[Show abstract][Hide abstract] ABSTRACT: Abstract Splenectomy is considered as one of the first-line treatments for symptomatic patients with splenic marginal zone lymphoma (SMZL). Between 1997 and 2012, 100 hepatite C virus-negative patients with SMZL were treated by splenectomy as first-line treatment. At 6 months, all patients but three recovered from all cytopenia. The median lymphocyte count at 6 months and 1 year was 11.51x10(9)/L and 6.9x10(9)/L, respectively. Median progression free survival (PFS) was 8.25 years. The respective 5-year and 10-year overall survival (OS) rates were of 84% and 67%, respectively. Histological transformation occurred in 11% of the patients. It was the only parameter significantly associated with a shorter time to progression (p=.0001). Significant prognostic factors for OS were age (p=.0356) and histological transformation (p=.0312). In this large retrospective cohort, we confirmed that splenectomy as first-line treatment in SMZL patients corrected cytopenias and lymphocytosis within the first year and was associated with a good PFS.
Full-text · Article · Nov 2013 · Leukemia & lymphoma
[Show abstract][Hide abstract] ABSTRACT: The combination of pomalidomide and dexamethasone can be safely administered to Multiple Myeloma (MM) and has significant efficacy although the optimal regimen remains to be determined. MM who progressed after multiple lines of therapy have limited treatment options. We designed a multicenter phase 2 randomized study assessing 2 different dose regimens of pomalidomide and dexamethasone in advanced MM. Treatment response was assessed centrally. Pomalidomide (4 mg) was given orally on days 1 to 21 (arm 21/28) or continuously (arm 28/28) over a 28-day cycle, plus Dexamethasone given weekly. Eighty four patients (43 arm 21/28 and 41 arm 28/28) were randomized. The median number of prior lines was 5. ORR was 35% (arm 21/28) and 34% (arm 28/28), independent of the number of prior lines and level of refractoriness. Median DOR, TTP and PFS was 7.3, 5.4 and 4.6 months, similar across cohorts. At 23 months follow up, median OS was 14.9 months, with 44% of the patients alive at 18 months. Toxicity consisted primarily of myelosuppression, which was manageable. The efficacy and safety data presented here, along with data from other phase 2 trials, suggest that pomalidomide 4 mg/day on days 21/28 with dexamethasone should be investigated in future trials. This trial is registered at ClinicalTrials.gov (No. NCT01053949).
[Show abstract][Hide abstract] ABSTRACT: In multiple myeloma, many prognostic parameters have been proposed. However, all of these predict shorter survival. To identify patients with a longer life expectancy, we updated the data of patients treated in the IFM (Intergroupe Francophone du Myelome) 99-02 and 99-04 trials.
A series of 520 patients was analyzed. Median follow-up was 90.5 months. To perform a comprehensive analysis of the major prognostic factors, we reanalyzed all patients for 1q gains [in addition to updating del(13), t(4;14), and del(17p) analyses].
It was possible to identify a subgroup of patients (representing 20% of total patients) with an 8-year survival of 75%. These patients were defined by the absence of t(4;14), del(17p), and 1q gain and β(2)-microglobulin less than 5.5 mg/L.
We propose that all patients with newly diagnosed multiple myeloma be evaluated for these three chromosomal changes, not only to define high-risk patients but also to identify those with a longer life expectancy.
[Show abstract][Hide abstract] ABSTRACT: The Intergroupe Francophone du Myelome conducted a randomized trial to compare bortezomib-dexamethasone (VD) as induction before high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) to a combination consisting of reduced doses of bortezomib and thalidomide plus dexamethasone (vtD) in patients with multiple myeloma. Overall, a total of 199 patients were centrally randomly assigned to receive VD or vtD. After 4 cycles, the complete response (CR) rate was the same in both groups (13% in the vtD arm, 12% in the VD arm, P = .74). However, the CR plus very good partial response (VGPR) rate was significantly higher in the vtD arm (49% vs 36%, P = .05). After ASCT, the CR plus VGPR rate was significantly higher in the vtD arm (74% vs 58%, P = .02). The reduced doses of bortezomib and thalidomide translated into a reduced incidence of peripheral neuropathy (PN): grade ≥ 2 PN were reported in 34% in the VD arm versus 14% in the vtD arm (P = .001). vtD, including reduced doses of bortezomib and thalidomide, yields higher VGPR rates compared with VD and can be considered a new effective triplet combination before HDT/ASCT.
