Trends in Utilization of Stored Cryopreserved Autologous Peripheral Hematopoietic Cells (APBHC) Intended for a Second (or beyond) Autologous Hematopoietic Cell Transplantation (AHCT) in Patients with Multiple Myeloma (MM): A Single Center Experience

Abstract Background: AHCT is a standard of care treatment for eligible patients (pts) with MM. Most consensus guidelines recommend that at the time of first AHCT, enough APBHC should be collected to perform two AHCT. However, recent studies have shown that with each decade after 1990, the use of cryopreserved APBHC for a salvage AHCT has declined and is now in the range of 4.6-15% in the decade between 2010-2018. The collection and storage of APBHC for two AHCT incurs additional costs and a prior single center cost analysis revealed that having had collected for just one AHCT in a cohort of 726 MM pts would have saved 3.8 million USD between 1993 and 2011. 1 Most centers that perform AHCT for MM pts continue to collect and store PBAHC for 2 AHCT. Herein we evaluate utilization trends and costs associated with cryopreserved APBHC in patients with MM. Methods: We retrospectively evaluated the clinicopathologic data from 440 patients with MM who underwent APBHC mobilization and collection at Mayo Clinic Florida between 2010 and 2019. The number of apheresis/collection sessions and APBHC product collection yields were determined for patients who were mobilized by any method. We estimated the costs involved in PBSC collection (apheresis) and cryopreservation storage based on our institution-specific charges as of May 2021. The cost of 1 session of APBHC collection/apheresis was $4,680 and the cost of 1 year of APBHC cryopreservation was $4,790 per patient. Statistical analysis was performed using JMP Pro 15 (SAS). Chi-square and Fischer exact tests were used to carry out univariate analysis for categorical variables and Wilcoxon rank sum/Kruskal Wallis for continuous variables. Results: Patient demographics are shown in Table 1. 440 pts underwent at least one collection session and 347 underwent at least 1 AHCT. The median number of mobilization sessions was 1 (95% CI 1.0-1.03), the median number of collection/apheresis sessions was 2.0 (95% CI 2.39-2.59), 84.3% (n=371) required ≥1 collection session. The median number of CD34 stem cells collected was 7.6 x10 6 (95% CI 7.76-8.19 x10 6), and the median number of infused CD34 cells was 4 x10 6(95% CI 4.13-4.37x10 6). The median cost of total collection sessions (defined as # of apheresis/collection sessions x $4,680) was $9,360 per pt (95% CI $11,181-$12,100). The median cost of cryopreservation (defined as # of years of storage x $4,790) was $19,160 per pt (95% CI $9,682-$22,252). The median number of years of storage was 4 (95% CI 4.11-4.65). 77(17.5%) pts have had APBHC in storage for <2 years, 218 (49.5%) have had APBHC in storage for 2-5 years, and 145 (33%) had have APBHC in storage for >5 years. The median time from MM diagnosis to AHCT was 9.0 months (range 13.8-18.5). 82% of patients collected enough APBHC (≥6x10 6, at least 3x10 6 per AHCT)for 2 AHCT. 8% of patients had all APBHC infused during their first AHCT, 83.5% had half of their APBHC infused during their first AHCT, and 8.1% had a different amount of APBHC infused during their first AHCT thus 91.6% of patients who collected APBHC had cells in storage. The median OS for the entire cohort after AHCT was 94.7 months (95% CI 88.6-100). Out of 347 patients who had stem cells in cryopreservation, 5 (1.4%) underwent a salvage AHCT and 3 (0.9%) underwent a tandem AHCT. 61% percent of patients had ≥1 excess collection sessions for APBHC that ultimately went unused. The median cost of excess collection sessions was $4,680 per pt (range, $4,680-$32,760) and the median total cost for excess collection sessions plus costs for storage was $23,840 per pt (range, $4,680-$85,450). The sum of costs of excess collection sessions was $2,077,920 and the sum of costs of cryopreservation was $5,812,665. Conclusion: The results of this single center analysis show that only 1.4% of patients underwent a salvage AHCT between 2010 and 2019 while 91.6% had APBHC left in storage which confirms the increase in storage of cryopreserved APBHC and declining trend in the use of stored APBHC for salvage AHCT in pts with MM. This is likely due to the advent of next generation novel therapies such as monoclonal antibodies, proteasome inhibitors and immunomodulatory agents. Excess collections, and cryopreservation of unused APBHC incur a cost of nearly $8 million. Institutional policies regarding universal APBHC collection and long-term storage should be reevaluated. 1Phipps C, et al. Bone Marrow Transplantation 2015:50;663-667. Figure 1 Figure 1. Disclosures Murthy: CRISPR Therapeutics: Research Funding. Ailawadhi: Sanofi: Consultancy; Medimmune: Research Funding; Genentech: Consultancy; Ascentage: Research Funding; Pharmacyclics: Consultancy, Research Funding; Xencor: Research Funding; Janssen: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; AbbVie: Consultancy; Beigene: Consultancy; GSK: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Takeda: Consultancy; Cellectar: Research Funding; Karyopharm: Consultancy.

