auto-SCT For Multiple Myeloma Research Articles

Allogeneic (Allo-SCT) Versus Autologous Stem-Cell Transplantation (Auto-SCT) after Relapse to First Line Auto-SCT in Multiple Myeloma: A Meta-Analysis with Predominantly Individual Patient Data

PFS Introduction A second allogeneic transplantation (allo- SCT) in patients who relapse after first-line autologous transplantation (auto- SCT) is mentioned in a recent statement of the European Society for Blood and Bone Marrow Transplantation (EBMT) as a valuable clinical option, especially when novel immunotherapies such as bispecific antibodies or CAR -T cells are not available. However, it is still unclear whether allo- SCT achieves better results compared to auto-SCT in patients who relapse after first-line treatment with auto-SCT. Objectives To compare progression-free (PFS) and overall survival (OS) between allo-ASCT and auto-ASCT as second-line therapy in patients who relapsed after first-line therapy with auto-SCT by analyzing individual patient data and extracting results from published reports when individual patient data were not available. Methods We searched the electronic databases PubMed, EMBASE, and the Cochrane Library and Up to Date. The search was limited to English-language publications from 1995 to February 2022, and only 6 studies were found that met the requirements for comparing allo SCT and auto- SCT as second-line therapy for patients who had relapsed after the first Auto- SCT. Individual patient data on survival were available for 512 patients from the Japanese Society for Hematopoietic Cell Transplantation registry data (Ikeda T et al. Hematol Oncol 2019) and for PFS and OS for 289 patients from the CIMBMTR registry (Freytes CO et al., BMT 2014). For the other 3 studies, which included 170 patients, data were extracted from the original publications (Mehta J et al, BMT 1998, Qazilbash M et al, Cancer 2006, and Wirk B et al. J Clin Res 2013). We used standard meta-analysis techniques to calculate pooled estimates from random-effects models as incorporated in the software Review Manager V. 5 (The Cochrane Collaboration). Fixed-effect models used as sensitivity analyzes yielded similar results (data not shown). I² = [(Q - df)/Q] X 100%, where Q is the chi² statistic for heterogeneity and df is the degrees of freedom, in order to quantify inconsistency between study outcomes. Results All comparisons of included studies were retrospective in nature, with one study using a cross-case approach (Mehta J et al). Conditioning regimens used for allo-SCT varied between reduced-intensity conditioning (Freytes CO et al and Qazilbash MH et al) and ablative regimens (Mehta J et al). Our analysis was based on individual patient data from 801 patients and data from 170 patients from published reports. No data on PFS were available in the study by Ikeda T et al. The results showed a HR of 1.85 (CI, 1.49-2.22, p < 0.00001) for PFS in favor of the auto-SCT group (Figure 1A). No relevant heterogeneity was observed between reports (Chi² = 3.12, df = 3 (P = 0.37), I² = 3.8%). OS: Similar results were observed for overall survival with a HR of 1.91 (CI, 1.49-2.44, p < 0.00001) in favor of the auto-SCT group at relapse (Figure 1B). The test for heterogeneity showed marked heterogeneity between studies but, similar to PFS, did not reach statistical significance (Chi² = 6.28, df = 4 (P = 0.18), I² = 36.3%). Discussion and Conclusion The included studies showed some heterogeneity but the corresponding test did not reach a significance level. The main reasons for the differences between studies could be different ablative regimens and different patient characteristics. In some studies, the median age was lower in the Allo-SCT group, which favored it, a finding that was not observed in all comparative studies. Allo-SCT appears to benefit only a small proportion of patients with multiple myeloma, whereas graft-versus-host disease and infectious complications affect outcome in a much larger proportion of patients, resulting in a worse prognosis for the entire allo-SCT group. This scenario is supported by our analysis showing a statistically significant advantage of a second auto-SCT over allo-SCT in terms of PFS and OS in patients who relapse after first-line auto-SCT.

