Autologous Stem Cell Transplantation For Treatment Research Articles

Additional copies of 1q negatively impact the outcome of multiple myeloma patients and induce transcriptomic deregulation in malignant plasma cells

Additional copies of chromosome 1 long arm (1q) are frequently found in multiple myeloma (MM) and predict high-risk disease. Available data suggest a different outcome and biology of patients with amplification (Amp1q, ≥4 copies of 1q) vs. gain (Gain1q, 3 copies of 1q) of 1q. We evaluated the impact of Amp1q/Gain1q on the outcome of newly diagnosed MM patients enrolled in the FORTE trial (NCT02203643). Among 400 patients with available 1q data, 52 (13%) had Amp1q and 129 (32%) Gain1q. After a median follow-up of 62 months, median progression-free survival (PFS) was 21.2 months in the Amp1q group, 54.9 months in Gain1q, and not reached (NR) in Normal 1q. PFS was significantly hampered by the presence of Amp1q (HR 3.34 vs. Normal 1q, P < 0.0001; HR 1.99 vs. Gain1q, P = 0.0008). Patients with Gain1q had also a significantly shorter PFS compared with Normal 1q (HR 1.68, P = 0.0031). Concomitant poor prognostic factors or the failure to achieve MRD negativity predicted a median PFS < 12 months in Amp1q patients. Carfilzomib–lenalidomide–dexamethasone plus autologous stem cell transplantation treatment improved the adverse effect of Gain1q but not Amp1q. Transcriptomic data showed that additional 1q copies were associated with deregulation in apoptosis signaling, p38 MAPK signaling, and Myc-related genes.

Real-world prognostic significance of attaining minimal residual disease negativity in newly diagnosed multiple myeloma

The aim of the study was to evaluate the prognostic impact of minimal residual disease (MRD) in the real-world setting and the interaction between MRD and molecular risk, clinical response and autologous stem-cell transplant (ASCT). A retrospective analysis of 275 newly diagnosed multiple myeloma (NDMM) patients who achieved very good partial remission (VGPR) or better before maintenance were involved. We examined MRD status by multiparameter flow cytometry (MFC). At a median follow-up of 37 months (4–88 months), In patients who achieved ≥ VGPR, those with MRD negativity had significantly longer PFS (51 vs. 26 months; P < 0.001) and OS (Not reached: NR vs. 62 months, P < 0.001) than those with MRD positivity. MRD positivity was the independent prognostic factor for PFS with hazard ratios of 2.650 (95% CI 1.755–4.033, P < 0.001) and OS with hazard ratios of 2.122 (95% CI 1.155–3.899, P = 0.015). Achieving MRD negativity was able to ameliorate a poor prognosis associated with genetic high risk. MRD negativity was associated with better PFS regardless of ASCT treatment. MRD status was more predictable for clinical outcome than conventional clinical responses. Moreover, Sustained MRD negativity ≥ 12 or ≥ 24 months improved both PFS and OS. Patients with NDMM who achieved MRD-negative status or sustained MRD negativity had deep remission and improved clinical outcomes regardless of high-risk cytogenetics, ASCT and clinical responses in a real-world setting.

Comparison of Inpatient Outcomes Between HIV Positive and Negative Hospitalizations for Autologous Stem Cell Transplant Treatment among Lymphoid Malignancies

BackgroundComorbidity burden is higher among people living with HIV (PLWH). In addition, they experience adverse effects associated with antiretrovirals. In this study we looked for differences in adverse hospital outcomes between those with and without HIV among hospitalizations for autologous stem cell transplantations (ASCTs) for lymphoid malignancies. Materials and MethodsThe current study was a retrospective analysis using the National Inpatient Sample (NIS) database, for the years 2005 to 2014. Adult hospitalizations ≥18 years of age, for ASCTs were included for the analysis, and were stratified into those with and without HIV. The primary outcome variables were in-hospital mortality, prolonged length of stay, and adverse dispositions. ResultsWe included a total of 117,686 ASCT hospitalizations, of which, 468 (0.4%) were HIV positive. Among HIV-positive hospitalizations, there were 251 (53.4%), non-Hodgkin lymphoma, 128 (27.4%), Hodgkin lymphoma, and 89 (19.2%) multiple myeloma cases. Only half of the PLWH among Black population received ASCT, compared to Whites (26.8% vs. 54.8%). Regression analyses showed that the odds of in-hospital mortality (OR, 0.77; 95% CI, 0.13-4.44), prolonged length of stay (OR, 1.18; 95% CI, 0.67-2.11), and dispositions other than home (OR, 1.26; 95% CI, 0.61-2.59) did not differ significantly between 2 groups. DiscussionWe found that adverse hospital outcomes did not differ between those with and without HIV among hospitalized autologous stem cell transplant recipients. However, the rates of ASCT were substantially lower among Black PLWH. New interventions and approaches should be developed to improve ASCT rates among HIV positive racial minorities.

