Maintenance Treatment with Thalidomide after Autologous Transplantation for Myeloma : First Analysis of a Prospective Randomized Study of the Intergroupe Francophone du Myelome (IFM 99 02).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 535-535 ◽  
Author(s):  
Michel Attal ◽  
Jean-Luc Harousseau ◽  
Serge Leyvraz ◽  
Chantal Doyen ◽  
Cyrille Hulin ◽  
...  
Keyword(s):  
Maintenance Treatment ◽  
High Dose ◽  
High Dose Therapy ◽  
Free Survival ◽  
Chromosome 13 ◽  
Dose Therapy ◽  
Autologous Transplant ◽  
Beta 2 ◽  
The Impact ◽  
To Receive

Abstract High dose therapy (HDT) supported with autologous stem cell transplantation has been introduced in the management of aggressive myeloma. However, after single or tandem transplantation, almost all patients ultimately relapse. New strategies are required to control any residual disease after HDT. The Intergroupe Francophone du Myelome (IFM) initiated a trial designed to evaluate the impact of maintenance treatment with Thalidomide on the duration of response after HDT. From April 2000 to October 2003, 1004 myeloma patients at diagnosis under the age of 65 years were enrolled in the IFM 99 protocol. 780 of them, without or with only one adverse prognostic factor (beta-2 microglobuline >3 mg/l or deletion of chromosome 13), were enrolled in the IFM 99 02 protocol. They were to receive the following treatment: 1) 3–4 cycles of the VAD regimen; 2) a first autologous transplant prepared with Melphalan 140 mg/m2; 3) a second autologous transplant prepared with Melphalan 200 mg/m2. Patients without progressive disease 2 months after the second transplant were randomized to receive: no maintenance treatment (arm A), maintenance treatment with Pamidronate (arm B) or maintenance treatment with Thalidomide and Pamidronate (arm C). As of May 2004, 580 patients (74%) have been randomized: 195 in arm A, 190 in arm B and 195 in arm C. Clinical characteristics of each group were similar. The median follow-up from diagnosis was 26 months (range: 6–50) Thalidomide was found to improve the Progression-free survival (PFS; p<0.007) and the Event-free-survival (EFS; p<0.01). Indeed, the 40-months post-diagnosis probability of PFS was 70% (95% CI= 42–80) in the Thalidomide arm versus 53% (95% CI= 37–65) in arm A, and 52% (95% CI= 36–68) in arm B. Most patients (60%) enrolled in arm A and B received Thalidomide at time of relapse. The overall survival was similar in the 3 treatment groups. Among the 580 randomized patients, 2 factors were found to be associated with a longer EFS : low beta-2-microglobulin at diagnosis (p<0.01) and treatment arm (p<0.01). Deletion of chromosome 13 (FISH analysis) was not related to EFS. In conclusion, the first analysis of the IFM9902 trial strongly suggests that Thalidomide is an effective maintenance treatment after high dose therapy for myeloma. The next analysis (November 2004) will be presented during the meeting.

Maintenance Treatment with Thalidomide after Autologous Transplantation for Myeloma: Final Analysis of a Prospective Randomized Study of the “Intergroupe Francophone du Myelome”.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1148-1148 ◽  
Author(s):  
Michel Attal ◽  
Jean-Luc Harousseau ◽  
Serge Leyvraz ◽  
Chantal Doyen ◽  
Cyrille Hulin ◽  
...  
Keyword(s):  
Maintenance Treatment ◽  
Final Analysis ◽  
High Dose ◽  
High Dose Therapy ◽  
Chromosome 13 ◽  
Treatment Groups ◽  
Autologous Transplant ◽  
Duration Of Response ◽  
Beta 2 ◽  
Beta 2 Microglobulin

