scholarly journals Patient-Reported Outcomes in Long-Term Survivors of Autologous Hematopoietic Cell Transplantation for Multiple Myeloma: Secondary Analysis of Two Randomized Controlled Trials on Survivorship Care Plans

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 431-431
Author(s):  
Rajshekhar Chakraborty ◽  
Lisa A. Rybicki ◽  
Jaime M. Preussler ◽  
Steven Devine ◽  
K. Scott Baker ◽  
...  
Keyword(s):  
General Population ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Patient Reported ◽  
Mental Hrqol ◽  
The Mean ◽  
Clinically Significant ◽  
Physical Hrqol

Abstract Background: With advances in multiple myeloma therapy, approximately 1/3 rd of patients receiving frontline autologous hematopoietic cell transplantation (AHCT) are alive and progression-free at 8 years (Perrot et al. ASH. 2020). Although patient-reported outcomes (PROs) with induction therapy and early after AHCT are well-described, little is known regarding PROs in long-term disease-free survivors specifically in myeloma. The objective of our study was to assess health-related quality of life (HRQoL), distress, and healthcare care adherence (HCA) in myeloma survivors who are in a stable remission after AHCT. Methods: The data were obtained from two randomized controlled trials (RCTs), namely, SCP (Survivorship Care Plan) and INSPIRE (Internet and Social media Program for Long Term Hematopoietic Cell Transplant Survivors). Both RCTs enrolled patients who are in a stable remission 1-10 years after AHCT. Our primary objective was to evaluate patient-reported HRQoL, distress and HCA. The secondary objective was to examine association of PROs with available patient (age, sex, race, body mass index [BMI], and health behaviors) and transplant (time since AHCT) variables. BMI was categorized as obese (≥30), overweight (25-29.9), and normal/underweight (<25). HRQoL was assessed by SF-12 v 2 as physical component summary (PCS) and mental component summary (MCS) T scores, with higher scores indicating better functioning and a general population mean of 50 (Standard Deviation [SD] 10). Distress was assessed by Cancer and Treatment-Related Distress (CTXD) instrument, which reports mean scores from 0 to 3, with higher scores indicating greater distress. A CTXD score >1.10 was considered as clinically significant distress based on prior data. HCA was assessed by a standard questionnaire, with scores from 0-1, indicating the proportion of age/sex-specific recommendations adhered to. Results: A total of 345 patients were included, with the median age at AHCT of 61 years (range, 29-76). Median time from AHCT to study entry was 4 years (1.4-11.0). The mean (SD) PCS and MCS T-scores in the study population were 45.5 (±10.5) and 51.3 (± 10.1) respectively, compared to general population T-score of 50 (±10) for both (p-value for differences being <0.001 and 0.021 resp.; Figure 1). The mean CTXD distress score was 0.9 (± 0.6), with 32% of patients having a score of ≥1.1, indicating clinically significant distress. The two CTXD domains with highest burden of clinically significant distress were "Health Burden" and "Uncertainty" (Figure 2). The proportion of patients who met guideline for tobacco, alcohol, exercise, sunscreen, and diet were 94%, 92%, 33%, 23%, and 13% respectively. The proportion of patients who were obese, overweight, normal weight, and underweight was 31.2%, 40.5%, 27.7%, and 0.6% respectively. On multivariable analysis (MVA), factors significantly associated with decreased PCS score were obesity (Parameter Estimate [PE]: -5.0 [±1.6]; p=0.002) and meeting alcohol guidelines (PE: -4.2 [±2.0]; p=0.039), while meeting exercise guidelines was associated with a higher PCS score (PE: 3.4 [±1.3]; p=0.007). Obesity was significantly associated with a decreased MCS score (PE: -3.0 [±1.5]; p=0.05) and meeting sunscreen guidelines was associated with an increased MCS score (PE: 3.0 [±1.4]; p=0.029). Factors associated with lower distress were years since AHCT (PE: -0.04 [±0.02]; p=0.024) and meeting sunscreen guidelines (PE: -0.21 [+/-0.8]; p=0.005). Notably, increased time since AHCT was associated with lower distress in all domains except for identity and medical demands. Better overall HCA was associated with older age (PE: 0.005 [±0.0001]; p<0.001) and female sex (PE: 0.04 [±0.02]; p=0.01) on MVA. Conclusion: To our knowledge, this is the first study to characterize PROs in long-term myeloma survivors post-AHCT. Myeloma survivors have significantly worse physical HRQoL compared to general population but comparable mental HRQoL. Approximately 1/3rd are obese, with obesity being associated with worse physical and mental HRQoL. The inverse association between physical HRQoL and meeting alcohol guidelines could be secondary to abstinence from heavy drinking in those with poor physical functioning. Survivorship programs should address ongoing issues of health burden and uncertainty in myeloma survivors, encourage exercise and physical activity, and focus on groups at risk of poor HCA. Figure 1 Figure 1. Disclosures Devine: Johnsonand Johnson: Consultancy, Research Funding; Magenta Therapeutics: Current Employment, Research Funding; Orca Bio: Consultancy, Research Funding; Be the Match: Current Employment; Sanofi: Consultancy, Research Funding; Tmunity: Current Employment, Research Funding; Vor Bio: Research Funding; Kiadis: Consultancy, Research Funding. Shaw: mallinkrodt: Other: payments; Orca bio: Consultancy. Majhail: Incyte Corporation: Consultancy; Anthem, Inc: Consultancy.