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Efficacy, Complication Rates, and Cost Effectiveness of Chemotherapy Plus Granulocyte Colony Stimulating Factor Conditioned Mobilisation of Peripheral Blood Haematopoietic Stem Cells in Over 150 Patients with Haematological Malignancies

Blood ◽

10.1182/blood.v112.11.2378.2378 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2378-2378 ◽

Cited By ~ 4

Author(s):

Ian H Gabriel ◽

Juliet Sharon ◽

Eduardo Olavarria ◽

Amin Rahemtulla ◽

Edward Kanfer ◽

...

Keyword(s):

Stem Cells ◽

Multivariate Analysis ◽

Stem Cell ◽

Peripheral Blood ◽

Univariate Analysis ◽

Significant Risk ◽

Organ Damage ◽

Complication Rates ◽

Median Cost ◽

The Cost

Abstract Autologous stem cell transplantation (ASCT) remains the standard consolidation therapy for patients with multiple myeloma (MM) and chemosensitive relapsed lymphoma (r-Ly). Peripheral blood as a source of stem cells (PBSC) has largely replaced marrow and has the advantage of improved engraftment rates. PBSC are routinely collected following administration of chemotherapy in combination with GCSF. However, the resultant pancytopenia poses a significant risk to patients and additional chemotherapy prior to ASCT may lead to increased end organ damage potentially precluding future therapies (including ASCT). Novel agents can achieve PBSC mobilisation without the use of cytotoxics. In the advent of such drugs, we reviewed the efficacy of, and complications experienced by patients during PBSC mobilisation. We also analysed the cost implications of adverse events. Of 151 consecutive attempts, 13.2% of patients failed to reach our criteria in order to attempt pheresis (1 × 104 CD34 cells/ml). Of those achieving target and undergoing pheresis, 6% did not achieve an adequate cell dose for future ASCT (2 × 106CD34+cells/kg) giving an overall failure rate of 19.2%. Furthermore 17.9% failed to harvest our ideal of 4 × 106/kg (permitting >1 ASCT procedure). Factors contributing to failure in achieving target CD34+ve PB count on univariate analysis were; >2 lines of previous chemotherapy and occurrence of neutropenic sepsis (NS (p=0.002, and 0.005 respectively). These factors remained significant on multivariate analysis (RR: 4.4 and 6.2). These same factors also affected CD34+ cell yield on both univariate and multivariate analysis (RR: 3.3 and 4.6). No differences were seen between MM and r-Ly. Overall, the complication rate was 34.4%, with 24.1% of patients suffering NS requiring admission. The mortality rate was 1.3% (NS and intra-cranial bleed). Of those developing NS, only 52% eventually harvested sufficient cells, but with a median delay of 3 days. The median cost of PBSC collection was $17,381.46 ($1,978.97–$39,355.73). NS significantly increased the cost of mobilisation at a median cost of $25,532.95 vs $16,4921) (p=<0.0001). Conclusion: Our results suggest that patients who are potential candidates for ASCT should be harvested as soon as they achieve remission to prevent failure following additional therapy upon relapse. One fifth of patients will fail. The risks associated with current mobilisation protocols are substantial, and also impact greatly on cost, particularly relevant in the current climate of economic probity. Therefore these data suggests that transplant centres should consider the use of non-myelosuppressive agents either in place of, or as a dose reduction strategy for autologous stem cell procurement.

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Cost Analysis of Stored Autologous Peripheral Blood Stem Cells for a Second Autologous Transplantation in Multiple Myeloma Patients: A Markov Model

Blood ◽

10.1182/blood.v128.22.1184.1184 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1184-1184

Author(s):

Anca Prica ◽

Vinita Dhir ◽

Nuchanan Areethamsirikul ◽

Christine Chen ◽

Donna Reece ◽

...