A critical assessment of dose effects of post-thaw CD34 on autologous stem cell transplantation treatment of haematological malignancies.

A consensus threshold of pre-cryopreservation CD34-positive cells (CD34s) has been used as the minimum dose to initiate autologous stem cell transplantation (ASCT). Advances in cryopreservation posed a debate whether post-thaw CD34s might be a superior surrogate instead. We addressed the debate in this retrospective study of 217 adult ASCTs in five different haematological malignancies treated at a single centre. We showed that post-thaw CD34s was highly correlated with pre-cryopreservation CD34s (r=0.97) and explained ∼2.2% (p=0.003) of the variation of the post-thaw total nucleated cell viability that however had no power to predict engraftment outcomes. After stratifying the ASCT cases into four dose groups based on post-thaw CD34s reinfused, stepwise multivariate regression analyses detected significant effects in dose group and interactions with diseases for neutrophil and platelet recovery respectively. The significant dose effects and interactions were triggered by two technical outliers in the low dose group, and disappeared in the repeated regressions after exclusion of the outliers where disease and age were the significant predictors remained. Our data clearly support the validity of the consensus threshold in ASCT applications but also highlight neglected conditions where monitoring post-thaw CD34s and clinical attributes are valuable.

Experience of Autologous Stem Cell Transplant in Multiple Myeloma: The Patient and Caregiver Perspective.

A qualitative study of the experiences of patients who received autologous stem cell transplant (ASCT) for the treatment of multiple myeloma (MM) was conducted to better understand their MM disease journey, including first symptoms, diagnosis, ASCT, and recovery. Sixteen participants, including 12 patients with MM and 4 caregivers of patients with MM, were interviewed in focus group meetings. Pain, weakness, and bone pain were common first symptoms among patients. The MM diagnosis was often made by a hematologist or oncologist. Patients were referred to a specialized oncologist after diagnosis, who was the primary driver in making ASCT treatment decisions. Eight patients received their ASCT in the inpatient setting, with some having lengthy hospital stays; 4 received their ASCT in an outpatient setting with 3 eventually being hospitalized. The focus groups identified that patients and caregivers perceived various unmet needs and impacts on quality of life throughout their transplant journey. Educational resources and innovative therapies are needed to reduce the disease burden of MM and enhance the quality of life for both patients and their caregivers.

The Impact of Infused Autograft Absolute Numbers of Immune Effector Cells on Survival Post-Autologous Stem Cell Transplantation.

Autologous stem cell transplantation treatment has been viewed as a therapeutic modality to enable the infusion of higher doses of chemotherapy to eradicate tumor cells. Nevertheless, recent reports have shown that, in addition to stem cells, infusion of autograft immune effector cells produces an autologous graft-versus-tumor effect, similar to the graft-versus-tumor effect observed in allogeneic-stem cell transplantation, but without the clinical complications of graft-versus-host disease. In this review, I assess the impact on clinical outcomes following infusions of autograft-antigen presenting cells, autograft innate and adaptive immune effector cells, and autograft immunosuppressive cells during autologous stem cell transplantation. This article is intended to provide a platform to change the current paradigmatic view of autologous stem cell transplantation, from a high-dose chemotherapy-based treatment to an adoptive immunotherapeutic intervention.

Resource utilization for chimeric antigen receptor T cell therapy versus autologous hematopoietic cell transplantation in patients with B cell lymphoma

CD19-directed chimeric antigen receptor T cells (CAR-T) have emerged as a highly efficacious treatment for patients with relapsed/refractory (r/r) B cell lymphoma (BCL). The value of CAR-T for these patients is indisputable, but one-off production costs are high, and little is known about the ancillary resource consumption associated with CAR-T treatment. Here, we compared the resource use and costs of CAR-T treatment with high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) for patients with r/r BCL. Standard operating procedures were used to develop a process model in ClipMedPPM, which comprises all activities and processes to sustain or generate treatment components that together constitute a treatment path. The software allows a graphic representation and the use of standardized linguistic elements for comparison of different treatment paths. Detailed processes involved in CAR-T treatments (n = 1041 processes) and in ASCT (n = 1535) were analyzed for time consumption of treatment phases and personnel. Process costs were calculated using financial controlling data. CAR-T treatment required ~ 30% less staff time than ASCT (primarily nursing staff) due to fewer chemotherapy cycles, less outpatient visits, and shorter hospital stays. For CAR-T, production costs were ~ 8 × higher, but overall treatment time was shorter compared with ASCT (30 vs 48 days), and direct labor and overhead costs were 40% and 10% lower, respectively. Excluding high product costs, CAR-T uses fewer hospital resources than ASCT for r/r BCL. Fewer hospital days for CAR-T compared to ASCT treatment and the conservation of hospital resources are beneficial to patients and the healthcare system.