Effect of transplanted cells with CD184 and CD26 expressions and reconstitution of CD3+ lymphocyte population on long-term survival after autologous hematopoietic stem cell transplantation for multiple myeloma

Autologous hematopoietic stem cell transplantation (auto-SCT) is the recommended treatment for responding patients with multiple myeloma (MM). However, we do not know the risk factors influencing long-term survival without progression after auto-SCT. Therefore, this prospective study aimed to investigate the influence of transplanted cells with cluster of differentiation (CD)184+ expression, CD26+ lymphocytes and monocytes, and reconstitution of CD3+ lymphocytes on overall survival (OS) and progression-free survival (PFS) after auto-SCT in MM. Forty-eight patients with MM underwent auto-SCT at our center from 2011 to 2013. The numbers of CD184+ cells, CD26+ lymphocytes, and CD26+ monocytes were measured in the harvested material. In addition, the number of lymphocyte subpopulations (CD3+ lymphocytes, helpers, suppressors, natural killer (NK), cytotoxic NK, and B lymphocytes) was measured in peripheral blood during regeneration after auto-SCT. Flow cytometry was performed in both cases. The median OS was 92 months. Our analysis revealed a statistically significant effect of the number of transplanted CD184+ cells on OS and a statistically significant correlation between PFS and the number of transplanted CD184+ cells and reconstitution of CD3+ lymphocytes. In conclusion, our study showed that the increasing numbers of transplanted CD184+ cells, CD26+ lymphocytes, and CD26+ monocytes augmented the risk of death.

CT-448 Academic Center Outreach to Community Practices Increases Transplant Referrals and Possibly Reduces Racial Disparities

Racial disparities are evident in transplant utilization rates. Outcomes improve for multiple myeloma (MM) with an autologous stem cell transplant (autoSCT) but despite the guidelines, African Americans (AA) receive fewer autoSCT when compared to whites (W). Multiple single-institution studies have confirmed that rates of autoSCT for MM in AA are similar to W when patients are referred for evaluation. Lower referral to a transplant center may contribute to these disparities. Emphasis on physician communication to facilitate an improved referral network represents an intervention to overcome this disparity. We reviewed our center data to assess the impact of outreach on transplant referrals and impact on race. We reviewed transplants (both autoSCT and alloSCT) performed at Augusta University between fiscal years 2015 to 2021. Patients were divided into two cohorts (cohort A: FY2014-17 and cohort B: FY2019-21) based on initiation of physician outreach by our program. FY2018 was used in our analysis for a year of outreach which included visiting practices within catchment area. In addition, two outreach clinics were established in collaboration with large community practice sites. Statistics are descriptive. 389 transplants analyzed included patients age >18 years with 52% males and 45% age ≥ 61 years. Cohort B had a significant increase with 266 vs 123 in cohort A, a 116% increase. There was increased median distance travelled to our center from 15.2 to 52.3 miles. Considering 15 miles as our urban area, >60% of transplants in cohort B were from outside our area. The increase in median distance travelled was found in both autoSCT and alloSCT (15.2 vs 40.3 and 15.2 vs 79.3, respectively). More significantly, cohort B had a 147% increase in AA compared to 96% in W. The distance travelled to our center was higher for W but also increased for AA at 15.4 vs 69.3 and 15.2 vs 34.8 miles, respectively. Of note, review of regional transplant center data suggests the increased volume at our center is not related to redistribution between programs across GA and SC. Our model confirms that academic outreach increases transplant referrals. The increase includes patients of minority thus may be an effective model to reduce healthcare disparities.

Cyclophosphamide-glucocorticoids versus lenalidomide-dexamethasone as treatment for multiple myeloma at first relapse after autologous stem cell transplantation – a retrospective analysis

There have been significant improvements in therapeutic options for relapsed multiple myeloma (MM) over the past two decades, with many novel agents including proteasome inhibitors, immunomodulatory agents, and more recently monoclonal antibodies demonstrating efficacy in this setting. However, there is a paucity of real-world data comparing outcomes seen in patients treated with novel agents as opposed to older agents. We report a historical single center cohort of patients diagnosed with myeloma between the years 1991–2012 in order to explore possible differences in outcomes. A total of 139 patients who underwent stem cell transplantation were included in our study. In our study, 88 patients were treated with cyclophosphamide and steroids alone at relapse whereas 51 patients were treated with Len-Dex. In the multivariate analysis, TTNT was shorter for patients who received Cyclo compared to Len-Dex (HR=1.74; 95% CI, 1.01–2.99; p=0.04); however, we could not detect an overall survival benefit (HR=1.20; 95% CI 0.63–2.29; p=0.57). Adverse event rates were similar in the two groups. In this retrospective single center analysis, Len-Dex was associated with longer TTNT compared with Cyclo at first relapse following autoSCT in MM; however its effect on overall survival in this setting was less clear.