scholarly journals Neurological Adverse Events Determine Morbidity and Mortality Post Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5732-5732
Author(s):  
Ioanna Sakellari ◽  
Eleni Gavriilaki ◽  
Sotirios Papagiannopoulos ◽  
Maria Gavriilaki ◽  
Ioannis Batsis ◽  
...  
Keyword(s):  
Adverse Events ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Wide Spectrum ◽  
Chronic Gvhd ◽  
Human Herpesvirus ◽  
Neurological Complications ◽  
Hematopoietic Cell

Abstract Introduction: Despite advances in the field, diagnosis and management of the wide spectrum of neurological events as sequelae of allogeneic hematopoietic cell transplantation (alloHCT) remain challenging. Therefore, we investigated the incidence, diagnosis, management and long-term prognosis of neurological complications in alloHCT recipients. Methods: We enrolled consecutive allogeneic HCT recipients transplanted in our center (7/1990-9/2017). We performed a retrospective review of data in our prospectively acquired database. Results: Among 758 alloHCT recipients, 127 (16.8%) patients presented with neurological complications. Interestingly, neurological complications were more common in unrelated or alternative donors (p<0.001), ALL diagnosis (p<0.001) reduced intensity or toxicity regimens (p=0.037). In the multivariate model, these variables remained independent predictors of neurological complications. Neurological adverse events presented late post-transplant (median +140day, interquartile range/IR 232). Timing of neurological complications was associated only with acute and chronic graft-versus-host-disease/GVHD (p=0.001 and p<0.001, respectively). The majority of patients developed central nervous system/CNS complications (89.7%). 11 patients (8.7%) presented with >1 episodes (median 10.4 months, IR 25.1). Based on symptoms, timing and additional testing, neurological complications were classified into: CNS relapse (24), thrombotic microangiopathy (12), CNS hemorrhage (7), posterior reversible encephalopathy (6), drug-associated polyneuropathy (7) and seizure (6), other leukoencephalopathy (8), thromboembolic events (5), neuralgia (4), myopathy (3), sinusoidal obstruction syndrome (1), Guillain-Barre syndrome (1), Wernicke encephalopathy (1), myelitis (1) and multiple sclerosis (1). Opportunistic CNS infections were attributed to aspergillosis (12), mucormycosis (3), Cytomegalovirus (9), Epstein-Barr encephalitis (3) or lymphoproliferative disease (4), Human herpesvirus 6 (5), Human herpesvirus 7 (2), toxoplasmosis (3); while others could not be otherwise specified (10). Resolution of neurological complications was achieved in only 37 (29%) patients. With a median follow-up of 11.4 months (IR 30.3) in patients with neurological complications, incidence of chronic GVHD was 52.8%, relapse mortality 48.6%, treatment-related mortality 39.1% and 5-year overall survival (OS) 25.8% in patients with neurological complications. In the multivariate analysis, favorable OS was independently associated with resolution of neurological syndromes, absence of chronic GVHD and sibling transplantation. In the whole cohort, acute, chronic GVHD and relapse rates did not differ between patients with or without neurological complications. However, bacterial, viral and fungal infections were significantly increased in patients with neurological complications (p<0.001), possibly reflecting the immunosuppression status of these patients. Patients with neurological complications exhibited significantly decreased 10-year disease-free survival (21.7% versus 41.1%, p<0.001) in our cohort. 10-year OS was also significantly lower in patients with neurological complications (24.9% versus 46%, p<0.001), as shown in Figure. The same was true for 10-year OS when analysis was limited to non-relapsed patients with or without neurological complications (30.2% versus 57.9%, p<0.001). In the multivariate survival analysis of the whole cohort, unfavorable independent predictors of OS were: acute and chronic GVHD (beta=0.566, p<0.001 and beta=1.541, p<0.001, respectively), relapse (beta=0.566, p<0.001), fungal and bacterial infections (beta=0.705, p=0.013 and beta=0.784, p=0.039, respectively) and neurological complications (beta=0.685, p=0.008). Conclusions: Our large retrospective study highlights the wide spectrum of manifestations and etiologies of neurological complications in alloHCT recipients. Prompt diagnosis is required for adequate management, a major of determinant of survival. Thus, long-term increased awareness and collaboration between expert physicians is warranted to improve patient outcomes. Figure. Figure. Disclosures Gavriilaki: European Hematology Association: Research Funding. Vardi:Janssen: Honoraria; Gilead: Research Funding.

scholarly journals Stable long-term mixed chimerism achieved in a canine model of allogeneic in utero hematopoietic cell transplantation

Blood ◽  
2014 ◽  
Vol 124 (12) ◽  
pp. 1987-1995 ◽  
Author(s):  
Jesse D. Vrecenak ◽  
Erik G. Pearson ◽  
Matthew T. Santore ◽  
Carlyn A. Todorow ◽  
Haiying Li ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Canine Model ◽  
Hematopoietic Cell ◽  
Mixed Chimerism ◽  
Graft Versus Host ◽  
Key Points ◽  
Clinically Significant

Key Points Optimization of IUHCT in a preclinical canine model yields stable long-term donor engraftment. Clinically significant levels of chimerism can be achieved without conditioning, immunosuppression, or graft-versus-host disease.

