Age Is Not a Prognostic Variable With Autotransplants for Multiple Myeloma

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 51-54 ◽  
Author(s):  
D.S. Siegel ◽  
K.R. Desikan ◽  
J. Mehta ◽  
S. Singhal ◽  
A. Fassas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Peripheral Blood ◽  
Exclusion Criterion ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Prognostic Features ◽  
Β2 Microglobulin ◽  
Older Subjects ◽  
High Dose Melphalan

Multiple myeloma (MM) typically afflicts elderly patients with a median age of 65 years. However, while recently shown to provide superior outcome to standard treatment, high-dose therapy (HDT) has usually been limited to patients up to 65 years. Among 550 patients with MM and a minimum follow-up of 18 months, 49 aged ≥65 years were identified (median age, 67; range, 65 to 76 years). Their outcome was compared with 49 younger pair mates (median, 52; range, 37 to 64 years) selected among the remaining 501 younger patients (<65 years) matched for five previously recognized critical prognostic factors (cytogenetics, β2-microglobulin, C-reactive protein, albumin, creatinine). Nearly one half had been treated for more than 1 year with standard therapy and about one third had refractory MM. All patients received high-dose melphalan-based therapy; 76% of the younger and 65% of the older group completed a second transplant (P = .3). Sufficient peripheral blood stem cells to support two HDT cycles (CD34 > 5 × 106/kg) were available in 83% of younger and 73% of older patients (P = .2). After HDT, hematopoietic recovery to critical levels of granulocytes (>500/μL) and of platelets (>50,000/μL) proceeded at comparable rates among younger and older subjects with both first and second HDT. The frequency of extramedullary toxicities was comparable. Treatment-related mortality with the first HDT cycle was 2% in younger and 8% among older subjects, whereas no mortality was encountered with the second transplant procedure. Comparing younger/older subjects, median durations of event-free and overall survival were 2.8/1.5 years (P = .2) and 4.8/3.3 years (P = .4). Multivariate analysis showed pretransplant cytogenetics and β2-microglobulin levels as critical prognostic features for both event-free and overall survival, whereas age was insignificant for both endpoints (P = .2/.8). Thus, age is not a biologically adverse parameter for patients with MM receiving high-dose melphalan-based therapy with peripheral blood stem cell support and, hence, should not constitute an exclusion criterion for participation in what appears to be superior therapy for symptomatic MM.

Age Is Not a Prognostic Variable With Autotransplants for Multiple Myeloma

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 51-54 ◽  
Author(s):  
D.S. Siegel ◽  
K.R. Desikan ◽  
J. Mehta ◽  
S. Singhal ◽  
A. Fassas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Peripheral Blood ◽  
Exclusion Criterion ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Prognostic Features ◽  
Β2 Microglobulin ◽  
Older Subjects ◽  
High Dose Melphalan

Abstract Multiple myeloma (MM) typically afflicts elderly patients with a median age of 65 years. However, while recently shown to provide superior outcome to standard treatment, high-dose therapy (HDT) has usually been limited to patients up to 65 years. Among 550 patients with MM and a minimum follow-up of 18 months, 49 aged ≥65 years were identified (median age, 67; range, 65 to 76 years). Their outcome was compared with 49 younger pair mates (median, 52; range, 37 to 64 years) selected among the remaining 501 younger patients (&lt;65 years) matched for five previously recognized critical prognostic factors (cytogenetics, β2-microglobulin, C-reactive protein, albumin, creatinine). Nearly one half had been treated for more than 1 year with standard therapy and about one third had refractory MM. All patients received high-dose melphalan-based therapy; 76% of the younger and 65% of the older group completed a second transplant (P = .3). Sufficient peripheral blood stem cells to support two HDT cycles (CD34 &gt; 5 × 106/kg) were available in 83% of younger and 73% of older patients (P = .2). After HDT, hematopoietic recovery to critical levels of granulocytes (&gt;500/μL) and of platelets (&gt;50,000/μL) proceeded at comparable rates among younger and older subjects with both first and second HDT. The frequency of extramedullary toxicities was comparable. Treatment-related mortality with the first HDT cycle was 2% in younger and 8% among older subjects, whereas no mortality was encountered with the second transplant procedure. Comparing younger/older subjects, median durations of event-free and overall survival were 2.8/1.5 years (P = .2) and 4.8/3.3 years (P = .4). Multivariate analysis showed pretransplant cytogenetics and β2-microglobulin levels as critical prognostic features for both event-free and overall survival, whereas age was insignificant for both endpoints (P = .2/.8). Thus, age is not a biologically adverse parameter for patients with MM receiving high-dose melphalan-based therapy with peripheral blood stem cell support and, hence, should not constitute an exclusion criterion for participation in what appears to be superior therapy for symptomatic MM.

