scholarly journals Outcomes of Salvage Autologous Stem Cell Transplantation in Relapsed Multiple Myeloma: A Meta-Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5699-5699
Author(s):  
Neelakanta Dadi ◽  
Venkata Vosuri ◽  
Samip R Master ◽  
Richard Preston Mansour
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cell Transplant ◽  
Free Survival

Background: Salvage autologous stem cell transplant (SAT)is an alternative treatment option for relapsed multiple myeloma patients that offers additional progression-free survival (PFS2) and overall survival (OS2) advantage over salvage chemotherapy. We conducted a meta-analysis to evaluate the outcomes of salvage transplant in patients with relapsed multiple myeloma after initial transplant. Methods: This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search on PubMed, Embase, Cochrane and Web of Science was conducted up to December 31st, 2018. Two independent reviewers screened the literature and extracted data. All studies including randomized, retrospective or prospective studies in multiple myeloma patients who underwent salvage autologous transplant were included. Abstracts, posters, review articles, case reports and studies with syngeneic and tandem transplant were excluded. Articles were excluded if they did not provide transplant related outcomes data. The search terms included "Salvage autologous stem cell transplantation", "Second autologous stem cell transplantation", "multiple myeloma". 'Meta' and "Metafor' libraries in R software (CRAN Project) were used for the analysis. Pooled estimates and 95% confidence intervals were calculated using DerSimonian-Laird (DL) random effects model. Heterogeneity between studies was evaluated using Q test and sensitivity analysis. Results: The search strategy identified over 3260 articles; 16 studies (n = 1113 patients; 1 randomized trial; 15 retrospective studies) were selected for this meta-analysis. The sample size of the studies varied between 25 and 200 patients. All studies used melphalan conditioning for salvage transplant. A significant number of patients in about 10 studies received maintenance after initial transplant. Only one study included patients who received maintenance therapy after salvage transplant. Pooled rate of patients achieving partial response or more(≥PR) after salvage transplant was 76% (95%CI: 68-83; I2=84%). Pooled rate of transplant related mortality (TRM2) was 5.5% (95%CI: 2.6-9.3; I2=78%). The pooled estimates showed a median progression free survival (PFS2) 13.5 months (95%CI: 11.3 - 15.6; I2=100%), overall survival (OS2) 34.3 months (95%CI: 27.9 - 40.7; I2=100%). The results are shown in figures 1&2. Conclusion: SAT approach had favorable outcomes of achieving durable PFS and OS in relapsed myeloma patients. A Higher TRM was observed with salvage transplant than in upfront transplant. Prospective randomized trials are needed to define benefits of SAT in comparison with "best non-ASCT" therapy in patients with MM who relapse after primary therapy. Figure 1 Disclosures Mansour: Abbvie: Other: Stock; Astra Zeneca: Other: Stock; Bluebird Bio: Other: Stock; CRISPR: Other: Stock; Editas: Other: Stock; Johnson and Johnson: Other: Stock; Novartis: Other: Stock.

scholarly journals Multiple Myeloma Patients at Various Cytogenetic Risks Benefit Differently from Autologous Stem Cell Transplantation as a Consolidation Therapy

2015 ◽  
Vol 2015 ◽  
pp. 1-7
Author(s):  
Tianmei Zeng ◽  
Lili Zhou ◽  
Hao Xi ◽  
Weijun Fu ◽  
Juan Du ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Progression Free Survival ◽  
Intermediate Risk ◽  
Free Survival

Aim.To evaluate whether patients with multiple myeloma at various risks can still benefit the same from autologous stem cell transplantation consolidation in the era of novel agents. We retrospectively analyzed 67 consecutive myeloma patients receiving autologous stem cell transplantation after bortezomib and/or thalidomide based inductions. Totally 17 high-risk, 24 intermediate-risk, and 26 low-risk patients were enrolled, based on fluorescence in situ hybridization and ISS stage. Meanwhile, another 67 risk-, response depth-, and age-matched patients not proceeding to autologous stem cell transplantation were chosen as controls. Our preliminary data indicated that, in the high-risk subgroup, progression-free survival and overall survival were both significantly prolonged after autologous stem cell transplantation (P<0.001andP=0.015) while, in the intermediate-risk subgroup, neither progression-free survival nor overall survival was prolonged significantly after autologous stem cell transplantation (P>0.05), and in the low-risk subgroup, only progression-free survival was extended significantly (P=0.012) after autologous stem cell transplantation. Multiple variables analysis further indicated that autologous stem cell transplantation and risk stratification were two independent prognostic factors for overall survival. Our results indicated that myeloma patients at different risks all benefit from autologous stem cell transplantation consolidation even in the era of novel agents.