[Show abstract][Hide abstract] ABSTRACT: Leukemia is one of the leading journals in hematology and oncology. It is published monthly and covers all aspects of the research and treatment of leukemia and allied diseases. Studies of normal hemopoiesis are covered because of their comparative relevance.
[Show abstract][Hide abstract] ABSTRACT: Deletion of the 17p13 chromosomal region [del(17p)] is associated with a poor outcome in multiple myeloma. Most of the studies have targeted the TP53 gene for deletion analyses, although no study showed that this gene is the deletion target. In order to address this issue, we sequenced the TP53 gene in 92 patients with multiple myeloma at diagnosis, 54 with a del(17p) and 38 lacking del(17p). At least one mutation was found in 20 patients, all of them presenting a del(17p). The analysis of the mutation location showed that virtually all of them occurred in highly conserved domains involved in the DNA-protein interactions. In conclusion, we showed that 37% of the myeloma patients with del(17p) present a TP53 mutation versus 0% in patients lacking the del(17p). The prognostic significance of these mutations remains to be evaluated.
[Show abstract][Hide abstract] ABSTRACT: Incidence rates of bacteraemia and catheter-related infections were measured prospectively amongst haematological patients having long-term catheters and hospitalised in the ambulatory care unit between November 2005 and October 2006. The following risk factors were collected: age, sex, catheter type, follow-up duration, level of personal hygiene, pathology, number of lines of treatment, autograft and erythropoietin treatment. 340 patients were included, having 353 catheters (100 of the Groshong-type, followed during 17,621 days, and 253 of the type with implantable ports, followed during 51,049 days). 0.13 catheter-related infections and 0.07 bacteraemia per 100 catheter days were observed with the Groshong-type catheter, whereas 0.05 (P<10(-5)) catheter-related infections and 0.05 (P=0.048) bacteraemia were observed amongst patients with implantable ports. A multivariate analysis (Cox method taking into account the length of follow-up) on risk factors highlighted a significant effect of the type of catheter on catheter-related infections (Groshong versus implantable port OR=5.74, P<10(-3)), and of several factors on bacteraemia (lymphoma versus other pathologies OR=3.19, P=0.041; erythropoietin treatment OR=2.88, P=0.009; autograft OR=3.35, P=0.011; number of lines of treatment OR=0.68, P=0.047). It was not possible to determine if poor levels of personal hygiene had a significant impact, due to large numbers of missing data. These results, consistent with other studies, are not only useful in validating prevention policy but also in demonstrating lack of catheter traceability.
[Show abstract][Hide abstract] ABSTRACT: The role of rituximab retreatment in relapsed B-cell lymphoma is not well known. We undertook a single center retrospective cohort study to investigate the efficacy of retreatment with rituximab with or without chemotherapy in patients with relapsed and refractory B-cell lymphomas. We only included patients treated first-line and in first progression; 178 patients were included in the study, of whom 29% had diffuse large B-cell lymphoma (DLBCL) and 28% had follicular lymphoma (FL). The overall response rate for the first treatment was 81% and for the second treatment was 66%. The median progression-free survival (PFS) for all patients from diagnosis was 13.2 months and from relapse was 12.5 months (not statistically different). For DLBCL the median PFS from diagnosis was 9.6 months and from relapse was 8.4 months, and for FL the median PFS from diagnosis was 26.4 months and from relapse was 19.2 months (not statistically different). The 5-year overall survival was 57%. In a historical comparison with rituximab-naive patients, rituximab-retreated patients had a shorter time to initial relapse than control patients, but there was no difference between the two groups for PFS from relapse. In conclusion, retreatment with rituximab, with or without chemotherapy, yields a high overall response rate in patients with relapsed and refractory B-cell lymphomas. Relapse occurring after rituximab-containing therapy appears to be more aggressive than that occurring after chemotherapy alone. The outcome of retreatment, in terms of progression-free survival, is similar to that of primary treatment.
