scholarly journals Patient-Reported Outcomes in Systemic Light-Chain Amyloidosis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4832-4832
Author(s):  
Rajshekhar Chakraborty ◽  
Lisa Rybicki ◽  
Christy J. Samaras ◽  
Beth M. Faiman ◽  
Jason Valent ◽  
...  
Keyword(s):  
Patient Reported Outcomes ◽  
Well Being ◽  
Al Amyloidosis ◽  
First Line ◽  
T Score ◽  
First Line Therapy ◽  
Outpatient Visits ◽  
Line Therapy ◽  
Patient Reported ◽  
The Mean

Abstract Background: Patients with systemic light-chain (AL) amyloidosis have a high symptom burden which can negatively impact their health-related quality of life (HRQoL). However, there is a lack of data on patient-reported outcomes (PROs) in this population in the current era of effective plasma cell directed therapies. The primary objectives of our study were to assess baseline HRQoL using FACT-G (Functional Assessment of Cancer Therapy-General) and PROMIS-GH (Patient Reported Outcomes Measurement Information System-Global Health), evaluate the degree of correlation between FACT-G and PROMIS-GH, and compare HRQoL by hematologic response to first-line therapy in systemic AL amyloidosis. Method: This was an observational study using the Cleveland Clinic Knowledge Program database, which contains HRQoL data captured at outpatient visits. FACT-G was administered every 90 days since its implementation on September 2012. PROMIS-GH was implemented in October 2015, initially administered every 30 days and subsequently every 90 days since July 2017. Results: A total of 81 patients with systemic AL amyloidosis diagnosed between September 2012 and December 2017 and ≥1 HRQoL measurement were included in our analysis. The median age at diagnosis was 64 years. Cardiac involvement at diagnosis was present in 49% of patients. The most common induction therapy was Bortezomib-Cyclophosphamide-Dexamethasone (86%). Autologous stem cell transplantation was performed in 38% of patients. Data on HRQoL at baseline (≤2 months from diagnosis) using FACT-G was available for 43 patients. The mean FACT-G total score at baseline was 74 (standard deviation [S.D.] ±15). In comparison, the mean FACT-G total score for general US population is 80.1 (±18.1) and that of US cancer patients is 79.3 (±17.0) [Normative data from Pearman et al; Cancer. 2014]. Maximal HRQoL deficit was seen in the functional well-being (FWB) domain of FACT-G, with the mean score being >0.5 S.D. below that of the general population (Table 1). Data on HRQoL at baseline using PROMIS-GH was available for 18 patients. There was a significant deficit in global physical health (GPH) compared to the general population, with a mean T-score of 37.7 (±7.8) [Mean T-score in general US population being 50±10]. The mean T-score for global mental health (GMH) was 44.4 (±6.7). A total of 72 patients had 128 outpatient visits where FACT-G and PROMIS-GH were captured concurrently (range, 1-4 visits per patient). Using Cohen's criterion, GPH domain of PROMIS-GH had a large and statistically significant correlation with FACT-G total (r=0.66), physical well being (PWB) (r=0.77) and FWB (r=0.66) scores. PROMIS GMH domain also had a strong and statistically significant correlation with FACT-G total (r=0.73), PWB (r=0.60), emotional well-being (EWB) (r=0.64) and FWB (r=0.73) scores. The scatterplots for correlation between PROMIS-GH domains and FACT-G total score is shown in Figure I. At follow-up, a total of 50 patients had data on best hematologic response and HRQoL assessment. Patients achieving a complete response (CR) to first-line therapy had a significantly superior FACT-G score at all domains compared to those with less than CR or no response. Maximal benefit in complete responders was noted in the FWB domain of FACT-G (Mean score ≥2 S.D. higher than patients with less than CR or no response; P=0.002). Conclusion: Patients with AL amyloidosis have a worse HRQoL at diagnosis compared to US cancer and general adult population. Deficit in HRQoL was most prominent in the FWB domain of FACT-G and GPH domain of PROMIS-GH. Most domains of FACT-G and PROMIS-GH had strong and significant correlation. Patients achieving a CR to first-line therapy had significantly superior HRQoL at all FACT-G domains. Clinical trials in AL amyloidosis should include patient-reported HRQoL as a key endpoint and focus on the domains of physical health and functioning to assess meaningful benefit of novel therapies. Psychometric validation of FACT-G and PROMIS-GH in AL amyloidosis would be helpful in generating robust PRO data in future studies. Disclosures Majhail: Anthem, Inc.: Consultancy; Incyte: Honoraria; Atara: Honoraria.

