We performed a prospective, randomized study of single (arm A) versus double (arm B) autologous stem-cell transplantation (ASCT) for younger patients with newly diagnosed multiple myeloma (MM).
A ...total of 321 patients were enrolled onto the study and were randomly assigned to receive either a single course of high-dose melphalan at 200 mg/m2 (arm A) or melphalan at 200 mg/m2 followed, after 3 to 6 months, by melphalan at 120 mg/m2 and busulfan at 12 mg/kilogram (arm B).
As compared with assignment to the single-transplantation group (n = 163 patients), random assignment to receive double ASCT (n = 158 patients) significantly increased the probability to attain at least a near complete response (nCR; 33% v 47%, respectively; P = .008), prolonged relapse-free survival (RFS) duration of 18 months (median, 24 v 42 months, respectively; P < .001), and significantly extended event-free survival (EFS; median, 23 v 35 months, respectively; P = .001). Administration of a second transplantation and of novel agents for treating sequential relapses in up to 50% of patients randomly assigned to receive a single ASCT likely contributed to prolong the survival duration of the whole group, whose 7-year rate (46%) was similar to that of the double-transplantation group (43%; P = .90). Transplantation-related mortality was 3% in arm A and 4% in arm B (P = .70).
In comparison with a single ASCT as up-front therapy for newly diagnosed MM, double ASCT effected superior CR or nCR rate, RFS, and EFS, but failed to significantly prolong overall survival. Benefits offered by double ASCT were particularly evident among patients who failed at least nCR after one autotransplantation.
Castleman disease (CD) is a rare lymphoproliferative disorder that includes various clinico-pathological subtypes. According to clinical course, CD is divided into unicentric CD (UCD) and ...multicentric CD (MCD). MCD is further distinguished based on the etiological driver in herpes virus-8-related MCD (that can occur in the setting of HIV); in MCD associated with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes); and idiopathic MCD (iMCD). The latter can also be divided in iMCD-TAFRO (thrombocytopenia, anasarca, fever, myelofibrosis, organomegaly) and iMCD not otherwise specified. To date, CD pathogenesis is still uncertain, but CD may represent the histological and clinical result of heterogeneous pathomechanisms. Transcriptome investigations in CD lymph nodes have documented the expression and up-regulation of different cytokines; furthermore, few recent studies have shown alterations of different T-cell subsets in CD patients, suggesting a possible role of the nodal microenvironment in CD development. On this basis, our study aimed to investigate the distribution of T-cell subsets in the clinico-pathological spectrum of CD. We evaluated the CD4/CD8 ratio and the number of T-regulatory (T-reg) FOXP3+ cells in 28 CD cases. In total, 32% of cases showed a decreased CD4/CD8 ratio due to increased CD8+ T-cells, including both UCD, iMCD, and HHV8+ MCD cases. The T-reg subset analysis revealed a statistically significant (
< 0.0001) lower mean number of FOXP3+ T-reg cells in CD cases when compared with non-specific reactive lymph nodes. We did not find statistically significant differences in T-reg numbers between the different CD subtypes. These findings may suggest that alterations in T-cell subpopulations that can lead to disruption of immune system control may contribute to the numerous changes in different cellular compartments that characterize CD.
Hepatitis C virus (HCV) is endemic in some areas of Northwestern Europe and the United States. HCV has been shown to play a role in the development of both hepatocellular carcinoma and B-cell ...non-Hodgkin's lymphoma (B-NHL). The biologic mechanisms underlying the lymphomagenic activity of the virus so far are under investigation. In this study, the role of antiviral (anti-HCV) treatment in B-NHL associated with HCV infection is evaluated.
Thirteen patients with histologically proven low-grade B-NHL characterized by an indolent course (ie, doubling time no less than 1 year, no bulky disease) and carrying HCV infection were enrolled on the study. All patients underwent antiviral treatment alone with pegilated interferon and ribavirin. Response assessment took place at 6 and 12 months.
Of the twelve assessable patients, seven (58%) achieved complete response and two (16%) partial hematologic response at 14.1 +/- 9.7 months (range, 2 to 24 months, median follow-up, 14 months), while two had stable disease with only one patient experiencing progression of disease. Hematologic responses (complete and partial, 75%) were highly significantly associated to clearance or decrease in serum HCV viral load following treatment (P = .005). Virologic response was more likely to be seen in HCV genotype 2 (P = .035), while hematologic response did not correlate with the viral genotype. Treatment-related toxicity did not cause discontinuation of therapy in all but two patients, one of whom, however, achieved complete response.
