Haematology and Bone Marrow Transplant Unit

Sotto il Monte Giovanni XXIII, Italy

Haematology and Bone Marrow Transplant Unit

Sotto il Monte Giovanni XXIII, Italy
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Martino M.,Haematology and Bone Marrow Transplant Unit | Olivieri A.,Clinica di Ematologia | Offidani M.,Clinica di Ematologia | Moscato T.,Haematology and Bone Marrow Transplant Unit | And 5 more authors.
Expert Opinion on Investigational Drugs | Year: 2013

Introduction: The role of high-dose chemotherapy (HDC) followed by autologous-progenitor cell transplantation (auto-HPCT) in the treatment of multiple myeloma (MM) continues to evolve in the novel agent era. Administration of high-dose melphalan (HDM) is considered the standard conditioning regimen. Nevertheless, several attempts have recently been made to improve the conditioning phase of the HDC procedure. Areas covered: We reviewed all the reported experiences and illustrated current knowledge in the field of conditioning regimens. Expert opinion: For fit MM patients, HDC followed by auto-HPCT remains the standard of care. The available data confirm that melphalan (MEL) 200 mg/mshould continue to be considered the gold standard conditioning regimen, with dose reduction based on age and renal function. Targeting exposure to MEL by using area under the curve is a particularly appealing approach that could be explored to maximize efficacy and minimize toxicity of this drug. Other strategies are currently being evaluated in different trials, and the most interesting areas of research involve the incorporation of newer agents like bortezomib (BOR) into conditioning regimens. Moreover, intravenous busulfan has become available and this formulation may reduce toxicity and result in greater efficacy in association with MEL-based conditioning. © 2013 Informa UK, Ltd.


Ballen K.K.,Massachusetts General Hospital | Woolfrey A.E.,Fred Hutchinson Cancer Research Center | Zhu X.,Medical College of Wisconsin | Ahn K.W.,Medical College of Wisconsin | And 25 more authors.
Biology of Blood and Marrow Transplantation | Year: 2012

Allogeneic hematopoietic cell transplantation (HCT) is curative for selected patients with advanced essential thrombocythemia (ET) or polycythemia vera (PV). From 1990 to 2007, 75 patients with ET (median age 49 years) and 42 patients with PV (median age 53 years) underwent transplantations at the Fred Hutchinson Cancer Research Center (FHCRC; n = 43) or at other Center for International Blood and Marrow Transplant Research (CIBMTR) centers (n = 74). Thirty-eight percent of the patients had splenomegaly and 28% had a prior splenectomy. Most patients (69% for ET and 67% for PV) received a myeloablative (MA) conditioning regimen. Cumulative incidence of neutrophil engraftment at 28 days was 88% for ET patients and 90% for PV patients. Acute graft-versus-host disease (aGVHD) grades II to IV occurred in 57% and 50% of ET and PV patients, respectively. The 1-year treatment-related mortality (TRM) was 27% for ET and 22% for PV. The 5-year cumulative incidence of relapse was 13% for ET and 30% for PV. Five-year survival/progression-free survival (PFS) was 55%/47% and 71%/48% for ET and PV, respectively. Patients without splenomegaly had faster neutrophil and platelet engraftment, but there were no differences in TRM, survival, or PFS. Presence of myelofibrosis (MF) did not affect engraftment or TRM. Over 45% of the patients who undergo transplantations for ET and PV experience long-term PFS. © 2012 American Society for Blood and Marrow Transplantation.


Gentile M.,Unita Operativa di Ematologia Azienda Ospedaliera di Cosenza | Offidani M.,Clinica di Ematologia | Vigna E.,Unita Operativa di Ematologia Azienda Ospedaliera di Cosenza | Corvatta L.,Ospedale Stelluti Scala | And 5 more authors.
Expert Opinion on Pharmacotherapy | Year: 2015

