasia, impaired differentiation and genomic instability. Cytokine secretion and apoptotic pathways are altered and as well as may be impairment of immune responses. Presumably, in the early stages, increased production of proapoptotic cytokines leads to excessive apoptosis, correlating clinically with cytopenias and a cellular bone marrow. As the disease progresses, further genetic and epigenetic events occur, resulting in decreased apoptosis, clonal expansion and progression to AML. Clinical testing of a number of molecules that affect these myriad molecular mechanisms is currently being done, characterization of genomic expression patterns will inform both diagnosis and prognostication. Further insight into the molecular mechanisms of MDS will provide an avenue for more tailored and effective therapy in the future.

Onkologie, 2008

Cases of discordant responses in multiple myeloma (MM) patients after thalidomide therapy have be... more Cases of discordant responses in multiple myeloma (MM) patients after thalidomide therapy have been sometimes reported, in which extramedullary masses progress or present de novo with a simultaneous serum monoclonal protein reduction. We hereby report, for the first time, on two cases of MM patients with extramedullary myeloma localizations that developed during Velcade (bortezomib, PS341) treatment with a concomitant serum monoclonal protein reduction. We observed in both patients a very good response in the serum monoclonal protein level, while extramedullary lesions appeared in the central nervous system and subcutaneously. We discuss pharmacokinetics of bortezomib and physiopathology of this unusual event and review the literature.

Leukemia Research, 2010

Very late relapse in a patient with chronic myeloid leukemia in sustained complete cytogenetic re... more Very late relapse in a patient with chronic myeloid leukemia in sustained complete cytogenetic response under imatinib

Hematology, 2005

Fungal infections due to Aspergillus are a frequent cause of transplant-related mortality. For th... more Fungal infections due to Aspergillus are a frequent cause of transplant-related mortality. For this reason, leukemic patients with severe fungal infection are usually excluded from conventional allotransplantation. Recently, some authors suggested a role for non-myeloablative hematopoietic stem cell transplantation (HSCT) in this subset of patients. We used this therapeutic approach in a patient with high-risk acute myeloid leukemia in second complete remission (CR) with pre-existing hepatic aspergillosis refractory to conventional anti-fungal therapy. A complete regression of hepatic lesions was observed after 3 months from allogeneic stem cell transplantation. Our work confirms previous reports suggesting that non-myeloablative HSCT is effective in patients not eligible for conventional transplantation because of invasive aspergillosis.

Hematological Oncology, 2013

Angioimmunoblastic T-cell lymphoma (AITL) is characterized by an aggressive clinical course and u... more Angioimmunoblastic T-cell lymphoma (AITL) is characterized by an aggressive clinical course and unfavourable prognosis. Refractory AITL patients have very few treatment options. Lenalidomide has previously been reported to have clinical efficacy in this setting; however, long-term reports are limited. A 59-year-old man was referred to the hospital with fatigue, skin rash, weight loss and generalized lymphadenopathy and was diagnosed with AITL; clinical stage was IV B with bone marrow involvement. The patient had an unsatisfactory response despite three lines of conventional chemotherapy and radiotherapy. The patient received lenalidomide monotherapy (25 mg once daily) on days 1 to 21 of every 28-day cycle for six cycles, followed by maintenance therapy with six cycles of lenalidomide 15 mg once daily on days 1 to 21 of every 28-day cycle. A computed tomography scan was assessed before lenalidomide treatment, after the third cycle, at disease restaging 2 months after completion of the induction phase, every 3 months during the maintenance phase and every 6 months during the follow-up period. At the last evaluation, after a follow-up of 30 months, the patient maintained a clinical and radiological complete response. The treatment was well tolerated with manageable toxicity. Lenalidomide treatment demonstrated for the first time in the literature impressive and long-term clinical efficacy in a heavily pretreated chemorefractory AITL patient.

British Journal of Haematology, 2010

Effect of a p210 multipeptide vaccine associated with imatinib or interferon in patients with chr... more Effect of a p210 multipeptide vaccine associated with imatinib or interferon in patients with chronic myeloid leukaemia and persistent residual disease: a multicentre observational trial. Lancet, 365, 657-662. Fig 1. BCR-ABL1/ABL1 molecular monitoring by RQ-PCR in two patients treated with imatinib and p210 vaccine.

International Journal of Hematology, 2014

Journal of biological regulators and homeostatic agents, 2016

T-cell Acute Lymphoblastic Leukemia (T-cell ALL) is a rare haematological neoplasia, that affects... more T-cell Acute Lymphoblastic Leukemia (T-cell ALL) is a rare haematological neoplasia, that affects children and less commonly adults. Female genital tract and particularly uterus involvement in acute ALL is rare. This report presents the CT features of a 64-year-old woman with uterine relapse of T-cell ALL, occurring 11 months after the diagnosis, as a second, unique relapse of disease. The patient was asymptomatic when a CT examination showed a homogenous thickness of the uterine wall in comparison with the previous CT examination. Histology from biopsy specimens, obtained through hysteroscopy, confirmed T-cell ALL localisation (TdT+, CD10+, CD3c+ and CD2+). The uterus could be a site of relapse in patients suffering from ALL. Even though an MRI examination could better demonstrate the disease in cases of suspected female genital tract involvement by ALL, the comparison of differences between a present and a previous CT examination is sufficient to suspect the diagnosis.