Outcomes of Primary Systemic Light Chain (AL) Amyloidosis in Patients Treated Upfront with Novel Agents and the Importance of Risk Adapted Treatment Strategies

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1786-1786
Author(s):  
Efstathios Kastritis ◽  
Maria Roussou ◽  
Maria Gavriatopoulou ◽  
Magdalini Migkou ◽  
Alexandra Gkougkoutsi ◽  
...  
Keyword(s):  
Cardiac Biomarkers ◽  
Novel Agents ◽  
Al Amyloidosis ◽  
First Line ◽  
Hematologic Response ◽  
First Line Therapy ◽  
Line Therapy ◽  
Initiation Of Therapy ◽  
Intent To Treat ◽  
Stage 1

Abstract Abstract 1786 Novel antimyeloma agents (thalidomide, lenalidomide and bortezomib) may induce high rates of hematologic responses in patients with AL amyloidosis in whom they are increasingly used. Due to the multisystemic involvement many patients with AL are frail and vulnerable to treatment related toxicity and often succumb to their disease early after initiation of therapy, mainly due to complications associated with cardiac amyloidosis. In order to investigate the outcomes of AL patients in the era of novel agents and explore strategies to reduce complications and early mortality, we analyzed 81 consecutive patients in a single center (Department of Clinical Therapeutics, University of Athens, Greece). All patients were assessed and followed rigorously and received similar supportive care according to our institution's practice. Bortezomib (B) was given as first line or salvage therapy after 1/9/2005 and lenalidomide (L) was given as primary therapy or salvage after 1/1/2008. Beginning on 1/1/2011, we follow a risk-adapted strategy, in which previously untreated patients with AL received bortezomib at a dose and schedule adjusted according to performance status (PS), levels of cardiac biomarkers and age (BDa). Patients were divided in those who started therapy from 2005 to 31/12/2007 (23 patients), those who received therapy between 1/1/2008 to 31/12/2010 (36 patients) and those who started therapy after 1/1/2011 (22 patients): 54% received first line therapy with B, 40% with L and 6% received conventional therapy upfront (mostly melphalan with dexamethasone; all received novel agents at later stages of their disease). Most patients (57%) were males; the median age was 67 years (range 42–82 years); 55% had a PS ≥2; the heart was involved in 68% of patients, the kidneys in 70%, the liver in 9%, and the peripheral nerve in 25%. Median eGFR was 70 ml/min and 4% required dialysis at diagnosis. Median NTproBNP was 2318 ng/l (range 36–75000 ng/l) and according to cardiac biomarkers, 26% were Mayo stage 1, 42% stage 2 and 32% stage 3. There were no significant differences in the demographic and disease characteristics between the three groups but 80% of patients, who started therapy from 2005 to 31/12/2007, received upfront BD, 80% of patients, who started therapy from 1/1/2008 to 31/12/2010, received upfront L and 82% of patients after 1/1/2011 received upfront BDa. On intent to treat, 65% of patients achieved hematologic response to first line therapy, including 20% hemCRs. Hematologic response rates were not different between the three groups (p=0.118); however, hemCRs were more frequent in patients treated before 31/12/2007 and after 1/1/2011 (30% and 27% vs. 9% in those treated from 1/2008-12/2010). The respective hemCR rates for patients treated with B vs. L were 32% vs. 6% (p=0.025). On intent to treat, organ responses were achieved by 28% of patients. Hematologic or organ progression or death has occurred in 60.5% of patients; the median PFS was 10 months and the 1-year PFS rate was 50%, 27% and 59% for patients treated in the three consecutive time periods, respectively (p=0.011). For patients treated upfront with B- vs. L-based regimens the respective 1-year PFS rate was 51% vs. 31% (p=0.054). After progression to first line therapy, 21 (26%) patients received second line therapy: 17 received B and 4 L. The median survival of all patients was 34 months; the 1-year survival rate for patients with Mayo stage 1 disease was 94%, for stage 2 was 56% and for stage 3 was 28% (p<0.001); 18 (22%) patients died within the first 3 months from initiation of therapy (all except one had cardiac involvement). The respective early death rates were 17%, 34% and 4% for patients treated in the three time periods, respectively (p=0.024) and were 22% and 25% for B- and L-based regimens (p=0.443), indicating that the reduction of early deaths was mainly due to the risk-adapted treatment strategy after 1/2011. In conclusion, our data indicate that novel agents, and especially bortezomib, resulted in significant response rates in patients with AL amyloidosis; however, 22% of AL patients die within 3 months form initiation of therapy due cardiac amyloidosis-associated complications. A risk-adapted treatment strategy with bortezomib dose and schedule adjusted according to individual patient characteristics may reduce early mortality and allow patients to achieve a hematologic response. Updated results will be presented at the meeting. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Optimizing Deep Response Assessment for AL Amyloidosis Using Involved Free Light Chain Level at End of Therapy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3227-3227
Author(s):  
Eli Muchtar ◽  
Angela Dispenzieri ◽  
Nelson Leung ◽  
Francis K. Buadi ◽  
David Dingli ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Light Chain ◽  
Research Funding ◽  
Response Assessment ◽  
Al Amyloidosis ◽  
First Line ◽  
Advisory Committees ◽  
First Line Therapy ◽  
Line Therapy ◽  
Organ Response

