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 ◽  
...  

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.

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 4008-4010 ◽  
Author(s):  
Raman Desikan ◽  
Bart Barlogie ◽  
Jeffrey Sawyer ◽  
Dan Ayers ◽  
Guido Tricot ◽  
...  

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.


Blood ◽  
2006 ◽  
Vol 108 (8) ◽  
pp. 2540-2544 ◽  
Author(s):  
Catherine Sebban ◽  
Nicolas Mounier ◽  
Nicole Brousse ◽  
Coralie Belanger ◽  
Pauline Brice ◽  
...  

AbstractThe purpose of this study is to compare our standard chemotherapy regimen (CHVP [cyclophosphamide, doxorubicin, teniposide, and prednisone]) plus interferon with 4 courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by high-dose therapy with autologous stem cell transplantation (ASCT) in treatment-naive patients with advanced follicular lymphoma. Four hundred one patients were included from July 1994 to March 2001: 209 received 12 cycles of CHVP plus interferon α for 18 months (CHVP-I arm) and 192 received 4 cycles of CHOP followed by high-dose therapy (HDT) with total body irradiation and ASCT (CHOP-HDT arm). Overall response rates were similar in both groups (79% and 78% after induction chemotherapy, respectively). One hundred thirty-one of the 150 patients eligible for HDT underwent transplantation (87%). Intent-to-treat analysis after a median follow-up of 7.5 years showed that there was no difference between the 2 arms for overall survival (P = .53) or event-free survival (P = .11). Patients with a complete response at the end of the induction therapy had a statistically longer event-free survival and overall survival (P = .02 and < .001, respectively). After long-term follow-up, our study showed that there was no statistically significant benefit in favor of first-line high-dose therapy in patients with follicular lymphoma. High-dose therapy should be reserved for relapsing patients.


Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1260-1265 ◽  
Author(s):  
A Kessinger ◽  
JO Armitage ◽  
DM Smith ◽  
JD Landmark ◽  
PJ Bierman ◽  
...  

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.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1151-1151
Author(s):  
Bart Barlogie ◽  
Guido Tricot ◽  
Athanasios Fassas ◽  
Raman Desikan ◽  
Elias Anaissie ◽  
...  

Abstract Background: Melphalan-based high-dose therapy (HDT) with autologous peripheral blood stem cell support has become the standard of care for newly diagnosed patients with MM, based on IMF90 and MRC7 trial results of single HDT vs. standard-dose therapy and on IMF94 data demonstrating superior EFS and OS with TAT over single HDT. The aim of this report is to provide a detailed account of the long-term outcome of all 231 patients originally enrolled in TT1 between 8/1990 and 6/1995 of whom 63 remain alive. Patients and Methods: Outcome data on TT1 have been reported previously (Blood93, 1999; 101, 2003). Here we give final account of patient status with a median follow-up of 12 years (range, 9–15). Results: Of 231 patients, 195 had received at least 1 and 165 the 2 scheduled transplants; 7 without insurance coverage were given intermediate dose melphalan 70mg/sqm. Of 87 (38%) initially achieving CR (median, 27 mo), 17 (20%) remain in uninterrupted 1st CR. The median EFS duration was 31mo, and 32 (14%) remain continuously event-free. The median OS duration is 68 mo with a 12-yr estimate of almost 30%. Of all 63 survivors, 19% had cytogenetic abnormalities (CA) prior to therapy, and 38% had CA intermittently. Of the 17 patients in continuous CR, 10 never had CA at any time, 4 developed CA subsequently with resolution in 3; of 3 with baseline CA, 2 normalized and 1 persisted. A detailed account of CA type and frequency as well as salvage therapies such as thalidomide, bortezomib and further auto- or allotransplants will be provided. Conclusion: TT1 was the first tandem autotransplant protocol applied to 231 newly diagnosed patients MM that yielded an unprecedented positive outcome with 12-yr rates of CCR, EFS and OS of 20%, 14%, and 30%, respectively. The Figure displays a 3-phasic relapse pattern: an initial steep slope spanning years 1-3, a more shallow slope between years 4 to 10, merging into a cure-consistent “hockey-stick”. Event-Free Survival- TT1 Patients Event-Free Survival- TT1 Patients Overall Survival- TT1 Patients Overall Survival- TT1 Patients


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5489-5489
Author(s):  
Emilio P. Alessandrino ◽  
Letizia Zenone Bragotti ◽  
Anna A. Colombo ◽  
Alessandra Algarotti ◽  
Paolo Bernasconi ◽  
...  