Introduction: Smoldering multiple myeloma (SMM) is an asymptomatic disorder characterized by the presence of ≥ 30 g/l serum M-protein and/or ≥ 10% bone marrow plasma cell infiltration. The progression risk to active multiple myeloma (MM) is not uniform, and several prognostic parameters are useful for identifying patients at high risk of progression. A watch-and-wait approach has been the standard of care up to now. However, recently, it has been demonstrated that a subset of high-risk cases can benefit from early treatment with new drugs.Areas covered: In this editorial, we focus on SMM and evaluate the diagnostic work-up and the prognostic factors predicting progression to symptomatic MM. We also review the studies in which the role of early treatment has been evaluated for patients with SMM.Expert opinion: After the update performed by the International Myeloma Working Group regarding MM diagnosis, it is now time to change the therapeutic paradigm for this disease. While "ultra high-risk" myeloma should now be considered as active MM, for low-risk patients the "watch-and-wait" strategy is still recommended. More caution is needed for the high-risk group: physicians should continue monitoring patients using every tool now available while waiting for results from ongoing trials that will establish if this group will benefit from an early intervention. © 2015 Informa UK, Ltd.


Lussana F.,Haematology and Bone Marrow Transplant Unit | Randi M.L.,University of Padua | Elena C.,University of Pavia | Rumi E.,University of Pavia | And 13 more authors.
British Journal of Haematology | Year: 2014

Summary: In patients who do not meet the World Health Organization (WHO) criteria for overt polycythaemia vera (PV), a diagnosis of masked PV (mPV) can be determined. A fraction of mPV patients may display thrombocytosis, thus mimicking essential thrombocythaemia (ET). No previous studies have examined clinical outcomes of mPV among young JAK2-mutated patients. We analysed a retrospective cohort of 538 JAK2-mutated patients younger than 40 years, after a re-assessment of the diagnosis according to the haemoglobin threshold for mPV. In this cohort of patients, 97 (18%) met the WHO criteria for PV, 66 patients (12%) were classified as mPV and 375 (70%) as JAK2-mutated ET. Surprisingly, a significant difference in the incidence of thrombosis was found when comparing mPV versus overt PV patients (P = 0·04). In multivariate analysis, the only factor accounting for the difference in the risk of thrombosis was the less frequent use of phlebotomies and cytoreduction in mPV patients compared to those with overt PV. Thus, we emphasize the need for the identification of mPV in young JAK2-mutated patients in order to optimize their treatments. © 2014 John Wiley & Sons Ltd.


Lussana F.,Haematology and Bone Marrow Transplant Unit | Squizzato A.,Medicina 1 | Permunian E.T.,Medicina 1 | Cattaneo M.,University of Milan
Thrombosis research | Year: 2014

INTRODUCTION: Major surgery is associated with increased risk of venous thromboembolism (VTE), which is decreased by anticoagulant drugs. Evidence is growing that major surgery is associated with increased risk of arterial thrombosis (AT). With the aim of testing aspirin ability in reducing the risk of post-operative AT, we performed a systematic review of studies in which acetylsalicylic acid (ASA) was compared to anticoagulant drugs in VTE prophylaxis of patients undergoing total hip replacement (THR) or total knee replacement (TKR).MATERIALS AND METHODS: Studies were identified by reviewing the reference of the ACCP guidelines and by electronic search of MEDLINE database from January 2012 to December 2013 and of the web database www.trialresultscenter.org.RESULTS: We analyzed 5 of the 78 studies that were identified by our search strategy; they included 5179 patients; the median follow-up was 90 days. The incidence of post-operative AT tended to be lower in ASA-treated patients, compared to anticoagulant-treated patients, although the difference did not reach statistical significance (OR 0.56, 95%CI 0.23-1.35). In contrast, the incidence of post-operative VTE tended to be higher in ASA-treated patients, compared to anticoagulant-treated patients (1.48, 95% CI 0.93-2.36).CONCLUSIONS: Due to the heterogeneity and low quality of the studies, which do not allow firm conclusions, it is uncertain whether aspirin is effective in reducing the incidence of postoperative AT. Our results do emphasize the need for developing specifically designed studies to test the safety and efficacy of ASA in the prevention of post-operative AT. Copyright © 2014 Elsevier Ltd. All rights reserved.


