[Show abstract][Hide abstract] ABSTRACT: Intestinal acute GVHD (I-aGVHD) is a life-threatening complication after allografting. Non-invasive bed-side procedures to evaluate extension and treatment response are still lacking. We hypothesized that, during I-aGVHD, contrast-enhanced ultrasound sonography (CEUS) could detect microcirculation changes (MVC) of the bowel wall (BW) and help to monitor treatment response. We prospectively employed CEUS in 83 consecutive patients. Of these, 14 patients with biopsy-proven intestinal GVHD (I-GVHD) were defined as the study group, whereas 16 patients with biopsy-proven stomach GVHD (U-GVHD) without intestinal symptoms, 6 normal volunteers and 4 patients with neutropenic enterocolitis were defined as the control group. All patients were evaluated with both standard ultrasonography (US) and CEUS at the onset of intestinal symptoms, during clinical follow-up and at flare of symptoms. Standard US revealed BW thickening of multiple intestinal segments, useful to determine the extension of GVHD. CEUS showed MVC, which correlated with GVHD activity, treatment response, and predicted flare of intestinal symptoms. US and CEUS findings were superimposable at diagnosis and in remission. CEUS was, however, more sensitive and specific to identify subclinical activity in patients with clinical relevant improvement. These findings were not observed in the control groups. CEUS is a non-invasive, easily reproducible bed-side tool useful to monitor I-aGVHD.Bone Marrow Transplantation advance online publication, 13 May 2013; doi:10.1038/bmt.2013.65.
Bone marrow transplantation 05/2013; 48(11). DOI:10.1038/bmt.2013.65 · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oral mucositis is an important side effect of hematopoietic stem cell transplantation (HCST), mainly due to toxicity of conditioning regimens. It produces significant pain and morbidity. The present study reports a prospective, randomized, non-blinded study testing the efficacy of a new mouthwash, called Baxidil Onco(®) (Sanitas Farmaceutici Srl, Tortona, Italy) in 60 hematologic patients undergoing HCST (28 autologous, 32 allogeneic). Baxidil Onco(®), used three times a day from Day -1 to Day +30, in addition to standard prophylactic schedules, was administered to 14 patients undergoing autologous and 14 patients undergoing allogeneic HCST. The remaining 32 patients (14 autologous and 18 HCST) were treated only with standard prophylactic schedules and served as control. In our study, the overall incidence of oral mucositis, measured according to the World Health Organization 0-4 scale, was 50% in the Baxidl Onco(®) group versus 82% in the control group (P=0.022). In addition, a significant reduction in scale 2-4 oral mucositis was observed in the Baxidil Onco(®) group (25% vs 56.2%; P=0.0029). The results obtained indicate that incidence, severity and duration of oral mucositis induced by conditioning regimens for HCST can be significantly reduced by oral rinsing with Baxidil Onco(®), in addition to the standard prophylaxis scheme. Since Camelia Sinensin extract, which is used to produce green tea, is the main agent in this mouthwash, we hypothesize that the anti-oxidative properties of polyphenolic compounds of tea might exert protective effects on oral mucosa.
[Show abstract][Hide abstract] ABSTRACT: Paroxysmal nocturnal hemoglobinuria is an acquired clonal disorder of the hemopoietic stem cells for which the only curative treatment is allogeneic hematopoietic stem cell transplantation.
The aim of this retrospective study was to assess the long-term clinical and hematologic results in 26 paroxysmal nocturnal hemoglobinuria patients who received hematopoietic stem cell transplantation in Italy between 1988 and 2006. The patients were aged 22 to 60 years (median 32 years). Twenty-three donors were HLA-identical (22 siblings and one unrelated) and 3 were HLA-mismatched (2 related and one unrelated).
