Update of the FL2000 randomized trial combining rituximab to CHVP-Interferon in follicular lymphoma (FL) patients (pts)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7508-7508 ◽  
Author(s):  
C. Foussard ◽  
N. Mounier ◽  
A. Van Hoof ◽  
V. Delwail ◽  
O. Casasnovas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Randomized Study ◽  
Bone Marrow Involvement ◽  
Risk Groups ◽  
Tumor Burden ◽  
Event Free Survival ◽  
Free Survival ◽  
High Tumor Burden ◽  
Ecog Ps

7508 Background: The GELA-GOELAMS FL2000 trial investigated the role of rituximab in the first line treatment of FL pts. Methods: This prospective randomized study compared the CHVP regimen (12 courses) +18 months α2b-IFN (CHVP-I) to 6 CHVP courses combined with 6 rituximab infusions + 18 months IFN (R-CHVP-I). The primary endpoint was event-free survival (EFS). Inclusion criteria consisted in untreated stage II-IV FL pts; 18–75 years old; with a high tumor burden defined by at least one of the following criteria: B symptoms, ECOG PS>1, LDH>normal value, β2-microglobulin ≥3 mg/L, largest tumor ≥7 cm, 3 distinct nodes ≥3 cm, serous effusion, compression or symptomatic spleen enlargement. Results: From 05/00 until 05/02, 358 eligible pts were randomized (CHVP-I 183 pts and R-CHVP-I 175 pts) with the following characteristics: M/F = 1; median age = 60 years [25–75]; ECOG > 1 = 8%; B symptoms = 27%; AA stage > II = 87%; bone marrow involvement = 58%; β2-m ≥3 mg/L = 31%; LDH > N = 37%; Hb <12 g/dL = 18%; FLIPI score ≥3 in 57% of the pts. The first analysis [ASH 2004] showed a significant better treatment response in R-CHVP-I as compared to CHVP-I and a improvement of event free survival (EFS) in the R-CHVP-I arm (Log-Rang, P = .003). As initially planned, a second analysis on all pts has now been performed with a median follow-up of 3½ years, all pts with data >01/01/05. The median EFS for the whole population has not yet been reached. In the CHVP-I arm, median EFS was 3 years and 46% of the pts are event-free at 42 months (mo.). In contrast, the median has not been reached in the R-CHVP-I arm and the EFS is 67% at 42 mo. (P < .0001). This improvement in EFS was found both in the 150 pts with a low or intermediate FLIPI score (P = .019) and in those (n = 201) with a high score (P = .0005). When considering the 230 pts responders at the end of 18 mo. of therapy, 42 mo. EFS is 62% in CHVP-I arm versus 81% in R-CHVP-I arm (P = .002). Finally, the overall survival at 42 mo. of patients in the CHVP-I arm is of 84% versus to 91% in the R-CHVP-I arm (P = .029) with a reduction of death risk by approximately 2 (RR = 0.55). Conclusions: These results demonstrate that rituximab combined with CHVP-I has a durable benefit, in all FLIPI risk groups, allows to reduce the duration of chemotherapy and improves overall survival in high-tumor burden FL pts. [Table: see text]

scholarly journals Outcome of Infants Younger Than 1 Year With Acute Lymphoblastic Leukemia Treated With the Interfant-06 Protocol: Results From an International Phase III Randomized Study

2019 ◽  
Vol 37 (25) ◽  
pp. 2246-2256 ◽  
Author(s):  
Rob Pieters ◽  
Paola De Lorenzo ◽  
Philip Ancliffe ◽  
Luis Alberto Aversa ◽  
Benoit Brethon ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Randomized Study ◽  
Disease Free Survival ◽  
Risk Groups ◽  
Study Groups ◽  
Phase Iii ◽  
Free Survival ◽  
Wbc Count

