[Show abstract][Hide abstract] ABSTRACT: Purpose:
This study evaluated the efficacy of pediatric-like acute lymphoblastic leukemia (ALL) therapy in adults with lymphoblastic lymphoma (LL).
Patients and methods:
This was a prospective phase II study in adults 18 to 59 years old with previously untreated LL. Patients were treated with an adapted pediatric-like ALL protocol, which included a corticosteroid prephase, a five-drug induction reinforced by sequential cyclophosphamide administration, dose-dense consolidation, late intensification, CNS prophylaxis, and a 2-year maintenance phase. Treatment response was assessed by computed tomography and optional positron emission tomography. Allogeneic hematopoietic stem cell transplant was offered to selected patients in first complete remission (CR) or unconfirmed CR.
The study enrolled 148 patients (131 with T-lineage LL [T-LL] and 17 with B-lineage LL [B-LL]). A total of 119 patients with T-LL (90.8%) and 13 with B-LL (76.5%) reached CR/unconfirmed CR, including 26 with T-LL and two with B-LL who needed a second induction salvage course. Relapse occurred in 34 patients with T-LL and four with B-LL. In patients with T-LL, 3-year event-free survival was 63.3% (95% CI, 54.2% to 71.0%), disease-free survival was 72.4% (95% CI, 63.0% to 79.7%), and overall survival was 69.2% (95% CI, 60.0% to 76.7%). Multivariate analysis identified serum lactate dehydrogenase level and the NOTCH1/FBXW7/RAS/PTEN oncogene (a four-gene oncogenetic classifier) status but not positron emission tomography or hematopoietic stem cell transplant as independent prognostic factors for outcome in T-LL.
In adults with LL, an intensive pediatric-like ALL treatment protocol was associated with a good response rate and outcome. In patients with T-LL, the four-gene oncogenetic classifier and lactate dehydrogenase level were independent prognostic indicators.
Preview · Article · Dec 2015 · Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: We recently defined event-free survival at 24 months (EFS24) as a clinically relevant outcome for patients with DLBCL. Patients who fail EFS24 have very poor overall survival, while those who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. Here, we develop and validate a clinical risk calculator (IPI24) for EFS24. Model building was performed on a discovery dataset of 1348 patients with DLBCL and treated with anthracycline-based immunochemotherapy. A multivariable model containing age, Ann Arbor stage, normalized serum LDH, ALC, ECOG performance status, bulky disease and sex was identified. The model was then applied to an independent validation dataset of 1177 DLBCL patients. The IPI24 score estimates the probability of failing to achieve the EFS24 endpoint for an individual patient. The IPI24 model showed superior discriminatory ability (c-statistic=0.671) in the validation dataset compared to the IPI (c-statistic=0.649) or the NCCN-IPI (c-statistic=0.657). After recalibration of the model on the combined dataset, the median predicted probability of failing to achieve EFS24 was 36% (range, 12% to 88%), and the IPI24 showed an EFS24 gradient in all IPI groups. The IPI24 also identified a significant percentage of patients with high risk disease, with over 20% of patients having a 50% or higher risk of failing to achieve EFS24. The IPI24 provides an individual patient level probability of achieving the clinically relevant EFS24 endpoint. It can be utilized via electronic apps. This article is protected by copyright. All rights reserved.
