The Impact of Continuity of Care On Survival Outcomes After Allogeneic Hematopoietic Stem Cell Transplantation; Improved Overall Survival in the Absence of Severe Graft Vs. Host Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4521-4521
Author(s):  
Yasser Khaled ◽  
Melhem M. Solh ◽  
Robert B. Reynolds ◽  
Carlos Alemany ◽  
Raul Castillo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Continuity Of Care ◽  
Cumulative Incidence ◽  
Older Patients ◽  
Patient Characteristics ◽  
Hematopoietic Stem ◽  
Graft Vs Host Disease ◽  
One Year ◽  
The Impact ◽  
Grade Iii

Abstract Abstract 4521 Continuity of care (COC) is acknowledged as a core quality measure in HIV, heart failure and family medicine. Allogeneic hematopoietic stem cell transplantation (Allo-HCT) is complex therapeutic option where is the selection of patient, donor, conditioning and immune-suppression plays a pivotal role in overall survival (OS) outcome. Although the team concept is an integral part of care in Allo-HCT, there is little literature known about the impact of personnel COC (care from the same provider) on OS. Method: Between July 2009 and May 2012, 74 consecutive Allo-HCT were performed at our center. The patient's clinical care for the first consecutive 41 patients was shared between the physicians independent of primary transplant physician (Non- COC group). To assess the impact of COC on OS after Allo-HCT, the subsequent 33 patients (COC group) were followed by their transplant physician both as in-patient and outpatient. Physician's contribution into the care of each individual patient was calculated from physicians billing visits. Patient characteristics of COC & Non-COC groups are shown in table I. Graft vs. host disease (GVHD) prophylaxis was Tacrolimus/MTX or Cyclosporine/Mycophenolate with the addition of Thymoglobulin for MUD and mismatched RD. Results: The average contribution of the primary transplant physician into their patients care during year one post-transplant was 49% vs. 80% for Non-COC and COC groups respectively (P=0.01). There was no difference in patient characteristics between COC and Non-COC groups except for older patients in Non-COC. With median duration of follow up of 815 days for Non-COC and 320 days for COC groups, the 1- year OS was 56% vs. 75% respectively (P=0.07). Similarly, there was a trend toward improved DFS for COC (1-year DFS of 68% vs. 48%, P=0.11). On Univariate analysis, Age (≤ 55, P=0.26), Donor source (MUD vs. RD, p=0.65), diagnosis (acute leukemia vs. other, p=0.18), status at transplant (P= 0.23), cytogenetic risk (p=0.79) and conditioning (FIC vs. RIC, p=0.62) were not predictive of improved OS. Both cumulative incidence of relapse and treatment related mortality (TRM) at 1-year were lower in COC compared to Non-COC groups; 9.5% vs. 25% and 17% vs. 25% respectively. The cumulative incidence of grade II –IV acute GVHD (aGVHD) at day 100 and day 180 was 64% & 64% for Non-COC vs. 46% & 72% for COC respectively. There was more patients with grade III/IV aGVHD; 13/41 (32%) in Non-COC compared to 6/33(18%) in COC, however this difference was not statistically significant (p=0.27). Additionally, there was no difference in OS in patients with grade III/IV aGVHD in Non-COC (13 patients) vs. COC (6 patients), P=0.85. In contrast, Patients without grade III/IV aGVHD had a statistical OS advantage in favor of COC (27 patients) vs. Non-COC (28 patients) with one year OS of 90% vs. 68% respectively, P=0.05. Cumulative incidence of chronic GVHD at one year was 77% for COC and 48% for Non-COC patients, P=0.02. Conclusion: Physician-Patient continuity of care may favorably impact OS in Allo-HCT for hematological malignancy. The reason for lower relapse and TRM in COC group is unclear but could be attributed to older patients and differences in aGVHD management in Non-COC group. In this small study, COC did not impact OS in patients with severe aGVHD but may result in OS advantage in Allo-HCT patients without grade III/IV aGVHD. Larger studies are needed to address the impact of COC on outcomes after Allo-HCT. Disclosures: Khaled: Celgene and Takeda Pharmacutical: Honoraria, Speakers Bureau. Solh:Celgene: Speakers Bureau.