PURPOSE Infant acute lymphoblastic leukemia (ALL) is characterized by KMT2A ( MLL) gene rearrangements and coexpression of myeloid markers. The Interfant-06 study, comprising 18 national and international study groups, tested whether myeloid-style consolidation chemotherapy is superior to lymphoid style, the role of stem-cell transplantation (SCT), and which factors had independent prognostic value. MATERIALS AND METHODS Three risk groups were defined: low risk (LR): KMT2A germline; high risk (HR): KMT2A-rearranged and older than 6 months with WBC count 300 × 109/L or more or a poor prednisone response; and medium risk (MR): all other KMT2A-rearranged cases. Patients in the MR and HR groups were randomly assigned to receive the lymphoid course low-dose cytosine arabinoside [araC], 6-mercaptopurine, cyclophosphamide (IB) or experimental myeloid courses, namely araC, daunorubicin, etoposide (ADE) and mitoxantrone, araC, etoposide (MAE). RESULTS A total of 651 infants were included, with 6-year event-free survival (EFS) and overall survival of 46.1% (SE, 2.1) and 58.2% (SE, 2.0). In West European/North American groups, 6-year EFS and overall survival were 49.4% (SE, 2.5) and 62.1% (SE, 2.4), which were 10% to 12% higher than in other countries. The 6-year probability of disease-free survival was comparable for the randomized arms (ADE+MAE 39.3% [SE 4.0; n = 169] v IB 36.8% [SE, 3.9; n = 161]; log-rank P = .47). The 6-year EFS rate of patients in the HR group was 20.9% (SE, 3.4) with the intention to undergo SCT; only 46% of them received SCT, because many had early events. KMT2A rearrangement was the strongest prognostic factor for EFS, followed by age, WBC count, and prednisone response. CONCLUSION Early intensification with postinduction myeloid-type chemotherapy courses did not significantly improve outcome for infant ALL compared with the lymphoid-type course IB. Outcome for infant ALL in Interfant-06 did not improve compared with that in Interfant-99.

The Impact of Rituximab and Radiotherapy On Treatment Outcome of Patients with DLBCL and Skeletal Involvement

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 690-690
Author(s):  
Gerhard Held ◽  
Samira Zeynalova ◽  
Niels Murawski ◽  
Marita Ziepert ◽  
Barbara Kempf ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Event Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Skeletal Involvement ◽  
The Impact

Abstract Abstract 690 Background: There is limited information on the role of skeletal involvement in DLBCL patients treated with rituximab. Methods: In a retrospective subgroup analysis patients with aggressive B-cell lymphomas with and without skeletal involvement were compared with respect to clinical presentation, event-free and overall survival. Results: Of 3840 patients 292 (7.6%) had skeletal involvement. In a multivariable analysis of patients treated within the randomized MInT and RICOVER-60 trials, the two largest randomized trials addressing the role of rituximab in DLBCL to date, skeletal involvement was associated with a reduced hazard ratio (HR) of 0.8 (p=0.181) for event-free survival and 0.7 (p=0.083) for overall survival for patients treated without, but with an increased HR (1.5; p=0.048) for event-free and (1.1; p=0.828) for overall survival in patients treated with rituximab. This was due to the failure of rituximab to improve the outcome of patients with skeletal involvement. In the MInT trial, the 3-year EFS rates were 64% without and 63% with rituximab (p=0.680) and the 3-year OS rates were 83% without and 90% with rituximab (p=0.542). similarly, in the RICOVER-60 trial, the 3-year EFS rates were 45% without and 50% with rituximab (p=0.593) and the 3-year OS rates were 68% without and 68% with rituximab. In a Cox regression model for event-free survival adjusted for the IPI risk factors a relevant interaction (HR 1.5; p=0.056) term between rituximab and skeletal involvement was observed. In contrast to rituximab, additive radiotherapy to sites of skeletal involvement was associated with a better outcome: 3-year EFS rates were 40% without and 75% with radiotherapy (p<0.001), 3-year OS rates were 70% without and 86% with radiotherapy to sites of skeletal involvement (p=0.064). In a multivariable analysis radiotherapy reduced the risk for an event in EFS by 70% (HR=0.3; p=0.001) and by 50% in OS (HR=0.5; p=0.111). Conclusion: Addition of rituximab failed, but radiotherapy to sites of skeletal involvement did improve the outcome of DLBCL patients with skeletal involvement. Radiotherapy to sites of skeletal involvement, though abandoned by many cooperative groups world-wide, is recommended in the rituximab era, unless prospective trials demonstrate that it might be omitted in cases with a negative PET after immunochemotherapy. Disclosures: Dreyling: Roche: Membership on an entity's Board of Directors or advisory committees. Hallek:Roche: Membership on an entity's Board of Directors or advisory committees. Schmitz:Chugai: Membership on an entity's Board of Directors or advisory committees. Pfreundschuh:Roche: Membership on an entity's Board of Directors or advisory committees; Chugai: Consultancy.