Abstract High dose therapy (HDT) supported with autologous stem cell transplantation has been introduced in the management of myeloma. However, after a single or a double transplantation, almost all patients ultimately relapse. New strategies are required to control the residual disease after HDT. The “Intergroupe Françophone du Myélome” (IFM) initiated a trial designed to evaluate the impact of maintenance treatment with Thalidomide on the duration of response after HDT. From April 2000 to October 2003, 1017 myeloma patients at diagnosis under the age of 65 years were enrolled in the IFM 99 protocol. 780 of them, without or with only one adverse prognostic factor (beta-2 microglobuline ≥ 3 mg/l or deletion of chromosome 13), were enrolled in the IFM 99 02 protocol. They received the following treatment: 1) 3–4 cycles of the VAD regimen; 2) a first autologous transplant prepared with Melphalan 140 mg/m2; 3) a second autologous transplant prepared with Melphalan 200 mg/m2. Patients without progressive disease 2 months after the second transplant were randomized to receive: no maintenance treatment (arm A), maintenance treatment with Pamidronate (arm B) or maintenance treatment with Thalidomide and Pamidronate (arm C). As of June 2005, 593 patients (76%) have been randomized: 197 in arm A, 195 in arm B and 201 in arm C. Clinical characteristics of each group were similar. The median follow-up from diagnosis was 3 years (1 to 6 y). Thalidomide was found to improve the Event-free-survival (EFS). Indeed, the 4-year post-diagnosis probability of EFS was 39% (95% CI= 29–51) in arm A, 37% (95% CI= 26–48) in arm B, and 50% (95% CI= 37–60) in arm C (p&lt;0.02). We compared EFS according to the treatment groups in different subgroups of patients (beta-2-microglobulin ≤ 2.5 mg/l, beta-2-microglobulin &gt; 2.5 mg/l, deletion of chromosome 13, and no deletion of chromosome 13). Thalidomide was found to improve the 4-year EFS of patients without deletion of chromosome 13 (39% in arm A, 38% in arm B, 52% in arm C, p&lt;0.01) and of patients with a beta-2-microglobulin &gt; 2.5 mg/l at diagnosis (28% in arm A, 21% in arm B, 57% in arm C, p&lt;0.001). On the opposite, patients with a deletion of chromosome 13 or with a beta-2-microglobulin ≤ 2.5 mg/l at diagnosis did not benefit significantly from Thalidomide (p=0.5 and p=0.9, respectively). The 4-year overall survival was similar in the 3 treatment groups: 86% in arm A, 78% in arm B, and 86% in arm C (NS). Among the 593 randomized patients, 3 factors were found to be associated with a longer EFS in the multivariate analysis: low beta-2-microglobulin at diagnosis (p&lt;0.03), treatment arm (p&lt;0.02), and deletion of chromosome 13 (p&lt;0.03). In conclusion, the final analysis of the IFM9902 trial demonstrates that Thalidomide improves the duration of response after high dose therapy among patients with myeloma, especially those who have a beta-2-microglobulin &gt;2.5 mg/l without deletion of chromosome 13.

Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 4008-4010 ◽  
Author(s):  
Raman Desikan ◽  
Bart Barlogie ◽  
Jeffrey Sawyer ◽  
Dan Ayers ◽  
Guido Tricot ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Dose ◽  
Event Free Survival ◽  
High Dose Therapy ◽  
Free Survival ◽  
Chromosome 13 ◽  
Dose Therapy ◽  
Reactive Protein ◽  
Beta 2 Microglobulin

High-dose therapy (HDT) has increased complete remission (CR) rates and survival in multiple myeloma (MM). We now report on continuous CR (CCR) and associated prognostic factors in 1000 consecutive patients receiving melphalan-based tandem HDT. Five-year CCR was 52% among 112 CR patients without chromosome 13 (▵13) abnormalities and with beta-2-microglobulin ≤ 2.5 mg/L, C-reactive protein ≤ 4 mg/L, and pre-HDT standard chemotherapy ≤ 12 months. Of all 390 CR patients without ▵13 abnormalities, 35% enjoyed 5-year CCR but none of 54 with ▵13 abnormalities. ▵13 abnormalities, present in overall 16%, reduced 5-year event-free survival from 20% to 0% and overall survival from 44% to 16% (both P < .0001). CR and a second HDT cycle applied within 6 months both extended event-free and overall survival significantly, justifying further pursuit of HDT, especially toward curing non-▵13 MM.

Polymorphic variation in GSTP1 modulates outcome following therapy for multiple myeloma

Blood ◽  
2003 ◽  
Vol 102 (7) ◽  
pp. 2345-2350 ◽  
Author(s):  
Ranjit K. Dasgupta ◽  
Peter J. Adamson ◽  
Faith E. Davies ◽  
Sara Rollinson ◽  
Philippa L. Roddam ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Standard Dose ◽  
Progression Free Survival ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Glutathione S Transferase ◽  
High Dose Therapy ◽  
Free Survival ◽  
Dose Therapy ◽  
The Impact