Reduced Intensity Hematopoietic Cell Transplantation in Active Disease AML Is Associated with Leukemia Free Survival and Relapse Comparable to Myeloablative Conditioning

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3477-3477
Author(s):  
Se young Han ◽  
Rizwan Romee ◽  
Michael Slade ◽  
Pavan Kumar Bhamidipati ◽  
John F DiPersio ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Free Survival ◽  
Conditioning Regimens ◽  
Active Disease ◽  
Reduced Intensity

Abstract Introduction: Up to 40% of new acute myeloid leukemia (AML) patients fail to achieve complete remission (CR), and a significant number of patients achieving remission eventually relapse. Allogeneic hematopoietic cell transplantation (allo-HCT) remains the best curative option for these patients with a long-term leukemia free survival (LFS) of around 20-30% with the use of intensive myeloablative condition (MAC) transplants. Active disease AML patients otherwise deemed unfit for MAC regimens have limited treatment options. Although reduced intensity condition (RIC) has broadened transplant eligibility in the elderly AML patients particularly in CR, there is a paucity of data on the use RIC allo-HCT in AML patients with active disease. To answer this question, we retrospectively analyzed data from active disease AML patients who underwent RIC allo-HCT and compared their outcomes with contemporaneous patients who underwent MAC allo-HCT at our institution. Patients and methods: Our cohort included all patients with active disease AML (primary induction failure, relapsed refractory or cytogenetic persistence) at the time of transplantation, who underwent allo-HCT at Washington University Medical Center in St. Louis between January 2006 and June 2015. Patients were classified according to the intensity of conditioning regimens: MAC versus RIC. The primary study endpoints were leukemia free survival (LFS) and overall survival (OS). LFS was defined as the time from the achievement of CR after allo-HCT to the time of relapse, death in remission, or last follow-up. OS was defined as the time from transplantation to the time of death from any cause or last follow-up. The between-group differences in LFS and OS were described using Kaplan-Meier (KM) survival curves and compared by log-rank test. Univariate Cox regression analysis for LFS was performed. All analyses were two-sided, and significance was set at a p-value of 0.05, using SAS 9.4 (SAS Institutes, Cary, NC). Results: 138 patients were included. 30 patients (21.7%) underwent RIC allo-HCT and 108 (78.3%) underwent MAC allo-HCT. Their baseline characteristics are listed in Table 1. 21 patients (72.4%) in RIC and 77 (81.9%) in MAC achieved CR on day-28 bone marrow biopsy. Notably, there were 16 patients (1 RIC and 15 MAC) who died prematurely without post-transplant evaluation; subsequently they were excluded from LFS, relapse and NRM calculations. There was no difference in the LFS in these two groups; 1-year and 3-year LFS were 40.6% (95% CI 23-70) and 33.1% (95% CI 17-66) in the RIC patients while 40.7% (95% CI 31-54) and 33.2% (95% CI 23-47) in the MAC patients, respectively (p=0.99) (Figure 1A). Similarly the CI of relapse at 1 year and 3 year was not different in the two groups; 45.8% (95% CI 30-71) and 50.5% (95% CI 33-76) in RIC group vs. 51.9% (95% CI 43-63) and 56.8% (95% CI 48-67) in MAC group, respectively (p=0.61) (Figure 1B). The CI of NRM at 1-year and 3-year was 28.1% (95% CI 16-50) and 32.6% (95% CI 19-56) in RIC group compared to 17.9% (95% CI 11-28) and 21.0% (95% CI 14-31) in the MAC group (p = 0.21). However, OS in both groups remained poor with 1-year and 3-year OS of 25.1% (95% CI 14-44) and 13.2% (95% CI 6-31) in RIC vs. 35.5% (95% CI 28-46) and 22.0% (95% CI 15-32) in MAC, respectively (p = 0.21). On univariate analysis for LFS and relapse, only cGvHD was associated with higher LFS (p<0.01, HR 0.27, 95% HR 0.13-0.52) and lower relapse risk (p= 0.01, HR 0.37, 95% HR 0.15-0.89) in these patients. On multivariate analysis for LFS, only cGvHD was statistically significant (p<0.01, HR 0.32, 95% HR 0.18-0.56). On the other hand, intermediate cytogenetic risk (p=0.01, HR 1.59, 95% HR 1.08-2.34) and cGvHD (p<0.01, HR 0.12, 95% HR 0.05-0.27) were significant for OS. Conclusion: The use of RIC allo-HCT in active disease AML is associated with LFS and relapse comparable to MAC allo-HCT. However, high relapse rates and NRM, in both groups translated into poor long term OS. Careful selection of patients and early utilization of transplant without subjecting these patients to multiple salvage regimens might help lower NRM rates in future studies. Notably, our study might open a window for future prospective studies aimed at finding improved ways to harness the graft versus leukemia (GvL) effect associated with RIC transplantation in patients who are otherwise not able to tolerate more toxic intensive conditioning regimens. LFS LFS Figure 1 Relapse Figure 1. Relapse Figure 2 Figure 2. Disclosures DiPersio: Incyte Corporation: Research Funding. Vij:Karyopharm: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; Novartis: Honoraria; Amgen: Honoraria, Research Funding; Celgene: Consultancy; Takeda: Honoraria, Research Funding.