IPI24: An International Study To Create An IPI For The Event-Free Survival At 24 Months (EFS24) Endpoint For DLBCL In The Immunochemotherapy Era

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 362-362 ◽  
Author(s):  
Matthew J Maurer ◽  
Herve Ghesquieres ◽  
Jean-Philippe Jais ◽  
Thomas E Witzig ◽  
Corinne Haioun ◽  
...  
Keyword(s):  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Individual Risk ◽  
Parameter Estimates ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Bulky Disease ◽  
Free Survival ◽  
Clinical Variables ◽  
Ecog Ps

Abstract We have recently reported that event-free survival at 24 months from diagnosis (EFS24) is a robust endpoint for assessment of disease related outcome for newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-based immunochemotherapy (IC). Patients who achieve EFS24 following IC have a subsequent overall survival that is equivalent to the age and sex matched general population. The IPI was developed in the pre-rituximab era using OS/EFS endpoints. While the IPI is associated with outcome in the IC era, the original survival estimates for the IPI risk groups are outdated. The IPI is also a discrete risk classifier, with only 6 possible groups. Here we remodel the IPI using EFS24 as the endpoint in a large international cohort of patients treated with IC. This model provides an individual level 0-100% risk of failing to achieve EFS24 for each patient and can be used for patient prognosis, treatment stratification, and risk assessment. Methods Newly diagnosed DLBCL patients treated with immunochemotherapy from the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource, NCCTG N0489 clinical trial, GELA LNH2003B program, and a Lyon, France based hospital registry were included in the original EFS24 study. Patients with a relapse, progression, unplanned re-treatment, or death due to any cause within 730 days of diagnosis were considered a failure for the EFS24 endpoint. Patients alive and progression/relapse free at 730 days from diagnosis with no subsequent treatment following initial IC were considered a success for the EFS24 endpoint. Variables selected for potential model inclusion were the IPI components (age, stage, ECOG PS, number of extranodal sites, and LDH), as well as standard clinical variables typically reported in studies of DLBCL: presence of B-symptoms, bone marrow involvement, bulky disease (>10 cm), and sex. The IPI24, a prognostic model for EFS24, was developed using logistic regression models. Model building began by fitting the classic IPI score (0-5), then allowing individual IPI variables to carry different model weights and number of categories, followed by dropping insignificant variables, finally adding any additional significant variables. Model performance was assessed using bias corrected c-statistics, AIC, and R2 values. Model selection was done using the complete case set with multiple imputation on the full dataset used to refine parameter estimates for the final model. Results 1596 total patients were available for modeling. The median age was 62 (range 18-93) and 53% were male; 33% were IPI 0-1, 25% were IPI 2, 25% were IPI 3, and 17% were IPI of 4-5. The failure rate for achieving EFS24 was 29%. All variables but sex (p=0.33) were univariately associated with EFS24 (p<6.4x10-5). The original IPI had good prognostic ability for EFS24 (c=0.696, p=2.2x10-32). Allowing multiple categories for ECOG PS, stage, and age (continuous) improved model fit and prognostic ability (c=0.727). The number of extranodal sites was not significant when IPI variables were modeled separately and was removed from the model. Sex and bulky disease were additional significant variables when added to the model. Thus, the final IPI24 model contained the following risk predictors: male sex, ECOG PS (0 vs. 1 vs 2 vs 3-4), stage (I vs. II, vs. III vs. IV), LDH (elevated vs. normal range), bulky disease > 10cm, and age (continuous). This model resulted in improved fit and prognostic ability (c=0.749) over the standard IPI (c=0.696, bootstrap p<0.001). Model validation was performed on an additional 158 patients from the SPORE MER and showed good concordance (c=0.697). Additional validation is planned in a larger set of independent patients. Conclusion The IPI24, generated using standard clinical variables, yields an individual risk prediction for failing to achieve EFS24 following IC for treatment of DLBCL. The IPI24 has superior prognostic ability to the standard IPI and can be implemented in the clinic using a nomogram or as a simple electronic application. Disclosures: No relevant conflicts of interest to declare.