Abstract Introduction: Light chain burden in light chain (AL) amyloidosis is often low, making accurate response assessment challenging. Methods: AL amyloidosis patients achieving very good partial or complete response to first line therapy and had serial sFLC studies during and after completion of therapy were included (n=396). Involved free light chain (iFLC), difference in involved-to-uninvolved free light chains (dFLC) and sFLC ratio (sFLCR) were assessed at the end of first line therapy and at nadir iFLC. Survival analysis was done using the Kaplan-Meier method. Hematological progression-free survival (hemPFS) was defined as the time from diagnosis until hematological progression or death, where patients known to be alive and progression-free at the end of follow-up were censored. Hematological progression was defined according to consensus criteria or upon initiation of second line therapy, whichever came first. Results: The median iFLC and dFLC at the end of therapy was 1.7 mg/dL and 0.5 mg/dL, respectively. sFLCR normalization occurred in 70% of patients. iFLC ≤2 mg/dL and dFLC ≤0.5 mg/dL were associated with a longer hemPFS compared to their counterparts (Figure). Only iFLC ≤2 mg/dL was associated with a significantly longer overall survival (Figure). sFLCR normalization did not predict hemPFS or overall survival. Organ response was predicted by iFLC ≤2 mg/dL and dFLC ≤0.5 mg/dL (Table), with best discrimination seen with iFLC ≤2 mg/dL. Organ response was not predicted by sFLC normalization (Table). The median nadir iFLC was 1.4 mg/dL and was reached 3.9 months from the end of therapy, longer in transplanted patients compared to patients treated with non-transplant regimens (7.3 vs 1.8 months, respectively; P<0.001). iFLC ≤2 mg/dL at the completion of therapy and nadir iFLC reached >12 months from the end of therapy were favorable predictors of hemPFS/OS in a multivariate analysis. Conclusion: iFLC at the end of first line therapy better predicts for organ response and survival than dFLC among deep responders. Normalization of sFLCR does not predict for organ response or survival and should not be used as measure of therapeutic efficacy. Figure. Figure. Disclosures Dispenzieri: Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Dingli:Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding; Millennium Takeda: Research Funding. Kapoor:Celgene: Research Funding; Takeda: Research Funding. Russell:Vyriad: Equity Ownership. Kumar:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding. Gertz:Alnylam: Honoraria; celgene: Consultancy; Ionis: Honoraria; Abbvie: Consultancy; annexon: Consultancy; janssen: Consultancy; spectrum: Consultancy, Honoraria; Research to Practice: Consultancy; Medscape: Consultancy; Apellis: Consultancy; Teva: Consultancy; Amgen: Consultancy; Prothena: Honoraria; Physicians Education Resource: Consultancy.