Interval Progression Serves As a Predictor of Adverse Outcomes in Patients with Multiple Myeloma

Background: Multiple myeloma (MM) remains an incurable disease, but deep, lasting remission can be achieved with induction therapy and autologous stem cell transplant (ASCT). The current ASCT treatment timeline includes a gap between the end of induction and the day of ASCT to permit correct mobilization and collection of stem cells. During this interval, some patients experience increases in their MM markers. We specifically evaluated if patients with interval progression (IP) have different outcomes post-ASCT compared to patients without IP.Methods: We completed a retrospective analysis of 482 patients who underwent ASCT at The Ohio State University Wexner Medical Center between 2011 and 2016. MM labs, including protein electrophoresis with immunofixation and free light chains, were obtained at day of diagnosis, end of induction, and day of ASCT. A 20% increase in the index protein between the end of induction and the day of ASCT was defined as IP. The primary outcomes evaluated were time-to-progression (TTP), progression-free survival (PFS), and overall survival (OS). TTP was defined as time from ASCT to disease progression, treating death without progression as a competing risk. PFS was defined as the time from ASCT until either disease progression or death, while OS was defined as the time from ASCT until death or last follow-up. Poisson regression models with robust variance were used to evaluate the associations between patients' characteristics and IP, while competing risk regression models were used for TTP analysis, and Cox regression models for OS and PFS analysis.Results: 482 patients who underwent ASCT for MM between 2011 and 2016 were studied. The patient population was primarily male (n = 296, 61.4%), Caucasian (n = 420, 87.1%), and had IgG disease (n = 269, 55.8%). MM stage at diagnosis was equally represented. Cytogenetic analysis showed 108 (22.4%) patients with 1q21 amplification, 60 (12.4%) patients with t(11;14) translocation, 33 (6.8%) patients with t(4;14) translocation, and 40 (8.3%) patients with 17p deletion. More than 80% of patients underwent maintenance therapy following ASCT.One hundred and fifty-six (32.3%) patients were defined as having IP. Patients in the IP group were significant more likely to have LC disease (p = 0.0018), but no other patient characteristics varied significantly between the two groups. LC disease (relative risk (RR adj) = 2.12, 95% CI 1.37-3.30, p = 0.001) and deletion 17p (RR adj = 1.62, 95% CI 1.08-2.42, p = 0.02) were associated with increased risk of IP on multivariate analysis (MVA).Five-year PFS rates were 47.2% and 36.8% in the non-IP and IP groups, respectively. Five-year cumulative progression rates were 49.0% in the non-IP group and 57.8% in the IP group. Five-year OS rates were 76.8% in the non-IP group and 69.6% in the IP group. On univariate analysis (UVA), IP correlated with inferior outcomes in both TTP (hazard ratio (HR) = 1.39, p = 0.01) and OS (HR = 1.39, p = 0.04). In agreement with previous literature, other factors independently correlated with inferior TTP and OS outcomes, including MM stage, cytogenetics (amp1q, t(4;14), and del(17p)), and absence of maintenance therapy post-ASCT. On MVA, IP was no longer significantly associated with a shorter TTP (HR = 1.16, p = 0.35), but approached statistical significance in conferring inferior OS (HR = 1.40, p = 0.07). Notably, once deletion 17p was removed from the MVA, the presence of IP once again conferred significantly lower OS (HR = 1.45, 95% CI 1.01-2.07, p = 0.04), suggesting that deletion 17p, which is a significant risk factor for both IP and OS, may mediate the effect of IP. Combined, all data suggest that uncontrolled disease prior to ASCT trends towards worse long-term outcomes.Conclusion: In this study, we report the first data regarding patients who experienced rapid disease progression in the interval between induction therapy and ASCT. These patients have inferior TTP, PFS, and OS, likely due to the presence of LC disease or deletion 17p. IP may provide a valuable predictor of robustness of response to ASCT and prompt the need for additional induction cycles or alternative regimens. This is especially relevant for patients with deletion 17p. Indeed, these data support a prospective study of concepts to improve outcomes for patients with IP prior to ASCT. DisclosuresBumma: Amgen: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Characteristics and survival trends in Finnish multiple myeloma patients-a nationwide real-world evidence study.