scholarly journals Quantification of Acute Lymphoblastic Leukemia Clonotypes in Leukapheresed Peripheral Blood Progenitor Cells Predicts Relapse Risk Following Autologous Hematopoietic Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1420-1420
Author(s):  
Gabriel N. Mannis ◽  
Thomas G. Martin ◽  
Lloyd E. Damon ◽  
Charalambos Andreadis ◽  
Rebecca L. Olin ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Ex Vivo ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Cell ◽  
Equity Ownership ◽  
B Lineage

Abstract Background Although multiple studies have shown superiority of allogeneic hematopoietic cell transplantation (alloHCT) over autologous hematopoietic cell transplantation (autoHCT) for patients with "high-risk" acute lymphoblastic leukemia (ALL), these findings may be explained, in part, by contamination of the peripheral blood progenitor cell (PBPC) leukapheresis product by residual leukemic cells in patients undergoing autoHCT. Methods We retrospectively evaluated minimal residual disease (MRD) via next-generation sequencing (NGS) (Adaptive Biotechnologies, S. San Francisco, CA) in the PBPC leukapheresis products from 32 ALL patients who underwent autoHCT. All patients had "high-risk" ALL, as defined by B-lineage disease with WBC at diagnosis >30,000/uL; high-risk cytogenetics including t(9;22), t(4;11), other 11q23 abnormalities, or monosomy 7; or primary refractory disease. Peripheral hematopoietic cell mobilization consisted of cytarabine 2000mg/m2 IV every 12 hours (16,000mg/m2 cumulative) concurrent with etoposide 40mg/kg cumulative by continuous IV infusion over 4 days. The autoHCT conditioning consisted of 1320cGy total body irradiation (TBI) given in 11 fractions from day -8 to -5, etoposide 60mg/kg IV on day -4, and cyclophosphamide 100mg/kg IV on day -2. Tyrosine kinase inhibitors (TKI) were allowed for patients with Philadelphia chromosome-positive (Ph+) B-ALL. Seven patients (22%) participated in a multi-institutional trial in which the PBPC graft underwent ex vivo complement-mediatedpurging using monoclonal antibodies against CD9/CD10/CD19/CD20 for patients with B-lineage disease, or against CD2/CD3/CD4/CD5/CD8 for patients with T-lineage disease. Kaplan-Meier curves were generated using GraphPad Prism (GraphPad Software, La Jolla, CA) and statistical differences assessed via Log-Rank and Wilcoxon analyses, with a p-value of <0.05 considered significant. Results Twenty-eight patients (88%) had diagnostic bone marrow samples with quantifiable immunoglobulin or T cell receptor (Ig/TCR) gene rearrangements suitable for MRD quantification in the PBPC collections. Twelve (38%) patients had Ph+ B-ALL, 12 (38%) had Ph-neg B-ALL, and 4 (14%) had T-cell ALL. The majority of patients were male, in first complete remission, and autografted between 2000-2009, with a median age at autoHCT of 32 (range 19-55). With a median follow-up of 41 months (range 3-217), median relapse-free survival (RFS) and overall survival (OS) for the entire cohort are 3.2 and 4.2 years, respectively. At 5 years post-autoHCT, 42% of patients remain alive and relapse-free. Of the 28 diagnostic bone marrow specimens, 21 (75%) had rearrangements in more than 1 immunoreceptor locus (Figure 1A). A total of 73 rearrangements were identified across all patients. Clonal Ig heavy chain (IGH) sequences with complete VDJ rearrangement were the most commonly identified rearrangement, present in 17 of 28 patients (61%) and representing 30 of the 73 (41%) total rearrangements. When stratified by graft MRD burden, the median RFS for patients with MRD detectable at a level ≥10-6 (n=13) was 6.5 months, and has not been reached for patients without detectable MRD above this threshold (n=15; p=0.0005; Figure 1B). Ex vivo antibody-based purging failed to eradicate leukemia cells from the PBPC collections of 3 patients with detectable MRD who received a purged graft (Figure 1C), all of whom ultimately relapsed. Of the Ph+ cohort, 6 (50%) had detectable MRD in the PBPC graft. Two (33%) of these patients were not treated with a TKI; 1 relapsed at 4 months post-autoHCT and the other died from non-relapse mortality. Of the 4 Ph+ patients with detectable MRD who received a TKI, 2 (50%) remain long-term relapse-free survivors. Of the 6 patients without MRD who were treated with a post-autoHCT TKI, 5 (83%) remain relapse-free. Conclusion We demonstrate that the NGS-based immunosequencing platform identifies ALL MRD in leukapheresed PBPC collections. The presence of MRD in the autograft strongly predicts relapse, with only 15% RFS in patients harboring ≥10-6 MRD at stem cell collection versus 73% in patients with undetectable MRD. The absence of MRD in PBPC may thus identify a subset of "high-risk" patients likely to achieve long-term remissions without alloHCT. TKI therapy for patients with Ph+ B-ALL may also, in some cases, abrogate the need for alloHCT, even with quantifiable MRD prior to high-dose therapy. Disclosures Damon: Atara: Consultancy; Sunesis: Research Funding; Sigma-Tau: Research Funding; McGraw-Hill: Patents & Royalties: Book Chapter. Andreadis:McGraw Hill: Honoraria; Novartis: Consultancy; Cellerant: Consultancy; Pharmacyclics: Honoraria. Olin:Daiichi-Sankyo: Research Funding. Kong:Adaptive Biotechnologies: Employment, Equity Ownership. Faham:Adaptive Biotechnologies: Employment, Equity Ownership.