scholarly journals Matching Patient Expectations after Ankle Fusion Based on Patient Reported Outcome Measures

2019 ◽  
Vol 4 (4) ◽  
pp. 2473011419S0025
Author(s):  
Jessica M. Kohring ◽  
Jeffrey R. Houck ◽  
Sam Flemister ◽  
John P. Ketz ◽  
Irvin Oh ◽  
...  
Keyword(s):  
Physical Function ◽  
Patient Reported Outcomes ◽  
Surgical Intervention ◽  
Threshold Value ◽  
Ankle Arthrodesis ◽  
Patient Expectations ◽  
T Score ◽  
Ankle Fusion ◽  
Patient Reported ◽  
The Mean

Category: Ankle Arthritis Introduction/Purpose: Much research on outcomes after ankle fusion focuses on gait changes, progression of adjacent joint arthritis, and other clinical measures, but little has been reported on the patient’s perspective. The purpose of this study was to determine the change in physical function and pain after undergoing ankle arthrodesis as determined by patient reported outcomes (PROs). Methods: This was a retrospective review of prospectively collected patient reported outcomes data in 88 consecutive ankle arthrodesis procedures performed from May 2015 to March 2018. Patient reported physical function (PF) and pain interference (PI) were measured as part of the routine care via the PROMIS computerized adaptive test at 6 months and 1 year post- operatively. Descriptive data and Spearman correlations were determined for PF and pain at 6 months and 1 year. Results: The mean pre-operative PF T-score was 37, less than the pre-determined threshold value of 42, indicating that this cohort was impaired physically and would respond positively to surgical intervention. The mean pre-operative PI T-score was 63 indicating moderate to high baseline pain and greater than the threshold value of 60, indicating that this patient cohort would have decreased pain after surgical intervention. The meaningful clinically important difference (MCID) was achieved for PI at 6 months and 1 year post-operatively (T-score of 4 and 6, respectively). At 6 months and 1 year, there was a moderate inverse correlation between PF and PI (r=-0.49, r=-0.61 respectively) suggesting less pain and more function. Demographic data, mean follow-up time, and mean PROMIS T-scores are seen in Table 1. Conclusion: The results of this study indicate that patients can expect to have a clinically meaningful improvement in pain after undergoing ankle fusion. Although patients do improve marginally in physical function, it is most likely the improvement in pain that is the greatest benefit to these patients at one year after ankle arthrodesis. This information is important to share with patients to align patient expectations with surgical results.

Weekly nab-paclitaxel in combination with carboplatin as first-line therapy in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7590-7590
Author(s):  
Mark A. Socinski ◽  
Corey J. Langer ◽  
Isamu Okamoto ◽  
Jeremy K. Hon ◽  
Vera Hirsh ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Entire Study ◽  
First Line Therapy ◽  
Line Therapy ◽  
Patient Reported ◽  
Study Population