Current understanding of the epidemiology and outcomes for patients with multiple myeloma in Finland is scarce due to lack of comprehensive real-world evidence in clinical practice. The aim of this study was to gain understanding of epidemiological characteristics and treatment and survival outcomes by utilizing multiple real-world data sources with information of adults treated for active multiple myeloma (MM) during years 2005-2016 in Finland. A total of 3851 adult MM patients with C90.0 diagnosis fulfilling all inclusion criteria were included in the analysis. The average myeloma incidence was six cases per 100,000, which slightly increased (p = 0.011) during the follow-up. The age-standardized incidence was three cases per 100,000 in the years 2005-2016. On average, 25% of patients received autologous stem cell transplantation (ASCT), and this proportion increased during the years 2005-2015 from 17 to 30%. The majority of patients under 65 years of age received ASCT treatment (60.5%), whereas only 8.7% of patients 65 years of age or older were treated with ASCT. The net median overall survival improved by approximately 5 months from 2005-2010 (3.44 years) to 2011-2016 (3.89 years); after adjusting for covariates, this presented an annual 4% reduction in the risk of death. Longer median survival and decreased risk of death indicate improved treatment outcomes from 2005 to 2016 among adult MM patients in Finland.

Interrupted Identities: Autologous Stem Cell Transplant in Patients With Multiple Myeloma.

In the current study, we sought to examine whether patients incorporate the identity of a patient receiving autologous stem cell transplant (ASCT) for multiple myeloma (MM) into their daily lives. Multiple myeloma patients receive education before initiating the ASCT treatment process. In this ethnographic study using interpretative phenomenological analysis, we observed pretransplant education visits with 30 MM patients, followed by semistructured interviews in their hospital rooms during transplant. The experience of receiving ASCT for MM required effort by patients to not only maintain their past identity but also establish a new patient identity. Reconciling these 2 identities required deliberate and emotionally draining effort from the patient. Results were organized into 2 overarching themes of social relationships and aesthetics with subthemes for each. Understanding methods MM patients who are receiving ASCT use to negotiate normalcy during treatment may be helpful for developing interventions for alleviating distress during this difficult time.

Comparison of single and double autologous stem cell transplantation in multiple myeloma patients

Background Autologous stem cell transplantation (ASCT) is one of the standard treatments of choice for eligible multiple myeloma (MM) patients. Herein, we aimed to analyze MM patients at our center and compare the clinical outcomes of single and double ASCT patients. Materials and methods Patients who were diagnosed as having MM and had undergone single or double ASCT in our clinic between the years 2003 and 2020 were retrospectively examined. Results In this study, the median time of second ASCT is approximately 3.6 years from the first ASCT. Overall survival (OS) duration of the single and double transplanted groups was 4,011 ± 266 vs 3,526 ± 326 days, respectively (p: 0.33). Progression-free survival (PFS) duration of the single and double transplanted groups was 2,344 ± 228 vs 685 ± 120 days, respectively (p: 0.22). Disease assessment after ASCT stable or progressive disease, partial remission, and very good partial or complete remission (CR) in single and double ASCT groups was 62/44/105 and 8/4/5, respectively (p: 0.22). Conclusion The present study points out that the second ASCT treatment option for MM patients may not be effective as suggested, especially in the era of novel MM drugs, since our results come from the past data that novel drugs were not exist. In conclusion, we found no benefit with second ASCT in MM patients in terms of PFS and OS or CR rates, and the novel anti-myeloma drugs might decrease the need for a second transplant.

The Quality of Life on Effect and the Cost of Tandem Transplantation in Multiple Myeloma Patients

Autologous stem cell transplantation (ASCT) plays a significant role in the treatment of multiple myeloma. Although the result of STaMINA trial showed no extra survival benefit of second transplantation or consolidation therapy in addition to single ASCT, there is still an argument about the optimal treatment intensity. In the light of the patient's QOL and the cost, the effect of the post ASCT treatment has not been well discussed. Therefore, we investigated the impact of the single and tandem ASCT on the QALY and the cost.