This experience strongly provides a role for antiviral treatment in patients affected by HCV-related, low-grade, B-cell NHL.
Patients with hematological cancer are at major risk of developing infectious complication. The prevention and treatment of COVID‐19 in these patients is challenging. This experience, with the ...limitation of a small number of patients, highlights that early treatment of COVID‐19 can overcome the infection, also in hematological patients.
Patients with hematological cancer are at major risk of developing infectious complication. The prevention and treatment of COVID‐19 in these patients is challenging. This experience, with the limitation of a small number of patients, highlights that early treatment of COVID‐19 can overcome the infection, also in hematological patients.
Thermal paper is widely used as a print medium for different applications but it constitutes a tricky substrate for fingermark visualization. An earlier work (J Forensic Sci 2015;60:1034) reported ...how to visualize fingermarks on untreated thermal paper by illuminating the item with a UV‐A light source. In the present paper, the potential of the near infrared (NIR) luminescence has been tested on thermal paper compared to the mentioned method. A controlled study was carried out utilizing eccrine enriched fingermarks. The promising outcomes obtained were further confirmed by performing a pseudo‐operational trial. Data clearly showed that the use of the NIR filter gave better results. Finally, preliminary tests suggested a different mechanism of reaction induced by fingermarks with respect to the one behind the thermal printing. Thus, NIR luminescence represents a refinement to the suite of optical examination processes, including the potential to increase the number of marks recovered in a noncontact, nondestructive way.
A central venous catheter (CVC) currently represents the most frequently adopted intravenous line for patients undergoing infusional chemotherapy and/or high-dose chemotherapy with hematopoietic ...stem-cell transplantation and parenteral nutrition. CVC insertion represents a risk for pneumothorax, nerve or arterial punctures. The aim of this prospective observational study was to explore the safety and efficacy of CVC insertion under ultrasound (US) guidance and to confirm its utility in clinical practice in cancer patients.
Consecutive adult patients attending the oncology-hematology department were eligible if they had solid or hematologic malignancies and required CVC insertion. Four types of possible complication were defined a priore: mechanical, thrombotic, infection and malfunctioning. The patient was placed in Trendelenburg's position, a 7.5 MHZ puncturing US probe was placed in the supraclavicular site and a 16-gauge needle was advanced under real-time US guidance into the last portion of internal jugular vein. The Seldinger technique was used to place the catheter, which was advanced into the superior vena cava until insertion into right atrium. Within two hours after each procedure, an upright chest X-ray and ultrasound scanning were carried out to confirm the CVC position and to rule out a pneumotorax. CVC-related infections, symptomatic vein thrombosis and malfunctioning were recorded.
From December 2000 to January 2009, 1,978 CVC insertional procedures were applied to 1,660 consecutive patients. The procedure was performed 580 times in patients with hematologic malignancies and 1,398 times those with solid tumors. A single-needle puncture of the vein was performed on 1,948 of 1,978 procedures (98.48%); only eighteen attempts among 1,978 failed (0.9%). No pneumotorax, no major bleeding, and no nerve puncture were reported; four cases (0.2%) showed self-limiting hematomas. The mean lifespan of CVC was 189.7 +/- 18.6 days (range 7-701). Symptomatic deep-vein thrombosis of the upper limbs developed in 48 patients (2.42%). Catheter-related infections occurred in 197 (9.96%) of the catheters inserted. They were successfully treated with antibiotics and only in 48 (2.9%) patients definitive CVC removal was required for infection and/or thrombosis or malfunctioning.
This study represents the largest published series of consecutive patients with cancer undergoing CVC insertion under US guidance; this procedure allowed the completion of the therapeutic program for 1,930/1,978 (97.6%) of the catheters inserted. The absence of pneumotorax and other major complications indicates that US guidance should be mandatory for CVC insertion in patients with cancer.