Abstract From 1996 to 2003, 113 consecutive patients with multiple myeloma were treated with four different high dose approaches rescued by autologous peripheral blood progenitor cells (PBPC) after four cycles of VAD or other combinations. The median age was 53 years 31–68), 58% were male and 42% female, the median interval from diagnosis to transplant was 252 days (range 160–3116 days). Twenty-five patients received as preparative regimen Carmustine, Etoposide and Melphalan (BVM) at the total dose of 600 mg/m2, 900mg/m2 and 140–180 mg m2 respectively. Nineteen pts had as preparative regimen Thiotepa and Melphalan at the total dose of 10 mg/kg and 140–180 mg/m2 respectively, 38 pts received a double transplant with Melphalan given as a single agent at the dose of 200 mg/m2, while 31 pts received a single transplant with Melphalan 200 mg/m2. In patients with poor performance status at transplant or previous history of infection or renal impairment, the dose of melphalan was reduced by 20% respect to the standard planned dose. in the group of 25patients treated by BVM, 10 had progressive disease, 6 stable disease (SD), 7 partial remission (PR), 1 very good partial remission (VGPR). At day +90 from transplant, 17 patients were in CR or PR (68%). The actuarial probability of overall survival and event free survival at 5 years were 40% and 20%, respectively. One pt died of transplant, one developed a solid tumor 24 mos after transplant. in the group of 19 pts treated with TT and Mel (TT-Mel), 3 pts were with progressive disease, 3 with stable disease, 6 in partial remission, 3 with minimal response, 3 in VGPR, 1 in CR. At day +90, 15 pts were in CR or PR (78%). The actuarial probability of survival was 50% at 5 years, and event free survival 28%. in the group of 38 pts who received a double transplant, 7 pts were with progressive disease, 3 with stable disease, 14 in PR, 12 in VGPR or CR. At day +90 after the second transplant, 31 of 38 patients (81%) were in CR or PR. Overall survival and event free survival was respectively 48% and 20% at five years. in the group of 31 pts receiving a single transplant with Melphalan alone, 8 were with progressive disease, 1 with stable disease, 6 in VGPR, 1 in CR, 13 in PR. At day +90, 21 of 31 patients (67%) were in CR or PR. Overall survival and event free survival was respectively 45% and 22% at five years. In conclusion, double transplant seems better than one transplant with melphalan alone in terms of EFS and OS (p<0.03); the BVM combination produces high response rates, the regimen, however, is toxic with a high rate of life threatening mucositis. the addition of Carmustine and Vepeside or Thiotepa to Melphalan does not produce significant improvement of OS and EFS.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18550-e18550
Author(s):  
Matthew Risendal ◽  
Allison Hazlett ◽  
Roy T. Sabo ◽  
Priscilla Mpasi ◽  
Joan Bolling ◽  
...  