Full-text · Article · Oct 2015 · American Journal of Hematology
[Show abstract][Hide abstract] ABSTRACT: Nodular lymphocyte predominant Hodgkin lymphoma represents a distinct entity from classical Hodgkin lymphoma. We conducted a retrospective study to investigate the management of patients with nodular lymphocyte predominant Hodgkin lymphoma. Clinical characteristics, treatment and outcome of adult patients with nodular lymphocyte predominant Hodgkin lymphoma were collected in the Lymphoma Study Association centers. Progression-free survival and overall survival were analyzed, and the competing risks formulation of Cox model regression was used to control the effect of risk factors on relapse or death as competing events. Among 314 evaluable patients, 82.5% had early-stage nodular lymphocyte predominant Hodgkin lymphoma. Initial management consisted in watchful waiting (36.3%), radiotherapy (20.1%), rituximab (8.9%), chemotherapy or immuno-chemotherapy (21.7%), combined modality treatment (12.7%), or radiotherapy and rituximab (0.3%). With a median follow-up of 55.8 months, the 10-year PFS and OS estimates were 44.2% and 94.9%, respectively. The 4-year PFS estimates were 79.6% after radiotherapy, 77.0% after rituximab alone, 78.8% after chemotherapy or immuno-chemotherapy, and 93.9% after combined modality treatment. For the whole population, early treatment with chemotherapy or radiotherapy, but not rituximab alone (Hazard ratio 0.695 [0.320-1.512], p=0.3593) significantly reduced the risk of progression compared to watchful waiting (HR 0.388 [0.234-0.643], p=0.0002). Early treatment appears beneficial over watchful waiting in terms of progression-free survival but has no impact on overall survival. Radiotherapy in selected early stage nodular lymphocyte predominant Hodgkin lymphoma, and combined modality treatment, chemotherapy or immuno-chemotherapy for other patients are the main options to treat adult patients with a curative intent.
[Show abstract][Hide abstract] ABSTRACT: Treatment with escalated BEACOPP achieved a superior time to treatment failure over ABVD in patients with disseminated Hodgkin lymphoma. However, recent clinical trials have failed to confirm BEACOPP Overall Survival (OS) superiority over ABVD. In addition, the gain in low-risk patients is still a matter of debate.
We randomly compared ABVD (8 cycles) with BEACOPP (escalated 4 cycles => baseline 4 cycles) in low-risk patients with an International Prognostic Score (IPS) of 0-2. The primary endpoint was Event-Free Survival (EFS). This parallel group, open-label phase 3 trial was registered under #RECF0219 at French National Cancer Institute.
One hundred fifty patients were randomized in this trial (ABVD 80, BEACOPP 70): 28 years was the median age, 50 % were male and IPS was 0-1 for 64 %. Complete Remission rate was 85 % for ABVD and 90 % for BEACOPP. Progression or relapses were more frequent in the ABVD patients than in the BEACOPP patients (17 vs. 5 patients). With a median follow-up period of 5.5 years, 7 patients died: 6 in the ABVD arm and 1 in the BEACOPP arm (HL 3 & 0, 2(nd) cancer 2 & 1, accident 1&0). The EFS at 5 years was estimated at 62 % for ABVD vs. 77 %, for BEACOPP (HR=0.6, p=0.07). The Progression-Free Survival (PFS) at 5 years was 75 % vs. 93 % (HR=0.3, p=0.007). The Overall Survival at 5 years was 92 % vs. 99 % (HR=0.18, p=0.06).
Fewer progressions/relapses were observed with BEACOPP, demonstrating the high efficacy of the more intensive regimen, even in low-risk patients. However, additional considerations, balancing treatment-related toxicity and late morbidity due to salvage may help with decision making with regard to treatment with ABVD or BEACOPP.