Autologous Stem Cell Transplantation (auto-SCT) in Elderly Patients with Multiple Myeloma (MM): Age per se Does Not Affect Outcome.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 947-947
Author(s):  
Jean El-Cheikh ◽  
Elias Kfoury ◽  
Christian Chabannon ◽  
Anne-Marie Stoppa ◽  
Reda Bouabdallah ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
The Elderly ◽  
High Dose ◽  
Prognostic Features ◽  
Comorbidity Index ◽  
Older Subjects ◽  
High Dose Melphalan ◽  
Related Mortality

Abstract Auto-SCT for MM can provide superior outcome to standard treatments. Since its introduction, auto-SCT has usually been limited to MM patients aged up to 60–65 years. However, traditional upper age limits for auto-SCT are being currently challenged along with the definition of “elderly” itself, especially that no obvious differences in MM biology has been elucidated to justify an arbitrary cut-off of 65 years. This retrospective single centre analysis assessed the outcome of 186 consecutive MM patients aged over 60 years treated with auto-SCT, with the specific aim to compare the outcome of the 82 “elderly” (age>65 y.) patients subgroup, with their 104 “younger” mates aged between 60 and 65 years treated in the same period and in the same auto-SCT program. Median age among the total 186 patients population was 64 (range, 60–77). Except for age, both groups were comparable (P=NS) as for demographic features, disease characteristics (S&D stage, monoclonal component), and prognostic factors (b2-microglobulin). The majority of patients (91%) received homogeneous “induction” VAD chemotherapy, with this being comparable between the “elderly” (87%) and “younger” (94%) group. In this population, and prior to auto-SCT, the calculated hematopoietic cell transplantation-specific comorbidity index (adapted from the Charlson Comorbidity Index) was also comparable between both groups (77% of the “younger” patients with a 0–1 index, vs. 74% in the “elderly” group; P=NS). The peripheral blood stem cells mobilization procedures (G-CSF with or without chemotherapy) were also comparable between both groups. 97% of the patients received high-dose melphalan conditioning for auto-SCT. 33% of the “younger” and 28% of the “older” group (P=NS) completed a second auto-SCT. ANC and platelets recovery were comparable between both groups (P=NS), and the median length of hospitalization for the first auto-SCT was not different between the two groups: 19 (range, 2–32) days in the “younger” group vs. 17 (range, 2–39) in the “older” group; P=NS). Infectious and other “serious” auto-SCT-related complications were also comparable between groups (P=NS). With a median follow-up of 41 (range, 5–227) months after auto-SCT, 120 patients are still alive. Disease progression (n=40; 61%) was the main cause of death, with this being comparable between both groups. Auto-SCT-related mortality was 3.8% (n=4/104) in “younger” and 3.7% (n=3/82) among “older” subjects. Comparing “younger”/”older” subjects, progression-free survival was significantly higher in the younger group (P<10e-4). However, disease response rate after the first auto-SCT was comparable (CR, VGPR and PR rates: 88% vs. 90%, P=NS), and overall survival (OS) was also comparable (57% vs. 54% at 5 years, P=NS; 32% vs. 24% at 10 years, P=NS). In a Cox multivariate analysis model, none of the relevant characteristics was shown to be a critical prognostic features for OS. Of note, age was insignificant for both OS and transplant-related mortality. We conclude that there is no clear justification for an age-discriminant policy for MM therapy. “Physiologic” aging is likely more important than “chronologic” aging. Thus, all treatment options, including auto-SCT in the “elderly” population, must be rigorously evaluated, as age does not appear to be an adverse parameter for selected MM patients receiving high-dose melphalan therapy with peripheral blood stem cell support.