e18550 Background: Multiple myeloma (MM) is a plasma cell malignancy with variable prognosis depending on disease features such as β2m and cytogenetics. High dose therapy and stem cell transplantation (SCT) remains the current standard of care for MM, however the role of tandem SCT is controversial, particularly in the era of novel induction therapy. Methods: Our program has a practice of risk-stratified transplant allocation in MM patients referred for SCT, those with high-risk (HR) disease (β2m >5.5, adverse cytogenetics, >1st remission) are preferentially assigned tandem SCT, and those with standard risk (SR), a single SCT. Between 2008 and 2011, 129 MM patients underwent SCT, 43% SR patients received a single SCT (SRS), 22% HR received tandem SCT (HRT) & 36% HR a single SCT (HRS). Median age at SCT was 57 years. Maintenance therapy was administered in 51% SRS, 57% HRT & 67% HRS patients. Results: Complete response (CR) or very good partial response was achieved in 0.68, 0.72 and 0.80 for the HRT, HRS, and SRS groups. The HRT group (0.39) was more likely to achieve CR than HRS (0.20) (P=0.02). At a median follow up of 23.4 months, the overall survival for HRS was inferior to SRS (P=0.01) but there was no difference in the overall survival between HRT and SRS cohorts. Two-year survival rates were 0.81, 0.91 and 0.97 in the HRS, HRT and SRS cohorts (HRS vs. SRS P=0.02). This was attributable to a higher 1-year relapse rate in HRS (0.29) compared to HRT (0.07) and SRS (0.07) (P<0.01). Conclusions: Using a risk-stratified allocation system, we report that HR MM patients undergoing tandem SCT have outcomes comparable to SR patients. However, HR MM patients receiving a single SCT have inferior outcomes compared to those with SR. Notably, higher rate of CR and a lower relapse rate were observed in the HRT cohort when compared to HRS. This suggests that greater depth of remission achieved in HR patients undergoing tandem SCT may result in longer time to relapse and survival advantage compared to HR patients receiving a single SCT. In contrast, a single SCT may suffice for SR MM patients. These results demonstrate that risk-stratification based on disease prognostic features is an important treatment consideration when planning high dose therapy in MM patients.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3400-3400
Author(s):  
Hartmut Goldschmidt ◽  
Gerlinde Egerer ◽  
Ute Hegenbart ◽  
Markus Munder ◽  
Thomas Hielscher ◽  
...  

Abstract Abstract 3400 Poster Board III-288 To analyse the impact of complete response (CR), near CR (nCR) and very good partial response (VGPR) before and after first high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) on overall survival (OS) and progression-free survival (PFS), we evaluated all patients with multiple myeloma (MM) who underwent an ASCT in frontline treatment at our centre. The transplantations were performed between June 1992 and February 2009 giving a minimum follow up of 5 months after ASCT. The retrospective analysis included a total of 994 patients (579 males and 415 females) with a median age of 58 years at time of first ASCT (range 25 - 76 years). Median follow-up after first ASCT was 5.8 years. All patients suffered from symptomatic MM. Before induction treatment 48%, 31% and 21% of patients were in ISS-stage I, II and III, respectively. The following induction regimes were applied prior to HDT: VAD (n=683), TAD (n=74), PAD (n=64), and other regimes (n= 173). The patients were treated with HDT once (n= 460), twice (n=437) or thrice (n=97). 91 patients received an allogeneic SCT, 30 of these before first progression after ASCT. These were censored for PFS at time of allogeneic SCT. Maintenance therapy (interferon n=332, thalidomide n=203, bortezomib n=48 or others n=13) was administered in 596 patients. Overall survival and progression-free survival were calculated from the time of first ASCT. The median OS time was 5.7 years and the median PFS was 2.2 years. Log-rank test, univariate and multivariate Cox PH regression as well as landmark analyses were utilized to assess the prognostic impact of response. We analysed the effect of achievement of CR, of nCR or CR and of VGPR or CR or nCR before and after HDT, respectively. Achieving CR or nCR is a highly significant prognostic factor for PFS and OS before (p<0.001 and p=0.01, respectively) and after first HDT (both p<0.001). The group including VGPR showed superior outcome when assessed after HDT, driven by the effect of CR/nCR. When adjusting for the effect of age, beta-2 microglobulin before ASCT, albumin before ASCT, new drugs before ASCT (thalidomide and bortezomib; yes/no), second ASCT within 9 months (yes/no), maintenance therapy (yes/no), and date of first ASCT, achieving CR or nCR remained a significant prognostic factor (PFS after ASCT: HR=0.66 [0.54;0.80], p<0.001; OS after ASCT: HR=0.65 [0.51;0.83], p=0.001). In addition, we analyzed the effect of duration of response compared to response achievement per se. Patients who sustained their remission (overall response = PR and better) at 3 yrs after first ASCT had a favourable prognosis with respect to OS compared to patients losing remission. Conclusion: In our single-center cohort achieving CR or nCR before and after first HDT is highly prognostic for PFS and OS in MM. Sustained duration of response is also associated with an improved prognosis (3 years landmark analysis). At our centre we recommend that patients not achieving at least an nCR should be treated with a second cycle of HDT. Disclosures: No relevant conflicts of interest to declare.