Full-text · Article · May 2014 · Annals of Oncology
[Show abstract][Hide abstract] ABSTRACT: A previous pilot study with rituximab, gemcitabine and oxaliplatin has shown promising activity in refractory/relapsed B-cell lymphoma. Therefore, we conducted a phase II study, in order to determine whether these results could be reproduced in a multi-institutional setting. This phase II study includes 49 patients with refractory (n=6) /relapsing (n=43) diffuse large B-cell lymphoma. Patients had a median age of 69 years. Prior treatment included rituximab in 31 (63%) and autologous transplant in 17 (35%) patients. International Prognostic Index at enrolment was > 2 in 34 patients (71%). Primary objective was overall response rate after 4 cycles. Patients were planned to receive 8 cycles given in case if they reached partial remission after 4 cycles. After 4 cycles, responses were: complete remission 21 (44%), partial remission 8 (17%) resulting in an overall response rate of 61 %. Factors significantly affecting overall response rate were: early (< 1year) progression/relapse 18% vs 54% (p=0.001) and prior exposure to rituximab 23% vs 65% (p=0.004). Five-year Progression-Free and Overall Survival were 12.8% and 13.9%, respectively. Rituximab, gemcitabine and oxaliplatin was well tolerated with grade 3-4 infectious episodes in 22% of the cycles. These results are the first confirmation by a multi-institution study that Rituximab, gemcitabine and oxaliplatin provides a consistent response rate in refractory/relapsed patients. It can now be considered as a platform for new combinations with targeted treatments. This trial was registered at clinicaltrial.gov under #NCT00169195. The results were partly presented in an oral session at the American Society of Hematology annual meeting in Chicago, USA, in December 2010.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has become the standard of care for elderly patients with diffuse large B-cell lymphoma. We aimed to ascertain if a dose-dense R-CHOP regimen administered every 2 weeks (R-CHOP14) was superior to the standard 3-week schedule (R-CHOP21). METHODS: We did a randomised phase 3 trial at 83 centres in four countries. 602 patients aged 60-80 years with untreated diffuse large B-cell lymphoma and at least one adverse prognostic factor (age-adjusted international prognostic index ≥1) were eligible for the study. We randomly allocated individuals to R-CHOP-ie, rituximab (375 mg/m(2)), cyclophosphamide (750 mg/m(2)), doxorubicin (50 mg/m(2)), vincristine (1·4 mg/m(2), up to 2 mg) all on day 1, and prednisone 40 mg/m(2) daily for 5 days-administered every 14 days (n=304) or every 21 days (n=298) for eight cycles. We did permuted-block randomisation (block size four, allocation ratio 1:1) stratified by centre and number of adverse prognostic factors. The primary endpoint was event-free survival. Our analysis was of the intention-to-treat population, and we present the final analysis. This study is registered with ClinicalTrials.gov, number NCT00144755. FINDINGS: Two patients allocated R-CHOP21 were ineligible for the study and were excluded from analyses. After median follow-up of 56 months (IQR 27-60), 3-year event-free survival was 56% (95% CI 50-62) in the R-CHOP14 group and 60% (55-66) in the R-CHOP21 group (hazard ratio 1·04, 95% CI 0·82-1·31; p=0·7614). Grade 3-4 neutropenia occurred in 224 (74%) of 304 patients allocated R-CHOP14 and 189 (64%) of 296 assigned R-CHOP21, despite increased use of granulocyte colony-stimulating factor in the R-CHOP14 group compared with the R-CHOP21 group. 143 (47%) patients in the R-CHOP14 group received at least one red-blood-cell transfusion versus 93 (31%) in the R-CHOP21 group (p=0·0001). 35 (12%) patients allocated R-CHOP14 received at least one platelet transfusion versus 25 (8%) assigned R-CHOP21 (p=0·2156). 155 (51%) patients who were assigned R-CHOP14 had at least one serious adverse event compared with 140 (47%) who were allocated R-CHOP21. INTERPRETATION: In elderly patients with untreated diffuse large B-cell lymphoma and at least one adverse prognostic factor, a 2-week dose-dense R-CHOP regimen did not improve efficacy compared with the 3-week standard schedule. The frequency of toxic side-effects was similar between regimens, but R-CHOP14 was associated with increased need for red-blood-cell transfusion. FUNDING: Groupe d'Etude des Lymphomes de l'Adulte (GELA), Amgen.