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Stem Cell ◽

Cost Analysis ◽

Research Funding ◽

Median Number ◽

Time Period ◽

The Mean ◽

The Cost ◽

Cell Storage

Abstract Background: Autologous stem cell transplantation (ASCT) is a standard part of first-line therapy for pts <70 years of age with multiple myeloma. If remission length is ≥ 2 years, our policy is to offer a salvage transplant upon relapse if the patient is eligible. Many centers, including ours, collect adequate CD34+ cells for two transplantations, as there is concern for poor mobilization post-therapy, including lenalidomide. However, no good data truly quantifies this rate, given plerixafor availability. The advent of novel therapies has reduced the use of second salvage ASCT (ASCT2), and the prolonged storage of cryopreserved stem cells imposes a significant economic burden. We performed a cost analysis to compare the cost of mobilizing and storing stem cells for ASCT2 in all patients versus remobilizing and collecting for ASCT2 upon relapse in eligible patients. Methods: We developed a Markov decision-analytic model to compare the two strategies in a hypothetical cohort of 60 year old patients newly-diagnosed with multiple myeloma. The model simulates the clinical course of 10,000 patients over a 10 year time horizon, with the end point of costs per patient per strategy. Baseline probabilities were derived from published studies as well as analysis of multiple myeloma patients who underwent ASCT1 at Princess Margaret Cancer Centre between January 2003 and December 2012. Key health states include probability of progression (pPD) and death in the 1st 2 years post-ASCT1, pPD >2 years post-transplantation, probability of having an ASCT2 upon relapse vs. a non-ASCT approach. Direct costs were collected from a Canadian public health payer's perspective. Costs were obtained from hospital and provincial databases, as well as the literature and presented in 2016 Canadian dollars. Key costs collected were the cost of mobilization for 2 transplants vs. 1, the cost of remobilization and the cost of stem cell storage. Costs were discounted at 3%. All patients were assumed ASCT2 eligible at relapse. In the re-mobilization arm, all patients were successfully remobilized, with an assumed >50% rate of plerixafor use. Results: 938 patients underwent ASCT1 at Princess Margaret Cancer Centre during this time period, with stem cells stored for a salvage transplant. The mean age of transplanted patients at ASCT1 was 58.4 yrs. The mean number of aphaeresis days required to collect enough cells for 2 stem cell transplants was 1.53 days. The calculated mean aphaeresis days required to collect for 1 transplant was 1.15 days. The median number of bags processed for 2 ASCT was 4, as such, after ASCT1, the median number of bags stored per person was 2. 74 patients (7.9%) underwent ASCT2 over the 10 year period. Most (73%) occurred early, 2-5 yrs post-ASCT1, with only 27% beyond this time period. Over the 10 yr horizon, the total mobilization and storage cost of the stored stem cells strategy was C$9702, versus C$7229 for the re-mobilization strategy, thus storing stem cells for a potential ASCT2 costs an extra C$2473 per patient. Our centre collects such stem cells in >100 pts/yr, at a cost of approximately $250,000. The model was robust to one-way sensitivity analyses of all variables. Storing stem cells only becomes the less costly strategy if the storage costs are less than C$125/6mo or C$10/bag/month (figure 1). Conclusions: The use of salvage ASCT for patients who sustain at least a 2 yr remission with their first is low (less than 10%), and it is associated with significant costs to the system unless the costs of stem cell storage are minimal. With the availability of plerixafor, the cost savings would justify a re-mobilization approach for the minority of patients that are eligible for a salvage ASCT. Figure 1 Figure 1. Disclosures Prica: Janssen: Honoraria; Celgene: Honoraria. Chen:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Research Funding. Reece:Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Novartis: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; BMS: Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Trudel:Glaxo Smith Kline: Honoraria, Research Funding; Celgene: Honoraria; Novartis: Honoraria; Oncoethix: Research Funding. Tiedemann:Takeda Oncology: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Amgen: Honoraria; BMS Canada: Honoraria. Kukreti:Celgene: Honoraria; Lundbeck: Honoraria; Amgen: Honoraria.

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Antiretroviral Resistance and Pregnancy Characteristics of Women with Perinatal and Nonperinatal HIV Infection

Infectious Diseases in Obstetrics and Gynecology ◽

10.1155/2016/4897501 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Gweneth B. Lazenby ◽

Okeoma Mmeje ◽

Barbra M. Fisher ◽

Adriana Weinberg ◽

Erika K. Aaron ◽

...

Keyword(s):

Drug Resistance ◽

Hiv Infection ◽

Univariate Analysis ◽

Categorical Variables ◽

Continuous Variables ◽

Resistance Mutations ◽

Hiv Drug Resistance ◽

Fourfold Increase ◽

Perinatal Hiv ◽

Adverse Pregnancy

Objective. To compare HIV drug resistance in pregnant women with perinatal HIV (PHIV) and those with nonperinatal HIV (NPHIV) infection.Methods. We conducted a multisite cohort study of PHIV and NPHIV women from 2000 to 2014. Sample size was calculated to identify a fourfold increase in antiretroviral (ARV) drug resistance in PHIV women. Continuous variables were compared using Student’st-test and Wilcoxon rank-sum tests. Categorical variables were compared usingχ2and Fisher’s exact tests. Univariate analysis was used to determine factors associated with antiretroviral drug resistance.Results. Forty-one PHIV and 41 NPHIV participants were included. Women with PHIV were more likely to have drug resistance than those with NPHIV ((55% versus 17%,p=0.03), OR 6.0 (95% CI 1.0–34.8),p=0.05), including multiclass resistance (15% versus 0,p=0.03), and they were more likely to receive nonstandard ARVs during pregnancy (27% versus 5%,p=0.01). PHIV and NPHIV women had similar rates of preterm birth (11% versus 28%,p=0.08) and cesarean delivery (47% versus 46%,p=0.9). Two infants born to a single NPHIV woman acquired HIV infection.Conclusions. PHIV women have a high frequency of HIV drug resistance mutations, leading to nonstandard ARVs use during pregnancy. Despite nonstandard ARV use during pregnancy, PHIV women did not experience increased rates of adverse pregnancy outcomes.

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Financial Incentives to Increase Stool Collection Rates for Microbiome Studies in Adult Bone Marrow Transplant Patients

Blood ◽

10.1182/blood-2019-128702 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5775-5775

Author(s):

Jillian C. Thompson ◽

Yi Ren ◽

Kristi M. Romero ◽

Meagan V. Lew ◽

Amy T. Bush ◽

...