7590 Background: The median age of advanced NSCLC pts in the US is 71 years; yetelderly pts (≥70 years) are generally undertreated, with only ≈30% receiving systemic therapy. Hence, better, more tolerable therapeutic options are needed for this cohort. In a phase III trial nab-paclitaxel (nab-P, 130 nm albumin-bound paclitaxel particles) + carboplatin (C) vs solvent-based paclitaxel (sb-P) + C, significantly improved ORR, the primary endpoint (25% vs 33%, P = 0.005), with a 1-month improvement in OS (P = NS) and improved safety. This analysis evaluated efficacy and safety in pts ≥70 and <70 years old. Methods: Pts with untreated stage IIIB/IV NSCLC and with an ECOG score of 0/1 were randomized 1:1 (stratified by age [≥70 vs <70 years], region, stage, gender, and histology) to C AUC 6 day 1 and either nab-P 100 mg/m2 on days 1, 8, 15 or sb-P 200 mg/m2 day 1 q 21 days. ORR and progression-free survival (PFS) were determined by blinded centralized review. Results: Of the phase III study population, 15% were elderly (156/1052; 74 pts in the nab-P/C and 82 in the sb-P/C arms). Most elderly pts were male (72%), Caucasian (71%), and had stage IV disease (64%). In pts both ≥70 and <70 years old, ORR was higher in the nab-P/C vs sb-P/C arm (≥70: 34% vs 24%, P = 0.196; <70: 32% vs 25%, P = 0.013). In pts ≥70 years old, PFS trended in favor of nab-P/C (median 8.0 vs 6.8 months, HR: 0.687, P = 0.134); OS was significantly improved (median 19.9 vs 10.4 months, HR: 0.583, P = 0.009). In contrast, PFS (6.0 vs 5.8 median months, HR: 0.903, P = 0.256) and OS (11.4 vs 11.3 median months, HR: 0.999, P = 0.988) were similar for both treatment arms in pts <70 years old. Adverse events were similar in pts ≥70 years old vs the entire study population, with less grade 3/4 neutropenia (P < 0.05) and neuropathy (P < 0.05) and increased thrombocytopenia (P = NS) and anemia (P < 0.05) in the nab-P/C vs sb-P/C arms. In pts ≥70 years old, patient-reported FACT-taxane subscales revealed significantly less neuropathy, pain, and hearing loss in the nab-P/C vs sb-P/C arms (P < 0.001). Conclusions: In elderly pts with advanced NSCLC, nab-P/C as first-line therapy was well tolerated and led to improved ORR and PFS, with significantly longer OS vs sb-PC.

scholarly journals PB2138 LIGHT CHAIN (AL) AMYLOIDOSIS: A SINGLE CENTRE EXPERIENCE AND THE EFFECTIVENESS OF BORTEZOMIB BASED THERAPY AS FIRST LINE THERAPY

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 962-963
Author(s):  
H. Ngu ◽  
D. Simpson ◽  
M. Hanna ◽  
R. Henderson ◽  
E. Merriman ◽  
...  
Keyword(s):  
Light Chain ◽  
Al Amyloidosis ◽  
First Line ◽  
Single Centre ◽  
First Line Therapy ◽  
Line Therapy ◽  
Single Centre Experience

A randomized, multicenter, double-blind, placebo (PBO)-controlled phase III study of paclitaxel (PTX) with or without ramucirumab (IMC-1121B; RAM) in patients (pts) with metastatic gastric adenocarcinoma, refractory to or progressive after first-line therapy with platinum (PLT) and fluoropyrimidine (FP).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4139-TPS4139 ◽  
Author(s):  
Hansjochen Wilke ◽  
David Cunningham ◽  
Atsushi Ohtsu ◽  
Ulrike Nuber ◽  
Rolf Bruns ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Phase Iii ◽  
Vegf Receptor ◽  
First Line ◽  
Vegf Expression ◽  
First Line Therapy ◽  
Line Therapy ◽  
Patient Reported