1 Dipartimento di Oncologia ed Ematologia Università di Modena Centro Oncologico Modenese, Policlinico Modena
2 Dipartimento di Oncologia, Ospedale Santo Spirito, Pescara
3 Dipartimento di Oncologia, ...Sezione Ematologia, Ospedale Santa Chiara, Pisa
4 Medicina Oncologica ed Ematologica, Ospedale Civile, Piacenza
5 Clinica Medica, IRCCS Policlinico San Matteo, Università di Pavia, Pavia
6 Divisione di Ematologia, Presidio Ospedali Riuniti Bianchi, Melacrino, Morelli, Reggio Calabria
7 Unità Operativa di Ematologia, Azienda Ospedaliera dellAnnunziata, Cosenza
8 Divisione di Ematologia, Presidio Ospedaliero A. Perrino, Brindisi
9 Divisione di Ematologia, Azienda Ospedaliera Papardo, Messina, Italy
Correspondence: Stefano Sacchi, MD Dipartimento di Oncologia ed Ematologia, Università di Modena Centro Oncologico Modenese Policlinico, 41100 Modena, Italy. E-mail: ssacchi{at}unimo.it
Background: Relatively little information is available on the incidence of secondary cancer in non-Hodgkins lymphoma. The aim of this long-term follow-up study was to determine the incidence, the time free of second tumors, and risk factors for developing secondary cancer in a homogeneous group of patients with non-Hodgkins lymphoma.
Design and Methods: We evaluated a total of 563 patients with indolent non-Hodgkins lymphoma enrolled in Gruppo Italiano Studio Linfomi trials from 1988 to 2003.
Results: After a median follow-up of 62 months, 39 patients (6.9%) developed secondary cancer: 12 myelodysplastic syndromes/acute myeloid leukemia, and 27 solid tumors. The overall standardized incidence ratio of secondary malignancy in patients with non-Hodgkins lymphoma was higher than the risk of malignancy in the general population. The standardized incidence ratio was elevated in male patients and in patients under 65 years old at first treatment. Overall, the cumulative incidence of secondary cancer at 12 years was 10.5%, after correction in a competing-risk model. Univariate and multivariate Cox regression analyses showed that older age at the time of diagnosis, male sex, and fludarabine-containing therapy had significant negative impacts on the time free of second tumors.
Conclusions: We have identified subgroups of non-Hodgkins lymphoma patients with increased standardized incidence ratios of secondary malignancy and variables that have a negative impact on the time free of second tumors. This information could help physicians to select the most appropriate treatments. Finally, taking into account the possible occurrence of secondary neoplasia, long-term monitoring must be considered.
Key words: second cancer, non-Hodgkin lymphoma, follicular lymphoma, small lymphocytic lymphoma, treatment.
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Reply to: Comment to: Secondary malignancies after treatment for indolent non-Hodgkins lymphoma: a 16-year follow-up study. Haematologica 2008; 93:398-403
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Secondary malignancies after therapy of indolent non-Hodgkins lymphoma
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Twice a week carfilzomib at 27 mg/m2 is approved for treatment of relapsed or refractory multiple myeloma. Phase 1/2 CHAMPION-1, the first study exploring once-weekly carfilzomib dosing, established ...the maximum tolerated dose at 70 mg/m2 in combination with dexamethasone. We aimed to compare progression-free survival in patients with relapsed and refractory multiple myeloma given once weekly carfilzomib or twice weekly carfilzomib.
In this prespecified interim analysis of the randomised, open-label, phase 3 A.R.R.O.W. trial, we recruited patients (aged 18 years and older) with relapsed and refractory multiple myeloma previously treated with two or three treatments, including a proteasome inhibitor and immunomodulatory agent, from hospital, clinic, oncology or medical centres. Key eligibility criteria were refractory to most recent therapy (including bortezomib or ixazomib) with measurable disease, and Eastern Cooperative Oncology Group Performance Status of 0 or 1. Patients were randomly assigned (1:1) to receive carfilzomib once a week (70 mg/m2) or twice a week (27 mg/m2). The randomisation sequence was generated using a validated randomisation software and implemented using an interactive response technology system that assigned patients to treatment sequentially based on the randomisation sequence as patients were enrolled at participating clinical sites. Patients were stratified by International Staging System stage at study entry or baseline, whether or not they were refractory to bortezomib treatment, and age (block size of 4). The once weekly group received carfilzomib (30 min intravenous infusion) on days 1, 8, and 15 of all cycles (20 mg/m2 day 1 cycle 1; 70 mg/m2 thereafter). The twice weekly group received carfilzomib (10 min intravenous infusion) on days 1, 2, 8, 9, 15, and 16 (20 mg/m2 days 1 and 2 during cycle 1; 27 mg/m2 thereafter). All patients received dexamethasone (40 mg on days 1, 8, 15 all cycles and 22 cycles 1–9 only). Treatment continued until disease progression or unacceptable toxic effects. The primary objective was to compare progression-free survival between groups in the intention-to-treat population. Safety analysis was done in all randomly assigned patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT02412878, and is no longer enrolling patients.