Lussana F.,Haematology and Bone Marrow Transplant Unit | Lussana F.,University of Milan | Squizzato A.,Medicina 1 | Permunian E.T.,Medicina 1 | Cattaneo M.,University of Milan
Thrombosis Research | Year: 2014

Introduction: Major surgery is associated with increased risk of venous thromboembolism (VTE), which is decreased by anticoagulant drugs. Evidence is growing that major surgery is associated with increased risk of arterial thrombosis (AT). With the aim of testing aspirin ability in reducing the risk of post-operative AT, we performed a systematic review of studies in which acetylsalicylic acid (ASA) was compared to anticoagulant drugs in VTE prophylaxis of patients undergoing total hip replacement (THR) or total knee replacement (TKR). Materials and Methods: Studies were identified by reviewing the reference of the ACCP guidelines and by electronic search of MEDLINE database from January 2012 to December 2013 and of the web database www.trialresultscenter.org. Results: We analyzed 5 of the 78 studies that were identified by our search strategy; they included 5179 patients; the median follow-up was 90. days. The incidence of post-operative AT tended to be lower in ASA-treated patients, compared to anticoagulant-treated patients, although the difference did not reach statistical significance (OR 0.56, 95%CI 0.23-1.35). In contrast, the incidence of post-operative VTE tended to be higher in ASA-treated patients, compared to anticoagulant-treated patients (1.48, 95% CI 0.93-2.36). Conclusions: Due to the heterogeneity and low quality of the studies, which do not allow firm conclusions, it is uncertain whether aspirin is effective in reducing the incidence of postoperative AT. Our results do emphasize the need for developing specifically designed studies to test the safety and efficacy of ASA in the prevention of post-operative AT. © 2014 Elsevier Ltd.


Festuccia M.,University of Turin | Martino M.,Haematology and Bone Marrow Transplant Unit | Ferrando F.,University of Turin | Messina G.,Haematology and Bone Marrow Transplant Unit | And 5 more authors.
Expert Opinion on Biological Therapy | Year: 2015

Introduction: Autologous (auto) stem cell transplantation (SCT) and the development of new drugs have improved the survival of multiple myeloma (MM) patients. By contrast, though potentially curative, the use of allogeneic (allo)-SCT is controversial.Areas covered: A review has been conducted to examine the current evidence for the use of allo-SCT in MM. We have examined novel cell therapies that may be exploited to induce myeloma-specific immune responses including the new promising frontier of chimeric antigen receptor (CAR)-T and -natural killer (NK) cells.Expert opinion: One of the major controversies facing researchers in exploring the allo approach is the remarkable recent treatment improvement observed with second- and third-generation proteasome inhibitors and immunomodulatory drugs, monoclonal antibodies and deacetylase inhibitors. Despite these great advances, the disease remains to be incurable and allo-SCT may still play a role in the cure of MM. We think that allo-SCT conserves a role in MM and its curative potential in high-risk patients should be explored in the setting of control clinical trials. Novel cell therapies such as CAR technologies may open new avenues of research toward a potential cure. Data from currently ongoing prospective studies will be helpful to clarify pending clinical questions. © Informa UK, Ltd. © 2015 Informa UK, Ltd.


Martino M.,Haematology and Bone Marrow Transplant Unit | Fedele R.,Haematology and Bone Marrow Transplant Unit | Massara E.,Haematology and Bone Marrow Transplant Unit | Recchia A.G.,Haematology and Bone Marrow Transplant Unit | And 5 more authors.
Expert Opinion on Biological Therapy | Year: 2012

Introduction: Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor that stimulates the proliferation and differentiation of neutrophil precursor cells. G-CSF-mobilized peripheral blood (PB) hematopoietic progenitor stem cells (HPSCs) collected by apheresis are being increasingly employed for allogeneic transplantation in patients with malignancies as an alternative to bone marrow (BM) transplant. Documenting the safety of G-CSF as a mobilizing agent for HPSC donation has long been a matter of importance for physicians, particularly when volunteer, unrelated adult donors are involved Areas covered: We review publications in the field with the goal of providing an overview of these approaches. Expert opinion: Trials and international donor registries have not shown any long-term effects associated with G-CSF therapy and a threefold-or-greater increased risk of leukemia or other malignancies through PB HPSC donation can be excluded. Our conclusions are that the administration of G-CSF to healthy donors has a favorable long-term risk-benefit profile, although it is essential to encourage the enrolment of donors in carefully designed programs for follow-up monitoring. © Informa UK, Ltd.

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