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Fara Petruzziello,
Pio Zeppa,
Lucio Catalano,
Immacolata Cozzolino,
Giuseppe Gargiulo,
Pellegrino Musto,
Fiorella D’Auria,
Vincenzo Liso,
Rita Rizzi,
Nadia Caruso, [......],
Eugenio Piro,
Maurizio Musso,
Vincenza Bonanno,
Antonietta Pia Falcone,
Salvatore Tafuto,
Francesco Di Raimondo,
Michelino De Laurentiis,
Fabrizio Pane,
Lucio Palombini,
Bruno Rotoli
[show abstract]
[hide abstract]
ABSTRACT: Systemic AL amyloidosis is associated with nearly 15% of cases of multiple myeloma, but data on the frequency and significance
of amyloid deposits in the bone marrow of patients affected by multiple myeloma without clinical signs of systemic amyloidosis
are scanty. Bone marrow smears of 166 unselected patients affected by multiple myeloma (126 at diagnosis and 40 after treatment)
were stained with Congo red and studied by transmission and birefringence microscopy. Both focal and diffuse storages were
considered positive. Overall, 67 patients were positive and 99 were negative to Congo red and apple-green birefringence. In
particular, 51 of the 126 patients studied at diagnosis and 16 of the 40 patients with advanced disease were positive. Seventeen
patients were reassessed after a mean follow-up of 32months (range: 6–91): disappearance of amyloid deposits was verified
in three cases, all responsive to bortezomib-based regimens. The preliminary data available suggest that amyloid deposition
in the marrow of myeloma patients is frequent, as it can be traced in nearly 40% of cases. We failed to find correlations
between bone marrow amyloid deposits and immunoglobulin type, disease stage, plasma cells percentage, hemoglobin, calcium,
creatinine, albumin, or β2microglobulin. Significantly higher incidence of moderate/severe peripheral neuropathy was found in patients with marrow amyloid
exposed to potentially neurotoxic antineoplastic agents. Further studies and prolonged follow-up are needed to validate our
findings and to define possible prognostic aspects.
KeywordsAmyloidosis-Multiple myeloma-Congo red staining-Bone marrow amyloid
Annals of Hematology 04/2012; 89(5):469-474. · 2.62 Impact Factor
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Fara Petruzziello,
Pio Zeppa,
Giuseppe Ciancia,
Immacolata Cozzolino,
Laura Sosa Fernandez,
Mariarosaria Cervasio,
Pellegrino Musto,
Fiorella D'Auria,
Giulia Vita,
Fortunato Morabito,
Eugenio Piro,
Maria Rita Costanza Ponti,
Guido Pettinato,
Rosanna Ciancia,
Fabrizio Pane,
Lucio Catalano
[show abstract]
[hide abstract]
ABSTRACT: We recently published a study aiming to verify the frequency of amyloid deposits in the bone marrow of patients with multiple myeloma (MM) who did not present any signs or symptoms of systemic amyloidosis, applying the Congo red technique on bone marrow smears obtained by aspiration from the posterior iliac spine. The results suggested that nearly 40% of patients affected by MM may have amyloid deposits in their bone marrow. Subsequently, this finding has not been confirmed by another study performed with histological specimens of bone marrow in a similar clinical setting. To explain this discrepancy, we performed a comparative study on the bone marrows of 36 patients affected by MM, evaluated by both cytological and histological techniques. The results of this study confirm the high frequency of amyloid deposits in the bone marrow of patients affected by MM when the analysis is made on cytological smears, and indicate that the presence of amyloid on marrow smears is confirmed by core biopsies simultaneously performed in only 25% of cases. Should further studies confirm our findings, cytological assessment could be considered a sensitive technique to detect bone marrow amyloid deposits.
Leukemia & lymphoma 06/2011; 52(12):2304-7. · 2.40 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.
Leukemia & lymphoma 06/2010; 51(6):1063-71. · 2.40 Impact Factor
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Fara Petruzziello,
Pio Zeppa,
Lucio Catalano,
Immacolata Cozzolino,
Giuseppe Gargiulo,
Pellegrino Musto,
Fiorella D'Auria,
Vincenzo Liso,
Rita Rizzi,
Nadia Caruso, [......],
Eugenio Piro,
Maurizio Musso,
Vincenza Bonanno,
Antonietta Pia Falcone,
Salvatore Tafuto,
Francesco Di Raimondo,
Michelino De Laurentiis,
Fabrizio Pane,
Lucio Palombini,
Bruno Rotoli
[show abstract]
[hide abstract]
ABSTRACT: Systemic AL amyloidosis is associated with nearly 15% of cases of multiple myeloma, but data on the frequency and significance of amyloid deposits in the bone marrow of patients affected by multiple myeloma without clinical signs of systemic amyloidosis are scanty. Bone marrow smears of 166 unselected patients affected by multiple myeloma (126 at diagnosis and 40 after treatment) were stained with Congo red and studied by transmission and birefringence microscopy. Both focal and diffuse storages were considered positive. Overall, 67 patients were positive and 99 were negative to Congo red and apple-green birefringence. In particular, 51 of the 126 patients studied at diagnosis and 16 of the 40 patients with advanced disease were positive. Seventeen patients were reassessed after a mean follow-up of 32 months (range: 6-91): disappearance of amyloid deposits was verified in three cases, all responsive to bortezomib-based regimens. The preliminary data available suggest that amyloid deposition in the marrow of myeloma patients is frequent, as it can be traced in nearly 40% of cases. We failed to find correlations between bone marrow amyloid deposits and immunoglobulin type, disease stage, plasma cells percentage, hemoglobin, calcium, creatinine, albumin, or beta(2)microglobulin. Significantly higher incidence of moderate/severe peripheral neuropathy was found in patients with marrow amyloid exposed to potentially neurotoxic antineoplastic agents. Further studies and prolonged follow-up are needed to validate our findings and to define possible prognostic aspects.