Systematic Reviews of the Clinical Efficacy and Safety of First-Line Treatments for Patients with Mantle Cell Lymphoma

Systematic Reviews of the Clinical Efficacy and Safety of First-Line Treatments for Patients with Mantle Cell Lymphoma

Post Relapse Survival Rates in Diffuse Large B-Cell Lymphoma

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is the most frequently observed hematologic malignancy with 45,000 patients newly diagnosed globally each year. DLBCL patients can be cured if successfully treated with first line therapy, but patients who relapse face a poor prognosis. OBJECTIVES: The aim of this analysis was to assess the prognosis for patients who relapse after first line treatment and to assess the impact of patient age on outcomes through a systematic review of the literature. METHODS: A systematic review of observational and interventional studies that describe survival outcomes in DLBCL was conducted. The review included studies published internationally since 2000 that enrolled adult patients with DLBCL who had relapsed or progressed following first line treatment with rituximab. Phase I interventional studies, case reports, and studies assessing novel therapies in second line treatment were excluded. Data were collected on median overall survival (OS), and 1-yr and 5-yr survival rates. OS data were reported according to the time point from which they were calculated: from the point of relapse (studies including patients who may or may not have received second line treatment), from initiation of treatment post relapse (studies including patients who received active treatment post relapse), and from the time of autologous stem cell transplant (ASCT) post relapse. Results were further analysed by patient age. RESULTS: The search retrieved 2,275 citations, of which 28 studies met the inclusion criteria. In studies reporting OS from the time of relapse, median survival was 10 months (range 4 - 22) (Table 1). The proportions of patients alive at 1 and 5 years post relapse were on average (range) 41% (20% - 68%) and 27% (12% - 42%) respectively. The patients included in these studies were a mix of those who went on to receive a second line treatment and those who did not. In studies of patients who relapsed and received a subsequent line of treatment, median survival from the initiation of treatment post relapse was 13 months (9 - 28) and the proportions of patients alive at 1 and 5 years post second line treatment initiation were on average 60% (41% - 70%) and 30% (14% - 100%) respectively. In studies where survival was calculated from the time of ASCT post relapse, median survival was 40 months (36 - 44), while the proportions of patients alive at 1 and 5 years post ASCT were 73% (70% - 75%) and 45% respectively. The longer survival times for patients who received treatment post relapse likely reflects the better prognostic profile of patients deemed suitable for subsequent treatment versus those post relapse who may not have received second line treatment. Survival after ASCT is significantly influenced by the usual practice of selecting for transplant only patients showing chemo-responsiveness to salvage therapy. In studies that reported survival by patient age, median survival was more than twice as long for patients aged CONCLUSIONS: The prognosis for patients with DLBCL who relapse is poor, with median survival of less than one year and less than half of patients who relapse still alive at one year post relapse. Despite the use of ASCT treatment, less than half of patients who met the eligibility criteria for and underwent ASCT were alive at 5 years post ASCT. Age was seen to be an important prognostic indicator in DLBCL patients who relapse, with poorer prognosis in patients aged ≥65 years than in those aged Disclosures McMillan:Celgene: Honoraria; Roche: Honoraria. Martin:Sevier: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Gilead: Membership on an entity9s Board of Directors or advisory committees; Janssen: Honoraria. Haioun:Roche: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Sandoz: Honoraria, Membership on an entity9s Board of Directors or advisory committees. Chiappella:Pfizer: Speakers Bureau; Teva: Speakers Bureau; Janssen-Cilag: Speakers Bureau; Celgene: Speakers Bureau; Roche: Speakers Bureau; Amgen: Speakers Bureau. Di Rocco:Celgene: Honoraria. Rueda:Roche: Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Takeda: Speakers Bureau; Janssen: Speakers Bureau; Mundipharma: Speakers Bureau. Palaska:Celgene: Consultancy. Davies:Pfizer: Research Funding; Celgene: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Other: Travel to scientific conferences, Research Funding; Janssen: Honoraria; Mundipharma: Honoraria; GSK: Research Funding; Karyopharma: Honoraria, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Other: Travel, accommodation, expenses, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Bayer: Research Funding.