Abstract Glutathione S-transferase P1 (GSTP1) is a phase 2 drug metabolism enzyme involved in the metabolism and detoxification of a range of chemotherapeutic agents. A single nucleotide polymorphism (Ile105Val) results in a variant enzyme with lower thermal stability and altered catalytic activity. We hypothesized that patients with the less stable variant have a decreased ability to detoxify chemotherapeutic substrates, including melphalan, and have an altered outcome following treatment for multiple myeloma. We have assessed the impact of GSTP1 codon 105 polymorphisms in 222 patients entered into the Medical Research Council (MRC) myeloma VII trial (comparing standard-dose chemotherapy with high-dose therapy). In the standard-dose arm, patients with the variant allele (105Val) had an improved progression-free survival (PFS) (adjusted hazard ratios for PFS were 0.55 for heterozygotes and 0.52 for 105Val homozygotes, compared with 105Ile homozygotes; P for trend = .04); this was supported by a trend to improved overall survival, greater likelihood of entering plateau and shorter time to reach plateau in patients with the 105Val allele. No difference in outcome by genotype was found for patients treated with high-dose therapy. However, the progression-free survival advantage of the high-dose arm was seen only in patients homozygous for 105Ile (P = .008). (Blood. 2003;102:2345-2350)

Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 4008-4010 ◽  
Author(s):  
Raman Desikan ◽  
Bart Barlogie ◽  
Jeffrey Sawyer ◽  
Dan Ayers ◽  
Guido Tricot ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Dose ◽  
Event Free Survival ◽  
High Dose Therapy ◽  
Free Survival ◽  
Chromosome 13 ◽  
Dose Therapy ◽  
Reactive Protein ◽  
Beta 2 Microglobulin

Abstract High-dose therapy (HDT) has increased complete remission (CR) rates and survival in multiple myeloma (MM). We now report on continuous CR (CCR) and associated prognostic factors in 1000 consecutive patients receiving melphalan-based tandem HDT. Five-year CCR was 52% among 112 CR patients without chromosome 13 (▵13) abnormalities and with beta-2-microglobulin ≤ 2.5 mg/L, C-reactive protein ≤ 4 mg/L, and pre-HDT standard chemotherapy ≤ 12 months. Of all 390 CR patients without ▵13 abnormalities, 35% enjoyed 5-year CCR but none of 54 with ▵13 abnormalities. ▵13 abnormalities, present in overall 16%, reduced 5-year event-free survival from 20% to 0% and overall survival from 44% to 16% (both P &lt; .0001). CR and a second HDT cycle applied within 6 months both extended event-free and overall survival significantly, justifying further pursuit of HDT, especially toward curing non-▵13 MM.

scholarly journals High-dose therapy and autologous peripheral blood stem cell transplantation for patients with lymphoma

Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1260-1265 ◽  
Author(s):  
A Kessinger ◽  
JO Armitage ◽  
DM Smith ◽  
JD Landmark ◽  
PJ Bierman ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Event Free Survival ◽  
High Dose Therapy ◽  
Free Survival ◽  
Dose Therapy

Abstract Forty patients with refractory Hodgkin's disease (24 patients) or non- Hodgkin's lymphoma (16 patients) who were considered for high-dose therapy but not for autologous bone marrow transplantation (ABMT) due to BM metastases, previous pelvic irradiation, a history of marrow involvement by tumor or hypocellular marrow in conventional harvest sites received high-dose therapy and autologous peripheral blood (PB) hematopoietic stem cell transplantation. Disappearance of circulating neutrophils and development of RBC and platelet transfusion-dependence was followed, in the evaluable patients, by reappearance of 0.5 x 10(9)/L circulating granulocytes and sufficient platelets to obviate the need for platelet transfusions at a median of 25 days after transplantation. Twenty-three patients experienced a clinical complete remission (CR). The projected 2-year event-free survival was 24% for all 40 patients and 49% for the non-Hodgkin's lymphoma patients. The projected 18-month event-free survival for the Hodgkin's disease patients was 15%. PB stem cell transplantation provided an opportunity to administer high-dose salvage therapy to patients with refractory lymphoma who otherwise were not candidates for such therapy. For some of those patients, the high-dose therapy produced prolonged survival, free of tumor progression.