Keyword(s):

Financial Incentives ◽

Research Funding ◽

Intervention Group ◽

Outpatient Setting ◽

Historical Control Group ◽

Historical Control ◽

Categorical Variables ◽

Control Group ◽

Continuous Variables ◽

Stool Samples

Introduction: Dysbiosis of the gut microbiome during hematopoietic stem cell transplantation (HCT) is associated with adverse post-transplant outcomes such as graft-versus-host disease, bloodstream infections, and mortality. In order to learn more about the role of the microbiome in HCT in adverse clinical outcomes, researchers collect stool samples from patients at various time points throughout HCT. However, unlike blood samples or skin swabs, stool collection requires active subject participation, particularly in the outpatient setting, and may be limited by patient aversion to handling stool. By providing study participants with compensation for their stool samples, we hypothesize that we can significantly increase stool collection rates. Methods: We performed a prospective cohort study on the impact of financial incentives on stool collection rates for microbiome studies. The intervention group consisted of allogeneic (allo)-HCT patients from 05/2017-05/2018 who were compensated with a $10 gas gift card for each stool sample. The intervention group was compared to a historical control group consisting of allo-HCT patients from 11/2016-05/2017 who provided stool samples before the incentive was implemented. To control for potential changes in collections over time, we also compared a contemporaneous control group of autologous (auto)-HCT patients from 05/2017-05/2018 with a historical control group of auto-HCT patients from 11/2016-05/2017; neither auto-HCT groups were compensated. Allo-HCT patients were required to give samples at pre-HCT, day 0 (the day of HCT), and days 7, 14, 21, 30, 60, and 90 post-HCT. Auto-HCT patients were required to give samples at pre-HCT and days 7, 14, and 90 post-HCT. Collection rates were defined as the number of samples provided divided by the number of time points for which we attempted to obtain samples. Patient characteristics were summarized by proportions for categorical variables and median with interquartile ranges for continuous variables. Chi-square tests or Fisher's exact tests were used to compare categorical variables, as appropriate, and Wilcoxon Rank Sum tests or t-tests were used to compare continuous variables, as appropriate. This study was approved by the Duke Institutional Review Board, and informed consent was obtained from all patients. Results: There were 35 allo-HCT patients in the intervention group, 19 allo-HCT patients in the historical control group, 142 auto-HCT patients in the contemporaneous control group, and 75 auto-HCT patients in the historical control group. Groups were similar with regard to baseline demographics such as age, race, and gender. While allo-HCT patients were more likely to have leukemia and auto-HCT patients were more likely to have lymphoma and multiple myeloma, there were no differences in disease rates across the study periods. Allo-HCT patients in the intervention group had significantly higher average overall collection rates when compared to the historical control group allo-HCT patients (80% vs 37%, p<0.001), as well has significantly higher average outpatient collection rates (84% vs 23%, p<0.001) and average inpatient collection rates (71% vs 46%, p=0.04). In contrast, there were no significant differences in overall average collection rates between the auto-HCT patients in the contemporaneous control and historical control group (36% vs 32%, p=0.28), as well as the average outpatient collection rates (30% vs 28%, p=0.54) and the average inpatient collection rates (46% vs 59%, p=0.25). Discussion: Our results demonstrate that even a modest incentive can significantly increase collection rates. Use of a contemporaneous control group to account for potential differences in stool collection rates over time strengthens our finding that financial incentives increase stool collection rates. Furthermore, the significant increase in collection rates in the outpatient setting highlights the role of the incentive when patient participation is needed, as opposed to the inpatient setting in which the nurse assists with collection. While this study uses a specialized HCT patient population, these results may be generalizable to future studies and aid other researchers in obtaining stool samples needed for future microbiome studies. Disclosures Peled: Seres Therapeutics: Other: IP licensing fees, Research Funding. van den Brink:Acute Leukemia Forum (ALF): Consultancy, Honoraria; Juno Therapeutics: Other: Licensing; Merck & Co, Inc.: Consultancy, Honoraria; Seres Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Therakos: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Flagship Ventures: Consultancy, Honoraria; Evelo: Consultancy, Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Magenta and DKMS Medical Council: Membership on an entity's Board of Directors or advisory committees. Sung:Novartis: Research Funding; Merck: Research Funding; Seres: Research Funding.

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Non-Prescription Antibiotic Use For People Aged 15 Years Or Older For Cough In China: A Community-Based Survey

10.21203/rs.3.rs-539716/v1 ◽

2021 ◽

Author(s):

Yan Luo ◽

Xuewen Tang ◽

Lingling Ding ◽

Zhujun Shao ◽

Jianxing Yu ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Univariate Analysis ◽