Physician's Experience and Continuity of Care May Result in Superior Survival Outcomes After Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Hematological Malignancies with Standard Conditioning Regimens and GVHD Prophylaxis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4715-4715
Author(s):  
Yasser Khaled ◽  
Melhem M. Solh
Keyword(s):  
High Risk ◽  
Continuity Of Care ◽  
Cumulative Incidence ◽  
Survival Outcomes ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Gvhd Prophylaxis ◽  
Graft Vs Host Disease ◽  
Conditioning Regimens ◽  
Donor Source

Abstract Abstract 4715 Allogeneic hematopoietic stem cell transplantation (HCT) represents potential curative option for patients with high risk hematological malignancy. However, HCT is still associated with high treatment related mortality (TRM). Extensive research in graft vs. host disease (GVHD) prevention and treatment of relapse post-transplant is being done to improve HCT outcomes. Although the transplant center experience and transplant volume has been correlated with improved outcomes after allogeneic HCT, the effect of physician's experience and continuity of care on outcomes after HCT in hematological malignancies is not known. We hypothesized that continuity of care along with physician experience would improve outcomes after HCT. Retrospectively, we reviewed the survival outcomes of 28 consecutive patients with high risk malignancy that underwent HCT from July 2010 to May 2012. A single 9 years experienced physician followed up those patients both as inpatient and outpatient from the time of initial consult up to last follow. The average percentage of care provided by the transplant physician to the 28 patients was 84% of the total billing visits. Patients characteristics including age, diagnosis, disease risk, status at HCT, donor source, conditioning regimen, GVHD prophylaxis and survival status are shown in table 1. All the patients received an established conditioning regimens and standard GVHD prophylaxis according to the donor source (table 1). Median age at transplant was 53 y/o. Donor source was 9 related donors (RD), 18 MUD donors and 1 double cord blood. All patients engrafted except two patients. One graft failure was in a patient who received a marrow product with low CD34 count. The other graft failure was in a myelofibrosis patient who failed to engraft after 3 attempts. With median duration of follow up of 422 days; at one year the overall survival (OS) was 92.8% (C.I. 83%–100%) and disease free survival (DFS) was 80% (C.I. 64%–96%). The cumulative incidence of acute GVHD was 52.5%, 55% for RD and 51% for MUD. Only 2/28 patients developed grade III and IV acute graft vs. host disease (Both MUD). Surprisingly, the cumulative incidence of chronic graft vs. host disease was higher for RD compared to MUD, 100% vs. 64%, respectively (P=0.1). Overall cumulative incidence of chronic GVHD was 74%. Both cumulative incidence of relapse and TRM were low of 7% at 1 year post transplant. Conclusion: Continuity of care when combined with the physician experience may result in superior survival outcomes in patients with high risk malignancy undergoing allogeneic HCT. Despite the small sample size, this intervention resulted in unexpected improved survival rate with lower TRM and relapse rate. Design of future prospective studies to address the impact of continuity of care and physician experience on outcomes after HCT is needed. Disclosures: Khaled: Celgene and Takeda Pharmacutical: Honoraria, Speakers Bureau. Solh:Celgene: Speakers Bureau.

scholarly journals Post-Transplant High Dose Cyclophosphamide and Bortezomib As Graft-Versus-Host Disease Prophylaxis Following Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3892-3892
Author(s):  
Benedetto Bruno ◽  
Frank Cirrone ◽  
Kelli Cole ◽  
Kelsey Stocker ◽  
Maher Abdul-Hay ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Advisory Board ◽  
High Dose ◽  
Graft Versus Host ◽  
One Year ◽  
Grade Iii