Can High Dose Therapy Change the Course of Low Grade Lymphoma? A Study Considering Patients as Their Own Control.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1882-1882
Author(s):  
Stephane Vignot ◽  
Nicolas Mounier ◽  
Guillaume Sergent ◽  
Pauline Brice ◽  
Jean-Pierre Marolleau ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Tumor Burden ◽  
High Dose ◽  
Low Grade ◽  
High Dose Therapy ◽  
Free Survival ◽  
Dose Therapy ◽  
New Strategy ◽  
Disease Free

Abstract Low grade lymphoma patients (pts) have an indolent evolution with median survival ranging between 8–10 years. During disease’s course, high dose therapy (HDT) and autologous stem-cell transplantation (ASCT) can be considered as an alternative to sequential chemotherapies. However, efficacy of this strategy remains controversial. The purpose of our study is to evaluate ASCT efficacy by comparing retrospectively for each pts disease free survival (DFS) after ASCT with DFS observed with pts’ last chemotherapy regimen (LCR) just before intensification. Between apr 1988 and feb 2002, 109 low grade lymphoma pts were treated with HDT and ASCT in our department, 61 were male, the median age was 49 yrs [range 28–65]. Histological subtypes were mostly follicular small cell (86 %). At time of diagnosis, LDH were normal for 85 pts; 60 pts had high tumor burden. IPI was 0 for 16 %, 1 for 70 % and 2 for 14 %. Prior to ASCT, pts had experienced a median of 2 progressions (range 1 to 5). At time of graft, 102 pts present complete or partial response and 7 pts present stable disease. Two principal intensification chemo regimens were used before ASCT: VP16/cyclophosphamide in 84 pts and BEAM in 12. TBI was associated for 86 pts. At June 2002, the median follow up was 6.4 yrs from diagnosis and 4.5 yrs from ASCT. 3 years after ASCT, survival rate was 72 % and DFS rate was 50 %. Median DFS decreased with nb of progression (p=0.02): Median DFS according to nb of progression Nb of progression 1 2 3 > 3 Nb pts (%) 17 (16) 57 (52) 28 (26) 7 (6) Median DFS in yrs 6.4 5.1 1.8 1.0 Considering pt with more than 1 progression (n=92) as his own control, DFS was longer after ASCT than after LCR for 61 % of pts. Median DFS was 2.5 yrs after ASCT and 2.0 yrs after LCR. At 3 yrs, DFS rate was 48 % after ASCT and 37 % after LCR (p<0,001): Figure Figure This study demonstrates that HDT and ASCT significantly increase DFS in comparison with the LCR for low grade lymphoma patients. Such methodology could be useful to evaluate new strategy incorporating monoclonal antibody.

Evaluation of the Impact of Three Different Pre-Transplant Strategies On the Outcome of Myeloma Patients Candidates to High-Dose Therapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1223-1223
Author(s):  
Alessandro Corso ◽  
Silvia Mangiacavalli ◽  
Luciana Barbarano ◽  
Annalisa Citro ◽  
Paola Brasca ◽  
...  
Keyword(s):  
Patient Flow ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Oral Dexamethasone ◽  
Group 3 ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Abstract Abstract 1223 Poster Board I-245 Introduction This study aimed at evaluating the impact of three different pre-transplant therapies on the outcome of patients (pts) eligible for high-dose therapy. Methods two-hundred sixty eight newly diagnosed MM pts aged £65 years, Durie-Salmon stage III, II, or I in progression, were consecutively enrolled from 2000 to 2007 in three different protocols, with three different pre-transplant therapy: Group 1: (145 pts) 3 pulse-VAD cycles; Group 2: (67 pts) 3 pulse-VAD cycles plus 3 Thal-Dex cycles (thalidomide at the dose of 100 mg/day orally at bedtime, continuously for 3 months, oral dexamethasone at the dose of 20 mg on days 1-4 and 14-17 every 28 days); Group 3: (57pts) 4 Vel-Dex courses (Bortezomib 1.3 mg/m2 i.v. on days 1, 4, 8, 11; oral Dexamethasone 40 mg on days 1-4 and 8-11 every 3 weeks). After induction all pts received two DCEP-short cycles as mobilization (oral Dexamethasone 40 mg/day on days 1-4 + Cyclophosphamide 700 mg/m2/day i.v., Etoposide 100 mg/ m2/day i.v., cisPlatin 25 mg/m2/day for 2 days) with peripheral blood stem-cell (PBSC) collection prompted by G-CSF followed by one or two transplants (Tx) with melphalan 200 mg/m2 as conditioning regimen. Response was defined according to IMWG uniform criteria. Pts were considered responsive when obtaining at least a PR. Results pts in the three group were similar for age, gender, Ig type, ISS stage. A significant higher percentage of Durie and Salmon stages III was found in group 3 (83% vs 68% in group 1 and 67% in group 2, p=0.0002). The median follow-up was 46 (1-150) months for group 1, 43 (1-68) months for group 2, and 29.7 (1-79) months for group 3. At the time of this analysis in the three groups 51%, 65%, 90% of transplanted pts respectively were still alive, and progression after transplant was registered in 84%, 80%, 50% respectively. Patient flow before Tx was similar (p=0.45): 19% in group 1, 27% in group 2, 23% in group 3. In group 1, 2% of pts went off-study after VAD, and 17% after mobilization phase. In group 2, patient flow was equally distributed: 7% after pulse VAD, 10% after thal-dex, 9% after DCEP. In group 3, 12% of the pts went off-study after Vel-Dex, 11% after DCEP. Table 1 summarized responses. In group 3 (Vel-Dex) response was better along all protocol phases with respect to group 1 or 2 (p<0.00001). The number of responsive pts progressively increased from 87% after Vel-Dex (CR 31%), to 96% after transplant (CR 38%). Response rates of group 1 and 2 patients were not significantly different either after induction (p=0.6), after DCEP (p=0.5), and after Tx (p=0.65). On intention to treat basis, vel-dex induction produced a better, although not significant, PFS (34.6 months vs 29 in group 1 and 26.8 in group 2, p=0.56). OS were not statistically different among the three groups, event though the different follow-up could affect the analysis (median OS 110 in group 1, 66 months in group 2, and not reached in group 3, p=0.37). In multivariate analysis PFS was improved only by the achievement of CR (p=0.001). No significant difference was observed between VGPR or PR (p=0.43). Conclusion In this study, only CR not VGPR impacts on the outcome. Vel-Dex producing a significant high CR rate after TX (38%), seems to improve survival of MM patients candidate to high-dose therapy with respect to conventional pre-transplant strategies. Disclosures Morra: Roche:.