No preview · Article · Apr 2013 · The Lancet Oncology
[Show abstract][Hide abstract] ABSTRACT: Background
The superiority of a chemotherapy with doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone (ACVBP) in comparison with cyclophosphamide, doxorubicin, vincristin and prednisone plus radiotherapy for young patients with localized diffuse large B-cell lymphoma (DLBCL) was previously demonstrated. We report the results of a trial which evaluates the role of rituximab combined with ACVBP (R-ACVBP) in these patients.Patients and methodsUntreated patients younger than 66 years with stage I or II DLBCL and no adverse prognostic factors of the age-adjusted International Prognostic Index were randomly assigned to receive three cycles of ACVBP plus sequential consolidation with or without the addition of four infusions of rituximab.ResultsA total of 223 patients were randomly allocated to the study, 110 in the R-ACVBP group and 113 in the ACVBP group. After a median follow-up of 43 months, our 3-year estimate of event-free survival was 93% in the R-ACVBP group and 82% in the ACVBP group (P = 0.0487). Three-year estimate of progression-free survival was increased in the R-ACVBP group (95% versus 83%, P = 0.0205). Overall survival did not differ between the two groups with a 3-year estimates of 98% and 97%, respectively (P = 0.686).Conclusion
In young patients with low-risk localized DLBCL, rituximab combined with three cycles of ACVBP plus consolidation is significantly superior to ACVBP plus consolidation alone.
Full-text · Article · Dec 2012 · Annals of Oncology
[Show abstract][Hide abstract] ABSTRACT: PURPOSESystemic anaplastic large-cell lymphoma (ALCL) is a T-cell lymphoma, whose anaplastic lymphoma kinase (ALK) expression varies according to age. Long-term outcomes of chemotherapy-treated adults are not definitively established and should be evaluated. PATIENTS AND METHODS
Patients treated in three Groupe d'Étude des Lymphomes de l'Adulte prospective clinical trials with confirmed systemic ALCL after immunohistopathologic review and defined ALK expression status were analyzed.ResultsAmong the 138 adult patients with ALCL, 64 (46%) were ALK positive, and 74 (54%) were ALK negative. Median follow-up was 8 years. At diagnosis, significantly more patients younger than 40 years old were ALK positive than ALK negative (66% v 23%, respectively; P < .001). Comparing patients with ALK-positive and ALK-negative ALCL, β(2)-microglobulin was ≥ 3 mg/L in 12% and 33% (P = .017); International Prognostic Index was high (score, 3 to 5) in 23% and 48% (P = .03); complete response rates to first-line treatment were 86% and 68% (P = .01); and 8-year overall survival (OS) rates were 82% (95% CI, 69% to 89%) and 49% (95% CI, 37% to 61%), respectively (P < .001). The survival difference mostly affected patients age ≥ 40 years. Multivariate analysis identified β(2)-microglobulin ≥ 3 mg/L (P < .001) and age ≥ 40 years (P = .029), but not ALK status, as prognostic for OS. These two variables distinguished four survival risk groups, with 8-year OS ranging from 84% to 22%. CONCLUSION
Results of this long-term study enabled refinement of the prognosis of adult systemic ALCL, with ALK prognostic value dependent on age, and could provide guidance for eventual treatment adjustment.