Antibiotic Use ◽

Categorical Variables ◽

Continuous Variables ◽

Chi Square ◽

Main Driver ◽

Antibiotics Use ◽

Chi Square Test ◽

Use Behavior

Abstract Background Non-prescription antibiotic use at community is a main driver of antimicrobial resistance. Cough is a common condition and prevalent in all communities, including China. This study aims to investigate the non-prescription antibiotic use for cough in China and explore to which extent antibiotic use knowledge was correctly instructed in communities.Methods A probability-proportionate-to-size (PPS) sampling method was adopted to survey from all 14 communities in Yiwu city, China. All participants were investigated by face-to-face interview on Portable Android Devices (PADs). The continuous variables were presented by mean and standard deviation (SD) or medium and inter-quartile range (IQR). The categorical variables were presented using percentage or constituent ratio. Chi-square test for univariate analysis and logistic regression for multivariate analysis were conducted to assess the odds ratios (ORs) and 95% confidence intervals (CIs), respectively.Results A total of 3034 respondents across the 14 communities and the 50 natural villages/streets completed all key items of the questionnaire. Of 2400 (79.10%) respondents stated that they experienced cough in the past 12 months with the medium age of 36.5 (IQR: 26-49) and 12.21% (293/2400) respondents had the non-prescription antibiotic use behavior. Among those 293 respondents, the proportion of non-prescription antibiotic use for cough peaked at around 16% among people aged 30-39 years old. The major sources of antibiotics were pharmacy (77.70%) and/or family storage (43.92%). As for antibiotic knowledge in 3034 participants, 61.8% participants had minimal knowledge on broad-spectrum antibiotic and 53.76% were not familiar about the effects of joint use.Conclusions Non-prescription antibiotics use for cough is prevalent in the community, especially among people in their thirties. Strengthened drug purchase regulation and well-trained professional pharmacists would be promising alternatives to ameliorate AMR. Moreover, penetrating antibiotics knowledge to common citizens and is an urgent task to alleviate antimicrobial resistance. Therefore, proactive policies and regulations should be made to improve current situations.

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Impact of Induction Treatment on Stem Cell Collection: A COVID Related Study

Blood ◽

10.1182/blood-2021-149812 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4848-4848

Author(s):

Brad Rybinski ◽

Ashraf Z. Badros ◽

Aaron P. Rapoport ◽

Mehmet Hakan Kocoglu

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Research Funding ◽

Median Number ◽

Cell Transplant ◽

Cd34 Cells ◽

Significant Difference ◽

Number Of Cycles ◽

Time Required ◽

Stem Cell Collection

Abstract Introduction: Standard induction therapy for multiple myeloma consists of 3-6 cycles of bortezomib, lenalidomide, and dexamethasone (VRd) or carfilzomib, lenalidomide and dexamethasone (KRd). Receiving greater than 6 cycles of a lenalidomide containing regimen is thought to negatively impact the ability to collect sufficient CD34+ stem cells for autologous stem cell transplant (Kumar, Dispenzieri et al. 2007, Bhutani, Zonder et al. 2013). Due to the COVID-19 pandemic, at least 20 patients at University of Maryland Greenebaum Comprehensive Cancer Center (UMGCC) had transplant postponed, potentially resulting in prolonged exposure to lenalidomide containing induction regimens. Here, in the context of modern stem cell mobilization methods, we describe a retrospective study that suggests prolonged induction does not inhibit adequate stem cell collection for transplant. Methods: By chart review, we identified 56 patients with multiple myeloma who received induction with VRd or KRd and underwent apheresis or stem cell transplant at UMGCC between 10/1/19 and 10/1/20. Patients were excluded if they received more than 2 cycles of a different induction regimen, had a past medical history of an inborn hematological disorder, or participated in a clinical trial of novel stem cell mobilization therapy. We defined 1 cycle of VRd or KRd as 1 cycle of "lenalidomide containing regimen". In accordance with routine clinical practice, we defined standard induction as having received 3-6 cycles of lenalidomide containing regimen and prolonged induction as having received 7 or more cycles. Results: 29 patients received standard induction (Standard induction cohort) and 27 received prolonged induction (Prolonged induction cohort) with lenalidomide containing regimens. The median number of cycles received by the Standard cohort was 6 (range 4-6), and the median number of cycles received by the Prolonged cohort was 8 (range 7-13). The frequency of KRd use was similar between patients who received standard induction and prolonged induction (27.58% vs. 25.93%, respectively). Standard induction and Prolonged induction cohorts were similar with respect to clinical characteristics (Fig 1), as well as the mobilization regimen used for stem cell collection (p = 0.6829). 55/56 patients collected sufficient stem cells for 1 transplant (≥ 4 x 10 6 CD34 cells/kg), and 40/56 patients collected sufficient cells for 2 transplants (≥ 8 x 10 6 CD34 cells/kg). There was no significant difference in the total CD34+ stem cells collected at completion of apheresis between standard and prolonged induction (10.41 and 10.45 x 10 6 CD34 cells/kg, respectively, p = 0.968, Fig 2). Furthermore, there was no significant correlation between the number of cycles of lenalidomide containing regimen a patient received and total CD34+ cells collected (R 2 = 0.0073, p = 0.5324). Although prolonged induction did not affect final stem yield, prolonged induction could increase the apheresis time required for adequate collection or result in more frequent need for plerixafor rescue. There was no significant difference in the total number of stem cells collected after day 1 of apheresis between patients who received standard or prolonged induction (8.72 vs. 7.96 x 10 6 cells/kg, respectively, p = 0.557). However, patients who received prolonged induction were more likely to require 2 days of apheresis (44% vs. 25%, p = 0.1625) and there was a trend toward significance in which patients who received prolonged induction underwent apheresis longer than patients who received standard induction (468 vs 382 minutes, respectively, p = 0.0928, Fig 3). In addition, longer apheresis time was associated with more cycles of lenalidomide containing regimen, which neared statistical significance (R 2 = 0.0624, p = 0.0658, Fig 4). There was no significant difference between standard and prolonged induction with respect to the frequency of plerixafor rescue. Conclusions: Prolonged induction with lenalidomide containing regimens does not impair adequate stem cell collection for autologous transplant. Prolonged induction may increase the apheresis time required to collect sufficient stem cells for transplant, but ultimately clinicians should be re-assured that extending induction when necessary is not likely to increase the risk of collection failure. Figure 1 Figure 1. Disclosures Badros: Janssen: Research Funding; J&J: Research Funding; BMS: Research Funding; GlaxoSmithKline: Research Funding.