Abstract 5663: A potential role for NKG2A to influence post-transplant outcomes in multiple myeloma

Abstract While there is currently no clear consensus regarding optimal maintenance therapy after autologous stem cell transplant (autoSCT), the early post-transplant setting is a potential site of augmentation to improve post-transplant outcomes. We previously characterized stem cell graft lymphocytes in association with progression free survival (PFS) after autoSCT in multiple myeloma (MM), and showed that there was an inverse correlation between NKG2A expression on CD56dim NK cells and PFS. Therefore, we aimed to investigate a potential role for NKG2A modulation, especially in the post-transplant setting with maintenance chemotherapy. We performed immunophenotypic analyses of NK cells from patients in the immediate post-transplant setting as well as from patients at various time points after transplant on lenalidomide maintenance therapy. In the immediate post-transplant setting (mean time since transplant=13 days) NKG2A was upregulated on NK cells when compared with KIR2DL1 (p=0.001) and KIR2DL2 (p=0.002). Additionally, in immunophenotypic analyses of PBMC from MM patients on various treatments, patients receiving lenalidomide maintenance therapy that recently underwent stem cell transplant (mean time since transplant=0.53 years) had elevated NKG2A expression compared to patients receiving no treatment (p=0.029). Conversely, patients receiving lenalidomide maintenance therapy over years (mean time since transplant=4.21 years) after transplant showed reduced NKG2A expression compared to patients receiving no treatment (p=0.0161). In bone marrow aspirates from patients with MM, primary CD138-positive myeloma cells in the bone marrow express HLA-E, the cognate antigen for NKG2A, which makes the overexpression of NKG2A biologically relevant. These data suggest that the NKG2A/HLA-E checkpoint axis may be more biologically relevant than KIR in myeloma, particularly in the post-transplant setting. This has important potential implications for treatment, as it demonstrates that NKG2A could serve as a potential target for modulation in the immediate post-transplant setting to improve survival, especially in the setting of maintenance chemotherapy. Further investigation should be aimed delineating the potential effect of NKG2A modulation on immune recovery and tumor surveillance to increase survival in the post-transplant setting. Citation Format: Jennifer Cooperrider, Paul D. Ciarlariello, Tiffany Hughes, Nita Williams, Craig Hofmeister, Robert Baiocchi, Don M. Benson. A potential role for NKG2A to influence post-transplant outcomes in multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5663. doi:10.1158/1538-7445.AM2017-5663

Hospital Volume Does Not Influence in-Hospital Mortality of Autologous Hematopoietic Cell Transplant Among Multiple Myeloma Patients in the United States