Preview · Article · Oct 2012 · Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: PURPOSEWe investigated the impact of Hodgkin lymphoma (HL) on parenthood, including factors influencing parenthood probability, by comparing long-term HL survivors with matched general population controls. PATIENTS AND METHODSA Life Situation Questionnaire was sent to 3,604 survivors treated from 1964 to 2004 in successive clinical trials. Responders were matched with controls (1:3 or 4) for sex, country, education, and year of birth (10-year groups). Controls were given an artificial date of start of treatment equal to that of their matched case. The main end point was presence of biologic children after treatment, which was evaluated by using conditional logistic regression analysis. Logistic regression analysis was used to analyze factors influencing spontaneous post-treatment parenthood.ResultsIn all, 1,654 French and Dutch survivors were matched with 6,414 controls. Median follow-up was 14 years (range, 5 to 44 years). After treatment, the odds ratio (OR) for having children was 0.77 (95% CI, 0.68 to 0.87; P < .001) for survivors compared with controls. Of 898 survivors who were childless before treatment, 46.7% achieved post-treatment parenthood compared with 49.3% of 3,196 childless controls (OR, 0.87; P = .08). Among 756 survivors with children before treatment, 12.4% became parents after HL treatment compared with 22.2% of 3,218 controls with children before treatment (OR, 0.49; P < .001). Treatment with alkylating agents, second-line therapy, and age older than 35 years at treatment appeared to reduce the chances of spontaneous post-treatment parenthood. CONCLUSION
Survivors of HL had slightly but significantly fewer children after treatment than matched general population controls. The difference concerned only survivors who had children before treatment and appears to have more personal than biologic reasons. The chance of successful post-treatment parenthood was 76%.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The ACVBP regimen is an efficient induction regimen for poor-risk patients with diffuse large B-cell lymphoma (DLBCL) before consolidative autologous stem cell transplantation. Adjunction of the monoclonal anti-CD20 antibody rituximab (R-ACVBP) was recently found to be superior to ACVBP alone. This study assessed the impact of rituximab on stem cell mobilization in two similar consecutive groups of patients treated with ACVBP in two prospective, controlled trials. STUDY DESIGN AND METHODS: The first trial (LNH-98B-3) involved 137 patients treated with ACVBP alone. In the second trial (LNH-03-3B), 91 patients received an R-ACVBP regimen. Stem cell mobilization was performed after a course of (R)-ACVBP. RESULTS: The median peak numbers of blood CD34+ cell counts recorded before the first apheresis procedure in the ACVBP and R-ACVBP groups were 69 × 10(6) and 63 × 10(6) /L, respectively (p = 0.55). The median numbers of CD34+ cells collected were 7.1 × 10(6) and 6.0 × 10(6) CD34+ cells/kg for the ACVBP and R-ACVBP groups, respectively (p = 0.13). The median number of apheresis procedures required for gathering the minimum amount of CD34+ cells (2 × 10(6) /kg) was the same in the two groups. CONCLUSION: When compared with ACVBP alone, adjunction of rituximab does not impair stem cell mobilization.
[Show abstract][Hide abstract] ABSTRACT: In this large cohort of Hodgkin's lymphoma survivors with long follow-up, we estimated the impact of treatment regimens on premature ovarian failure (POF) occurrence and motherhood, including safety of nonalkylating chemotherapy and dose-response relationships for alkylating chemotherapy and age at treatment.
The Life Situation Questionnaire was sent to 1,700 women treated in European Organisation for Research and Treatment of Cancer and Groupe d'Étude des Lymphomes de l'Adulte trials between 1964 and 2004. Women treated between ages 15 and 40 years and currently not using hormonal contraceptives (n = 460) were selected to assess occurrence of POF. Cumulative POF risk was estimated using the life-table method. Predictive factors were assessed by Cox regression analysis.
Median follow-up was 16 years (range, 5 to 45 years). Cumulative risk of POF after alkylating chemotherapy was 60% (95% CI, 41% to 79%) and only 3% (95% CI, 1% to 7%) after nonalkylating chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine; epirubicin, bleomycin, vinblastine, and prednisone). Dose relationship between alkylating chemotherapy and POF occurrence was linear. POF risk increased by 23% per year of age at treatment. In women treated without alkylating chemotherapy at age younger than 32 years and age 32 years or older, cumulative POF risks were 3% (95% CI, 1% to 16%) and 9% (95% CI, 4% to 18%), respectively. If menstruation returned after treatment, cumulative POF risk was independent of age at treatment. Among women who ultimately developed POF, 22% had one or more children after treatment, compared with 41% of women without POF.
Nonalkylating chemotherapy carries little to no excess risk of POF. Dose-response relationships for alkylating chemotherapy and age at treatment are both linear. Timely family planning is important for women at risk of POF.