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Current Status of Core and Advanced Adult Gastrointestinal Endoscopy Training in Canada: Survey of Existing Accredited Programs

Canadian Journal of Gastroenterology ◽

10.1155/2013/186284 ◽

2013 ◽

Vol 27 (5) ◽

pp. 267-272 ◽

Cited By ~ 8

Author(s):

Xin Xiong ◽

Alan N Barkun ◽

Kevin Waschke ◽

Myriam Martel ◽

Keyword(s):

Endoscopic Ultrasonography ◽

Median Number ◽

Current Status ◽

Categorical Variables ◽

Continuous Variables ◽

Endoscopy Training ◽

Endoscopic Gastrostomy ◽

Canadian Association ◽

Training Fellowship ◽

Endoscopy Simulators

OBJECTIVE: To determine the current status of core and advanced adult gastroenterology training in Canada.METHODS: A survey consisting of 20 questions pertaining to core and advanced endoscopy training was circulated to 14 accredited adult gastroenterology residency program directors. For continuous variables, median and range were analyzed; for categorical variables, percentage and associated 95% CIs were analyzed.RESULTS: All 14 programs responded to the survey. The median number of core trainees was six (range four to 16). The median (range) procedural volumes for gastroscopy, colonoscopy, percutaneous endoscopic gastrostomy and sigmoidoscopy, respectively, were 400 (150 to 1000), 325 (200 to 1500), 15 (zero to 250) and 60 (25 to 300). Eleven of 13 (84.6%) programs used endoscopy simulators in their curriculum. Eight of 14 programs (57%) provided a structured advanced endoscopy training fellowship. The majority (88%) offered training of combined endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasonography. The median number of positions offered yearly for advanced endoscopy fellowship was one (range one to three). The median (range) procedural volumes for ERCP, endoscopic ultrasonography and endoscopic mucosal resection, respectively, were 325 (200 to 750), 250 (80 to 400) and 20 (10 to 63). None of the current programs offered training in endoscopic submucosal dissection or natural orifice transluminal endoscopic surgery.CONCLUSION: Most accredited adult Canadian gastroenterology programs met the minimal procedural requirements recommended by the Canadian Association of Gastroenterology during core training. However, a more heterogeneous experience has been observed for advanced training. Additional studies would be required to validate and standardize evaluation tools used during gastroenterology curricula.

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Impact of Molecular Mutations on Treatment Response to Hypomethylating Agents in MDS

Blood ◽

10.1182/blood.v118.21.461.461 ◽

2011 ◽

Vol 118 (21) ◽

pp. 461-461 ◽

Cited By ~ 5

Author(s):

Fabiola Traina ◽

Anna M Jankowska ◽

Valeria Visconte ◽

Yuka Sugimoto ◽

Hadrian Szpurka ◽

...

Keyword(s):