Introduction:Hospital volume and provider experience affects survival among patients with hematologic malignancies (Giri et al Blood 3359-60). Whether hospital volume affects outcomes of autologous hematopoietic cell transplant (autoSCT) among patients with multiple myeloma (MM) remains unclear.Methods:We utilized the Nationwide Inpatient Sample (NIS) database to identify all adults >18 years diagnosed with MM who underwent autoSCT in 2009-2011. NIS is the largest all-payer inpatient database in the US that captures about 20% of all US hospitalizations. Hospitals were divided into quartiles, based on the annual number of autoSCT performed, and classified into high volume (above 75th percentile) and low volume centers (below 25th percentile). In-hospital outcomes including inpatient mortality, infection, mechanical ventilation, and costs of hospitalization were compared between the two groups. All p-values were 2 sided, and the level of significance was chosen at 0.05. Statistical analysis was done using STATA 13.0 (StataCorp, College Station, TX).Results:A total of 2,750 autoSCTs were reported among patients with MM during the study period. The characteristics of study population included mean age of 58.7 ± 8.7 years, 56% males (n=1547) and 72% whites (n=1822). No significant difference existed in in-hospital mortality rate (0.86% vs. 1.59%; p=0.183) between high volume (≥178 autoSCTs per year) versus low volume centers (≤56 autoSCTs per year). The rate of fungal infection (5.32% vs. 4.94%; p=0.75), herpes simplex virus infection (1.58% vs. 1.59%; p=0.98), and the need for mechanical ventilation (1.87% vs. 1.27%) was similar between the high volume and low volume centers. Higher rates of stomatitis (57% vs. 46%; p<0.01), use of total parenteral nutrition (12.37% vs. 6.21%) and neutropenic fever (33.6% vs. 23.5%; p <0.01) were noted in high volume versus low volume centers. The cost of initial hospitalization was similar in the two groups (mean $ 161,085 vs. $ 154,161; p value 0.17).Conclusion:Our study demonstrates a low risk of inpatient mortality without center effect for autoSCT in MM in the recent years. The risks of fungal and herpes simplex virus infection were also similar between high volume and low volume centers. Higher rates of stomatitis, use of total parenteral nutrition and neutropenic fever were noted in high volume versus low volume centers. The reasons for these differences are not clear from our study but may relate to possible differences in patient characteristics or conditioning chemotherapy. DisclosuresNo relevant conflicts of interest to declare.

Long-term outcome of patients with mutiple myeloma-related advanced renal failure following auto-SCT

Renal failure commonly complicates multiple myeloma (MM) and is associated with reduced survival. It is not clear whether auto-SCT results in improved renal function or attainment of independence from dialysis in patients with advanced renal impairment due to MM. We conducted a retrospective cohort study of all patients who underwent auto-SCT for MM complicated by advanced renal failure at our institution over a 10-year period (2000-2010). We aimed to assess the association between auto-SCT and renal outcome in patients with serum creatinine (SCr) over 3 mg/dL, attributable to MM, including those who were dialysis dependent. Thirty patients (2.8% of all auto-SCT patients) met inclusion criteria. Fourteen of 15 patients who were dialysis dependent before auto-SCT remained dialysis dependent in the long term despite hematological response (HR). Of the remaining 15 patients with SCr >3 mg/dL, an improvement in glomerular filtration rate (GFR) from 15 to 19.4 mL/min/1.73 m(2) was noted post auto-SCT (P=0.035); however, neither HR post auto-SCT or pre-existing renal function were independently associated with renal outcome. Auto-SCT was not associated with independence from dialysis in patients with renal failure due to MM at our institution. Although auto-SCT was associated with an improvement in GFR in patients with SCr >3 mg/dL, this improvement was not related to HR.

Small-Sized Clone of T Cells in Multiple Myeloma Patient after Auto-SCT: T-LGL Leukemia Type or Clonal T-Cell Aberration?

Second cancers and particularly postransplant lymphoproliferative disorders (PTLDs) are extremely rare in patients undergoing autologous peripheral blood stem cell transplantation (auto-SCT). We report the case of clonally rearranged T-cell expansion which occurred after auto-SCT for Multiple Myeloma (MM). Does asymptomatic clonal T-cell large granular lymphocytic proliferation, in our experience, represent either a secondary cancer after auto-SCT or clonal T cell aberration or derive from expansion of coexisting undetected small-sized clone of T cells?

Patterns of relapse and progression in multiple myeloma patients after auto-SCT: implications for patients’ monitoring after transplantation