Plasmablastic Morphology Is an Independent Predictor of Poor Survival After Autologous Stem-Cell Transplantation for Multiple Myeloma

1999 ◽  
Vol 17 (5) ◽  
pp. 1551-1551 ◽  
Author(s):  
S. Vincent Rajkumar ◽  
Rafael Fonseca ◽  
Martha Q. Lacy ◽  
Thomas E. Witzig ◽  
Terry M. Therneau ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Survival Time ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Independent Predictor ◽  
Progression Free Survival ◽  
Poor Survival ◽  
Free Survival

PURPOSE: To study the prognostic value of plasmablastic morphology after autologous stem-cell transplantation for relapsed or primary refractory myeloma. PATIENTS AND METHODS: Seventy-five patients were studied. Investigators blinded to the clinical details of the individual cases reviewed bone marrow aspirate slides to determine plasmablastic classification. Plasmablasts were defined using strict, well-described criteria. Plasmablastic morphology was considered to be present (plasmablastic myeloma) when 2% or more plasmablasts were present in the plasma-cell population. RESULTS: Patients underwent transplantation 5 to 88 months (median, 20 months) after the initial diagnosis of myeloma. Twenty-eight percent of patients had plasmablastic morphology. A significantly greater proportion of patients with plasmablastic morphology had abnormal cytogenetics compared with those with nonplasmablastic classification (73% v 31%, respectively; P = .003). The overall survival rate measured from the time of transplantation was significantly worse in patients with plasmablastic morphology compared with those without (median survival time, 5 months v 24 months, respectively; P < .001). Progression-free survival time was shortened also, with a median time of 4 months compared with 12 months, respectively (P < .001). In the multivariate analysis, plasmablastic classification was the most powerful prognostic factor after transplantation for both overall (P = .001) and progression-free survival rates (P < .001). We also identified three risk groups based on plasmablastic morphology: plasma-cell labeling index, lactate dehydrogenase, and cytogenetics. The median overall survival time was 38 months when none of these factors was abnormal, 17 months with one abnormal factor, and 8 months with two or more abnormal factors (P < .001). CONCLUSION: Plasmablastic morphology is a powerful independent predictor of poor survival rate after autologous stem-cell transplantation for relapsed or primary refractory myeloma.

Tandem Autologous Stem Cell Transplantation in Chemorefractory Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4554-4554
Author(s):  
Catherine Garnett ◽  
Chrissy Giles ◽  
Osman Ahmed ◽  
Maialen Lasa ◽  
Holger W. Auner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Free Survival

Abstract Abstract 4554 High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is currently standard treatment for younger patients with multiple myeloma, resulting in improved survival and response rate compared to conventional chemotherapy. Disease relapse, however, remains almost inevitable and thus the role of two successive (tandem) autologous stem cell transplants has been evaluated in chemorefractory patients as a means of prolonging duration of disease response. We retrospectively analysed the results of nine patients with chemorefractory disease treated at a single UK institution who received tandem ASCT between January 1998 and February 2009. There were six men and three women. Median age at diagnosis was 56 years (range, 42–65 years). Paraprotein isotype was IgG in eight patients and IgA in one patient. Median serum paraprotein level was 41g/L (range 12–73g/L) at presentation. At time of 1st transplant six patients were in stable disease (SD) and three had evidence of progressive disease. Conditioning melphalan dose was 140mg/m2 in all but two patients who received 110mg/m2 and 200mg/m2. Median time between transplants was 3.7 months (range 2.3–6.4 months) with PR and SD being observed in 2/9 and 7/9 patients at time of 2nd transplant. None of the patients reached complete response (CR). One patient received melphalan 140mg/m2 prior to 2nd transplant. The remaining patients received melphalan 200mg/m2. Median follow up after tandem transplant was 54.3 months (range 15.6 –143.6 months). No treatment related mortality was reported. At the time of analysis, six patients were still alive and under follow up with an overall survival (OS) figure for the group of 52% at 10 years from diagnosis (Figure 1). Median progression free survival (PFS) was 20 months from 2nd transplant (range 6.7–62.6 months) (Figure 2). Tandem autologous stem cell transplant in chemorefractory patients has resulted in overall survival similar to autologous stem cell transplant in chemosensitive patients and should be considered in patients with chemorefractory disease. Figure 1: Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 1:. Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 2: Progression free survival following tandem transplant Figure 2:. Progression free survival following tandem transplant Disclosures: No relevant conflicts of interest to declare.