Prognostic Value of Sequencing-Based Minimal Residual Disease Detection in Patients with Multiple Myeloma Who Underwent Autologous Stem Cell Transplantation

Background: Autologous stem cell transplantation (ASCT) in conjunction with therapeutic drugs such as bortezomib, thalidomide, and lenalidomide can dramatically improve response rates and the prognosis of patients with multiple myeloma (MM). However, most patients with MM are considered to be incurable, and relapse owing to minimal residual disease (MRD) is the main cause of death among these patients. Here we utilized a next-generation sequencing (NGS) approach for MRD assessment, which offers at least 1 to 2 logs greater sensitivity (10-6) compared to allele-specific oligonucleotide PCR (ASO-PCR) and flow cytometry, respectively (Faham et al Blood 2012). Previous studies have shown that NGS-based MRD assessment 90 days post-ASCT has prognostic value (Martinez-Lopez et al Blood 2014). In this study, we compared the prognostic value of MRD assessment in autografts and bone marrow (BM) samples from MM patients in the ASCT setting.Methods: One hundred and twenty-three Japanese patients with newly diagnosed MM who received various induction regimens prior to ASCT were retrospectively analyzed. All patients received ASCT and were followed between June 15, 2004 and April 25, 2015. All patients had achieved a partial response (PR) or better after ASCT. Analyzed samples included: (1) BM slides from 96 MM patients at diagnosis, (2) fresh/frozen BM cells from 27 MM patients at diagnosis, (3) autografts and/or (4) post-ASCT BM cells obtained at the time of best response based on serum and urine tests. IGH-based ASO-PCR was performed as described previously (Methods Mol Biol 2009). NGS-based MRD assessment was performed using the immunosequencing platform (Adaptive Biotechnologies, South San Francisco, CA) (Martinez-Lopez et al Blood 2014).Results: We compared MRD results in 51 samples assessed by ASO-PCR and NGS. We observed a high correlation between NGS and ASO-PCR results at MRD levels of 10-5 or higher (r=0.86, P<0.0001). Twenty-seven samples were positive by NGS and negative by ASO-PCR, demonstrating the higher sensitivity of NGS (10-6 or higher) vs ASO-PCR (10-4-10-5). We evaluated the association of clinical outcome with post-ASCT BM MRD assessment. Patients who were MRD negative by NGS (defined as <10-6) in post-ASCT BM cases (N=21) showed a significantly better progression free survival (PFS) compared to MRD positive patients (N=31) (P =0.005) (Fig 1A). When restricting the analysis to the 39 patients in complete response (CR), patients who were MRD negative by NGS (N=20) showed a significantly better PFS than those that were MRD positive (N=19) (P =0.042). We also evaluated the association of clinical outcome with autograft MRD assessment. 53 patients received post-ASCT therapy using novel agents such as bortezomib/lenalidomide/thalidomide, and 45 patients did not. Among the 45 patients who did not receive post ASCT treatment, patients with NGS-based MRD negativity in the autograft (N=11) had a significantly better PFS (P=0.012) and tended to have a better OS (p=0.203) than those who were MRD positive (N=34), with prognosis clearly stratified by the quantitative level of MRD (Figs 1B, 1C). MRD assessment from the 53 patients who did receive post ASCT treatment tended to show a similar pattern. Finally, we studied whether clinical outcomes would have been altered by treatment in this cohort. Patients whose autografts were negative by NGS-based MRD assessment (N=19) had 100% PFS and OS at 5 years post ASCT irrespective of whether or not they received post ASCT treatment. Conversely, post ASCT treatment had a significant effect on the outcome of patients whose autografts were MRD positive by NGS. Specifically, the NGS-based MRD positive patients who received post ASCT treatment (N=45) had a significantly better PFS (P=0.003) and tended to have a better OS than those that were untreated (N=34) (Figs 1D, 1E).Conclusions: In this study, we show the prognostic value of NGS-based MRD assessment in autografts of patients with MM. The NGS platform has improved sensitivity compared with ASO-qPCR in detecting MRD in autografts. Importantly, this retrospective study suggests that therapeutic intervention based on NGS-based MRD positivity has a significant effect on patient outcome in the post-ASCT setting. [Display omitted] DisclosuresZheng:Adaptive Biotechnologies Corp.: Employment, Equity Ownership. Moorhead:Adaptive Biotechnologies Corp.: Employment, Equity Ownership. Faham:Adaptive Biotechnologies Corp.: Employment, Other: Stockholder.

Autologous stem cell transplantation for a monoclonal gammopathy of undetermined significance mimicking amyotrophic lateral sclerosis: A case report.

It is rare for patients with monoclonal gammopathy of undetermined significance (MGUS) to present with clinical features of fatal motor neuron disease, for example amyotrophic lateral sclerosis (ALS). There is no standard and effective therapy for either MGUS or ALS. In addition, stem cell transplantation appears to be ineffective for the treatment of this disease. In the present study, a 47-year old female with MGUS that mimicked ALS is presented. The M-protein levels of the patient were normalized following two cycles of chemotherapy and autologous stem cell transplantation treatment. MGUS was found to be alleviated and the symptoms of ALS did not deteriorate. The results showed a positive therapeutic effect of autologous stem cell transplantation for MGUS.