Anti-Cancer Agents in Medicinal Chemistry, 2016

In recent years there has been a great improvement in molecular characterization of acute myeloid... more In recent years there has been a great improvement in molecular characterization of acute myeloid leukemia (AML) allowing the stratification of patients in different rate of risk. Patients with FLT3 mutated AML have poor prognosis because of resistance to induction chemotherapy or early relapse. Several first and second generation molecules, able to inhibit FLT3 signaling have been developed and many single agent or combination studies are ongoing. Of these, quizartinib seems to have the best clinical activity. Unfortunately, resistance to FLT3 inhibitors has been observed and many scientists are currently investigating new strategy to restore sensitivity to FLT3 inhibitors.

Journal of the Siena Academy of Sciences, 2009

Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 2015

The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the cha... more The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0 cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kin...

Journal of the Siena Academy of Sciences, 2009

Journal of the Siena Academy of Sciences, 2009

The patogenesis of MDS is complex and remain elusive. shows a hypothetical model. The proposed mo... more The patogenesis of MDS is complex and remain elusive. shows a hypothetical model. The proposed models agree that a multistep process occurs through which a hematopoietic stem cell is mutated and attains a growth advantage. This may occur as a result of environmental damage or inherited predisposition. The mutated clone is associated with morphological dysplasia, impaired differentiation and genomic instability. Cytokine secretion and apoptotic pathways are altered and as well as may be impairment of immune responses. Presumably, in the early stages, increased production of proapoptotic cytokines leads to excessive apoptosis, correlating clinically with cytopenias and a cellular bone marrow. As the disease progresses, further genetic and epigenetic events occur, resulting in decreased apoptosis, clonal expansion and progression to AML. Clinical testing of a number of molecules that affect these myriad molecular mechanisms is currently being done, characterization of genomic expression patterns will inform both diagnosis and prognostication. Further insight into the molecular mechanisms of MDS will provide an avenue for more tailored and effective therapy in the future.

Onkologie, 2008

Cases of discordant responses in multiple myeloma (MM) patients after thalidomide therapy have be... more Cases of discordant responses in multiple myeloma (MM) patients after thalidomide therapy have been sometimes reported, in which extramedullary masses progress or present de novo with a simultaneous serum monoclonal protein reduction. We hereby report, for the first time, on two cases of MM patients with extramedullary myeloma localizations that developed during Velcade (bortezomib, PS341) treatment with a concomitant serum monoclonal protein reduction. We observed in both patients a very good response in the serum monoclonal protein level, while extramedullary lesions appeared in the central nervous system and subcutaneously. We discuss pharmacokinetics of bortezomib and physiopathology of this unusual event and review the literature.

Leukemia Research, 2010

Very late relapse in a patient with chronic myeloid leukemia in sustained complete cytogenetic re... more Very late relapse in a patient with chronic myeloid leukemia in sustained complete cytogenetic response under imatinib

Hematology, 2005

Fungal infections due to Aspergillus are a frequent cause of transplant-related mortality. For th... more Fungal infections due to Aspergillus are a frequent cause of transplant-related mortality. For this reason, leukemic patients with severe fungal infection are usually excluded from conventional allotransplantation. Recently, some authors suggested a role for non-myeloablative hematopoietic stem cell transplantation (HSCT) in this subset of patients. We used this therapeutic approach in a patient with high-risk acute myeloid leukemia in second complete remission (CR) with pre-existing hepatic aspergillosis refractory to conventional anti-fungal therapy. A complete regression of hepatic lesions was observed after 3 months from allogeneic stem cell transplantation. Our work confirms previous reports suggesting that non-myeloablative HSCT is effective in patients not eligible for conventional transplantation because of invasive aspergillosis.

Hematological Oncology, 2013

Angioimmunoblastic T-cell lymphoma (AITL) is characterized by an aggressive clinical course and u... more Angioimmunoblastic T-cell lymphoma (AITL) is characterized by an aggressive clinical course and unfavourable prognosis. Refractory AITL patients have very few treatment options. Lenalidomide has previously been reported to have clinical efficacy in this setting; however, long-term reports are limited. A 59-year-old man was referred to the hospital with fatigue, skin rash, weight loss and generalized lymphadenopathy and was diagnosed with AITL; clinical stage was IV B with bone marrow involvement. The patient had an unsatisfactory response despite three lines of conventional chemotherapy and radiotherapy. The patient received lenalidomide monotherapy (25 mg once daily) on days 1 to 21 of every 28-day cycle for six cycles, followed by maintenance therapy with six cycles of lenalidomide 15 mg once daily on days 1 to 21 of every 28-day cycle. A computed tomography scan was assessed before lenalidomide treatment, after the third cycle, at disease restaging 2 months after completion of the induction phase, every 3 months during the maintenance phase and every 6 months during the follow-up period. At the last evaluation, after a follow-up of 30 months, the patient maintained a clinical and radiological complete response. The treatment was well tolerated with manageable toxicity. Lenalidomide treatment demonstrated for the first time in the literature impressive and long-term clinical efficacy in a heavily pretreated chemorefractory AITL patient.