1997 ◽  
Vol 15 (2) ◽  
pp. 445-450 ◽  
Author(s):  
P J Bierman ◽  
J M Vose ◽  
J R Anderson ◽  
M R Bishop ◽  
A Kessinger ◽  
...  

PURPOSE This study evaluated the results of high-dose therapy followed by autologous bone marrow or peripheral-blood stem-cell transplantation for patients with follicular low-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS We performed a retrospective review of 100 patients undergoing autologous transplantation for follicular low-grade lymphoma between April 22, 1983 and December 31, 1993. RESULTS Sixty-seven patients remained alive and 48 were failure-free. The median follow-up duration of surviving patients was 2.6 years (range, 1.0 to 11.7). There were eight (8%) deaths within 100 days of transplantation. Six additional patients died of nonrelapse causes up to 912 days after transplantation. Overall survival at 4 years was estimated to be 65% (95% confidence interval [CI], 54% to 75%) and failure-free survival was estimated to be 44% (95% CI, 33% to 55%). There was no definite evidence of a plateau in the failure-free survival curve. The only factor significantly associated with overall survival and failure-free survival was the number of chemotherapy regimen received before transplantation. No significant differences in outcome were observed between patients with follicular small cleaved-cell lymphoma and follicular mixed lymphoma, or between patients who received peripheral-blood stem-cell transplants and unpurged autologous bone marrow transplants. CONCLUSION Prolonged failure-free survival is possible following high-dose therapy and autologous hematopoietic rescue for follicular low-grade lymphoma. It is unclear whether patients are cured with this therapy or if survival is prolonged.


2008 ◽  
Vol 26 (21) ◽  
pp. 3614-3620 ◽  
Author(s):  
Catherine Sebban ◽  
Pauline Brice ◽  
Richard Delarue ◽  
Corinne Haioun ◽  
Bertrand Souleau ◽  
...  

Purpose The treatment of patients with follicular lymphoma has changed with the introduction of high-dose therapy (HDT) with autologous stem-cell transplant then with rituximab. The effect of these two strategies on the outcome of relapsing patients with follicular lymphoma has never been compared. Patients and Methods We analyzed two cohorts of patients treated in two successive randomized studies with the same treatment, cyclophosphamide, doxorubicin, teniposide, and prednisolone plus interferon, to evaluate the role of rituximab and HDT in salvage therapy after first disease progression or relapse. Results Of the 364 patients included in these two studies, 254 progressed or relapsed and constitute the population of this analysis. Among them, 98 had been treated with HDT, including 33 of them after rituximab-containing salvage regimen, and 69 with rituximab alone or combined with chemotherapy but without HDT. Patients’ characteristics at diagnosis were similar in all subgroups. If event-free survival was identical for patients treated within Groupe d'Etude des Lymphomes Folliculaires (GELF) -86 or GELF-94 studies, overall survival was longer in GELF-94 study. HDT was associated with a statistically significant benefit in terms of event-free survival from relapse and survival after relapse (SAR). Rituximab was associated with a greater benefit than HDT for these two end points. When both treatments were combined, patients treated with rituximab-containing salvage regimen followed by HDT had 5-year SAR more than 90%. Conclusion In follicular lymphoma, for patients treated with first-line chemotherapy the combination of a salvage regimen containing rituximab with or without HDT leads to a dramatic improvement of long-term outcome.


Haematologica ◽  
2007 ◽  
Vol 92 (10) ◽  
pp. 1399-1406 ◽  
Author(s):  
H. J.K. van de Velde ◽  
X. Liu ◽  
G. Chen ◽  
A. Cakana ◽  
W. Deraedt ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document