Annals of Hematology 11/2009; 89(5):469-74. · 2.62 Impact Factor
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Adele Bolognese,
Anna Esposito,
Michele Manfra,
Lucio Catalano, Fara Petruzziello,
Maria Carmen Martorelli,
Raffaella Pagliuca,
Vittoria Mazzarelli,
Maria Ottiero,
Melania Scalfaro,
Bruno Rotoli
[show abstract]
[hide abstract]
ABSTRACT: The (R)-3-methyl-1-((S)-3-phenyl-2-(pyrazine-2-carboxamido)propanamido)butyl-boronic acid, bortezomib (BTZ), which binds the 20S proteasome subunit and causes a large inhibition of its activity, is a peptidomimetic boronic drug mainly used for the treatment of multiple myeloma. Commercial BTZ, stabilized as mannitol derivative, has been investigated under the common conditions of the clinical use because it is suspected to be easily degradable in the region of its boronic moiety. Commercial BTZ samples, reconstituted according to the reported commercial instructions and stored at 4 degrees C, were analyzed by high-field nuclear magnetic resonance spectroscopy in comparison with identical samples bubbled with air and argon, respectively. All the samples remained unchanged for a week. After a month, the air filled samples showed the presence of two main degradation products (6% of starting material), the N-(1-(1-hydroxy-3-methylbutylamino)-1-oxo-3-phenylpropan-2-yl) pyrazine-2-carboxamide (BTZ1; 5%, determined from NMR integration) and the (S)-N-(1-(3-methylbutanamido)-1-oxo-3-phenylpropan-2-yl)pyrazine-2-carboxamide (BTZ2; 1%, determined from NMR integration), identified on the basis of their chemical and spectroscopic properties. The BTZ1 and BTZ2 finding suggests that, under the common condition of use and at 4 degrees C, commercial BTZ-mannitol is stable for a week, and that, in time, it undergoes slow oxidative deboronation which partially inactivates the product. Low temperature and scarce contact with air decrease the degradation process.
Advances in Hematology 01/2009; 2009:704928.
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[show abstract]
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ABSTRACT: The treatment of meningeal relapse in acute lymphoblastic leukemia (ALL) remains a challenging clinical problem. Liposomal cytarabine (DepoCyte) permits to decrease frequency of lumbar punctures, without loss of efficacy, because intrathecal levels of the drug remain cytotoxic for up to 14 days. We investigated the efficacy and safety of intrathecal DepoCyte in six children with meningeal relapse, treated in two pediatric institutions. DepoCyte was well tolerated in all patients, who achieved complete clearance of blasts from the cerebrospinal fluid after the first three intrathecal drug administrations. Five of the six patients were concurrently treated with high-dose administration of systemic cytarabine, without additional neurological side effects. Our results suggest that DepoCyte is a valid option for children with ALL experiencing meningeal relapse; it deserves further investigation in intensive treatment regimens, taking into due consideration potential neurotoxicity.
Leukemia & lymphoma 09/2008; 49(8):1553-9. · 2.40 Impact Factor
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Rosa Fonti,
Barbara Salvatore,
Mario Quarantelli,
Cesare Sirignano,
Sabrina Segreto, Fara Petruzziello,
Lucio Catalano,
Raffaele Liuzzi,
Bruno Rotoli,
Silvana Del Vecchio,
Leonardo Pace,
Marco Salvatore
[show abstract]
[hide abstract]
ABSTRACT: New imaging techniques have been introduced to assess the extent and severity of disease in multiple myeloma (MM) patients. The aim of our study was to compare newer imaging modalities-such as (18)F-FDG PET/CT, (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) scintigraphy, and MRI-to assess their relative contribution in the evaluation of MM patients at diagnosis.
Thirty-three newly diagnosed patients with MM were prospectively studied. Diagnosis and staging were made according to standard criteria. All patients underwent whole-body (18)F-FDG PET/CT, whole-body (99m)Tc-MIBI, and MRI of the spine and pelvis within 10 d, and imaging findings were compared.