TPS4139 Background: Vascular endothelial growth factor (VEGF) expression in gastric cancer (GC) is associated with more aggressive clinical disease. VEGF expression in resected GC is associated with tumor recurrence and shorter survival. Data from Phase 2 and 3 studies suggest that agents targeting the VEGF pathway improve the efficacy of some chemotherapy regimens in 1st- and 2nd-line treatment of patients with gastric or gastroesophageal carcinomas. RAM, a fully human monoclonal antibody, binds to the VEGF receptor-2 (VEGFR-2), potently blocks the binding of VEGF to VEGFR-2, inhibits VEGF-stimulated activation of VEGFR-2, and neutralizes VEGF-induced mitogenesis of human endothelial cells. Methods: Pts are randomized 1:1 to receive PTX + RAM or PTX + PBO until disease progression or intolerable toxicity (28-day cycle; RAM/PBO 8 mg/kg Days 1, 15; PTX 80 mg/m2 Days 1, 8, 15). Eligibility includes metastatic or locally advanced, unresectable gastric or gastroesophageal junction adenocarcinoma; prior first-line therapy with any PLT/FP doublet with or without anthracycline; progressive disease during or following first-line therapy; ECOG PS 0-1; bilirubin ≤ 1.5 × upper limit of normal (ULN), transaminases ≤ 3 × ULN for ALAT/ASAT if no liver metastases, < 5 × ULN if liver metastases; creatinine ≤ 1.5 × ULN; absolute neutrophil count ≥ 1.5 × 109/L, hemoglobin ≥ 9 g/dL; platelets ≥ 100 × 109/L. The primary endpoint is overall survival (OS). Secondary endpoints include progression-free survival, time to progression, best overall response, objective response rate, safety, patient-reported outcome measures, pharmacodynamics, immunogenicity, and pharmacokinetics. This study, powered at 90% to show an increase in OS (mdn: 7 m PTX + PBO, 9.33 m PTX + RAM) at a 1-sided 2.5% significance level, will randomize 663 pts. As of 18 January 2012, approximately 58% of planned pts were randomized. The IDMC reviewed this study 23 June and 01 December 2011 and recommended the study continue unmodified.

scholarly journals Biologic Augmentation of Tibiotalocalcaneal Arthrodesis with Autologous Bone Block is Associated with High Rates of Fusion

2020 ◽  
Vol 5 (4) ◽  
pp. 2473011420S0043
Author(s):  
Alain E. Sherman ◽  
Mitesh P. Mehta ◽  
Rusheel Nayak ◽  
Anish R. Kadakia
Keyword(s):  
Bone Marrow ◽  
Femoral Head ◽  
Patient Reported Outcomes ◽  
Bone Marrow Aspirate ◽  
Bone Block ◽  
T Score ◽  
Patient Reported ◽  
Foot Function ◽  
The Mean ◽  
Tissue Defects

Category: Ankle; Hindfoot Introduction/Purpose: Tibiotalocalcaneal (TTC) arthrodesis is an established salvage procedure for severe deformities of the hindfoot. Despite its prevalence, end-stage pathology, systemic comorbidities, and the physical demands of surgery often precipitate unsuccessful outcomes, with nonunion rates as high as 85% in medically complex patients. Given the considerable morbidity associated with TTC arthrodesis, there has been recent interest in maximizing the physiologic potential of fusion by means of surgical technique, osteoinductive and osteoconductive biological agents, and vascularized bone flaps. Here, we present a novel approach to TTC arthrodesis using femoral head allograft bone block, bone marrow aspirate, and demineralized bone matrix (DBM) in the absence of tourniquet. Additionally, we explore the role of the medial femoral condyle (MFC) free flap as a reconstructive adjunct to arthrodesis. Methods: The sample consisted of 14 patients presenting to a tertiary care facility for reconstructive limb salvage. TTC arthrodesis was performed without tourniquet and biologically augmented with fresh-frozen femoral head allograft, pelvic bone marrow aspirate, and DBM. Three patients with severe soft tissue defects also underwent vascularized osseous reconstruction with MFC free flap. Recovery protocol included three months of prolonged non-weightbearing mechanical stabilization followed by conversion to weightbearing AFO boot for one year. Post-operative plain radiographs and computed tomography (CT) scans were assessed for fusion at regular follow-up. After fusion, participants completed a survey on patient-reported outcomes, which included the modified Foot Function Index (FFI) and Patient-Reported Outcomes Measurement Information System (PROMIS) scales for pain and physical function. Results: Successful TTC fusion was documented on plain radiograph in 13 patients (92.9%) and confirmed via CT in 10 patients (90.9%). The mean time-to-fusion was 183.2 +- 83.2 days. One patient (7.1%) failed to achieve fusion and underwent amputation secondary to infectious wound complications. Patients who underwent vascularized bone grafting had more robust healing and significantly shorter time-to-fusion (112.3 +- 31.7 days vs. 204.4 +- 82.7 days, p = 0.05). The mean patient-reported FFI score was found to be 40.96% +- 23.08%, indicating mild-to-moderate impairment in foot function. Similarly, PROMIS data revealed that patients who underwent TTC arthrodesis had a pain T-score of 58.34 (z = 0.83) and a physical function T-score of 39.00 (z = - 1.10), corresponding to mild pain and moderate impairment, respectively. Conclusion: We sought to biologically optimize the osteoinductive and osteoconductive potential of TTC arthrodesis using femoral head allograft bone block, bone marrow aspirate, and DBM in the absence of tourniquet. This approach resulted in excellent rates of fusion with minimal pain and preserved function of the lower extremity. Osseous healing was significantly enhanced by MFC flap in patients with soft tissue defects. We, therefore, recommend biologic augmentation of TTC arthrodesis as a viable salvage option for patients facing amputation or other undesirable outcomes.