scholarly journals Burden and Impact of Geriatric Syndromes Associated with Allogeneic Hematopoietic Cell Transplantation in Older Adults

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3370-3370
Author(s):  
Richard J Lin ◽  
Theresa A Elko ◽  
Patrick Hilden ◽  
Parastoo B. Dahi ◽  
Ann A. Jakubowski ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Older Patients ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Geriatric Syndromes ◽  
The Impact

Abstract While there has been significant increase in the number of older patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT), the prevalence and the impact of geriatric syndromes associated with allo-HCT remains unknown. Using an institutional database and the electronic medical record, we retrospectively examined the incidence, predictive factors, and the impact of common geriatric syndromes of delirium, urinary incontinence, pressure ulcer, and mechanical fall among 527 patients age 60 and above (range 60-78.7) who underwent first allo-HCT for hematological malignancies at our institution from 2001 to 2016. We hypothesize that allo-HCT-associated geriatric syndromes negatively impact non-relapse mortality and overall survival. We identified all relevant geriatric events from the start of the conditioning regimen to 100 days post stem cell infusion. Among common geriatric syndromes, we found that delirium had the highest 100-day cumulative incidence at 21% (95% CI 18-25), followed by falls at 7% (95% CI 5-9) (Figure 1). There were only 11 incidences of new urinary incontinence and 3 incidences of new pressure ulcers. With a median follow-up of 46 months for survivors, the 3-year probability of overall survival and progression-free survival is 47% (95% CI 42-51) and 40% (95% CI 36-44), respectively (Figure 1). The 2-year cumulative incidence of non-relapse mortality is 28% (95% CI 24-32). We assessed the association of standard, pre-transplant patient demographic, clinical, geriatric, and laboratory characteristics with the cumulative incidence of delirium and fall. We found that prior fall within last year, potentially inappropriate medications use prior to transplant admission (defined by 2015 American Geriatric Society updated Beers criteria), platelet count <50 k/µl, creatinine clearance <60 ml/min predicted delirium in the multivariate analysis. Age over 70 and impaired activities of daily living (ADL) predicted fall in the multivariate analysis with prior fall within last year close to be a significant variable (Table 1). We next investigated the impact of delirium and fall on transplant outcomes. Delirium, but not fall, is independently associated with significantly increased risk of death at 100 days adjusted for standard transplant variables (OR 6.3, 95% CI 3-13.4, p<0.001). In addition, patients who experienced delirium and fall during their initial transplant admission had significantly increased length of stay (11 and 15 days longer, respectively, both p<0.001). In a landmark analysis of 100-day post-transplant survivors, both delirium and fall are associated with significantly increased long-term non-relapse mortality, with hematopoietic cell transplantation comorbidity index (HCT-CI) as an additional significant predictor (Table 2). While limited by the retrospective design and likely under-reporting, our findings establish for the first time the baseline incidence and predictors of common geriatric syndromes associated with allo-HCT. Importantly, we have demonstrated significant negative impact of delirium and fall on the short- and long-term transplant-associated mortality and morbidities. The temporal pattern and impact of geriatric delirium and fall warrants preemptive, targeted, longitudinal, and multidisciplinary interventions to improve transplant outcomes and to expedite functional recovery after allo-HCT for older patients. Disclosures Perales: Takeda: Other: Personal fees; Novartis: Other: Personal fees; Abbvie: Other: Personal fees; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees and Clinical trial support; Merck: Other: Personal fees. Sauter:Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Precision Biosciences: Consultancy; Kite: Consultancy.