Abstract Introduction. Prevention of graft-versus-host disease (GvHD) following allogeneic hematopoietic cell transplantation (AHCT) remains a major challenge. The combination of methotrexate (MTX) and a calcineurin inhibitor has been the standard regimen for prophylaxis in patients receiving matched sibling donor (MSD) or matched unrelated donor (MUD) transplants for the past few decades. However, over 50% of patients undergoing AHCT still develop acute or chronic GvHD or even both, causing high rates of morbidity and mortality. Moreover, calcineurin inhibitors also have untoward toxic side effects. High dose post-transplant cyclophosphamide (PTCy), initially introduced for GvHD prevention in the setting of haploidentical transplantation, has now been studied in MSD and MUD transplants. We adopted a novel approach to prevent GvHD using a short course of PTCy and bortezomib. We hypothesized that such combination is safe and effective and omits the need for calcineurin or m-TOR inhibitors. Study Design. We report the outcomes of a prospective cohort of patients who received PTCy and bortezomib for GvHD prevention following MSD or MUD transplants. Twenty-eight patients were treated in a phase I-II trial and their clinical outcomes were previously reported (al-Homsi AS et al, BBMT 2019). Most of the remaining patients were treated on an extension trial. GvHD prevention consisted of PTCy 50 mg/kg IV on day +3 and +4, and bortezomib 1.3mg/m 2 IV 6 hours after transplant and again 72 hours after. Patients receiving MUD transplants also received rabbit ATG (thymoglobulin®) 5mg/kg total IV fractionated on day -4 to -2. All patients received peripheral blood grafts and standard supportive care as per Institutional policy. G-CSF was administered routinely until neutrophil engraftment. Results. Fifty-eight patients are included in this analysis. Median age was 60 (range 22-78) years. Fifty-three percent of patients were male. Underlying malignancies consisted of myeloid and lymphoid malignancies in 79.3% and 20.6%, respectively. Acute myeloid leukemia (50%) and myelodysplastic syndromes (24.1%) were the most common diseases. At transplant, disease risk index was low, intermediate, high and very high in 19.0%, 48.3%, 31.0% and 1.7% of patients, respectively. Median Pretransplant Assessment of Mortality Score (PAM) was 16.7 (5.4-29.4). Grafts were from MSD in 24.1% or MUD in 75.9% of patients. Recipient (R)/Donor (D) CMV status at transplant was as follows: R+/D+: 43%; R+/D-: 21%; R-/D+: 14% and R-/D-: 22%. Conditioning regimens consisted of reduced intensity fludarabine and busulfan in all but 2 patients who were conditioned with myeloablative fludarabine and busulfan. Overall, the regimen was remarkably well tolerated. Median times to neutrophil and platelet engraftment were 16 (13-28) and 26 (15-57) days respectively. No patient experienced primary graft failure. CMV and EBV reactivation rates were 46.6% and 24%. Cumulative incidences of grade II-IV and grade III-IV acute GVHD were 35% (95% CI: 22%-47%) and 15% (95% CI: 7%-25%) at day +120, respectively. Cumulative incidence of chronic GvHD was 14% at 1 year . Overall, 34% of patients required immunosuppression with systemic steroids after day +4 either for grade III-IV acute or chronic GvHD. Disease relapse rate was 26%. One-year cumulative incidence of transplant-related mortality was 14% (95% CI: 6%-25%). Median overall survival was 30.7 (95% CI: 15.7-not yet reached) months. One-year overall survival was 72% (95% CI: 57%-82%). One-year composite GvHD (acute and chronic) free and relapse free survival (GRFS) was 41.6% (95% CI: 28.9%-54%). Conclusion. PTCy and bortezomib combination for GvHD prophylaxis following MSD and MUD transplants is well tolerated and effective. It offers an alternative regimen to calcineurin and m-TOR inhibitor-containing regimens and may be preferred in certain settings including patients with limited resources, poor medication compliance, and with impaired renal function. A comparison of this cohort to a matched control group of patients receiving methotrexate and cyclosporine for GvHD prevention is ongoing. Disclosures Abdul-Hay: Amgen: Membership on an entity's Board of Directors or advisory committees; Servier: Other: Advisory Board, Speakers Bureau; Jazz: Other: Advisory Board, Speakers Bureau; Abbvie: Consultancy; Takeda: Speakers Bureau. Al-Homsi: Celyad: Other: Advisory Board; Daichii Sanyko: Consultancy. OffLabel Disclosure: Cyclophosphamide and Bortezomib are used for GvHD prevention

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.

scholarly journals Post-transplant cyclophosphamide containing regimens after matched sibling, matched unrelated and haploidentical donor transplants in patients with acute lymphoblastic leukemia in first complete remission, a comparative study of the ALWP of the EBMT

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jaime Sanz ◽  
Jacques-Emmanuel Galimard ◽  
Myriam Labopin ◽  
Boris Afanasyev ◽  
Moiseev Ivan Sergeevich ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cumulative Incidence ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Donor Type ◽  
Matched Sibling ◽  
The Impact