Treatment Response ◽

Predictive Value ◽

Research Funding ◽

Myeloproliferative Neoplasms ◽

Progression Free Survival ◽

Predictive Biomarker ◽

Median Number ◽

Categorical Variables ◽

Hypomethylating Agents ◽

Significant Difference

Abstract Abstract 461 Aberrant DNA methylation is a hallmark of myelodysplastic syndromes (MDS), MDS/myeloproliferative neoplasms (MDS/MPN) and secondary acute myeloid leukemia (sAML). It provides a rationale for treating these malignancies with hypomethylating agents like 5-azacitidine (AZA) and decitabine (DAC). However, treatment outcomes remain limited and heavily weighed on morphologic/cytogenetic results. The discovery of novel mutations has provided important insight into the pathogenesis of MDS and related disorders. Genes implicated in epigenetic regulation, including DNMT3A, TET2, IDH1/IDH2, EZH2, ASXL1 and UTX have been found mutated in MDS, while others have also been implicated in MDS pathogenesis. There is limited data on the predictive value of these genetic defects for treatment response and disease outcome. We hypothesized that these defects are important biomarkers predictive of response to hypomethylating agents. We studied 88 patients with MDS (RCUD=2, RARS=6, RCMD=11, MDS-U=3, RAEB-1/2=29, CMML1/2=16, MDS/MPN-U=5, RARS-T=5, AML from MDS=11) who received hypomethylating agents (AZA=53, DAC=24, both=11). The median number of cycles was 7 [range 1–35], median age was 69 years (range 42–82) and median follow-up was 18 months (range 0–76). Responses were scored according to IWG criteria. DNMT3A, TET2, IDH1/2, EZH2, ASXL1, UTX, KRAS, NRAS, CBL, RUNX1, TP53 and SF3B1 were sequenced using standard techniques. Categorical variables were analyzed using Chi-square statistics. Overall survival (OS) was analyzed using Kaplan-Meier; p-values ≤ 0.05 were considered statistically significant. Mutated patients were older than wild type (WT) cases (72 vs. 68 years, p=.01) but were well matched for marrow blast %, cytogenetic risk group and cycles of hypomethylating agents received. We found mutations in 40/88 (45%) patients. Mutations were most frequent in SF3B1 (6/11; 55%), ASXL1 (13/50; 26%), TET2 (18/88; 20%), KRAS (3/34; 9%), and DNMT3A (7/88; 8%). Less common were mutations in EZH2 (2/43; 5%), TP53 (1/23; 4%), IDH1 (4/88; 5%), IDH2 (3/88; 3%), and UTX (1/36;3%). No mutations were found in CBL, NRAS or RUNX1. Based on single mutations, overall response rate (ORR) was higher in mutated vs WT patients for DNMT3A (6/7 [86%] vs 33/81 [41%]; p=.02), ASXL1 (11/13 [85%] vs 14/37 [38%]; p=.003), and TET2 (12/18 [67%] vs. 27/70 [39%]; p=.03). All heterozygous DNMT3A mutants responded to hypomethylating agents. Differences remained significant when stratified to AZA treatment alone for DNMT3A (6/7 [86%] vs 21/56 [38%]; p=.01) and ASXL1 (9/11 [82%] vs 12/29 [41%]; p=.02) but not TET2 (6/10 [60%] vs 21/53 [40%]; p=0.22). The predictive value of combined mutations were analyzed for DNMT3A, TET2 and/or IDH1/2, showing better response to hypomethylating therapy in patients who had a mutation; ORR (mutated: 18/28 (64%) vs WT: 21/60 (35%); p=.01). This difference remained significant in patients receiving only AZA (n=53); ORR was 11/18 (61%) in mutant and 11/35 (31%) in WT patients (p=.03). No differences in ORR were noted for KRAS, EZH2 and IDH1/2 mutant and WT patients. No SF3B1 mutants responded to treatment while both patients with UTX and TP53 mutations responded. The frequency of AML evolution was also analyzed and showed no difference between mutant and WT cases for TET2 (7/18 [39%] vs 22/70 [31%];p=.52), ASXL1 (4/10 [40%] vs 11/35 [31%]; p=.61), and DNMT3A (3/7 [43%] vs 26/81 [32%];p=.56). No differences in OS and progression free survival (PFS) were noted between responders and non-responders to hypomethylating therapy (28 vs 17 mos, p=.25; 16 vs 8 mos, p=.54). Comparison of survival outcomes for mutant and WT patients showed no significant difference for DNMT3A (OS: 30 vs 21 mos, p=0.43; PFS: 20 vs 11, p=.53), ASXL1 (OS: 28 vs 22, p=.68; PFS: 16 vs 10, p=.88), and TET2 (OS: 30 vs 20 mos, p=.30). PFS was better in TET2 mutants compared to WT (19 vs 9, p=.03). No survival differences were noted between mutant and WT cases who responded to hypomethylating agents for DNMT3A (OS: 25 vs 28,p=.84; PFS: 14 vs 16, p=.78), ASXL1 (OS: 10 vs 18, p=.48; PFS: 10 vs 6, p=.76) TET2 (OS: 27 vs 16, p=.79; PFS: 18 vs10, p=.19). In conclusion, DNMT3A, ASXL1 and TET2 mutations were independently associated with a better response to hypomethylating drugs. Moreover, combined mutations in DNMT3A/TET2/IDH1/IDH2 may influence the response to hypomethylating agents, especially AZA supporting its role as a predictive biomarker in MDS treatment. Disclosures: Maciejewski: Celgene and Eisai, NIH, AA&MDS Foundation: Research Funding. Tiu:MDS Foundation Young Investigator Award: Research Funding.

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Non Interventional Prospective Clinical Study on Peripheral Blood Stem Cell Mobilization in Patients with Relapsed Lymphomas

Blood ◽

10.1182/blood.v124.21.3852.3852 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3852-3852

Author(s):

Gwendolyn van Gorkom ◽

Herve Finel ◽

Sebastian Giebel ◽

David Pohlreich ◽

Avichai Shimoni ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Clinical Study ◽