Auto-SCT (ASCT) is widely used in first-line treatment of multiple myeloma (MM). However, most patients eventually relapse or have progression of disease (R/POD). Although precise knowledge of R/POD patterns would be important to generate evidence-based surveillance recommendations after ASCT, such data is limited in the literature, especially after introduction of the free light chain assay (FLCA). This retrospective study examined the patterns of R/POD after first-line ASCT in 273 patients, using established criteria. At the time of R/POD, only 2% of patients had no associated serological evidence of R/POD. A total of 85% had asymptomatic R/POD, first detected by serological testing, whereas 15% had symptomatic R/POD with aggressive disease, early R/POD and short survival, with poor cytogenetics and younger age identified as risk factors. Although occult skeletal lesions were found in 40% of asymptomatic patients tested following serological R/POD, yearly skeletal surveys and urine testing were poor at heralding R/POD. We found a consistent association between paraprotein types at diagnosis and R/POD, allowing informed recommendations for appropriate serological monitoring and propose a new needed criterion using FLCA for patients relapsing by FLC only. Our findings provide important evidence-based recommendations that strengthen current monitoring guidelines after first-line ASCT in MM.

Improved outcomes with novel agents and auto-SCT for multiple myeloma in African-American patients

Improved outcomes with novel agents and auto-SCT for multiple myeloma in African-American patients

New developments in conditioning regimens before auto-SCT in multiple myeloma

The current standard conditioning regimen before auto-SCT in patients with multiple myeloma is melphalan 200 mg/m(2). Several attempts have recently been made to improve this aspect of the high-dose therapy procedure. The scope of this review article is to summarize current knowledge on conditioning regimens in this setting.

High-Dose Topotecan, Melphalan and Cyclophosphamide (TMC) with Autologous Stem Cell Support for Multiple Myeloma

Introduction High dose chemotherapy and autologous stem cell transplantation (auto SCT) was associated with prolonged event-free (EFS) and overall survival (OS) in selected patients with multiple myeloma (MM) in at least two randomized controlled trials. High-dose melphalan at 200 mg/m2 is considered the standard regimen, but the complete remission (CR) rate at best is 30–40% and the EFS approximately 2 years. Novel preparative regimens are being evaluated to improve the efficacy without increasing the toxicity. We evaluated the safety and efficacy of a new regimen, Topotecan, Melphalan and Cyclophosphamide (TMC) in patients undergoing auto SCT for MM.Methods The primary objectives were to determine the safety and to evaluate if TMC could increase the CR rate in MM patients undergoing auto SCT. Patients received cyclophosphamide at the dose of 1 g/m2 intravenously over 2 h on days -6, -5, -4; melphalan at the dose of 70 mg/m2 intravenously over 30 min on days -3 and -2 and topotecan at a dose of 3.5 mg/m2 over 30 min for 5 total doses on days -6 to -2.Results 44 patients (26 males, 18 females) with primary refractory disease or in first remission received the TMC regimen followed by auto SCT between August 2002 and March 2004. The median age of patients at auto SCT was 55 years (range 40–67) and the median interval between the diagnosis and auto SCT was 6.3 month (range 2.2– 42 months). Twelve patients (27%) had chromosomal abnormalities on conventional cytogenetic studies. Median follow-up in surviving patients was 47.8 months. Median time to neutrophil engraftment (ANC > 500/dl) and platelet engraftment (>20,000/dl) were 10 (range 7–11 days) and 9 days (range 6–9 days), respectively. Thirty seven patients (84%) were transplanted for consolidation of first remission and 7 for primary refractory disease (16%). Most common adverse events were: grade 1& 2 nausea (59%), grade 1 & 2 diarrhea (41%) and dysphagia (34%). Non-hematologic grade 3 & 4 toxicities were seen in 9 patients (20%) and included infectious complications (2 patients), congestive heart failure exacerbation (2 patients), electrolyte abnormalities including hypocalcemia and hypokalemia (1 patient each), GI complications like dysphagia and vomiting (1 patient each) and cardiac arrhythmia (1 patient). Febrile neutropenia occurred in 8 patients (18%). Thirty-three patients (75%) had a complete or partial response, 9 patients (21 %) had a minimal response or stable disease, while 2 patients had progressed within 3 months of auto SCT. At the time of this analysis, 31 patients are alive, 13 of whom in remission. Four-year EFS was 23.5%, and 4-year OS was 63%. Patients with chromosomal abnormalities had a shorter time to progression (13.9 vs. 19.7 months, p=0.18) that was not statistically significant. These results were similar to those reported by our group in 89 patients who received high-dose mephalan (200 mg/m2) only: complete + partial response rate of 66%; 4-year Kaplan-Meier estimates of EFS and OS 20% and 57%, respectively. (Anagnostoupoulos et al. Cancer 2004).Conclusion TMC is a safe preparative regimen for auto SCT for MM. There is no major advantage over high-dose melphalan alone in terms of CR rate or EFS in patients in first remission or primary refractory disease.