Abstract Background There is no information on the impact of donor type in allogeneic hematopoietic stem cell transplantation (HCT) using homogeneous graft-versus-host (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) in acute lymphoblastic leukemia (ALL). Methods We retrospectively analyzed outcomes of adult patients with ALL in CR1 that had received HCT with PTCy as GVHD prophylaxis from HLA-matched sibling (MSD) (n = 78), matched unrelated (MUD) (n = 94) and haploidentical family (Haplo) (n = 297) donors registered in the EBMT database between 2010 and 2018. The median follow-up period of the entire cohort was 2.2 years. Results Median age of patients was 38 years (range 18–76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II–IV and III–IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34% (p = 0.4); 13%, 15%, and 15% (p = 0.8); 35%, 50%, and 42% (p = 0.01); and 11%, 17%, and 21% (p = 0.2), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% (p = 0.8); and 21%, 18%, and 21% (p = 0.8) for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51% (p = 0.8); 66%, 69%, and 62% (p = 0.8); and 46%, 44%, and 35% (p = 0.9), respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better LFS. Conclusions Donor type did not significantly affect transplant outcome in patient with ALL receiving SCT with PTCy.

scholarly journals Low expression of MN1 associates with better treatment response in older patients with de novo cytogenetically normal acute myeloid leukemia

Blood ◽  
2011 ◽  
Vol 118 (15) ◽  
pp. 4188-4198 ◽  
Author(s):  
Sebastian Schwind ◽  
Guido Marcucci ◽  
Jessica Kohlschmidt ◽  
Michael D. Radmacher ◽  
Krzysztof Mrózek ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Hox Genes ◽  
De Novo ◽  
Prognostic Significance ◽  
The Impact ◽  
Favorable Group ◽  
Acute Myeloid

AbstractLow MN1 expression bestows favorable prognosis in younger adults with cytogenetically normal acute myeloid leukemia (CN-AML), but its prognostic significance in older patients is unknown. We analyzed pretherapy MN1 expression in 140 older (≥ 60 years) de novo CN-AML patients treated on cytarabine/daunorubicin-based protocols. Low MN1 expressers had higher complete remission (CR) rates (P = .001), and longer overall survival (P = .03) and event-free survival (EFS; P = .004). In multivariable models, low MN1 expression was associated with better CR rates and EFS. The impact of MN1 expression on overall survival and EFS was predominantly in patients 70 years of age or older, with low MN1 expressers with mutated NPM1 having the best outcome. The impact of MN1 expression was also observed in the Intermediate-I, but not the Favorable group of the European LeukemiaNet classification, where low MN1 expressers had CR rates and EFS similar to those of Favorable group patients. MN1 expresser-status-associated gene- and microRNA-expression signatures revealed underexpression of drug resistance and adverse outcome predictors, and overexpression of HOX genes and HOX-gene–embedded microRNAs in low MN1 expressers. We conclude that low MN1 expression confers better prognosis in older CN-AML patients and may refine the European LeukemiaNet classification. Biologic features associated with MN1 expression may help identify new treatment targets.

scholarly journals Pilot Study of Telmisartan (Micardis) for Prevention of Acute Graft Vs. Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation: Interim Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4546-4546
Author(s):  
Sujatha Iyengar ◽  
Scott D. Rowley ◽  
Caixin Zhan ◽  
Michele L. Donato ◽  
Themba Nyirenda ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Adverse Reactions ◽  
Acute Gvhd ◽  
Medical Center ◽  
Hematopoietic Stem ◽  
Graft Vs Host Disease ◽  
Grade Ii ◽  
Pre Treatment ◽  
Historical Controls ◽  
Grade Iii