Primary Splenic Diffuse Large B-Cell Lymphoma (PS-DLBCL): Splenectomy Improves Survival

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4439-4439 ◽  
Author(s):  
Osnat Bairey ◽  
Lev Shvidel ◽  
Chava Perry ◽  
Eldad J Dann ◽  
Rosa Ruchlemer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Stage I ◽  
Event Free Survival ◽  
Ecog Performance Status ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
The Mean ◽  
Ecog Ps

Abstract Introduction: Although the spleen is involved in about a third of patients with non-Hodgkin's lymphoma (NHL), primary splenic diffuse large B-cell lymphoma (PS-DLBCL) is rare having a reported incidence of less than 1% of all NHL. Most of the described series include small numbers of patients before the rituximab era and the role of splenectomy treatment in addition to immuno-chemotherapy is unknown. Methods: Data were retrospectively collected for 87 patients (pts) with PS-DLBCL treated in 7 medical centers in Israel during the years 1982-2013. Patients presenting with systemic disease with splenic involvement or those having a diagnostic biopsy from other nodal or extranodal disease were excluded. Results: The mean age was 59.6 years (range, 24-89 years); 57.5% were male. Abdominal pain was reported in 61 pts (81%), B symptoms in 49 pts (59%), ECOG performance status 0 - 1 in 85%. Stage I disease was recorded in 28%, II in 33%, III in 18%, and IV in 21%. Thrombocytopenia (<100,000/µl) was recorded in only 6 pts. Lactic dehydrogenase levels (LDH) were elevated in 69 pts (84%). Favorable International Prognostic Index (IPI) 0-2 was recorded in 62 pts (72%). The mean splenic length was 17.34±6 cm (range 7- 37 cm) and the mean splenic weight was 1216 gm±1243 gm (range 180-6000 gm). A splenic mass was found in 97% of pts, and its mean size was 9.26 cm (range 3-18 cm). The diagnostic procedure was core needle biopsy in 46 pts and splenectomy in 39 pts: 27 underwent open splenectomy and 12 laparoscopic splenectomy. Splenectomized pts had lower IPI (p<0.05) and lower stage (p<0.05) compared to non-splenectomized pts. Treatment: The CHOP regimen was given to 80 pts (92%), DA-EPOCH was given to 2 pts (2%) and 5 pts (6%) received other regimens. Rituximab was given to 68 pts (78%). Complete response was achieved in 67 pts (80%) and partial response in 8 (9%). Relapse occurred in 17 pts (22%). Survival: The median follow-up time was 7 years (range 0-19.4 years). During this period 24 pts died (27.5%). The 5-year overall survival (OS) was 76.6±4.9% and 5-year event-free survival (EFS) 67.2±5.5%. Splenectomy at diagnosis improved survival: the 5-year EFS was 85.4±6% and 54.7±8% for splenectomized and non-splenectomized pts respectively (p=0.02) and the 5-year OS was 91.2±5% and 67.9±7% respectively (p=0.08). For the 53 pts with stage I-II disease, both 5-year EFS and OS were better in the splenectomized pts (p<0.02, Fig 1). The 5-year EFS and OS in pts with stage I and II disease that were splenectomized at diagnosis was 89.6±6% and 96.4±3.5% as compared with 50.5±11% and 63.2±11% in pts who were not splenectomized (p=0.012 and 0.009). The EFS and OS were not influenced by the stage of the disease. Overall survival was associated with B symptoms (p=0.02), weight loss (p=0.04) and ECOG performance status (p=0.03). In a multivariate model, low ECOG PS and splenectomy independently predicted a better EFS (p=0.03 and 0.02 respectively), however for OS, low ECOG PS independently predicted better OS (p=0.03), while splenectomy had only marginal effect on the OS (p=0.056). Conclusions: In our group of pts, PS-DLBCL generally presented with abdominal pain, high LDH and a splenic mass. We demonstrate for the first time that splenectomy at diagnosis improves survival in early stages of PS-DLBCL. Our study is a retrospective one. Therefore, until prospective studies prove that early splenectomy in PS-DLBCL is beneficial in terms of overall survival, the risk and benefit of performing splenectomy should be weighed for each patient. Fig 1: (A) Event-free survival and (B) Overall survival in patients with primary splenic DLBCL and stages I - II disease who did or did not undergo splenectomy at diagnosis. Fig 1:. (A) Event-free survival and (B) Overall survival in patients with primary splenic DLBCL and stages I - II disease who did or did not undergo splenectomy at diagnosis. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Prerequisites to improvement of predictive model of childhood Hodgkin’s lymphoma

