Biomedical subjects
Publications and source records attributed to Andrea Piccin.
We report a case of successful allogeneic hematopoietic stem cell transplantation (HSCT) with full myeloablative conditioning in a patient with pre-existing invasive mucormycosis. The mucormycosis involved the maxilla, the nasal septum, and the hard palate. Sustained antifungal therapy and aggressive surgery both before and after HSCT were required.
Microparticles (MP) derived from vascular endothelium or circulating blood cells circulate in the peripheral blood. They originate from blebbing and shedding from cell membrane surfaces in physiological and pathological conditions and are present in low concentrations in normal plasma. Increased levels are generated by a number of mechanisms including platelet activation, direct vascular endothelial damage, thrombin activity on the cell surface, C5b-9 activation, and PF4-heparin-antibody interaction. Several techniques are currently used to study the generation and nature of circulating microparticles. In particular, the genesis and role of microparticles, derived from platelets, endothelial cells and monocytes, in sepsis (especially meningococcal-induced), heparin-induced thrombocytopenia (HIT), thrombotic thrombocytopenic purpura (TTP), aplastic anaemia, paroxysmal nocturnal haemoglobinuria (PNH) and sickle cell disease (SCD) have been well studied, and provide important insights into the underlying diseases. A defect in the ability to form microparticles leads to the severe bleeding disorder of Scott syndrome, which in turn provides a revealing insight into the physiology of coagulation. In addition the complex role of microparticles in vascular and cardiovascular diseases is an area of immense interest, that promises to yield important advances into diagnosis and therapy.
Between August 1993 and March 2003, 130 consecutive multiple myeloma (MM) patients eligible for high-dose treatment were offered a program including up-front autologous stem cell transplantation (ASCT) after conditioning with 200 mg/m(2) melphalan followed by a second ASCT in case of relapse or progression. A total of 107 (82%) patients completed the first ASCT. The best response obtained after ASCT was complete response (CR) 23%, very good partial response (VGPR) 28%, partial response (PR) 42%, and minimal response (MR) 7%. Median overall survival (OS) and event-free survival (EFS) were 65.4 and 27.7 months, respectively. Relapse or progression occurred in 70 patients; 26 received a second ASCT (with a median time of 20.4 months from first ASCT). A major response (> or =PR) was obtained in 69% of these patients. Median OS and EFS after the second ASCT were 38.1 and 14.8 months. Treatment-related mortality was 1.9% after the first ASCT but no deaths occurred after the second. Our experience suggests that elective up-front single ASCT followed by second ASCT after relapse or progression is a safe and effective global strategy to treat MM patients.
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BACKGROUND AND OBJECTIVES: Several polymerase chain reaction (PCR)-based techniques for tracking minimal residual disease (MRD) in B-lymphoproliferative disorders have been recently proposed. These procedures show significant variation in sensitivity and specificity. We describe an alternative assay based on fluorescent PCR combined with capillary electrophoresis and GeneScan analysis, to identify the monoclonal immunoglobulin heavy chain (IgH) rearrangement in multiple myeloma (MM) and to provide a semi-quantitative evaluation of MRD by limiting dilutions. DESIGN AND METHODS: Different sets of family specific primers derived from the leader region and from the framework-1 of IgH were used, with a unique reverse fluorescent primer JH. The malignant clone was identified by GeneScan and sequenced. Two tumor primers, mapping in the complementarity determining regions CDRII and CDRIII, were designed for each patient. A comparison between the nested-PCR approach and direct fluorescent PCR was performed for three patients in complete clinical remission after autologous or allogeneic bone marrow transplantation. RESULTS: Thirty-six consecutive patients with MM were screened and monoclonality was identified in about 70% of the cases. Molecular MRD evaluation was performed in 18 patients using tumor primers. This method allowed identification of 1 neoplastic cell among 10(4)-10(6) normal cells. In three cases, negative by nested-PCR and agarose gel electrophoresis, gene scanning showed persistence of the neoplastic clone, despite the negativity of the immunofixation. INTERPRETATION AND CONCLUSIONS: Capillary electrophoresis of fluorescent fragments with gene scanning provides a simple, rapid and reproducible method to detect IgH rearrangement and to evaluate MRD. Furthermore, the sensitivity reached is up to 1 log higher than that of the conventional approach with nested-PCR, even though two steps of specificity are maintained.