Six Years of Experience and Outcome with Maintenance Therapy with Very Low Dose Thalidomide after Auto-SCT in Multiple Myeloma

New drugs and high dose therapy with auto-transplantation (auto-SCT) has improved prognosis of multiple myeloma (MM). New drugs are promising in upfront therapy while the role of maintenance is still debated. Thalidomide (thal) is an active drug in the treatment of myeloma, and is been investigated as first line therapy, the limit of this drug is the toxicity dependent dose and this determines a poor compliance. It could be useful in the control of minimal residual disease. We used low dose of thal as maintenance after autologous transplantation in patient with MM from January 2002 and here we bring our experience after six years of observation. From January 2002 to August 2008 17 patients (8 males and 9 females) with MM have been treated in our institution. Median age was 59,5 years (range 48–72). 10 were IgG, 3 IgA, 3 light chains and 1 plasma-cell leukaemia. Treatment was 4 cycles of VAD regimen followed by auto-SCT. 4/17 performed double auto-SCT. Three months after SCT these patients has begun the maintenance with thal 50 mg/die, to start thal maintenance 9 patients were in CR, 5 in PR and 3 in resistant disease and the median somministration of thal has been of 12 months (range 3–24 months). Median follow up from the beginning of maintenance therapy was 40 months (range 4–76) with 11/17 (64%) patients in CR or stable disease, with progression free survival (PFS) and overall survival (OS) projected at 75 months respectively of 53% and 51% from to start thal. In our experience we have observed a neurological toxicity (grade I–III) in the 65% of the patients but only 4 have had to suspend the treatment; a haematological toxicity of grade I in the 55% of the patients that have not behaved interruption of the treatment and finally in any case we have documented thrombotic episodes. Finally we have compared this group of patients with another group (18 patients) with the same clinical characteristics that we have observed in the same period but that have not effected maintenance with thal. In this last group 13/18 patients (72%) relapsed with median follow-up of 36 months (range 14–75) and median PFS and OS of 16 and 30 months respectively. The difference between the 2 groups is statistically significant for PFS (p: 0.003) and OS (p: 0.04). The median overall survival observed after progression, in the two groups, has been of 13 months in thal group and 17 months in the group of patients that have not effected the maintenance, this difference is not statistically different (p:0.06). In conclusion in 6 years of observation our experience has shown, even if the number of the patients is small, that maintenance with low doses of thal, after auto-transplantation, it not only has a good compliance but it improves the PFS and OS in this cohort and it doesn't worsen the OS from the relapse.

Impact of early relapse after auto-SCT for multiple myeloma

Auto-SCT is an effective therapy for patients with multiple myeloma (MM), but nearly a fifth of these patients relapse within a year of auto-SCT. We studied 494 patients, undergoing auto-SCT within 12 months of diagnosis of MM. Patients were divided into two groups: early relapse (relapse <or=12 months from auto-SCT) and late relapse (either relapsed >12 months after auto-SCT or disease free at the last follow up). One hundred twenty patients (24%) were in the early relapse and 374 (76%) were in the late-relapse groups. The early relapse group had a significantly shorter median overall survival (OS) from diagnosis (26.6 vs 90.7 months; P<0.001) and from auto-SCT (20.1 vs 82.5 months; P<0.001). Among the 345 patients who have relapsed after auto-SCT, median OS from relapse was 10.8 months in the early relapse group compared to 41.8 months for the rest (P<0.001) and was longer with increasing duration of response to the SCT. In multivariate analyses, labeling index >or=1% at transplant, greater than one treatment regimen prior to auto-SCT, and failure to achieve a complete response were predictive of early relapse. Patients who relapse within 12 months of an auto-SCT have a poor outcome and should be offered trials evaluating novel treatment approaches.

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

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.