Comparison of Outcomes and Quality-of-Life Measures Following Haploidentical Vs. Matched Related/Unrelated Donor Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 16-17
Author(s):  
Sanghee Hong ◽  
Lisa Rybicki ◽  
Linda McLellan ◽  
Jane Dabney ◽  
Aaron T. Gerds ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Well Being ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Post Transplant ◽  
The Mean

Background: Haploidentical (haplo) transplantation using post-transplant cyclophosphamide (Cy) based GVHD prophylaxis is a well-established alternative donor approach for allogeneic hematopoietic cell transplantation (HCT). Although outcomes from haplo HCT have been compared to matched related (MRD) and unrelated donor (MUD) allo HCT, quality-of-life (QOL) recovery between these transplant modalities has not been described. We hypothesized that post-transplant QOL is similar between Haplo and MRD/MUD grafts. A single-institution, retrospective cohort study was therefore conducted to compare outcomes including QOL between these groups. Methods: From May 2014 through December 2019, 90 haplo, 102 MRD and 229 MUD adult 1st allo HCTs were performed. Myeloablative conditioning (MAC) for haplo grafts (n=35) included fludarabine (Flu)/ total body irradiation (TBI) and reduced-intensity conditioning (RIC) haplo transplants (n=55) included Flu/Cy/TBI. QOL was assessed prior to transplant and at days +100 and +180 by the FACT-BMT which consisted of the following subdomains: "Physical well-being," "Social well-being," "Emotional well-being," "Functional well-being," "Additional concerns," and sum of all these subdomains as "Total score." Outcomes were estimated and compared with the Kaplan-Meier and log-rank test or cumulative incidence and Gray test. FACT-BMT scores were compared with repeated measures analysis of variance. Results: Patient and transplant characteristics were comparable among the donor sources except for higher median age at HCT in MUD transplants, and haplo grafts were more commonly used non-Caucasians, used RIC regimens and bone marrow grafts (Table 1). Median transplant hospital length of stay was longer for haplo vs. MRD vs. MUD grafts (31 vs.25 vs. 25 days, p&lt;0.001) with longer median time until neutrophil and platelet recovery for haplo compared to MRD and MUD grafts (20 vs. 14 vs. 15 days, p&lt;0.001, and 31 vs. 21 vs. 22 days, p&lt;0.001, respectively). MAC haplo HCT had a higher incidence of CMV (p=0.05) and other infections (p=0.003), but no difference in other outcomes compared to MRD/MUD grafts, including all of the QOL domains. The mean Total scores from baseline to day +180 for haplo HCT were 157-157, MRD 153-166, and MUD HCT 152-163. RIC haplo HCT was associated with higher incidences of infections (p&lt;0.001) and relapse mortality (p=0.04), but lower NRM (p=0.008) and no differences in other outcomes. When comparing RIC haplo to MUD transplants there was significantly better Emotional well-being (p=0.008) and Functional well-being (p=0.011) at day+180; respective mean emotional well-being score for haplo 19-23 and MUD 16-19; mean functional well-being score for haplo 19-24 and MRD 19-19 (Figures 1a and 1b). No difference for the other QOL measures were found; the mean Total scores from baseline to day +180 for haplo HCT were 155-180, and MUD HCT were 150-158 (p=0.25). Discussion: Among MAC recipients, we observed no differences in total FACT QOL scores and individual domains among haplo, MRD and MUD HCT recipients through 6 months post-HCT. After RIC HCT, haplo recipients reported better Emotional and Functional well-being compared to those receiving a MUD graft, although Total FACT score and other QOL domains were comparable through 6 months. Future strategies to lessen infectious complications and relapse may further improve QOL outcomes. Interrogation of QOL among disease specific groups may also elucidate whether additional benefits exist between these different transplant modalities. Disclosures Gerds: Sierra Oncology: Research Funding; Gilead Sciences: Research Funding; Celgene: Consultancy, Research Funding; Imago Biosciences: Research Funding; Roche/Genentech: Research Funding; Incyte Corporation: Consultancy, Research Funding; CTI Biopharma: Consultancy, Research Funding; Apexx Oncology: Consultancy; AstraZeneca/MedImmune: Consultancy; Pfizer: Research Funding. Hamilton:Syndax Pharmaceuticals: Consultancy, Honoraria. Majhail:Nkarta Therapeutics: Honoraria; Incyte: Honoraria; Mallinckrodt: Honoraria; Anthem, Inc.: Consultancy.

scholarly journals Relapse and Late Mortality in 5-Year Survivors of Myeloablative Allogeneic Hematopoietic Cell Transplantation for Chronic Myeloid Leukemia in First Chronic Phase

2010 ◽  
Vol 28 (11) ◽  
pp. 1888-1895 ◽  
Author(s):  
John M. Goldman ◽  
Navneet S. Majhail ◽  
John P. Klein ◽  
Zhiwei Wang ◽  
Kathleen A. Sobocinski ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
General Population ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Phase ◽  
Mortality Rates ◽  
Hematopoietic Cell ◽  
Long Term Outcomes