Full-text · Article · Dec 2011 · Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: The outcome of diffuse large B-cell lymphoma has been substantially improved by the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy regimens. We aimed to assess, in patients aged 18-59 years, the potential survival benefit provided by a dose-intensive immunochemotherapy regimen plus rituximab compared with standard treatment plus rituximab.
We did an open-label randomised trial comparing dose-intensive rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) with subsequent consolidation versus standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). Random assignment was done with a computer-assisted randomisation-allocation sequence with a block size of four. Patients were aged 18-59 years with untreated diffuse large B-cell lymphoma and an age-adjusted international prognostic index equal to 1. Our primary endpoint was event-free survival. Our analyses of efficacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00140595.
One patient withdrew consent before treatment and 54 did not complete treatment. After a median follow-up of 44 months, our 3-year estimate of event-free survival was 81% (95% CI 75-86) in the R-ACVBP group and 67% (59-73) in the R-CHOP group (hazard ratio [HR] 0·56, 95% CI 0·38-0·83; p=0·0035). 3-year estimates of progression-free survival (87% [95% CI, 81-91] vs 73% [66-79]; HR 0·48 [0·30-0·76]; p=0·0015) and overall survival (92% [87-95] vs 84% [77-89]; HR 0·44 [0·28-0·81]; p=0·0071) were also increased in the R-ACVBP group. 82 (42%) of 196 patients in the R-ACVBP group experienced a serious adverse event compared with 28 (15%) of 183 in the R-CHOP group. Grade 3-4 haematological toxic effects were more common in the R-ACVBP group, with a higher proportion of patients experiencing a febrile neutropenic episode (38% [75 of 196] vs 9% [16 of 183]).
Compared with standard R-CHOP, intensified immunochemotherapy with R-ACVBP significantly improves survival of patients aged 18-59 years with diffuse large B-cell lymphoma with low-intermediate risk according to the International Prognostic Index. Haematological toxic effects of the intensive regimen were raised but manageable.
Groupe d'Etudes des Lymphomes de l'Adulte and Amgen.
[Show abstract][Hide abstract] ABSTRACT: Diffuse large B-cell lymphoma is a common cancer in elderly patients. Although treatment has been standardised in younger patients, no prospective study has been done in patients over 80 years old. We aimed to investigate the efficacy and safety of a decreased dose of CHOP (doxorubicin, cyclophosphamide, vincristine, and prednisone) chemotherapy with a conventional dose of rituximab in elderly patients with diffuse large B-cell lymphoma.
We did a prospective, multicentre, single-arm, phase 2 study of patients aged over 80 years who had diffuse large B-cell lymphoma. Patients were included from 38 centres in France and Belgium. All patients received six cycles of rituximab combined with low-dose CHOP (R-miniCHOP) at 3-week intervals. Patients received 375 mg/m(2) rituximab, 400 mg/m(2) cyclophosphamide, 25 mg/m(2) doxorubicin, and 1 mg vincristine on day 1 of each cycle, and 40 mg/m(2) prednisone on days 1-5. The primary endpoint was overall survival, both unadjusted and adjusted for treatment and baseline prognostic factors. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, NCT01087424.
150 patients were enrolled between Jan 9, 2006, and Jan 23, 2009 and 149 were included in the intention-to-treat analyses. Median age was 83 years (range 80-95). After a median follow-up of 20 months (range 0-45), the median overall survival was 29 months (95% CI 21 to upper limit not reached); 2-year overall survival was 59% (49-67%). In multivariate analyses, overall survival was only affected by a serum albumin concentration of 35 g/L or less (hazard ratio 3·2, 95% CI 1·4-7·1; p=0·0053). Median progression-free survival was 21 months (95% CI 13 to upper limit not reached), with a 2-year progression free survival of 47% (38-56). 58 deaths were reported, 33 of which were secondary to lymphoma progression. 12 deaths were attributed to toxicity of the treatment. The most frequent side-effect was haematological toxicity (grade ≥3 neutropenia in 59 patients; febrile neutropenia in 11 patients).