Third Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4548-4548
Author(s):  
Catherine Garnett ◽  
Chrissy Giles ◽  
Maialen Lasa ◽  
Osman Ahmed ◽  
Marco Bua ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Progression ◽  
Cell Transplantation ◽  
Median Time ◽  
Autologous Stem Cell Transplantation ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant

Abstract Abstract 4548 High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is currently standard treatment for younger patients with multiple myeloma (MM). In the face of almost inevitable disease relapse, there is growing evidence for second ASCT as salvage therapy in certain patient groups. However, few published data exist regarding efficacy and safety of third ASCT in relapsed disease. We retrospectively analysed the results of eight patients treated at a single UK institution who each received three separate autologous stem cell transplants for relapsed MM between May 1997 and April 2012. There were four men and four women. Median age at diagnosis was 48 years (range, 25–64 years). Paraprotein isotype was IgA in two patients and IgG in the remaining six patients. At the time of 1st transplant, seven patients were in partial response (PR) and one in complete response (CR). Conditioning melphalan dose was 200mg/m2 in all but two patients who received 140mg/m2. Three patients entered CR following 1st transplant and four patients showed PR. Median time to disease progression was 31 months (range, 11.8–52.9 months). Prior to 2nd transplant, five patients achieved very good partial response (VGPR) and three PR with induction chemotherapy. Melphalan dose was 200mg/m2 in five patients and 140mg/m2 in the remaining three. Median time to disease progression was 22.3 months (range, 10.1– 39.6 months). At the time of 3rd transplant, two patients had achieved VGPR following induction chemotherapy, one showed PR, two stable disease (SD) and three evidence of disease progression. For the 3rd transplant, melphalan dose was reduced in most cases. Median follow up post 3rd transplant was 8.3 months (range 1.1–29.3 months). One patient died of overwhelming sepsis within one month of transplantation (treatment related mortality). At the time of analysis, five patients had relapsed following 3rd ASCT, with median time to disease progression of 10.4 months (range, 2.7–23.7 months). Three of these patients died at 3.5, 17.6 and 27.1 months post 3rd transplant. The remaining two patients are alive with no evidence of disease relapse (progression free survival (PFS) time of 3.3 and 1.3 months). Overall survival (OS) for the group from diagnosis is 62% at 10 years with a median OS from diagnosis of 149 months (range 68.5 – 189.2 months) (Figure 1). Median OS for the group from 3rd transplant is 17.6 months (range, 1.1–29.3 months) (Figure 2). Median PFS is 10.4 months (range 1.1–23.7 months). These results demonstrate that third ASCT is a possible treatment strategy for patients with relapsed MM and may prolong patient survival. Figure 1: Overall survival from diagnosis for patients receiving 3rd autologous stem cell transplantation for relapsed multiple myeloma Figure 1:. Overall survival from diagnosis for patients receiving 3rd autologous stem cell transplantation for relapsed multiple myeloma Figure 2: Overall survival from time of 3rd autologous stem cell transplant Figure 2:. Overall survival from time of 3rd autologous stem cell transplant Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impact of Different Mobilization Methods on Graft Composition and Outcome after Autologous Stem Cell Transplantation: Implications for Upfront Use of Plerixafor

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1125-1125
Author(s):  
LaQuisa Hill ◽  
Oluchi C. Ukaegbu ◽  
Bipin N. Savani ◽  
Salyka Sengsayadeth ◽  
Stacey Goodman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Partial Remission ◽  
Progression Free Survival ◽  
Free Survival ◽  
Disease Response ◽  
Graft Composition