Autotransplants for Multiple Myeloma (MM) – An Update of the Arkansas Experience Since 1989 In Almost 4000 Patients with Special Emphasis on Third and Further Transplants.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1352-1352
Author(s):  
Bijay Nair ◽  
Elias J. Anaissie ◽  
Sarah Waheed ◽  
Yazan Alsayed ◽  
Rachael Sexton ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Outcome Data ◽  
Hematopoietic Progenitor Cell ◽  
High Dose ◽  
Front Line ◽  
High Dose Therapy ◽  
Free Survival ◽  
Treatment Groups ◽  
Dose Therapy ◽  
Previously Treated

Abstract Abstract 1352 Background: The Arkansas program has emphasized high hematopoietic progenitor cell (HPC) yields since its inception in 1989, in order to enable further high-dose therapy for relapse, rescue patients from hematopoietic compromise due to extensive cumulative genotoxic or novel agent dosing, and provide a fall-back option in the case MDS develops. Here we are examining the overall outcome data among 3888 patients undergoing HPC-supported therapy since 1989. Patients and Methods: Patients were grouped according to whether they received front-line Total Therapy (TT) protocols (TT-P, n=1452), non-TT protocols for previously treated MM (non-TT-P, n= 1155) or non-protocol therapies (non-P, n=1281). Overall survival (OS) and event free survival (EFS) were measured from the 1st high-dose therapy (Tx-1) intervention and examined in the context of baseline variables present prior to Tx-1, the aforementioned 3 treatment groups, and intervals between successive Tx interventions. Results: OS/EFS from Tx-1 was longest with TT-P (5-yr estimates, 67%/52%) followed by non-TT-P (5-yr estimates, 43%/30%) and non-P (5-yr estimates, 36%/27%) (p<0.0001, p<0.0001). Among all 3888 patients, 2773 (71%) received Tx-2 including 2385 (86%) within 6 months of Tx-1; 405 (10%) received Tx-3 including 140 (35%) within 2yr of Tx-2; 58 (1.5%) received Tx-4 including 44 (76%) within 2yr form Tx-3; 12 (0.3%) received Tx-5 all within 2yr from Tx-4; and 3 patients had Tx-6. When examined in the context of the 3 different treatment groups, 1157/1231 (94%) of the TT-P group had Tx-2 within 6mo, 51/169 (30%) had Tx-3 within 2yr of Tx-2, 51/169 (30%) had Tx-4 within 2yr of Tx-3, and 7/7 (100%) had a Tx-5 within 2 yr of Tx-4. Among 1155 non-TT-P patients, 646/822 (79%) had Tx-2 within 6mo of Tx-1, 37/129 (29%) had Tx-3 within 2yr of Tx-2, 14/18 (78%) had Tx-4 within 3yr of Tx-3, and all 4 (100%) receiving Tx-5 had done so within 2yr of Tx-4. Among 1281 non-P patients, 582/720 (81%) had received Tx-2 within 6mo of Tx-1, 52/107 (49%) had received Tx-3 within 2yr of Tx-2, 7/10 (70%) had received Tx-4 within 2yr of Tx-3, and 1 patient received Tx-5 within 2yr of Tx-4. KM plots from Tx-3 were similar among the 3 treatment groups with median OS of 16mo for TT-P, 14mo for non-TT-P and 11mo for non-P (p=0.13); median EFS were 7, 8, and 6 months (P=0.17). Timely application within 6mo resulted in superior OS and EFS from Tx-2 (OS: 79 v 23 months, EFS: 48 v 14 months; both P<0.0001). Multivariate Cox analyses examining post-Tx EFS and OS revealed TT-P superiority from Tx-1 and Tx-2 over non-TT-P and non-P; Tx-2 within 6mo of Tx-1 provided superior post-Tx-2 EFS and OS; while benefit from Tx-3 was not apparent until at least 2yr had elapsed since Tx-2. CA within 1 year of Tx-1 adversely affected EFS and OS from Tx-1, Tx-2 and Tx-3. Other adverse baseline parameters included low albumin for EFS and OS post-Tx-1; and B2M >=3.5mg/L for EFS and OS post-Tx-1 and post-Tx-2. Conclusions: We confirm that front-line TT-P provides superior clinical outcomes in comparison with back-up/salvage non-TT-P and non-P Tx, emphasizing the benefit from planned upfront protocol therapy. Timely application of Tx-2 within 6 months of Tx-1 extended both EFS and OS from Tx-2, validating our concept of maximum tumor cyto-reduction and avoiding MM re-growth. Tx-3 was useful when applied beyond 2yr from Tx-2, in support of the notion that longer disease control prior to relapse favorably impacts subsequent salvage Tx. Disclosures: No relevant conflicts of interest to declare.