PurposeAllogeneic hematopoietic cell transplantation (HCT) is curative therapy for chronic myeloid leukemia (CML), but its long-term outcomes are not well described. We studied the long-term outcomes of CML patients in first chronic phase who receive an allogeneic HCT.Patients and MethodsOur study included 2,444 patients who received myeloablative HCT for CML in first chronic phase between 1978 and 1998 and survived in continuous complete remission for at least 5 years (median follow-up, 11 years; range, 5 to 25 years). Donor sources were human leukocyte antigen–matched siblings in 1,692 patients, unrelated donors in 639 patients, and other related donors in 113 patients.ResultsOverall survival rates at 15 years were 88% (95% CI, 86% to 90%) for sibling HCT and 87% (95% CI, 83% to 90%) for unrelated donor HCT. Corresponding cumulative incidences of relapse were 8% (95% CI, 7% to 10%) and 2% (95% CI, 1% to 4%), respectively. The latest relapse was reported 18 years post-HCT. In multivariable analyses, history of chronic graft-versus-host disease increased risks of late overall mortality and nonrelapse mortality but reduced risks of relapse. In comparison with age-, race-, and sex-adjusted normal populations, the mortality of HCT recipients was significantly higher until 14 years post-HCT; thereafter, mortality rates were similar to those of the general population (relative mortality ratio at 15 years, 2.3; 95% CI, 0 to 4.9).ConclusionRecipients of allogeneic HCT for CML in first chronic phase who remain in remission for at least 5 years have favorable subsequent long-term survival, and their mortality rates eventually approach those of the general population.

scholarly journals Patient-Reported Quality of Life Is an Independent Predictor of Survival after Allogeneic Hematopoietic Cell Transplantation: A Secondary Analysis from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0902

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 206-206 ◽  
Author(s):  
William A. Wood ◽  
Jennifer Le-Rademacher ◽  
Mingwei Fei ◽  
Brent R. Logan ◽  
Karen L Syrjala ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Management Training ◽  
Change Score ◽  
Hematopoietic Cell ◽  
Morbidity And Mortality ◽  
Stress Management Training ◽  
Sf 36 ◽  
Patient Reported ◽  
Physical Hrqol

Abstract INTRODUCTION: Patient reported outcomes (PROs) including symptoms and health related quality of life (HRQOL) predict mortality in multiple cancers, such as myeloma, head and neck, lung and prostate cancer. The relationship of PROs with survival is not clear in hematopoietic cell transplantation (HCT). We tested three hypotheses about the relationship between HRQOL and survival after HCT: (1) Pre-HCT HRQOL (particularly physical HRQOL) reflects functional status and predicts survival after allogeneic (allo) HCT independently of traditional risk factors and indices; (2) Post-HCT change in physical HRQOL reflects the “toll” of the HCT and predicts subsequent outcomes, including survival, among early survivors; (3) Since autologous (auto) HCT is associated with lower risks for treatment-related morbidity and mortality, PROs may not be as predictive for this group. METHODS: We tested these hypotheses using data from the 711 participants in BMT CTN 0902 (sponsored by NHLBI and NCI, NCT 01278927), a randomized study of pre-transplant exercise and stress management training for patients undergoing auto or allo HCT. Because the primary analysis for BMT CTN 0902 did not show a significant effect for exercise or stress management training, intervention groups were combined for these analyses. However, auto and allo recipients were analyzed separately because of the expected substantial differences in the subsequent risks for morbidity and mortality in the two populations. The HRQOL measures used were the physical component score (PCS) and mental component score (MCS) from the SF-36, measured pre-HCT and at day 100. RESULTS: Among 310 alloHCT recipients with a median follow-up of 23 months, while there were no pre-HCT clinical covariates (including age, conditioning intensity, donor type, graft source, disease, disease stage) that predicted survival, pre-HCT physical HRQOL (PCS on the SF-36) was strongly prognostic for survival (HR for death of 0.72 per 10 points increase, 95% CI 0.60-0.85, p<0.001) while pre-HCT MCS was not (HR 0.99, 95% CI 0.84-1.16, p=0.29). Survival estimates for the first, second, third, and fourth quartiles of baseline PCS were, respectively, 67%, 72%, 81%, and 91% at 6 months and 50%, 65%, 75%, and 83% at one year (Figure 1). Among the eight SF-36 subscales, higher pre-HCT Physical Functioning and General Health scores were strongly associated with better survival. Among day 100 survivors, the PCS change score from baseline to Day 100 was also strongly prognostic for subsequent survival after adjusting for pre-HCT PCS (HR 0.55 per 10 points improvement, 95% CI 0.42-0.72, p<0.001) as was the MCS change score after adjusting for pre-HCT MCS (HR 0.70, 95% CI 0.56-0.89, p=0.003). In models that included patient age and the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI), the EBMT Score, or the Disease Risk Index (DRI), the findings for both pre-HCT values and change scores remained statistically significant with similar hazard ratios, suggesting that PROs convey independent prognostic information for survival despite inclusion of traditional risk factors. Analyses of transplant-related mortality (TRM) in alloHCT recipients showed similar patterns. Higher pre-HCT PCS was predictive of lower TRM. Among patients alive and disease-free at day 100, PCS change score was also associated with lower TRM after adjusting for pre-HCT PCS (HR 0.28, 95% CI 0.17-0.47, p<0.001) and the HCT-CI, EBMT and DRI; pre-HCT MCS and change in MCS did not predict TRM. Among autoHCT recipients (n=337), there were no pre-HCT clinical covariates that predicted survival. Pre-HCT HRQOL also was not prognostic of survival in autoHCT (physical PCS from the SF-36 p=0.82, mental MCS from the SF-36, p=0.56), nor were early changes in either the PCS or the MCS. CONCLUSION: In summary, among alloHCT recipients who participated in BMT CTN 0902, lower pre-HCT physical HRQOL and early decline in physical HRQOL were strongly predictive for worse overall survival and higher transplant-related mortality. These results suggest that patient-reported data are an important component of risk assessment and could assist in clinical decision-making. High-risk individuals could be targeted for different management strategies or more aggressive supportive care interventions to reduce treatment-related morbidity and mortality in this population. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Post-Relapse Survival after Haploidentical Hematopoietic Cell Transplantation (Haplo) with Post Transplant Cyclophosphamide (PTCY): Potential Impact of DLI Post-Relapse