Ex-Vivo Expanded Peripheral Blood Stem Cells (EVEC) Compared with Un Manipulated Peripheral Blood Stem Cells (PBSC) Autologous Transplantation for Multiple Myeloma: A Pair Match Analysis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 502-502 ◽  
Author(s):  
Noel-Jean Milpied ◽  
Gerald Marit ◽  
Bernard Dazey ◽  
Jean-Michel Boiron ◽  
Zoran Ivanovic ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Abstract 502 Autologous stem cell transplantation with PBSC after high-dose chemotherapy remains standard therapy for patients with symptomatic Multiple Myeloma (MM). Strategies to minimize complications could significantly reduce the morbidity of that procedure. One possibility could be to shorten the duration of induced neutropenia through the injection of an ex-vivo expanded graft. Nineteen patients (pts) received EVEC after high-dose Melphalan (HDM) (200 mg/m2) as the only graft. The ex-vivo expanded procedure has been described elsewhere (Boiron et al. Transfusion 2006 and Ivanovic et al. Transfusion 2006). Briefly, thawed peripheral blood CD 34+ cells collected after G-CSF mobilisation and selected with immunomagnetic devices were incubated for 10 days in a serum free medium (Maco Biotech HP01) with Stem Cell Factor (Amgen), G-CSF (Amgen) and TPO (Amgen: 7 pts; Cellgenix:12 pts). The expanded cells were then thoroughly washed and injected 48h after the HDM injection. The ex-vivo expansion lead to a median fold of 5,4 for CD34+ cells (1,3-11,8); 118 for CD33+ (1-703880); 3386 for CD14+ (4-101075); 28,5 for CD13+ (10-703880) and 13 for CFUs (6-21). The median N° of CD34+ cells injected was 14×10e6/kg (5,3-48). The results of these transplants were compared to those achieved in 38 pts who received unmanipulated PBSC after HDM. Pts and controls were matched for age, sex, stage of the disease, first line chemotherapy ( VAD or VD) status of the disease at time of transplant, year of transplant, time between diagnosis and transplant, CD34+ mobilisation technique (HD cytoxan + G-CSF or G-CSF alone) and the median N° of total nucleated cells and of CD34+ collected. The results are summarized on the table: There was no secondary neutropenia in the patients who received EVEC. With a median FU of the entire cohort of 30 m, the median OS for pts who received their first transplant with EVEC and with PBSC is 69 m and not reached respectively (p=NS), the median PFS is 18 m and 27 m (p = NS) and the median time to progression is 14 m and 15 m (p=NS). Conclusion: EVEC is feasible, safe and reduce significantly the morbidity of autologous stem cell transplantation after HDM for multiple myeloma. Disclosures: Milpied: Amgen France: Honoraria.

Engraftment, clinical, and molecular follow-up of patients with multiple myeloma who were reinfused with highly purified CD34+ cells to support single or tandem high-dose chemotherapy

Blood ◽  
2000 ◽  
Vol 95 (7) ◽  
pp. 2234-2239 ◽  
Author(s):  
Roberto M. Lemoli ◽  
Giovanni Martinelli ◽  
Elena Zamagni ◽  
Maria Rosa Motta ◽  
Simonetta Rizzi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Reconstitution ◽  
Cd34 Cells ◽  
Preparative Regimen ◽  
Total Body ◽  
High Dose Melphalan