scholarly journals Burden of Hospitalizations Due to Epstein-Barr Virus-Driven Post-Transplant Lymphoproliferative Disorder (EBV+PTLD) in Patients Who Failed First Line Rituximab or Rituximab Plus Chemotherapy Following Solid Organ Transplant (Post-SOT): A Retrospective Chart Review Study of German PTLD Registry

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 65-65
Author(s):  
Heiner Zimmermann ◽  
Hairong Xu ◽  
Arie Barlev ◽  
Yang Zhang ◽  
Dhanalakshmi Thirumalai ◽  
...  
Keyword(s):  
Research Funding ◽  
Index Date ◽  
Average Length ◽  
First Line ◽  
Employment Equity ◽  
Failure Index ◽  
First Line Therapy ◽  
Line Therapy ◽  
Equity Ownership ◽  
The Mean

Background: Post-transplant lymphoproliferative disorder (PTLD) is a rare and often aggressive disease in the setting of immunosuppression following solid organ transplant (post-SOT). About 50% of cases are associated with Epstein-Barr virus (EBV) infection of B cells, either due to reactivation of the virus after transplantation, or from primary EBV infection. Data remain very limited with respect to overall clinical and economic burden among EBV+PTLD patients (pts), particularly in the setting of pts who fail first line therapy. This retrospective chart review aimed to quantify the burden of hospitalization due to EBV+PTLD in post-SOT pts who failed first-line therapy in the real-world setting in Germany. Study Design and Methods: The German PTLD registry database was screened for pts with EBV+PTLD post-SOT who were refractory (failed to achieve complete [CR] or partial remission [PR]) to rituximab or rituximab plus chemotherapy (CT) or relapsed at any point after such therapy between 2000 to 2015. Pts with primary CNS PTLD were excluded. Pts without any outpatient visit or hospitalization record were excluded from the analysis (n of pts=1). Hospitalization data were reviewed by an experienced physician and adjudicated as PTLD relevant; details on diagnoses and procedures performed during hospitalization were collected from the first diagnosis of PTLD to the earliest of the following: death, loss to follow up or end of study period (Sep 1st, 2018). We estimated the mean number of hospitalizations, average length of inpatient stay per admission and the percentages of time spent in the hospital out of the total time following PTLD index date or treatment failure index date. The PTLD index date was defined as the first date of EBV+PTLD diagnosis; and the treatment failure index date was defined as the earliest date of pts who became refractory or relapsed to first-line therapy of rituximab or rituximab plus CT. Results: A total of 35 EBV+PTLD pts were analyzed. All had failed first line rituximab monotherapy. Median follow up time was 24.8 months from the PTLD index date. Median age at PTLD diagnosis was 47 years (range 18-75). Of these, 6 (17.1%) were polymorphic, 21 (60%) were diffuse large B cell lymphoma, 3 (8.6%) were Burkitt lymphoma, and 5 (14.3%) were other B-cell lymphoma. Among the 35 pts, 23 (65.7%) died: 12 from PTLD, 6 treatment-related, 1 from organ failure, and 4 from other causes. The vast majority of pts (29 out of 35) received CHOP-based CT following rituximab failure (2 other CT, 4 did not receive CT). All pts (100%) had at least one inpatient hospitalization after PTLD diagnosis and 16 (45.7%) pts had at least one ICU admission following PTLD index date. The mean number of PTLD hospitalizations following PTLD index date was 4 (SD 3.2, range 1-12) and the mean average length of stay per hospitalization was 23.8 days (SD 22.6, range 2-94). The mean proportion of time spent in the hospital out of total time at risk from PTLD index date was 20.5% (SD 27.6, range 0.1-100) with an average of 9.5% of time spent in the ICU setting during hospitalization stay (SD 22, range 0-99.5). The mean number of PTLD hospitalizations (n of pts=19) following first course CT failure index date was 2.1 (SD 1.9, range 0-7) and the mean average length of stay per hospitalization was 14.8 days (SD 8.6, range 6-31.6). The mean proportion of time spent in the hospital out of total time at risk from CT failure index date was 41.8% (SD 39.6, range 0-100) with an average of 26% time spent in the ICU setting (SD 39, range 0-100). Conclusions: This is the first study to quantify the hospitalization burden directly related to EBV+PTLD post-SOT in Germany. The results show that hospitalization burden in EBV+PTLD post-SOT pts failing first line rituximab monotherapy is substantial accounting for approximately 20% of patient's time after initial diagnosis of PTLD with around 10% spent in the ICU setting. This hospitalization burden is even higher and accounts for over 40% of time in pts after additional treatment failure to first CT with 26% spent in the ICU setting. Disclosures Zimmermann: Roche: Research Funding; Janssen: Other: Travel, accomodations expenses; Atara Biotherapeutics: Other: Travel, accomodations expenses, Research Funding; Celgene: Other: Travel, accomodations expenses. Xu:Atara Biotherapeutics: Employment, Equity Ownership. Barlev:Atara Biotherapeutics: Employment, Equity Ownership. Zhang:Atara Biotherapeutics: Employment, Equity Ownership. Thirumalai:Atara Biotherapeutics: Employment. Watson:Atara Biotherapeutics: Employment, Equity Ownership. Trappe:Atara Biotherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Other: Congress related travel support; Roche: Consultancy, Honoraria, Other: Congress related travel support, Research Funding; AbbVie: Consultancy, Other: Congress related travel support; Celgene: Other: Congress related travel support.

