This multicentre, open-label phase 1/2 trial determined safety and efficacy of weekly carfilzomib plus cyclophosphamide-dexamethasone (wKCyd) in newly diagnosed multiple myeloma (NDMM) patients aged ...⩾65 years or transplant ineligible. Patients received wKCyd for up to nine 28-day cycles, followed by maintenance with carfilzomib until progression/intolerance. The phase 1 portion used a 3+3 dose-escalation scheme to determine the maximum tolerated dose of weekly carfilzomib: 12 patients received wKCyd with carfilzomib doses of 45, 56 and 70 mg/m
. The recommended phase 2 dose was established at 70 mg/m
and 54 patients (phase 1 and 2) received weekly carfilzomib 70 mg/m
: 85% of them achieved ⩾partial response (PR), 66% ⩾very good PR, 30%⩾near-complete response (CR) and 15% CR. Responses improved in 40 patients who started maintenance: 98% achieved ⩾PR, including 29% CR and 10% stringent CR. After a median follow-up of 18 months, the 2-year progression-free survival and overall survival rates were 53.2% and 81%, respectively. The most frequent grade 3-5 toxicities were neutropenia (22%) and cardiopulmonary adverse events (9%). This is the first study of weekly carfilzomib plus an alkylating agent in elderly patients with NDMM. wKCyd was effective, with an acceptable risk/benefit ratio, and thus can be a valid option in this setting.
Epidemiological and clinical information on primary plasma cell leukemia (pPCL) are rarely reported. The aims are to evaluate the clinical features, prognostic factors, and efficacy of treatments in ...pPCL.
A multicenter retrospective cohort study was carried out from January 2000 to December 2008 in 26 Italian hematology divisions. A total of 128 cases of plasma cell leukemia were collected, and 73 of them (57%) were classified as primary (male/female 43/30).
Sixty-four patients had at least 1 sign of end-organ damage and 10 had extramedullary localization. One patient died early; of the remaining patients, 36 (50%) received anthracycline-based regimens as first-line therapy, 17 (24%) single alkylating agents, and 30 (42%) bortezomib or thalidomide as additional (n = 11) or unique treatments (n = 19). Twenty-three patients (31%) underwent autologous and/or allogeneic hematopoietic stem cell transplantation (HSCT). The median overall survival (OS) was 12.6 months; complete or partial response was achieved in 22 (30%) and 18 patients (25%), respectively; the median duration of response (DOR) was 16.4 months. HSCT patients had a longer OS and DOR (median 38.1 and 25.8 months, respectively) compared with nontransplanted patients (9.1 and 7.3 months, respectively, P < 0.001). OS was influenced by nonresponse to treatment, hypoalbuminemia, and HSCT. DOR was favorably influenced only by HSCT.
pPCL is an aggressive disease with a poor prognosis and a low response rate to conventional therapy. HSCT is effective, increasing OS and DOR by 69% and 88%, respectively. The use of bortezomib and thalidomide may improve outcomes.
AML patients (total 129; median age =50 years; range 16-72) in first CR received BU and melphalan (BU/Mel) as conditioning regimen before auto-SCT. In all, 82 patients (63.6%) received PBSCs and 47 ...patients (36.4%) received BM cells. The distribution of cytogenetic categories was conventionally defined as favorable (15.5%), intermediate (60.1%) and unfavorable (24.3%). With a median follow-up of 31 months, the 8-year projected OS and disease-free survival (DFS) was 62 and 56% for the whole population, respectively. The relapse rate was 46% and the non-relapse mortality was 4.65%. Although PBSC transplantation led to a faster hematological recovery than BM transplantation, in univariate analysis the stem cell source, cytogenetics and different BU formulations did not significantly affect OS and DFS, whereas age and the number of post-remission chemotherapy cycles did have a significant effect on the clinical outcome. Multivariate analysis identified age <55 years as the only important independent predictor for OS and DFS. Our data suggest that BU/Mel, being associated with a low toxicity profile (mainly mucositis) and mortality, is an effective conditioning regimen even for high-risk AML patients in first CR undergoing auto-SCT.