Eighty-two patients with advanced multiple myeloma (MM) were enrolled in 2 sequential clinical studies of 1 or 2 courses of myeloablative therapy with stem cell support. Conditioning regimens consisted of high-dose melphalan (MEL) with or without total body irradiation (TX1 = 35) and MEL as the first preparative regimen, followed within 6 months by busulfan and melphalan (TX2 = 47). On the basis of adequate stem cell harvest, 31 patients (TX1 = 13; TX2 = 18) were transplanted with highly purified CD34+ cells. Positively selected stem cells did not adversely affect hematopoietic reconstitution compared with unmanipulated peripheral blood stem cell. Overall, the complete remission (CR) rate of evaluative patients was 13.8% and 41% for single and double autotransplant, respectively (P = .04). Moreover, 3 patients undergoing TX2 achieved molecular remission and 2 remain PCR-negative after 36 and 24 months from autograft. The median event-free survival (EFS) durations for TX1 and TX2 were 17 and 35 months, respectively (P = .03). Actuarial 3-year overall survival for patients treated with 1 or 2 transplants are 76% and 92%, respectively (P = NS). On multivariate analysis, superior EFS was associated with low β2 microglobulin (β2-M) level at diagnosis and TX2, whereas overall survival was correlated with β2-M. Positive selection of CD34+ cells did not influence the achievement of clinical or molecular CR, as well as remission duration or survival of MM patients. Thus, whereas multiple cycles of high-dose therapy may be beneficial for patients with myeloma, the clinical impact of tumor cell purging remains highly questionable.

Feasibility of risk stratified allocation to single versus tandem autologous SCT in multiple myeloma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18550-e18550
Author(s):  
Matthew Risendal ◽  
Allison Hazlett ◽  
Roy T. Sabo ◽  
Priscilla Mpasi ◽  
Joan Bolling ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Relapse Rate ◽  
Survival Rates ◽  
Complete Response ◽  
High Dose ◽  
High Dose Therapy ◽  
Current Standard ◽  
Prognostic Features ◽  
Dose Therapy

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.

Lenalidomide plus high-dose dexamethasone provides improved overall survival compared to high-dose dexamethasone alone for relapsed or refractory multiple myeloma (MM): Results of a North American phase III study (MM-009)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7521-7521 ◽  
Author(s):  
D. M. Weber ◽  
C. Chen ◽  
R. Niesvizky ◽  
M. Wang ◽  
A. Belch ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Response Rate ◽  
Phase Iii ◽  
High Dose ◽  
Cell Transplant ◽  
Time To Progression ◽  
Prognostic Features ◽  
High Dose Dexamethasone ◽  
Grade 3

7521 Background: Lenalidomide is a novel, orally administered, immunomodulatory drug (IMiD) that has single-agent activity against MM and additive effects when combined with dexamethasone (Dex). Methods: In this phase 3, multicenter, double-blind trial, 354 patients (pts)with relapsed or refractory MM were treated with Dex 40 mg daily on days 1–4, 9–12, 17–20 every 28 days and were randomized to receive either lenalidomide (Len) 25 mg daily orally on days 1–21 every 28 days or placebo. Beginning with cycle 5, Dex was reduced to 40 mg daily on days 1–4 only, every 28 days. Patients were stratified with respect to B2M (≤ 2.5 vs. > 2.5 mg/mL), prior stem cell transplant (none vs. ≥ 1), and number of prior regimens (1 vs > 1). The treatment arms were well balanced for prognostic features. Results: The overall response rate was greater with Len-Dex than with Dex-placebo (59.4% vs. 21.1%; p < 0.001). Complete responses were achieved in 12.9% of pts treated with Len-Dex and 0.6% of pts treated with Dex-placebo. The median time to progression (TTP) for pts treated with Len-Dex was 11.1 months compared to 4.7 months for pts treated with Dex-placebo (p < 0.000001). Median overall survival was higher with Len-Dex (not reached) compared to Dex-placebo (24 months) (hazard ratio 1.76, p = .0125). Grade 3–4 neutropenia was more frequent with combination therapy than with Dex-placebo (24% vs. 3.5%), however ≥ grade 3 infections were similar in both groups. Thromboembolic events occurred in 15% of pts treated with Len-Dex and in 3.5% of pts treated with Dex-placebo. Atrial fibrillation occurred in 8 pts and CHF developed in 4 pts treated with Len-Dex. Conclusions: Considering the ease of oral administration, higher response rate, longer time to progression and overall survival benefit, the combination of lenalidomide-dexamethasone may very well represent the treatment of choice for early refractory or relapsing multiple myeloma. The relatively infrequent side effects should not detract from these improvements, but the use of prophylactic antithrombotic therapy should be considered for patients treated with the combination of lenalidomide and dexamethasone. [Table: see text]

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