Abstract Early lymphocyte recovery (ELC) is associated with improved outcomes of hematologic malignancies after autologous hematopoietic stem cell transplantation (auto-SCT). ELC, its composition and impact on outcome depends on many variables; however there is limited data on ELC after different mobilization strategies (G-CSF [G] vs. G + high dose cyclophosphamide [GC] vs. G + plerixafor [GP]). Results from a recent study showed that GP based mobilization can affect the number and subsets of immune competent cells contained in the graft. We studied whether these differences are associated with immune reconstitution (ELC), engraftment, or long-term outcomes. We retrospectively identified patients undergoing auto-SCT at the Nashville VA Transplant Center between January 2000 and December 2010 in our CIBMTR database. Disease response was determined by standard CIBMTR response criteria. At our center, GP mobilization is reserved for patients who failed prior mobilization, to rescue G or GC mobilization, or as upfront usage in heavily pre-treated patients. Our patient cohort primarily included patients with multiple myeloma (MM) and lymphoma (LY). We had evaluable data on 333 patients (MM=196; LY=127; others=10). Comparative analysis of different mobilization methods are summarized in Table 1. Median number of regimens pre-SCT for MM was 2 (range 1-5) and for lymphoma 2 (range1-7). Among LY patients, 60 (47.3%) patients were in complete remission (CR), 58 (45.7%) in partial remission (PR) and 9 (7%) had stable disease (SD). Among MM patients, 69 (35.2%) were in CR or very good partial remission (VGPR) pre-transplant, 105 (53.5%) were in PR, and 14 (7.1%) had SD. There was no significant difference between disease response status among different mobilization methods for either the MM or LY patients. A higher absolute WBC count was seen in grafts after GP mobilization compared to G or GC (p=0.01), despite a majority of patients having received GP mobilization after failed G or GC mobilization, or as a rescue regimen (n=20 [89%]). Similarly, absolute lymphocyte counts were higher in grafts mobilized after GP compared to G or GC (p=0.01). All patients engrafted and there was no difference in time to WBC or platelet engraftment between mobilization methods. Although the GP cohort was more heavily treated than the other cohorts (>2 regimens for GP 82%, vs. G 72% vs. GC 58% [p=0.02]), progression-free survival (PFS) and overall survival (OS) of G vs. GC vs. GP at 2-years was not significantly different between MM and LY cohorts (Table 1). In summary, grafts mobilized with GP exhibited major differences in graft composition in conjunction with favorable post- transplant outcomes compared with grafts mobilized with G or GC. GP mobilization accelerated lymphocyte engraftment in this heavily treated group compared to G or GC. For patients proceeding to transplant heavily pre-treated, GP is a better mobilization method to ensure a robust graft is collected while avoiding the need for multiple stem cell collections and providing similar outcomes as patients less heavily treated and mobilized by G or GC. A prospective randomized controlled trial would elucidate whether progression free survival and overall survival might be improved by utilizing GP mobilization as a first-line therapy rather than as a rescue method. Table 1. Graft composition and outcomes of different stem cell mobilization methods Variable G (n=97) GC (n=213) GP (n=23) P value Numbers of regimens pre-SCT, median 2.2 (95% CI, 2.0-2.4) 1.9 (1.8-2.0) 2.3 (1.9-2.7) 0.02 WBC in graft, median (range) 184.8 (12-777.7) 138.6 (11-542) 286.1 (186-400.3) 0.01 Absolute lymphocyte in graft (x103), median (range) 128.1 (13-321.1) 73.9 (3.4-433.6) 161.2 (47.4-302.0) 0.01 ANC >500 (days), median (range) 16 (11-25) 15 (7-86) 18 (13-24) 0.16 Platelets >20 (days), median (range) 13 (9-22) 12 (7-18) 12 (10-21) 0.07 OS (2 year) Lymphoma 74.5 77.9 72.7 0.054 Multiple myeloma 89.6 74.4 72 0.76 PFS (2 year) Lymphoma 58.2 57.6 46.1 0.1 Multiple myeloma 66.3 49 60 0.21 Disclosures No relevant conflicts of interest to declare.

Pretransplant hemoglobin and serum creatinine levels correlate with progression free survival in myeloma patients undergoing autologous stem cell transplantation.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19532-e19532
Author(s):  
Taner Demirer ◽  
Guldane Cengiz Seval ◽  
Selami Kocak Toprak ◽  
Sinem Civriz Bozdag ◽  
Meltem Kurt Yuksel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Serum Creatinine ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival ◽  
The Impact