R-miniCHOP offers a good compromise between efficacy and safety in patients aged over 80 years old. R-miniCHOP should be considered as the new standard treatment in this subgroup of patients.
Groupe d'Etude des Lymphomes de l'Adulte (GELA).
No preview · Article · May 2011 · The Lancet Oncology
[Show abstract][Hide abstract] ABSTRACT: The prognostic value of interim positron emission tomography (PET) interpreted according to visual criteria is a matter of debate in diffuse large B-cell lymphoma (DLBCL). Maximal standardized uptake value reduction (ΔSUVmax) may better predict outcome. To compare the prognostic value of both methods, we analyzed PET done at baseline (PET0) and after 2 (PET2) and 4 (PET4) cycles in 85 patients with high-risk DLBCL enrolled on a prospective multicenter trial. All images were centrally reviewed and interpreted visually according to the International Harmonization Project criteria and by computing ΔSUVmax between PET0 and PET2 (ΔSUVmaxPET0-2) or PET4 (ΔSUVmaxPET0-4). Optimal cutoff to predict progression or death was 66% for ΔSUVmaxPET0-2 and 70% for ΔSUVmaxPET0-4. Outcomes did not differ significantly whether PET2 and PET4 were visually positive or negative. Inversely, ΔSUVmaxPET0-2 analysis (> 66% vs ≤ 66%) identified patients with significantly different 2-year progression-free survival (77% vs 57%; P = .0282) and overall survival (93% vs 60%; P < .0001). ΔSUVmaxPET0-4 analysis (> 70% vs ≤ 70%) seemed even more predictive for 2-year progression-free survival (83 vs 40%; P < .0001) and overall survival (94% vs 50%; P < .0001). ΔSUVmax analysis of sequential interim PET is feasible for high-risk DLBCL and better predicts outcome than visual analysis. The trial was registered at http://clinicaltrials.gov as NCT00498043.
[Show abstract][Hide abstract] ABSTRACT: This study was designed to evaluate the safety and efficacy of a conventional dose of yttrium-90 ((90)Y) ibritumomab tiuxetan combined with the etoposide rabinoside acytarabine melphalan (BEAM) regimen before autologous stem cell transplantation (ASCT) in chemosensitive relapsed or refractory low-grade B-cell lymphomas.
From March 2005 to August 2006, 77 prospective patients were included, 69 (90%) with follicular lymphomas.
The last salvage chemotherapy regimen included rituximab for 74 patients and ASCT for 75 patients. Before ASCT, rates of complete response/unconfirmed response (CR/CRu) and partial response were 77% and 23%, respectively. After zevaline-BEAM (Z-BEAM), time to >1 × 10(9)/L neutrophils was 12 days (range, 9-35 days), and time to >20 × 10(9)/L platelets was 12 days (range, 3-42 days). No other significant extrahematologic toxicity was observed. Three months after ASCT, 68 patients (88%) were in CR/CRu. After a median follow-up of 28 months, 2-year event-free survival (EFS) and overall survival were 63% and 97%, respectively, but EFS for first-relapsed patients was 72%. When using patients as their own controls, 2-year EFS was superior after ASCT and compared favorably with the duration of response of last chemotherapy (62% vs. 37%, P = .007) (Point 1.10).
Z-BEAM appears safe and needs to be further evaluated in a randomized trial.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the activity and safety of nonpegylated liposomal doxorubicin (Myocet) when substituted for doxorubicin in the R-CHOP regimen (R-COMP).
Seventy-five elderly patients with diffuse large B-cell lymphoma (DLBCL) were studied. Only patients with left ventricular ejection fraction (LVEF) > or =50% were allowed. R-COMP regimen was administered every 3 weeks for three cycles, followed by additional five cycles in case of complete response (CR) or partial response.