Between September, 2015, and August, 2016, 578 patients were recruited from 118 sites. 478 patients were randomly assigned and included in the efficacy analyses (240 to receive once weekly carfilzomib; 238 to receive twice weekly carfilzomib). Median progression-free survival was higher in the once weekly group than the twice weekly group (11·2 months 95% CI 8·6–13·0 vs 7·6 months 5·8–9·2; hazard ratio HR 0·69, 95% CI 0·54–0·83; p=0·0029). The incidence of grade 3 or worse adverse events was higher in the once weekly group than the twice weekly group (68% n=161 vs 62% n=145); the most common events were anaemia, pneumonia, and thrombocytopenia (42 18% vs 42 18%, 24 10% vs 16 7%, and 17 7% vs 16 7%, respectively for once weekly carfilzomib vs twice weekly carfilzomib). A lower proportion of patients had grade 3 or worse cardiac failure in the once weekly group (7 3%) than in the twice weekly group (10 4%). Treatment-related deaths occurred in five (2%) of 238 patients in the once weekly group (sepsis n=1, death n=1, acute lung injury n=1, acute respiratory distress syndrome n=1, and tumour lysis syndrome n=1) and in two (1%) of 235 patients in the twice weekly group (plasma cell myeloma n=1 and congestive heart failure n=1). There were 58 deaths in the once weekly group and 68 deaths in the twice weekly group at the time of data cutoff.
Once weekly carfilzomib at 70 mg/m2 significantly prolonged progression-free survival versus the twice weekly schedule. Overall safety was comparable between the groups. Once weekly carfilzomib appears safe and more effective with a convenient dosing regimen versus the twice weekly schedule for the treatment of patients with relapsed and refractory multiple myeloma.
Amgen, Inc.
Splenic metastases are very rare and are mostly diagnosed at the terminal phase of the disease or at the time of autopsy. The cytohistological diagnosis, when done, is made prevalently by ...splenectomy. Reports on splenic percutaneous biopsies in the diagnosis of splenic metastasis are fragmentary and very poor. The aims of this study are to analyse retrospectively the accuracy, safety and the clinical impact of ultrasound (US)-guided fine-needle aspiration biopsy (UG-FNAB) in patients with suspected splenic metastasis.
A retrospective analysis of 1800 percutaneous abdominal biopsies performed at our institute during the period from 1993 to 2003 was done and 160 patients that underwent splenic biopsy were found. Among these 160 patients, 12 cases with the final diagnosis of solitary splenic metastases were encountered and they form the basis of this report. The biopsies were performed under US guidance using a 22-gauge Chiba needle. All the patients underwent laboratory tests, CT examination of the abdomen and chest, US examination of abdomen and pelvis.
There were 5 women and 7 men, median age 65 years (range 48-80). Eight patients had a known primary cancer at the time of the diagnosis of splenic metastasis: 3 had breast adenocarcinoma, 2 colon adenocarcinoma, 2 melanoma and 1 lung adenocarcinoma. Four patients were undiagnosed at the time of the appearance of splenic metastasis and subsequent investigations showed adenocarcinoma of the lung in 2 patients and colon adenocarcinoma in the remaining 2. There was a complete correspondence between the US and Computed Tomography (CT) in detecting focal lesions of the spleen. The splenic biopsies allowed a cytological diagnosis of splenic metastasis in all the 12 patients and changed clinical management in all cases. Reviewing the 160 patients that underwent UG-FNAB of the spleen we found no complications related to the biopsies.
These results indicate that UG-FNAB is a successful technique for diagnosis of splenic metastasis allowing an adequate treatment of the affected patients.
Background and Objectives Although serum β2 microglobulin (β2 M) is an easy parameter to measure, and over-expressed in a large number of lymphoproliferative diseases, its prognostic value has been ...largely underestimated. The present study examined the influence of β2M levels on overall survival (OS) of patients with follicular lymphoma (FL).Design and Methods The prognostic role of β2M was evaluated in 236 patients with FL identified from the databases of the Gruppo Italiano per lo Studio dei Linfomi (GISL) and treated with anthracycline-based regimens from 1993 to 2003.Results Elevated serum β2M levels were found in 82 patients (35%). According to multivariate logistic regression analysis, elevated β2M levels were associated with elevated lactate dehydrogenase (LDH) (p=0.021), age (p=0.029), and number of involved nodal areas (p
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