Bacillus subtilis is a gram-positive, aerobic, spore-forming soil bacterium ubiquitous in the environment. The beneficial effects of B. subtilis spores on the balance of the intestinal microflora is ...the rationale for its general use as a probiotic preparation in the treatment or prevention of intestinal disorders. B. subtilis spores are available in Italy as a pharmaceutical preparation for oral use. Each dose contains a mixture of 10 super(9) spores of four distinct antibiotic-resistant derivatives of ATCC 9799 (Enterogermina; distributed by Sanofi Winthrop, Milan, Italy) per vial. The pathogenic potential of B. subtilis is generally described as low or absent. Data on the general importance of infections due to B. subtilis are incomplete, since it is a general practice of most microbiological laboratories to discard these strains or to report them as contaminants. Also, in the cause-of-death statistics of the World Health Organization no data on B. subtilis infections are present since, even if reported, they would be "invisible" at the international comparative level due to the coding used for classification of death causes. In the literature, only a few cases of infections due to B. subtilis are reported and only one retrospective study describes the isolation of antibiotic-resistant strains of B. subtilis.
Background The objective of this study was to evaluate the similarities between solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EP). Patients and methods The clinical features, ...treatment and survival of 54 patients with localized plasmacytoma (LP) seen at 4 Italian institutions between May 1968 and February 1990 were carefully reviewed. Follow-up was expected to continue until June 1993. Results Thirty-two patients were classified as having SPB and 22 EP. Most of the patients were males, particularly those in the SPB group. Their median age at diagnosis was 54 years and no significant difference between the two groups was observed. SPB occurred most frequently in the vertebral column (42%) and EP in the upper respiratory tract (73%). Fifteen patients with SPB and 2 with EP had parapro-teinemia at diagnosis, multiple myeloma (MM) became evident in 75% of the patients with persistent paraprotein after therapy, and in only 22% of those in whom it disappeared. Four patients in the SPB group had immunopa-resis, and 3 developed MM. Disease progression toward MM was significantly different (p —0.003) in the two groups, while overall survival differences were not significant (p —0.07) unless unrelated causes were excluded (p = 0.02). Adjuvant chemotherapy did not seem to limit diffusion of the disease. Conclusions Although EP and SPB are both localized forms of plasma cell dyscrasias, SPB seems to have a greater tendency to progress in MM. It appears, however, that the apparent stronger propensity of SPB to progress is actually due to the great number of cases that at diagnosis conceal an occult MM.
Nongastrointestinal locations represent about 30% to 40% of all low-grade mucosa-associated lymphoid tissue (MALT) lymphomas. We report a retrospective analysis of 75 patients with ...nongastrointestinal low-grade MALT lymphoma, presenting their clinical, therapeutic, and follow-up data with respect to the initial location of the lymphoma.
From January 1988 to October 1997, 75 patients with untreated nongastrointestinal low-grade MALT lymphoma were subjected to treatments ranging from local radiotherapy and local interferon alfa administration to chemotherapy. The lymphomas were located in the lung (19 patients), orbital soft tissue (16 patients), skin (seven patients), thyroid (seven patients), lachrymal gland (six patients), conjunctiva (six patients), salivary gland (six patients), breast (three patients), eyelid (two patients), larynx (one patient), bone marrow (one patient), and trachea (one patient).
Complete and partial remissions were achieved in 59 (79%) and 16 (21%) of the 75 patients, respectively, with an overall response rate of 100%. All but two of the patients are still alive, with a median follow-up of 47 months; these two patients died from other causes. The estimated time to treatment failure rate is 30% at 5 years. In the thyroid and lachrymal gland sites, no relapses were reported.
Our data regarding the largest reported series of nongastrointestinal MALT lymphomas confirm the good prognosis of this particular clinicopathologic entity and the significant efficacy of different therapeutic approaches to specific sites.
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