From November 2002 to April 2005, 75 patients were registered, of which 72 were evaluated. Median age was 72 years (range 61-83); 56% of patients had high or high-intermediate International Prognostic Index score. Median LVEF at baseline was 61%. Thirty-eight patients had history of abnormal cardiovascular conditions. The overall response rate was 71%, with a CR rate of 57%. After a median follow-up of 33 months, the 3-year overall survival, failure-free survival, and progression-free survival rates were 72%, 39%, and 69%, respectively. Neutropenia (54%) was the most frequent grade 3-4 adverse event (AE); 21% of patients experienced cardiac AEs, graded as 3-4 in 4% of the cases.
R-COMP is an effective regimen for the treatment of DLBCL in elderly patients, with an acceptable tolerability profile.
Full-text · Article · Dec 2009 · Annals of Oncology
[Show abstract][Hide abstract] ABSTRACT: The effects of L-asparaginase on hemostasis during induction chemotherapy are less defined in adults than in children. We, therefore, studied the effects of L-asparaginase in adult patients.
This was a retrospective analysis of 214 patients treated with L-asparaginase (7500 IU/m(2) x 6) for acute lymphoblastic leukemia or lymphoblastic lymphoma. Between day 1 of the induction course and discharge, clinical events, and biological and therapeutic modifications were reviewed.
Antithrombin and fibrinogen levels were lower than 60% and 1 g/L in 71% and 73% of patients, respectively. Twenty thromboses occurred in 9.3% of the patients; these patients had a median antithrombin level of 53% (range, 21-111) at the time of the event. Forty-two episodes of bleeding occurred in 31 patients with a median fibrinogen level of 1.3 g/L. Infusions of L-asparaginase were reduced or delayed in 64% of patients due to low fibrinogen and/or antithrombin levels. Fresh-frozen plasma, antithrombin and fibrinogen were infused in 31%, 41% and 52% of patients, respectively. The mean antithrombin and fibrinogen levels increased from 61% to 88% and from 1 to 1.4 g/L after infusion of antithrombin or fibrinogen respectively, while both levels remained unchanged after the infusion of fresh-frozen plasma. In patients who received antithrombin concentrates L-asparaginase injections were less frequently omitted or delayed (53% vs. 72%, p=0.005), the rate of thrombosis was lower (4.8% vs. 12.2%, p=0.04) and the disease-free survival was also reduced (p=0.05).
This retrospective study suggests that antithrombin concentrates may have a beneficial effect on the outcome of adults treated for acute lymphoblastic leukemia with L-asparaginase; prospective studies are essential to confirm this hypothesis.
[Show abstract][Hide abstract] ABSTRACT: T-lymphoblastic lymphoma is an infrequent disease usually treated as T-acute lymphoblastic leukemia with an induction chemotherapy course and sequential reinduction and maintenance chemotherapy. The T-LBL/ALL-GOELAL02 study evaluated the impact of randomized reinduction chemotherapy against intensified conditioning followed by autologous stem cell transplantation (ASCT), after an induction regimen of the type used for acute lymphoblastic leukemia (ALL).
Patients with favorable characteristics were randomized to receive chemotherapy or ASCT. Patients with unfavorable characteristics (bone marrow involvement and age over 35 years old or leukocytosis >30 x 10(9)/L or failure to achieve medullar complete remission [CR] after one induction course) received a second induction course and ASCT.
Among 45 patients, the CR rate was 71% after induction and 87% after a second induction course. Within the group of 27 patients with favorable characteristics, ten received ASCT and 17 chemotherapy. Ten patients in the group with unfavorable characteristics received ASCT. The 7-year overall survival and progression-free survival rates were 64 and 65%, respectively. Surprisingly, CR obtained after only two induction courses was associated with improved overall survival (p=0.04). None of the known prognostic factors significantly affected survival.
Randomized maintenance or high-dose therapy (HDT) and ASCT or intensified HDT according to initial presentation gave similar overall and relapse-free survival rates. However, HDT allowed sparing of mediastinal irradiation and shortened treatment duration.