High-Dose Therapy and Autologous Stem-Cell Transplantation Versus Conventional-Dose Consolidation/Maintenance Therapy as Postremission Therapy for Adult Patients With Lymphoblastic Lymphoma: Results of a Randomized Trial of the European Group for Blood and Marrow Transplantation and the United Kingdom Lymphoma Group

2001 ◽  
Vol 19 (11) ◽  
pp. 2927-2936 ◽  
Author(s):  
John W. Sweetenham ◽  
Gino Santini ◽  
Wendi Qian ◽  
Monica Guelfi ◽  
Norbert Schmitz ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Induction Therapy ◽  
Lymphoblastic Lymphoma ◽  
High Dose ◽  
Relapse Free Survival ◽  
High Dose Therapy ◽  
Free Survival ◽  
Dose Therapy ◽  
Conventional Dose ◽  
Postremission Therapy

PURPOSE: To determine whether a combination of high-dose therapy and autologous stem-cell transplantation (ASCT) is superior to conventional-dose consolidation and maintenance chemotherapy as postremission therapy in adults with lymphoblastic lymphoma. PATIENTS AND METHODS: One hundred nineteen patients were entered onto this prospective randomized trial from 37 centers. Patients received standard remission induction therapy, and responding patients were randomized either to continue with a conventional consolidation/maintenance protocol (CC) or to receive high-dose therapy and ASCT. In some centers, patients with HLA-identical sibling donors were registered on the trial but proceeded to allogeneic bone marrow transplantation (BMT) without randomization. RESULTS: Of the 119 patients entered, 111 were assessable for response to induction therapy. The overall response rate was 82% (56% complete response, 26% partial response). Of the 98 patients eligible for randomization, 65 were randomized, 31 to ASCT and 34 to CC. Reasons for failure to randomize included patient refusal (12 patients), early progression or death on induction therapy (eight patients), excessive toxicity of induction regimen (six patients), and elective allogeneic BMT (12 patients). With a median follow-up of 37 months, the actuarial 3-year relapse-free survival rate is 24% for the CC arm and 55% for the ASCT arm (hazards ratio = 0.55 in favor of the ASCT arm; 95% confidence interval [CI], 0.29 to 1.04; P = .065). The corresponding figures for overall survival are 45% and 56%, respectively (hazards ratio = 0.87 in favor of the ASCT arm; 95% CI, 0.42 to 1.81; P = .71). CONCLUSION: The use of ASCT in adults with lymphoblastic lymphoma in first remission produced a trend for improved relapse-free survival but did not improve overall survival compared with conventional-dose therapy in this small randomized trial.

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