Risk-adapted maintenance therapy (MaintRx) after ASCT in first-line therapy for multiple myeloma (MM).

8607 Background: Maintenance lenalidomide improves survival in patients who have undergone induction therapy and then autologous stem cell transplant (ASCT) as first line management for MM. We studied how the extent of cytoreduction after induction therapy à ASCT (as measured by CR, VGPR, or PR as best response) influences MAINTRX prescribing preferences among American Hematology-Oncology physicians (AHOP). Methods: We studied 284 individual AHOPs using a proprietary, live, case-based market research tool to assess prescribing preferences. A core case scenario and variations based on extent of response to induction à ASCT was constructed. Preference data were acquired using blinded audience response technology. All responses for each scenario were obtained contemporaneously prior to any display of respondent selections. All sources of research support were double blinded. The core scenario involved a 59-year-old patient (42% plasma cells in BM, no cytogenetic abnormalities, CrCl 65ml/min, B2M 5.8, PS 1) treated with induction therapy of choice à ASCT. The same query was then posed in each of 3 settings: Following CR (or following VGPR or following PR) as best response, what, if any, further therapy would you recommend now? Results: See Table. Conclusions: Among patients with myeloma getting first-line therapy, MaintRx is almost uniformly preferred by AHOPs. Specific single or doublet therapy preferences are dependent upon best response to induction à ASCT treatment. Compared to the CR setting, preferences for 2 drug MaintRx are significantly increased in patients with VGPR (p &lt;.0.001) or with PR (p &lt; 0.001)] as best overall response. The potential for benefit from intensified MaintRx in these response subsets needs prospective phase III testing. [Table: see text]

Autologous Blood Stem Cell Transplantation Results In Better Relapse-Free Survival Than Consolidation Chemotherapy: Results of a HOVON/SAKK Phase III Trial In 519 AML Patients In First Complete Remission

AbstractAbstract 367Autologous bone marrow transplantation as post remission treatment in patients with acute myeloid leukemia (AML) has been associated with reduced relapse rates as compared to postremission chemotherapy but this advantage was offset by delayed hematopoietic recovery, excess mortality, and frequent premature withdrawals from planned transplantation. Autologous stem cell transplantation (ASCT) following myeloablative chemotherapy has regained interest when peripheral blood stem cells became available because many of the disadvantages of marrow grafts could be circumvented by the use of peripheral blood transplants. However, the clinical benefit of ASCT in comparison to consolidation chemotherapy has not been critically assessed in large prospective cohorts of patients with long term follow up. To define the optimal postremission strategy, AML patients up to 60 yrs in complete remission after two cycles of intensive chemotherapy according to the HOVON 29 or HOVON 42 protocol (NEJM 2003;349:743) and not eligible for allogeneic SCT were randomly assigned to a third cycle of chemotherapy with etoposide (100 mg/m2 days 1–5) and mitoxantrone (10 mg/m2 days 1–5) vs. ASCT with busulfan (4 mg/kg days 1–4) and cyclofosfamide (60 mg/kg days 5–6) as conditioning regimen followed by reinfusion of G-CSF mobilized peripheral blood stem cells. 261 patients were assigned to the third course of consolidation chemotherapy and 258 patients were assigned to ASCT. At least 90% of the patients received the planned treatment arm. The two groups were evenly matched with respect to various factors, including age and cytogenetic risk (intermediate risk group: 82% of chemotherapy arm and 79% of ASCT-arm). Median follow up of patients alive is more than 8 years. A significantly faster recovery of peripheral blood granulocyte and platelet count was seen following ASCT (ANC >0.5 109/l at day +14 and +28 was demonstrated in 42% vs. 1% and 88% vs. 32% of patients in the ASCT vs. chemotherapy arm respectively (p= .000). Comparable results were obtained for platelet recovery. Non-relapse mortality was estimated 4% in the ASCT arm and 1% in the chemotherapy arm. The ASCT treatment arm showed a better relapse free survival (RFS) at five years than the chemotherapy arm (39% vs. 29%, p= 0.055, HR 0.82 (0.66-1.1). In the ASCT arm 151 patients had recurrence of AML, while 186 patients relapsed in the chemotherapy arm, corresponding with actuarial relapse rate of 57% and 70% respectively. Overall survival (OS) was not different between both arms (44% vs. 40% at 5 years, p=0.9) due to a greater number of patients of the chemotherapy arm receiving salvage therapy by allogeneic SCT (25% vs. 17% of relapsed patients in the ASCT arm) or salvage by ASCT (15% vs. 1%). The relapsed patients that were given SCT salvage reached a 5 year survival of 30% against only 3% for the patients without SCT salvage. It resulted in 5 year survival probabilities after relapse of 15% in the chemotherapy arm versus 7% in the ASCT arm. Collectively, the findings from this large and mature randomized study demonstrate an advantage of consolidation by ASCT as compared to chemotherapy for AML patients in first complete remission both in terms of RFS and hematopoietic regeneration. No difference in OS was observed, possibly due to better salvage options in case of relapse after chemotherapy. Disclosures:Ossenkoppele:Bristol-Myers Squibb: Honoraria, Participated in advisory boards; Novartis: Particpated in advisory boards, Research Funding.