2015 ◽  
Vol 6 (4) ◽  
pp. 13-18
Author(s):  
Svetlana Aleksandrovna Kulyova ◽  
Andrei Petrovich Karitsky ◽  
Svetlana Viacheslavovna Ivanova
Keyword(s):  
Overall Survival ◽  
Hodgkin’S Lymphoma ◽  
Roc Analysis ◽  
Risk Group ◽  
Survival Rates ◽  
Late Results ◽  
Tumor Burden ◽  
Hodgkin's Lymphoma ◽  
Event Free Survival ◽  
Free Survival

Background. Calculation of relative tumor burden in Hodgkin’s lymphoma patients is the simplest and significant parameter which can be used in daily clinical practice as a risk factor. The aim of study was the assessment of influence of relative tumor burden on the late results of a disease. Material and methods. This research included data on 126 patients with Hodgkin’s lymphoma aged from 0 till 18 years (middle age of 11 years), treated risk-adapted treatment according to the DAL-HD and SPBLH-05. Boys was 70, girls - 56 (a ratio 1,25 : 1). Fifty-eight patients (46 %) are stratified in favorable risk group, 50 (39,7 %) - in intermediate risk group, and 50 (39,7 %) are included in unfavorable risk group. Results. Overall survival at 5 years was 93 % (range 91-95 %), event-free survival - 88 % (85-91 %). The average relative tumor burden was 129,4 cm3/m2 (7-609,7 cm3/m2). When carrying out ROC-analysis value of 122,7 cm3/m2 (р ˂ 0,0001) appeared the critical parameter, which worsen the prognosis of a disease. Overall survival in a patients cohort with this volume was 69,6 %, with the volume less than 122,7 cm3/m2 overall survival was 97,2 % (р = 0,00002). Conclusions. The relative tumor burden is the parameter which is significantly reducing survival rates in children with Hodgkin’s lymphoma. Opinion on interrelation of clinical and laboratory parameters with “sarkoma’s saturation” or tumor volume as end result of immunological frustration, it is represented the most perspective direction of studying of Hodgkin’s lymphoma.