Fifteen patients received a myeloablative conditioning consisting of busulfan and cyclophosphamide (in all cases from identical donor) and 11 were given a reduced intensity conditioning (8 from identical donor and 3 from mismatched donor). The cumulative incidence of graft failure was 8% (4% primary and 4% secondary graft failure). Transplant-related mortality for all patients was 42% (26% and 63% for patients transplanted following myeloablative or reduced intensity conditioning, respectively). As of October 31, 2009, 15 patients (11 in the myeloablative conditioning group and 4 in the reduced intensity conditioning group) are alive with complete hematologic recovery and no evidence of paroxysmal nocturnal hemoglobinuria following a median follow-up of 131 months (range 30-240). The 10-year Kaplan-Meier probability of disease-free survival was 57% for all patients: 65% for 23 patients transplanted from identical donor and 73% for 15 patients transplanted with myeloablative conditioning. No thromboembolic event nor recurrence of the disease were reported following transplant.
The findings of this study confirm that most patients with paroxysmal nocturnal hemoglobinuria may be definitively cured with hematopoietic stem cell transplantation.
[Show abstract][Hide abstract] ABSTRACT: Polycythemia vera (PV) is a chronic myeloproliferative disease. The use of recombinant α2a Interferon (IFN) therapy in this disease is a novel approach. We applied Fourier-transform infrared microspectroscopy (FT-IR-M) to investigate the behavior and therapeutic responsiveness of PV patients treated with IFN. A spectroscopic parameter (A1/A2) was used, corresponding to the ratio of the integrated areas of the bands at 1080 cm-1 and at 1540 cm-1 due to nucleic acids and proteic components, respectively, calculated on the spectra of single megakaryocytes (MKs). In previous studies, we have pointed out that MKs in PV have a surprisingly strong myeloproliferative impulse when compared to MKs from other chronic myeloproliferative diseases. Nine patients out of the 11 studied exhibited a satisfactory responsiveness to the IFN treatment. Ten patients were evaluated by the A1/A2 parameter. In 8 of these, a good agreement was seen between this parameter and the laboratory data commonly used for the assessment of this disease. The infrared parameter, which we propose, proves to be an original, reliable method for the evaluation of recombinant α2a IFN responsiveness in this disease.
European Journal Of Haematology 10/2009; 53(4):213-217. DOI:10.1111/j.1600-0609.1994.tb00191.x · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report here a 50-years old female with multiple myeloma-associated chronic renal failure who underwent high-dose chemotherapy supported by autologous hematopoietic stem cell transplantation. She developed progressive encephalopathy on day 5 progressing to coma despite hemodialysis and no obvious organ failure. She finally recovered after a single 1-liter plasma exchange. The final diagnosis was metabolic encephalopathy due to hypercytokinemia, particularly high serum TNF levels. We discuss here the pathogenesis and raise an alert for monitoring cytokine levels in patients with renal failure undergoing high-dose chemotherapy.
[Show abstract][Hide abstract] ABSTRACT: Human cytomegalovirus (HCMV) reactivation can cause a wide range of complications in hematopoietic stem cell transplant recipients, ranging from pneumonia to graft failure. Although reactivations are usually seen in the early post-transplant period, ongoing and untreated HCMV reactivation at the time of high-dose chemotherapy and autologous stem cell support is an exceedingly rare circumstance whose consequences remain largely unknown. This case report describes a patient who underwent high-dose melphalan and autologous transplantation with unknown active HCMV replication.
Journal of Medical Virology 05/2009; 81(5):857-60. DOI:10.1002/jmv.21440 · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hemorrhagic cystitis is a common complication in hematopoietic stem cell transplant recipients. We report here a case of severe BKV-associated hemorrhagic cystitis who did not respond to intravenous cidofovir. Overt hematuria successfully resolved after a few days on hyperbaric oxygen and intravesical instillations of cidofovir, while BK viruria dropped after a few weeks and remained low. We review the literature for therapeutic options in hemorrhagic cystitis and try to explain how hyperbaric oxygen stimulates mucosal repair in the urinary bladder.