Research Funding ◽

Median Number ◽

Stem Cell Mobilization ◽

Prospective Clinical Study ◽

Cd34 Cells ◽

Relapsed Lymphoma ◽

Cell Mobilization

Abstract Introduction: Autologous stem cell transplantation (ASCT) is the standard of care for many patients with relapsed chemosensitive lymphoma. Peripheral blood stem cells have become the main source for the ASCT worldwide, because of its advantages over bone marrow. Several risk factors have been identified for poor stem cell mobilization, and diagnosis of lymphoma is one of the most important ones, with an inadequate stem cell harvest reported in 4 to 25% of the cases. Even though stem cell mobilization in relapsed lymphoma patients can be relatively difficult, mobilization strategies have not been standardized and there is a significant variation amongst centers. The aim of this non-interventional prospective clinical study was to review the mobilization strategies used by EBMT centers in relapsed lymphoma and to evaluate the failure rates. Methods: All EBMT centers were invited to participate in this non-interventional prospective clinical study that was started in 2010 and ended in 2014. Centers were requested to collect data on all consecutive patients with relapsed lymphoma considered to be candidates for an ASCT and were 18 years of age or older. Data collected included age, sex, diagnosis, number of prior chemotherapy regimens, mobilization regimen, collected CD34+ cells and marrow harvests. Results: In total, 275 patients with relapsed lymphoma from 30 EBMT centers were registered for this study. There were 158 males and 117 females with a median age of 51 (range 18 – 77) years; 181 patients (66%) with non-Hodgkin’s lymphoma (NHL) (DLBCL 28%, FL 17%, MCL 6%, PTL, 3%, other 12%) and 94 patients (34%) with Hodgkin’s lymphoma (HL). The median number of chemotherapy lines received before this relapse was one (range 1 – 8). 263 patients (96%) were mobilized with chemotherapy + G-CSF being DHAP (43%) and ESHAP (11%) the most frequent protocols, and 12 patients (4%) were mobilized with G-CSF alone. Thirteen patients (5%) who were mobilized with chemotherapy + G-CSF, received additional PLX in the first mobilization. These were all patients that were mobilized with chemotherapy as part of the mobilization regimen. Thirty patients (11%) failed to mobilize adequate stem cells (<2 x 10⁶ CD34+ cells/kg) during first mobilization despite the use of PLX in four patients. The median number of stem cells collected at first mobilization was 5.6 x 10⁶ CD34+ cells/kg (range: 0 – 82). In 255 patients (92.7%) only one mobilization course was given, 18 patients (6.5%) had two mobilization courses, 2 patients (0.7%) underwent three mobilization courses. Three patients had a mobilization failure after only G-CSF; they all were successfully harvested in a second attempt after chemotherapy + G-CSF. Five of the patients failing the first mobilization with chemotherapy + G-CSF received PLX at second mobilization, but only three succeeded. One patient failed both first and second mobilization and received PLX at third mobilization without success. 22 patients (8%) still had an inadequate amount of stem cells in the end. Of those, only 4 patients (1.5%) underwent bone marrow harvest. Conclusion: In the EBMT centers participating in this study, a primary mobilization strategy based on the combination of salvage chemotherapy plus G-CSF was used for virtually all patients with relapsed lymphoma. PLX was used in only 5% of the mobilization procedures during the time period analyzed. With 11% after the first mobilization attempt and 8% after several attempts, the failure rate was relatively low. Disclosures van Gorkom: Sanofi: Research Funding. Sureda:Takeda Pharmaceuticals International Co.: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics, Inc.: Research Funding.

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AGE-RELATED DIFFERENCES IN CO-MORBIDITY NUMBER, FUNDUS ATHEROSCLEROSIS LEVEL AND THE SERUM VALUES OF GSH-PX, HS-CRP AND HDL-C IN ELDERLY CHINESE PATIENTS

Journal of Aging Research and Lifestyle ◽

10.14283/jarcp.2016.89 ◽

2016 ◽

pp. 1-7

Author(s):

Q. Ruan ◽

Z. Yu ◽

C. Ma ◽

Z. Bao ◽

J. Li ◽

...

Keyword(s):

Oldest Old ◽

Univariate Analysis ◽

Apoe Genotype ◽

Chinese Patients ◽

Categorical Variables ◽

Continuous Variables ◽

Old Patients ◽

Biomarkers Of Aging ◽

Age Related ◽

Co Morbidity

Background: The ApoE genotype, atherosclerosis, status of inflammation, oxidative stress and co-morbidity may be detrimental to the elderly. Objectives: To identify biomarkers of aging. Setting: All subjects were Chinese elderly in Shanghai. Subjects: 549 outpatients (489 male, 60 female), divided into ≤74 year-old, 75-84 year-old and the oldest old (≥85 year-old ) groups. Methods: A univariate analysis was used to investigate 5 age-related categorical variables and 26 continuous variables. The related variables were used to find the independent biomarkers of aging by Multivariate logistic regression analyses. Results: The serum values of Glutathione peroxidase, HDL-C and C reactive protein, the number of co-morbidities and fundus atherosclerosis level were the main independent age-associated factors that influenced aging. Compared with ≥85 year-old individuals, ≤74 year-old individuals had fewer co-morbidities [OR, 0.757 (95% CI, 0.636, 0.902)], lower grades of fundus atherosclerosis [Grade 0: OR, 26.059 (95% CI, 4.705, 144.324)] and [Grade I: OR, 8.539 (95% CI, 3.555, 20.513)] and lower serum levels of HDL-C [OR, 0.127 (95% CI, 0.037, 0.433)]. However, 75-84 year-old patients had significantly lower plasma levels of GSH-px [OR, 0.986, (95% CI, 0.972, 1.00)], HDL-C [OR, 0.158 (95% CI, 0.054, 0.457)] and HsCRP [Grade I: OR, 8.516 (95% CI,1.630, 44.484)], [Grade II: OR,7.699 (95% CI,1.544, 38.388)] and [Grade III: OR,7.251 (95% CI,1.346, 39.070)]. Conclusion: The oldest old patients had significantly high anti-oxidant capability and serum HDL-C level. However, these patients also had a significantly high systemic inflammation, number of co-morbidities and grades of fundus atherosclerosis.

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