(18)F-FDG PET/CT was positive in 32 patients (16 focal uptake, 3 diffuse uptake, 13 focal and diffuse uptake), (99m)Tc-MIBI was positive in 30 patients (6 focal, 11 diffuse, 13 focal and diffuse uptake), and MRI of the spine and pelvis was positive in 27 patients (6 focal, 13 diffuse, 8 focal and diffuse uptake). (18)F-FDG PET/CT showed a total of 196 focal lesions (178 in bones and 18 in soft tissues), of which 121 were in districts other than the spine and pelvis, whereas (99m)Tc-MIBI visualized 63 focal lesions (60 in bones and 3 in soft tissues), of which 53 were in districts other than the spine and pelvis. In the spinal and pelvic regions, (18)F-FDG PET/CT detected 75 focal lesions (35 in spine and 40 in pelvis), (99m)Tc-MIBI visualized 10 focal lesions (1 in spine and 9 in pelvis), and MRI detected 51 focal lesions (40 in spine and 11 in pelvis).
In whole-body analysis, (18)F-FDG PET/CT performed better than (99m)Tc-MIBI in the detection of focal lesions, whereas (99m)Tc-MIBI was superior in the visualization of diffuse disease. In the spine and pelvis, MRI was comparable to (18)F-FDG PET/CT and (99m)Tc-MIBI in the detection of focal and diffuse disease, respectively. Because myelomatous lesions may often occur out of spinal and pelvic regions, MRI should be reserved to the evaluation of bone marrow involvement of these districts, whereas (18)F-FDG PET/CT can significantly contribute to an accurate whole-body evaluation of MM patients. Finally, whole-body (99m)Tc-MIBI, despite its limited capacity in detecting focal lesions, may be an alternative option when a PET facility is not available.
Journal of Nuclear Medicine 03/2008; 49(2):195-200. · 6.38 Impact Factor
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[show abstract]
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ABSTRACT: Cardiac involvement in primary systemic amyloidosis, due to amassing of fragments of light chains, is detected in the majority of cases. We report the case of a 56-year-old woman who came to our observation because of symptoms of congestive heart failure. Diagnosis of restrictive cardiomyopathy was made by echocardiographic examination, which showed right ventricular hypertrophy, disarray of interventricular septum and restrictive flow pattern at the mitral valve. Primary systemic amyloidosis was diagnosed by abdominal fat pad biopsy. Laboratory findings confirmed biopsy results, leading to the definite diagnosis of restrictive cardiomyopathy due to IgA kappa monoclonal gammopathy in primary systemic amyloidosis.
Giornale italiano di cardiologia (2006) 07/2007; 8(6):371-6.
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Lucio Catalano,
Silvana Del Vecchio, Fara Petruzziello,
Rosa Fonti,
Barbara Salvatore,
Carmen Martorelli,
Catello Califano,
Giuseppe Caparrotti,
Sabrina Segreto,
Leonardo Pace,
Bruno Rotoli
[show abstract]
[hide abstract]
ABSTRACT: Osteonecrosis of the maxillary or mandibular bone is an infrequent but often severe event occurring in patients who undergo prolonged treatment with bisphosphonates. Histology is in some cases mandatory to differentiate it from neoplastic osteolysis, but a biopsy can further contribute to bone damage. Functional imaging obtained by a tracer that shows oncotropic properties, such as Tc99m-sestamibi, in comparison to a non-tumor-specific substance such as FDG-PET, can support the differential diagnosis, thus avoiding invasive procedures. Four patients affected by multiple myeloma and jaw osteonecrosis were prospectively evaluated by sestamibi and FDG-PET scans. Local diagnosis was performed by clinical, radiological and, in some cases, histological evaluations. Each patient was studied by Tc99m-sestamibi, performed by planar anterior and posterior whole-body scans and SPECT of the head and neck, and by PET/CT. Two nuclear medicine physicians, unaware of the final diagnosis, reviewed the images. No sestamibi uptake was evident in the four patients with jaw osteonecrosis, while FDG-PET/CT showed focal uptake in all of them. Our study suggests that the combined use of sestamibi scintigraphy and FDG-PET/CT could support the clinical diagnosis of oral osteonecrosis avoiding the risks of a surgical biopsy. Studies on higher number of patients are necessary to validate these preliminary observations.
Annals of Hematology 07/2007; 86(6):415-23. · 2.62 Impact Factor
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[hide abstract]
ABSTRACT: Six patients with bone marrow micrometastases from solid cancers presented with increased numbers of circulating CD34+ cells; the CD34+ cell counts were very high in some cases. By contrast, no patient with metastatic cancer without bone marrow involvement showed raised numbers of circulating hemopoietic progenitors.
Haematologica 08/2005; 90(7):976-7. · 6.42 Impact Factor