Telmisartan (TMS) is an angiotensin receptor blocker with anti-inflammatory properties and little or no clinical immunosuppressive effect. We undertook an unblinded, single arm, pilot study of TMS (160 mg/d p.o.) for prevention of acute graft vs. host disease (aGvHD) in recipients of HLA matched allogeneic hematopoietic stem cell transplants (HSCTs). Primary endpoints of Grade II or >Grade III aGvHD (1994 Consensus Conference on Acute GVHD Grading) were compared with 178 similar HSCT historical controls over the preceding 3 yrs at our institution: 26% >Grade III, 74% Grade II. Safety endpoints included engraftment, relapse/progression by day (d) 180, non-relapse mortality by d 180, and serious drug-related adverse reactions. Experimental data were collected on blood endotoxin levels and stool microbiome composition. The study was powered to detect 20% or 50% reduced rates of, respectively, Grade II or >Grade III. We report results from a planned interim analysis triggered when the first 22 evaluable patients (pts) reached d 100. Of 27 evaluable pts, 24 were beyond d 180 by completion of this interim analysis. The study was designed to treat pts for two days prior to, and day of HSCT, and for an additional 98 days post-transplant, but pts were considered evaluable if they completed >14 days of post- transplant TMS, including pre-determined dose reductions. One enrollee received TMS for 13 days post-HSCT and was excluded from analysis. Five pts received 14-24 days of drug (4 by choice, 1 died of sepsis). More than half the evaluable patients (17/27) completed >94 days of post-HSCT therapy, including 6 who experienced an episode of hypotension. Almost half (13/27) received >80% of the full 101 day dose (16,160 mg), including 5 who experienced hypotension. Of the 6 enrollees receiving <24 days of drug, two had documented hypotension. No other serious drug-attributed adverse reactions were reported. Reasons cited for pts choosing to discontinue TMS were inconvenience of taking pills, and home stool sampling. Safety Endpoints: All pts engrafted promptly (ANC >500/uL, platelet >20,000/uL). Peripheral donor CD3+ T cell median and range of chimerism on days 28 and 84 were 99.5% (37-100) and 100.0% (36-100); bone marrow donor CD34+ cell chimerism was 97.0% (62-100). There was a single NRM during the 180 d study, and no graft rejection or increase in relapse or progression. Four relapses occurred within 180 days, and 2 more after d 180, resulting in two relapse deaths (d 370, and d 600). Primary Endpoints:A single individual developed hyperacute Grade III skin GvHD on day 7 p-HSCT. Another 12 of 27 patients developed Grade 2 aGvHD, one after the conventional 100 d window (d 141). Compared with historical controls, the incidence of aGvHD was significantly reduced for Grade II (p < 0.005) and Grade >III (p = 0.01), using the two-tailed Z-test of proportions. Experimental Endpoints: Acute GvHD is associated with increased gut permeability, bacterial translocation, and loss of gut microbiome diversity. Endotoxemia, an indicator of intestinal integrity, as measured by the endotoxin activity assay (EAA, Spectral Medical) reached septic levels in 40% of patients during pre-transplant conditioning (d -3 - d 0), and subsequently returned to, or maintained, non-septic levels from week 5 onward in 90% of patients, with an overall downward group trend of EAA scores during 180 days of follow up. Genotyping and analysis of bacterial V4 16S ribosomal DNA from weekly stool samples of the first 10 evaluable patients revealed no decrease in OTU richness or Shannon diversity at any time point pre- vs. post- treatment. Among the 5 most abundant phyla, Bacteroidetes was significantly less abundant post-treatment compared to pre-treatment. Among the 8 most abundant families, Bacteroidaceae significantly decreased post- vs. pre- treatment. While historic microbiome controls from our institution are not available, our finding of increased Bacteroidetes is in contrast to reported decreased Bacteroidetes in allogeneic HSCTs not receiving TMS, but may resemble changes after autologous HSCT. This trial, funded by the Gateway Foundation, is ongoing. Preliminary results indicate TMS is well tolerated, with a beneficial impact on aGvHD and no increased relapse or NRM, with excellent engraftment, and preservation of anti-tumor effect, intestinal barrier integrity, and gut microbial diversity. Disclosures Iyengar: Hackensack University Medical Center: Patents & Royalties: Telmisartan use patent.. Rowley:Allergan: Equity Ownership; Fate Therapeutics: Consultancy. Schwartz:Hackensack University Medical Center: Patents & Royalties: Telmisartan use patent. OffLabel Disclosure: Telmisartan. Indicated for treatment of hypertension.

Incidence and risk factors for severe tardive dyskinesia in older patients

1997 ◽  
Vol 171 (2) ◽  
pp. 148-153 ◽  
Author(s):  
Michael P. Caligiuri ◽  
Jonathan P. Lacro ◽  
Enid Rockwell ◽  
Lou Ann McAdams ◽  
Dilip V. Jeste
Keyword(s):  
Risk Factors ◽  
Tardive Dyskinesia ◽  
Movement Disorder ◽  
Cumulative Incidence ◽  
Older Patients ◽  
Negative Symptoms ◽  
Cox Regression ◽  
Effective Dosage ◽  
Regression Analyses ◽  
One Year

BackgroundSevere tardive dyskinesia (TD) represents a serious and potentially disabling movement disorder, yet relatively little is known about the incidence of and risk factors for severeTD.MethodWe report the results of a longitudinal prospective incidence study of severeTD in 378 middle-aged and elderly neuropsychiatric patients. Psychiatric, neuropsychological, pharmacological and motor variables were obtained at intake and at regular intervals for 36 months.ResultsThe cumulative incidence of severeTD was 2.5% after one year, 12.1% after two years, and 22.9% after three years. Individual univariable Cox regression analyses were conducted to identify demographic, psychiatric, motor and pharmacological predictors of severeTD. Results indicated that higher daily doses of neuroleptics at study entry, greater cumulative amounts of prescribed neuroleptic, and greater severity of worsening negative symptoms were predictive of severeTD Conclusions These findings suggest that conventional neuroleptics may be prescribed to older patients only when necessary and at the lowest effective dosage. Additional caution is recommended in patients exhibiting negative symptoms.