e19532 Background: High dose melphalan and autologous stem cell transplantation (ASCT) significantly prolong survival for patients with multiple myeloma (MM). The purpose of this study is to assess the effects of hemoglobin (Hgb) and serum creatinine (Crea) values at the time of transplantation on the overall outcome of patients with multiple myeloma treated at our transplant center. Material & Methods: This analysis included 247 consecutive patients who underwent ASCT for MM between 2010-2016. Hemoglobin was grouped as low or high relative to their sample median. Patients were also stratified according to serum Crea value at the time of transplantation ( < 2 or ³2 mg/dl). Results: The median age was 57 (29-75) years and most patients were male (n = 151, 61.1%), IgG subtype (n = 124, 50.2%), and ISS stage 3 (n = 122, 49.4%). The interval from the time of diagnosis to ASCT was median 7 months and median follow-up from ASCT was 49 months (range, 3-198 months). The most commonly induction regimens included VAD (vincristine, doxorubicin and dexamethasone) and VCD (bortezomib, cyclophosphamide, dexamethasone), respectively. Since maintenance was not an approved treatment in myeloma most patients did not receive any. For the entire cohort, the median Hgb and Crea were 11.5 g/dL and 0.9 mg/dL respectively. No difference in progression free survival (PFS) was observed between a lower and higher Hgb (82 vs. 81 months, p = 0.96). However, the median PFS was significantly longer in patients with a lower Crea compared to those with a higher Crea (83 vs. 48 months, p = 0.01). Patients with both a lower hemoglobin and higher Crea experienced shorter PFS compared to those with a higher hemoglobin and lower Crea (45 vs. 82 months, p < 0.001). We failed to demonstrate the impact of creatinin levels on time to neutrophil and platelet engraftment. There were no differences in OS according to lower vs. higher Hgb (58 vs. 52 months; p = 0.29, respectively) but in higher crea cohort worse OS was observed (41 months vs. 57 months; p = 0.02, respectively). Conclusions: We demonstrate that hemoglobin and creatinine represent important determinants of clinical outcomes after ASCT. A lower hemoglobin and higher creatinine, individually and when combined, were associated with shorter PFS. Therefore, further studies of larger randomized cohorts are required to clarify the impact of pre-transplant Hgb and Crea levels on ASCT outcomes.

The Survival of Multiple Myeloma Patients: A Single Institution Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5223-5223
Author(s):  
Zwi N. Berneman ◽  
An-Sofie Verstraete ◽  
Alain Gadisseur ◽  
Ann Van de Velde ◽  
Wilfried A. Schroyens
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Conventional Chemotherapy ◽  
Free Survival

Abstract Background: For a long time, multiple myeloma has been a disease with a poor outcome. High dose (melphalan) chemotherapy followed by autologous stem cell transplantation has been reported to improve the overall and progression-free survival of these patients. Objective: To determine the survival of multiple myeloma patients treated with conventional chemotherapy and compare it with that of patients treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation. Design/Methods: 83 myeloma patients treated at a single institution were included in this retrospective study. They were divided into two groups: one group of patients who were received high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (n=42) and one group of patients who only received conventional chemotherapy and were eventually also treated with thalidomide and/or corticosteroids (n=41). The distribution of the stages of the disease according to Salmon and Durie were similar in both groups of patients. For both groups, the overall and progression-free survival was calculated. Results: In the general analysis, myeloma patients who underwent an autologous transplant had a significantly longer overall survival (58.8 vs. 52.2 months, p=0.036) and progression-free survival (39.6 vs. 11.8 months, p &lt; 0.001) in comparison with the conventional chemotherapy group. If analysis was restricted to those patients who were transplanted as a first-line treatment, there was no significant difference in overall survival in comparison with conventional chemotherapy (51.8 vs. 52.2 months, p= 0.422); progression-free survival was significantly better in the first-line transplant arm as compared to the conventional chemotherapy arm (35.4 vs. 11.8 months, p= 0.003). As the median age in the transplant arm was significantly lower than in the conventional chemotherapy arm, we also performed a sub-analysis of patients who were between 60 and 70 years of age at diagnosis; there was no significant difference in overall survival between the two groups (60.7 vs. 69.5 months, p= 0.656), while the progression-free survival was again better in the autologous transplant group as compared to the conventional chemotherapy group (41.0 vs. 8.4 months, p= 0.020). Conclusion: High-dose chemotherapy and autologous stem cell transplantation in the treatment of myeloma is associated with improved progression-free survival and in the general analysis, with improved overall survival. The overall survival of patients who were only treated with conventional chemotherapy is somewhat higher (more than 4 years) as compared to that of historical controls (2–3 years).

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