Impact of prior autologous stem cell transplant (ASCT) in patients receiving bortezomib or dexamethasone for relapsed/refractory multiple myeloma in the APEX trial

7546 Background: The phase 3 international APEX trial demonstrated significantly superior overall survival (OS), time to progression (TTP), and overall response rate (ORR: CR+PR, EBMT criteria) with bortezomib (VELCADE [Vc]) therapy for relapsed myeloma compared with dexamethasone (Dex). ASCT is a common component of initial therapy and may affect the outcome of salvage therapies. Methods: This analysis aimed to evaluate the impact of prior ASCT on the APEX results. TTP, OS, and ORR were analyzed by prior ASCT treatment. Results: Of 669 randomized patients, 451 (67%) had received prior ASCT (median follow-up in survivors was 21.9 months); in this group, Vc led to higher ORR compared with Dex (41% vs 18%, p &lt; 0.001), higher CR rate (8% vs 0.5%, p &lt; 0.001), and longer TTP and OS (see table), the latter despite crossover to Vc of &gt;62% of patients originally assigned to Dex. A subset of 156 (23%) patients had ASCT as their only prior line of therapy (median follow-up in survivors was 20.0 months), with similar superiority of Vc compared with Dex in ORR (48% vs 29%, p = 0.004), CR rate (6% vs 2%, p &gt; 0.05), and TTP. Among 218 (33%) patients with no prior ASCT (median follow-up in survivors was 21.7 months), Vc was also superior to Dex in ORR (32% vs 18%, p = 0.025), CR rate (4% vs 1%, p &gt; 0.05), and TTP. Conclusions: Vc is consistently superior to Dex in ORR, CR rate, and TTP, regardless of prior ASCT status, and OS is superior in patients who had received prior ASCT. Vc is an effective therapy for myeloma relapsing after ASCT. NE = not estimable. [Table: see text] [Table: see text]

A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model

AbstractSalvage of patients with relapsed and refractory Hodgkin disease (HD) with high-dose chemoradiotherapy (HDT) and autologous stem cell transplantation (ASCT) results in event-free survival (EFS) rates from 30% to 50%. Unfortunately, the reduction in toxicity associated with modern supportive care has improved EFS by only 5% to 10% and has not reduced the relapse rate. Results of a comprehensive 2-step protocol encompassing dose-dense and dose-intense second-line chemotherapy, followed by HDT and ASCT, are reported. Sixty-five consecutive patients, 22 with primary refractory HD and 43 with relapsed HD, were treated with 2 biweekly cycles of ifosfamide, carboplatin, and etoposide (ICE). Peripheral blood progenitor cells from responding patients were collected, and the patients were given accelerated fractionation involved field radiotherapy (IFRT) followed by cyclophosphamide-etoposide and either intensive accelerated fractionation total lymphoid irradiation or carmustine and ASCT. The EFS rate at a median follow-up of 43 months, as analyzed by intent to treat, was 58%. The response rate to ICE was 88%, and the EFS rate for patients who underwent transplantation was 68%. Cox regression analysis identified 3 factors before the initiation of ICE that predicted for outcome: B symptoms, extranodal disease, and complete remission duration of less than 1 year. EFS rates were 83% for patients with 0 to 1 adverse factors, 27% for patients with 2 factors, and 10% for patients with 3 factors (P < .001). These results compare favorably with other series and document the feasibility and efficacy of giving uniform dose-dense and dose-intense cytoreductive chemotherapy and integrating accelerated fractionation radiotherapy into an ASCT treatment program. This prognostic model provides a basis for risk-adapted HDT.