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3928-3928
Author(s):  
Melhem Solh ◽  
Asad Bashey ◽  
Scott R. Solomon ◽  
Lawrence E Morris ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Disease Risk ◽  
Multivariable Analysis ◽  
Hematopoietic Cell ◽  
Remission Induction ◽  
Term Survival ◽  
Landmark Analysis

Abstract Relapse of malignancy remains a major cause of mortality among patients receiving allogeneic hematopoietic cell transplantation. We have previously published our center experience showing that patients who relapse after haplo had a worse 1 year post-relapse survival (PRS) compared to relapses after matched related or unrelated donors (17%, 46% and 40% respectively , p&lt;0.05)(Solh et al, BMT 2016). We hypothesized at that time that relative lack of donor lymphocyte infusion (DLI) use following haplo relapses could have contributed to the difference in outcomes between donor types, and commenced incorporation of DLI into the management strategy for relapse after haplo transplantation. To assess this hypothesis, we investigated the post-relapse survival among consecutive 392 patients who received their haplo transplant at our center between January of 2008 and January of 2020 and assessed for factors contributing to improved PRS. Methods: A total of 392 patients who received their first haplo at our center were included in this analysis. Patient, disease, and transplant related factors were retrieved from our data base where they were prospectively entered. All transplants were performed in the outpatient setting with admissions reserved for complications that required inpatient care. GVHD prophylaxis for all patients was tacrolimus (till day 180), mycophenolate (stop at day 35) and cyclophosphamide 50mg/kg on days 3 and 4. Supportive care and GVHD management were per our programmatic standards. Endpoints included OS, DFS, NRM, relapse and post-relapse survival was assessed as survival from time of relapse. A landmark analysis for patients surviving more than 4 months post haplo was performed to assess for treatment factors affecting long term survival. Results: out of 392 transplant recipients, 109 experienced relapse of malignancy after receiving their first haplo transplant with a median time from transplant to relapse of 194 days (range 43-1268) and median age at relapse of 53 years (20, 74). The patient characteristics for relapsing patients were as follows: diagnosis (AML 37%, ALL 21%, MDS 20%, Lymphoma 16%), prior auto (16%), HCT-CI 0-2 (45%), Disease risk (high/very high 51%). Transplant characteristics included myeloablative regimen (42%), peripheral blood cell source (75%), HLA match (5/10 in 72%, 6/10 in 16%, 7/10 in 12%), and female donor -male recipient in 23%. Post relapse remission induction with disease specific therapy was given to 102 out of 109 patients. Additionally, seventeen patients received DLI (cell dose (1x10 5 to 5x10 6 CD3+ cells/kg)and 10 patients received a second transplant post relapse. 3 patients developed GVHD (aGCVD 2, moderate severe cGHVD 1) after DLI infusion. 1 year and 3-year endpoints for the whole 392 patients were OS (79% and 63%), DFS (70% and 56%), NRM (11% and 15%) and relapse (19% and 29%). 1-year and 3-year post-relapse survival were 37% and 19%. IN a landmark analysis at 4 months, receiving DLI had significantly better OS than no DLI p=0.015(figure 1). On a multivariable analysis for OS, factors associated with improved OS included time from transplant to relapse (&gt;=1 year vs &lt;6 months, HR 0.29, 95% CI 0.16-0.54, p&lt;0.001)), DLI ( yes versus no, HR 0.61, p=0.015)) and patient sex ( male vs female, HR 1.74, 95% CI 1.07-2.81, p=0.025). In conclusion, some patients who relapse after Haplo with PTCY can still achieve long term remissions. The use of DLI in our experience is safe and contributed to improved survival. DLI should be considered in relapse management of haplo recipients. Figure 1 Figure 1. Disclosures Solh: Partner Therapeutics: Research Funding; BMS: Consultancy; ADCT Therapeutics: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy.

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