Rituximab Added αIFN+CHVP Improves the Outcome of Follicular Lymphoma Patients with a High Tumor Burden: to First Analysis of the GELA-GOELAMS FL-2000 Randomized Trial in 359 Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 160-160 ◽  
Author(s):  
Gilles Andre Salles ◽  
Charles Foussard ◽  
Mounier Nicolas ◽  
Morschhauser Franck ◽  
Doyen Chantal ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Response Rate ◽  
Bone Marrow Involvement ◽  
Tumor Burden ◽  
High Response Rate ◽  
Response To Therapy ◽  
High Tumor Burden ◽  
Classical Association ◽  
Anti Cd20 ◽  
Ecog Ps

Abstract The monoclonal anti-CD20 antibody rituximab has been shown to induce a high response rate in follicular lymphoma patients and to improve the outcome when associated with CVP or CHOP in newly diagnosed patients. Rituximab synergy with αIFN has also been established in experimental and clinical studies. In order to investigate the benefit of rituximab when added to the classical association of αIFN with CHVP (cyclophosphamide 600 mg/m2, doxorubicin 25 mg/m2, etoposide 100 mg/m2 on day 1 and prednisone 40 mg/m2 day 1–5), the intergroup GELA-GOELAMS FL-2000 trial was initiated. Inclusion criteria consisted in untreated histologically proven stage II-IV follicular lymphoma (any grade) patients (18–75 years) with a high tumor burden consisting in the presence of at least one of the following criteria: B symptoms presence; ECOG PS≥1; LDH>normal value; β2-microglobulin≥3 mg/L; largest tumor≥7cm; three distinct nodes≥3cm; serous effusion, compression or symptomatic splenomegaly). Treatment in arm A consisted in CHVP (6 monthly courses + 6 courses every 2 months) associated with αIFN-2a (4.5 MU [reduced at 3 MU > 70 years] 3 times a week) for 18 months and in arm B in 6 monthly courses of CHVP associated with 18 months of αIFN-2a combined with 6 infusions of 375 mg/m2 rituximab (Day 1 and 8 course 3 & 4 ; day 1 courses 5 & 6). Patients were evaluated for response at 6 months and 18 months and followed every 3 months. From 05/2000 until 05/2002, 359 eligible patients were included (Arm A 175 pts and Arm B 184 pts) with the following characteristics: M/F =1; median age =60 years [25–75]; ECOG>1 =8%; B symptoms =27%; AA stage>II =87%; bone marrow involvement =58%; β2−m≥3mg/L =31%; LDH>N =37%; Hb≤12g/dL =18%; the FLIPI score was ≥3 in 56% of patients. This first analysis of all patients demonstrated a significant improvement of response to therapy in arm B as compared to arm A, both at 6 months [CR+CRru 49% vs. 76%; PR 36% vs. 18%; stable, progression or death 15% vs. 6%; respectively (P<.0001)] and at 18 months [CR+CRu 79% vs. 63%; PR 5% vs. 10%; stable, progression or death 17% vs. 27%; respectively (P=.004)]. With a median follow-up of 30 months, the median EFS was not reached in both arms and 104 patients presented an event. In the control arm, estimated 2.5 years EFS is of 62% versus 78% in arm B (P=.003). In conclusion, this first analysis indicate that 1) the control arm reproduces earlier results with the same regimen 2) rituximab associated with α-IFN+CHVP induces a higher response rate in high tumor burden FL patients; 3) rituximab addition to αIFN+CHVP allows to reduce the number of CHVP chemotherapy cycles and 4) this rituximab association with αIFN+CHVP results in a marked improvement of event-free survival comparing favorably to the control arm or to other rituximab+chemotherapy combinations.

scholarly journals A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 1638-1645 ◽  
Author(s):  
Stefan Faderl ◽  
Farhad Ravandi ◽  
Xuelin Huang ◽  
Guillermo Garcia-Manero ◽  
Alessandra Ferrajoli ◽  
...  
Keyword(s):  
Older Patients ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Response Rate ◽  
Randomized Study ◽  
Event Free Survival ◽  
Front Line ◽  
Free Survival ◽  
Low Dose Cytarabine