Leukemia research 04/2009; 33(4):556-60. DOI:10.1016/j.leukres.2008.06.018 · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: D. Focosi, E. Benedetti, F. Maggi, F. Papineschi, S. Galimberti, L. Ceccherini-Nelli, M. Petrini. Preemptive valganciclovir for cytomegalovirus infection in hematological patients.Transpl Infect Dis 2008: 10: 375–376. All rights reserved
[Show abstract][Hide abstract] ABSTRACT: Neutropenic enterocolitis (NEC) can be a life-threatening complication of chemotherapy in leukemic patients. Early diagnosis and treatment is therefore crucial.
A 38-year-old woman with acute lymphoblastic leukemia and chemotherapy-induced neutropenia suddenly developed symptoms suspicious of NEC. Transabdominal ultrasound showed features consistent with NEC, later confirmed by computed tomography (CT) scan.
The patient was scanned using portable ultrasound (US) equipment (Esaote My Lab 25). US findings showed involvement of the cecum, appendix, ascending colon and proximal middle transverse colon, with features resembling gas containing fissures within the colon wall itself. The risk of colon rupture was confirmed by CT scan. The patient underwent successful hemicolectomy after intravenous treatment with broad spectrum antibiotics, granulocyte-colony stimulating factor (G-CSF), platelets and fresh frozen plasma transfusion.
A prompt bedside US examination upon development of symptoms allowed an early diagnosis of NEC and identified features consistent with imminent colon wall rupture, shifting the management of this life-threatening complication from medical to surgical. Multidisciplinary intervention was crucial for a successful hemicolectomy in a severely affected neutropenic patient.
Journal of Ultrasound 09/2008; 11(3):97-101. DOI:10.1016/j.jus.2008.05.001
[Show abstract][Hide abstract] ABSTRACT: Hematopoietic stem cell (HSC) transplantation fails if grafted HSCs fail to find and settle in an appropriate bone marrow niche where they can receive required trophic factors from stromal cells. Since intravenously injected HSCs are known to migrate into the bone marrow mainly in response to gradients of the CXCL12 chemokine, we reasoned that drugs that inhibit catabolism of CXCL12 could eventually increase the CXCL12 gradient and enhance engraftment. dipeptidyl peptidase IV (DPP-IV) catalyzes the first step in CXCL12 degradation, and oral DPP-IV inhibitors, such as sitagliptin, have been recently approved for type II diabetes mellitus. We report here a case of delayed graft failure in a T-cell-depleted (TCD) HSC transplant recipient, which was refractory to both retransplantation and high-dose granulocyte-colony stimulating factor (G-CSF). After beginning sitagliptin therapy our patient showed a sustained neutrophil rise and a reduction in transfusion dependence, which worsened again after drug discontinuation. Since these changes were paralleled by fluctuations in CXCL12 levels in serial peripheral blood samples, we discuss here the potential benefit of this class of drugs.
Leukemia Research 06/2008; 33(1):178-81. DOI:10.1016/j.leukres.2008.04.019 · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Progressive multifocal leukoencephalopathy (PML) is a central nervous system (CNS) disease usually observed in immunodeficient patients, especially human immunodeficiency virus (HIV)-positive, caused by John Cunningham virus. This infectious complication has been described in many HIV-negative hematological patients, especially affected by lymphoproliferative diseases. PML has been observed after both chemotherapy and bone marrow transplantation and, recently, in association with rituximab. Diagnosis can be complicated, and often a CNS biopsy is required. Current treatment approaches are not effective in both HIV-positive and HIV-negative patients, and the outcome remain very poor in the majority of cases, even after combination therapies. We report three cases of PML in hematological patients, treated respectively with conventional chemotherapy and autologous and haploidentical transplantation, and review the literature on PML. All of them received rituximab, which has recently been in the focus of a Food and Drug Administration warning.
Annals of Hematology 06/2008; 87(5):405-12. DOI:10.1007/s00277-007-0411-6 · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report on a 22-year-old female who developed aplastic anemia after administration of phenobarbital for 6 years. Being refractory to steroid and anti-lymphocyte serum, the patient received allogeneic stem cell transplantation, achieving complete remission. We discuss here the potential mechanisms by which phenobarbital and other anti-epileptic drugs can cause aplastic anemia and review the literature for previous case reports and epidemiological studies.