No preview · Article · Mar 2010 · Leukemia & lymphoma
[Show abstract][Hide abstract] ABSTRACT: Gastric mucosa-associated lymphoid tissue (MALT) lymphomas are uncommon tumours characterised by a tendency to remain localised for long periods. The aetiological association between MALT lymphomas and Helicobacter pylori is well established. The role of additional chemotherapy after H. pylori eradication in localised MALT lymphomas is unclear. The LY03 trial was designed to establish whether chlorambucil after treatment for H. pylori would help prevent recurrence. Patients were treated with antibiotics for H. pylori infection. Those with successful eradication of H. pylori and no evidence of progression of lymphoma were eligible for randomisation to chlorambucil or observation. Two hundred and thirty-one patients were registered. Ninety-seven percent patients had H. pylori eradicated after antibiotics and 59% achieved macroscopically normal gastric mucosa. One hundred and ten patients were randomised. With a median follow-up of 58 months, six patients were dead and 17 had recurrent/progressive disease. The recurrence/progression rates at 5 years were 11% for chlorambucil, and 21% for observation with a difference of 10%, 95% confidence interval (CI) = -9% to 29%, P = 0.15. No difference was detected in recurrence/progression-free survival [Hazard Ratio (HR) = 0.96, 95% CI = 0.41-2.2, P = 0.91] or overall survival (HR = 1.93, 95% CI = 0.39-9.58, P = 0.42). This is the first randomised trial to show there is no good evidence to support that additional single agent chemotherapy to anti-H. pylori treatment contributes to prevent recurrence in localised gastric MALT lymphomas.
Full-text · Article · Dec 2008 · British Journal of Haematology
[Show abstract][Hide abstract] ABSTRACT: Non-Hodgkin's lymphoma (NHL) in patients older than 80 years is not a rare disease and treatment strategies are often difficult because of associated comorbidities.
We entered 205 NHL patients older than 80 years treated in a single institution in a retrospective analysis to describe clinical presentation and outcome and to identify specific prognostic factors.
The median age was 83 years, and 91% of the cases were B-cell lymphomas consisting mainly of diffuse large B-cell lymphoma and marginal zone lymphoma. Among patients presenting comorbidities (87%), Charlson index was low in almost half of the patients (43%). Patients did not receive any treatment or received corticosteroids alone in 15%, surgery, radiotherapy, or monochemotherapy in 35%, polychemotherapy without anthracycline in 18%, and anthracycline based in 32%. Median overall survival was of 2.2 years. Main reason for death was disease progression (57%). Independent prognostic factors of survival were poor performance status (P < 10(-4)) and high lactate dehydrogenase level (P < 10(-5)). Comorbidities were not found to influence survival.
Very elderly NHL patients showed similar features and prognostic factors than younger patients. Death was related mainly to the disease, meaning that these patients should be more frequently treated with standard treatments.
No preview · Article · Apr 2008 · Annals of Oncology
[Show abstract][Hide abstract] ABSTRACT: One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.
[Show abstract][Hide abstract] ABSTRACT: Rituximab is the first monoclonal antibody to have been registered for the treatment of B-cell lymphomas. Randomized studies have demonstrated its activity in follicular lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma in untreated or relapsing patients. Rituximab has transformed the outcome of these patients because of its high activity and low toxicity. A combination of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, has the highest efficacy ever described with any chemotherapy in diffuse large B-cell lymphoma and follicular lymphoma.
[Show abstract][Hide abstract] ABSTRACT: Rituximab, an anti-CD20 monoclonal antibody, is increasingly used in the treatment of B-cell non-Hodgkin's lymphoma. Late-onset neutropenia in relation to rituximab has been recently described. In this report, we present six cases occurring after stem cell transplantation and discuss the potential impact of this complication.
Full-text · Article · Jun 2004 · Bone Marrow Transplantation
[Show abstract][Hide abstract] ABSTRACT: Alemtuzumab, the monoclonal anti-CD52 antibody, has clinical activity in B-cell and T-cell malignancies at the dose of 30 mg three times weekly for 9-12 weeks. This standard regimen induced responses usually shorter than 6 months. To prolong time to progression, we initialized a phase II study with an identical initial scheme until partial response, followed by a maintenance therapy lasting at least 4 months. Eleven heavily pretreated patients (8 with B-chronic lymhocytic leukemia (B-CLL) and 3 with small lymphoctyic lymphoma (SLL)) have been treated with this maintenance regimen (MR patients) and were retrospectively compared to 5 patients (3 B-CLL and 2 SLL) treated with the standard regimen (SR patients). Patients characteristics before treatment were identical in both groups. Objective response was reached by 9 (82%) MR patients and 3 (60%) SR patients (p NS). After the treatment, 8 (73%) MR patients and all SR patients progressed with a median time at 12.2 months and 3 months respectively. Survival time from alemtuzumab was significatively different (P < 0.005). None of the patients died in the MR group with a median follow-up at 16 months. In the SR group, the median survival from alemtuzumab was 5.9 months. We did not observe any differences in terms of hematological toxicites and infections between the two groups. In conclusion, maintenance alemtuzumab therapy seems to increase the time to progression and the survival, without adding hematological toxicities and infectious complications. More patients are needed to confirm this observation.
No preview · Article · Apr 2004 · Leukemia and Lymphoma