AbstractWe previously reported the feasibility of clofarabine and cytarabine combinations in AML. Questions remain as to (1) the therapeutic advantage of this combination and (2) the role of lower doses of clofarabine and cytarabine in older patients. We have conducted an adaptively randomized study of lower-dose clofarabine with or without low-dose cytarabine in previously untreated patients with AML aged 60 years and older. Patients received 30 mg/m2 clofarabine intravenously daily for 5 days with or without 20 mg/m2 cytarabine subcutaneously daily for 14 days as induction. Consolidation consisted of 3 days of clofarabine with or without 7 days of cytarabine. Seventy patients were enrolled. The median age was 71 years (range, 60-83 years). Sixteen patients received clofarabine and 54 the combination. Overall, 56% achieved complete remission (CR). CR rate was significantly higher with the combination (63% vs 31%; P = .025). Induction mortality was 19% with the combination versus 31% with clofarabine alone (P = .276). The combination showed better event-free survival (7.1 months vs 1.7 months; P = .04), but not overall survival (11.4 months vs 5.8 months; P = .1). Clofarabine plus low-dose cytarabine has a higher response rate than clofarabine alone with comparable toxicity. This trial is registered at www.clinicaltrials.gov as no. NCT00088218.

Total therapy 2 without thalidomide in comparison with total therapy 1: role of intensified induction and posttransplantation consolidation therapies

Blood ◽  
2006 ◽  
Vol 107 (7) ◽  
pp. 2633-2638 ◽  
Author(s):  
Bart Barlogie ◽  
Guido Tricot ◽  
Erik Rasmussen ◽  
Elias Anaissie ◽  
Frits van Rhee ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Response ◽  
Event Free Survival ◽  
Consolidation Chemotherapy ◽  
Free Survival ◽  
Second Transplantation ◽  
Total Therapy ◽  
Dose Response Effect

AbstractPatients with myeloma, treated on the thalidomide arm of total therapy 2 (TT2), had a higher complete response (CR) rate and improved event-free survival (EFS) but not overall survival (OS). To evaluate the benefit of TT2's posttandem autotransplant consolidation chemotherapy and dexamethasone maintenance, outcomes were compared on TT2 without thalidomide (n = 345; median follow-up, 3.5 years) and on predecessor trial TT1 (n = 231; median follow-up, 11.5 years). CR rates were similar (43% vs 41%); however, 5-year estimates of continuous CR (45% vs 32%, P < .001) and 5-year EFS (43% vs 28%, P < .001) were superior with TT2, with a trend for improved OS (62% vs 57%; P = .11). OS was also superior among patients achieving CR and receiving the second transplantation early after the first transplantation. Superior EFS and OS with TT2 versus TT1 was noted in the two thirds presenting without cytogenetic abnormalities (CAs); 4-year posttandem transplantation OS for patients with CAs was 47% with TT1 and 76% with TT2 when combination chemotherapy rather than DEX was applied for consolidation (P = .040). Thus, TT2 (without thalidomide) improved OS of patients without CAs; those with CAs benefited from posttransplantation consolidation chemotherapy. The favorable effects of CR and rapidly sequenced second transplantation attest to the validity of a melphalan dose-response effect in myeloma.

Role of High-Dose Chemotherapy with Autologous Haematopoetic Stem Cell Transplantation for Relapsed or Refractory Hodgkin’s Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5432-5432
Author(s):  
Ambuj Kumar ◽  
Benjamin Djulbegovic ◽  
Heloisa P. Soares
Keyword(s):  
Overall Survival ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Meta Analysis ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Event Free Survival ◽  
Conventional Chemotherapy ◽  
Free Survival