scholarly journals Clinical Value of Minimal Residual Disease Assessed by Multiparameter Flow Cytometry in Amyloid Light Chain Amyloidosis

2021 ◽  
Author(s):  
Xiaozhe Li ◽  
Beihui Huang ◽  
Junru Liu ◽  
Meilan Chen ◽  
Jingli Gu ◽  
...  
Keyword(s):  
Residual Disease ◽  
Multiparameter Flow Cytometry ◽  
Al Amyloidosis ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Organ Response ◽  
Therapy Completion ◽  
Amyloid Light Chain

Abstract Purpose: To assess the feasibility and prognostic value of minimal residual disease (MRD) evaluated by multiparameter flow cytometry (MFC) in newly diagnosed amyloid light chain (AL) amyloidosis.Methods: Clinical data from 25 consecutive newly diagnosed AL amyloidosis patients with MRD data tested at 3 months after first-line therapy completion were retrospectively analysed in a single centre from 2012 to 2019. First-line therapy included 8 courses of VD or 4 courses of VD plus sequential autologous stem cell transplantation (ASCT), both without maintenance therapy.Results: Of 25 patients with very good partial response (VGPR) or better, 19 (76%) achieved MRD negativity. Baseline characteristics were not different between MRD-negative and MRD-positive patients. More ASCT patients than non-ASCT patients (90.0% vs 53.3%, P＝0.043) achieved MRD negativity. In the MRD-negative and MRD-positive groups, cardiac response was observed in 93% and 25% (P=0.019) and any organ response in 94% and 50%, respectively (P=0.023). At a median follow-up of 25.1 months, MRD-negative patients showed significantly longer progression-free survival (PFS) from diagnosis than MRD-positive patients (24.52 vs 76.39 months, P=0.004).Conclusions: MRD negativity measured by MFC at 3 months after first-line therapy completion in patients with AL amyloidosis is measurable and associated with improved organ response rates and PFS over a long follow-up.

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