Toxicity, response, and survival in older adults with metastatic melanoma treated with checkpoint inhibitors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9544-9544
Author(s):  
Nienke A De Glas ◽  
Esther Bastiaannet ◽  
Frederiek van den Bos ◽  
Simon Mooijaart ◽  
Astrid Aplonia Maria Van Der Veldt ◽  
...  
Keyword(s):  
Older Adults ◽  
Overall Survival ◽  
Metastatic Melanoma ◽  
Older Patients ◽  
Regression Models ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Toxicity Response ◽  
Grade 3 ◽  
The Impact

9544 Background: Checkpoint inhibitors have strongly improved survival of patients with metastatic melanoma. Trials suggest no differences in outcomes between older and younger patients, but only relatively young patients with a good performance status were included in these trials. The aim of this study was to describe treatment patterns and outcomes of older adults with metastatic melanoma, and to identify predictors of outcome. Methods: We included all patients aged ≥65 years with metastatic melanoma between 2013 and 2020 from the Dutch Melanoma Treatment registry (DMTR), in which detailed information on patients, treatments and outcomes is available. We assessed predictors of grade ≥3 toxicity and 6-months response using logistic regression models, and melanoma-specific and overall survival using Cox regression models. Additionally, we described reasons for hospital admissions and treatment discontinuation. Results: A total of 2216 patients were included. Grade ≥3 toxicity did not increase with age, comorbidity or WHO performance status, in patients treated with monotherapy (anti-PD1 or ipilimumab) or combination treatment. However, patients aged ≥75 were admitted more frequently and discontinued treatment due to toxicity more often. Six months-response rates were similar to previous randomized trials (40.3% and 43.6% in patients aged 65-75 and ≥75 respectively for anti-PD1 treatment) and were not affected by age or comorbidity. Melanoma-specific survival was not affected by age or comorbidity, but age, comorbidity and WHO performance status were associated with overall survival in multivariate analyses. Conclusions: Toxicity, response and melanoma-specific survival were not associated with age or comorbidity status. Treatment with immunotherapy should therefore not be omitted solely based on age or comorbidity. However, the impact of grade I-II toxicity in older patients deserves further study as older patients discontinue treatment more frequently and receive less treatment cycles.[Table: see text]

scholarly journals HLA-E⁎01:03 Allele in Lung Transplant Recipients Correlates with Higher Chronic Lung Allograft Dysfunction Occurrence

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Julie Di Cristofaro ◽  
Mathieu Pelardy ◽  
Anderson Loundou ◽  
Agnès Basire ◽  
Carine Gomez ◽  
...  
Keyword(s):  
Overall Survival ◽  
Retrospective Study ◽  
Viral Infections ◽  
De Novo ◽  
Therapeutic Option ◽  
Univariate Analysis ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Hematopoietic Stem ◽  
The Impact

Lung transplantation (LTx) is a valid therapeutic option for selected patients with end-stage lung disease. HLA-E seems to play a major role in the immune response to different viral infections and to affect transplantation outcome, in Hematopoietic Stem Cell Transplantation, for example. Two nonsynonymous alleles, HLA-E⁎01:01 and HLA-E⁎01:03, have functional differences, involving relative peptide affinity, cell surface expression, and potential lytic activity of NK cells. The aim of this retrospective study was to determine the impact of these two alleles for LTx recipients on anti-HLA alloimmunization risk, overall survival, and chronic rejection (CLAD). HLA-E was genotyped in 119 recipients who underwent LTx from 1998 to 2010 in a single transplantation center. In univariate analysis, both HLA-E homozygous states were associated with impaired overall survival compared to heterozygous HLA-E alleles (p=0.01). In multivariate analysis, HLA-E⁎01:03 allele showed increased CLAD occurrence when compared to homozygous HLA-E⁎01:01 status (HR: 3.563 (CI 95%, 1.016–12),p=0.047). HLA-E allele did not affect pathogen infection or the production ofde novoDSA. This retrospective study shows an uninvestigated, deleterious association of HLA-E alleles with LTx and requires verification using a larger cohort.

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