Abstract Background: Hodgkin disease (HD) is a potentially curable lymphoma with overall survival exceeding 60% at 10 years. However, patients with relapsed Hodgkin’s disease have a dismal prognosis when treated with conventional salvage chemotherapy. The primary objective of our systematic review/meta-analysis was to evaluate the efficacy of high-dose chemotherapy and autologous stem-cell transplant (HSCT) versus conventional chemotherapy in patients with relapsed Hodgkin’s disease which has not been done before. Methods: Data search of published studies included Medline (1966–2006), Cochrane library and hand search of references. Studies were included if they were randomized controlled trials of HSCT versus conventional chemotherapy only. Data were extracted on benefits as well as harms (overall survival, event-free survival, and treatment related mortality). All data extraction was done in duplicate independently. Results: Out of 47 identified studies only 2 met the inclusion criteria of the current systematic review. Overall survival was similar for HSCT and conventional chemotherapy arms (see figure 1) with a pooled hazard ratio (HR) of 0.69 (95%CI 0.40, 1.18, p=0.2). However, the event-free survival was better in the HSCT arm than the conventional chemotherapy alone group (HR = 0.59, 95%CI 0.41, 0.85, p=0.005). Treatment related mortality was similar in both groups. (HR = 0.40, 95%CI 0.11, 1.44, p=0.2). Conclusion: Results from our meta-analysis indicate that treatment with HSCT compared with conventional chemotherapy only improves event free survival without excessive toxicity. However, overall survival was not affected by the HSCT therapy. In summary patients with relapsed Hodgkin’s disease should be offered HSCT therapy. Role of transplant in relapsed or resistant hodgkin’s disease Role of transplant in relapsed or resistant hodgkin’s disease

CNS Involvement in Children With Newly Diagnosed Non-Hodgkin’s Lymphoma

2000 ◽  
Vol 18 (16) ◽  
pp. 3018-3024 ◽  
Author(s):  
John T. Sandlund ◽  
Sharon B. Murphy ◽  
Victor M. Santana ◽  
Frederick Behm ◽  
Dana Jones ◽  
...  
Keyword(s):  
Overall Survival ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Large Cell ◽  
Tumor Burden ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Cns Involvement ◽  
Free Survival ◽  
Cns Disease

PURPOSE: To determine the frequency of CNS involvement at diagnosis of non-Hodgkin’s lymphoma (NHL), to characterize its pattern of presentation, and to determine its prognostic significance. PATIENTS AND METHODS: We reviewed the records of 445 children (1975 through 1995) diagnosed with NHL (small noncleaved cell NHL/B-cell acute lymphoblastic leukemia [SNCC NHL/B-ALL], 201 patients; lymphoblastic, 113; large cell, 119; other, 12). Tumor burden was estimated by serum lactate dehydrogenase (LDH) measurement and reclassification of disease stage irrespective of CNS involvement (modified stage). RESULTS: Thirty-six of 445 children with newly diagnosed NHL had CNS involvement (lymphoma cells in the CSF [n = 23], cranial nerve palsy [n = 9], both features [n = 4]), representing 13%, 7%, and 1% of small noncleaved cell lymphoma, lymphoblastic lymphoma, and large-cell cases, respectively. By univariate analysis, CNS disease at diagnosis did not significantly impact event-free survival (P = .095), whereas stage and LDH did; however, children with CNS disease at diagnosis were at 2.0 times greater risk of death than those without CNS disease at diagnosis. In a multivariate analysis, CNS disease was not significantly associated with either overall or event-free survival, whereas both serum LDH and stage influenced both overall and event-free survival. Among cases of SNCC NHL/B-ALL, CNS disease was significantly associated with event-free and overall survival (univariate analysis); however, in multivariate analysis, only LDH had independent prognostic significance. Elevated serum LDH or higher modified stage were associated with a trend toward poorer overall survival among children with CNS disease. CONCLUSION: A greater tumor burden at diagnosis adversely influences the treatment outcome of children with NHL and CNS disease at diagnosis, suggesting a need for ongoing improvement in both systemic and CNS-directed therapy.

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