scholarly journals Impact of Severity of Acute Graft-Versus-Host Disease on Healthcare Resource Utilization, Cost and Outcomes

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 37-38
Author(s):  
Nosha Farhadfar ◽  
Helen L Leather ◽  
Shu Wang ◽  
Nathan Burton ◽  
Vivian Irizarry Gatell ◽  
...  
Keyword(s):  
Electronic Medical Records ◽  
Medical Records ◽  
Research Funding ◽  
Acute Gvhd ◽  
Healthcare Resource Utilization ◽  
Total Cost ◽  
Icu Admission ◽  
The Mean ◽  
Hospital Days ◽  
Grade Iii

Introduction: Acute GVHD (aGVHD) contributes to poor outcomes and increased healthcare resource utilization (HRU) after allogeneic stem cell transplantation (allo-HCT). However, HRU and the economic burden of aGVHD based on severity of the disease and organ involvement is not well characterized. We examined the HRU, cost and mortality associated with aGVHD severity from initial hospitalization (index admission) up to 100 days post allo-HCT. Methods: Study cohort included 290 adult (≥ age 18) recipients of a first allo-HCT at the University of Florida between 1/2010 and 1/2019. The electronic medical records were reviewed for all patients who developed aGVHD as well as 116 patients without aGVHD who lived at least 1 month after HCT. Clinical measures that characterize the severity of aGVHD and extent of organ involvement were collected from electronic medical records. Medical costs and total hospital days were retrieved from administrative data that allocate costs to services based on departmental input for resource use and were adjusted to 2018 dollars. Wilcoxon rank sum test was used to compare number of inpatient days and total cost. Chi-squared test was used to compare ICU admission rate. Multivariable linear regression was fitted on log transformed cost. Results are shown as cost multipliers that represent ratios on original cost scale. Results: Of the 290 patients, 174 developed aGVHD within 100 days of allo-HCT. A higher proportion of patients with aGVHD had a Karnofsky performance status <80%, underwent matched unrelated donor HCT, and received calcineurin based GVHD prophylaxis. The mean number of days in the hospital for patients with aGVHD compared to those without aGVHD was 28 vs. 22 days, P<0.001 (Figure 1A). The mean number of hospital days for patients with grade I-II compared to those without aGVHD was 25 days vs. 22 days (P= 0.04) and for grade III-IV the mean number of days in the hospital compared to those without aGVHD was 48 days vs. 22 days (p < 0.001). In addition, presence of Lower gastrointestinal (GI) aGVHD was associated with more mean number of days in the hospital compared with those without aGVHD (43 vs. 22 days, P< 0.001). The ICU admission rates in patients with and without aGVHD were 13.2% and 6%, respectively (P=0.07) (Figure 1B). Analysis of ICU admissions based on grade of aGVHD revealed a significantly higher rate of ICU admission among patients with higher grade (grade III-IV) acute GVHD compared to those without aGVHD (22.3% vs. 6.0%, P=0.002). The early mortality rate in the first 100 days in aGVHD patients was twice that of the no aGVHD patients (14.9% vs. 7.8%; P=0.09). Compared to patients without aGVHD, early mortality was significantly higher in patients with aGVHD grade III-IV (7.8% vs. 33.9%; P< 0.001) and lower GI aGVHD (7.8% vs. 25.7%; P=0.001). Development of aGVHD was associated with a significantly higher total (inpatient and outpatient) cost. The mean total cost for patients with and without aGVHD were $226,545 and $165,622, respectively (P<0.001). Mean total costs associated with grades I, II and III-IV aGVHD were $183,693 (p = 0.44), $201,737 (p = 0.04) and $286,551 (<0.001), respectively (compared to $165,622 for those without aGVHD). Acute GVHD with GI involvement was significantly associated with higher mean total cost compared with aGVHD without GI involvement ($255,283 vs. $177,151, P<0.001). Among aGVHD cohort with GI involvement (Lower and/or upper GI), the mean cost was higher in patients with lower GI (LGI) compared with those without LGI aGVHD ($280,290 vs. $203,879, P=0.04). A multivariable analysis of risk factors for HCT cost identified presence of aGVHD, younger age at HCT, higher comorbidity index, and donor other than matched related donor as being associated with significantly higher costs (Table 1). Conclusion: HRU, cost, and clinical outcomes were associated with the severity of aGVHD. Development of higher grades of aGVHD and LGI aGVHD were associated with a poor clinical outcome and considerably increased healthcare economic burden. Given these clinical and economic risks it is imperative that new therapeutic strategies are developed for this patient population. Disclosures Farhadfar: Incyte pharmaceutical: Other: Member of GVHD advisory forum; CSL Behring: Research Funding. Leather:CSL Behring: Research Funding. Itzler:CSL Behring: Current Employment, Current equity holder in private company. Wingard:CSL Behring: Research Funding.

Inhibition of Lymphocyte Trafficking Using a CCR5 Antagonist – Final Results of a Phase I/II Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1011-1011 ◽  
Author(s):  
Ran Reshef ◽  
Selina M. Luger ◽  
Elizabeth O. Hexner ◽  
Alison W. Loren ◽  
Noelle V. Frey ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
Phase I ◽  
Research Funding ◽  
Acute Gvhd ◽  
Lymphocyte Trafficking ◽  
Comparator Group ◽  
Gvhd Prophylaxis ◽  
Grade Iii

Abstract Abstract 1011 Inhibition of lymphocyte trafficking early after allogeneic stem cell transplantation (SCT) may prevent GvHD without interfering with GvL activity. Animal models and genomic data in humans indicate that the interaction between CCR5 and its ligands CCL3, CCL4 and RANTES is pivotal in the pathogenesis of GvHD. Maraviroc (MVC; Selzentry®, Pfizer) is the first oral CCR5 antagonist in clinical use. The antiviral properties of MVC in HIV infection are known, but its effects on chemotaxis and immune function in patients without HIV infection have not been explored. We hypothesized that CCR5 inhibition early after allogeneic SCT would reduce lymphocyte chemotaxis and result in low rates of acute GvHD without impairing engraftment or antitumor activity. In vitro, MVC effectively and specifically inhibited CCR5 internalization and reduced RANTES-induced chemotaxis in concentrations achievable in humans, recapitulating a defect observed in homozygotes for the del32-CCR5 polymorphism. MVC had no effect on hematopoietic colony formation, T-cell mediated cytotoxicity and T-cell proliferation. Between May 2009 and March 2011, we enrolled 38 pts in a phase I/II study of reduced intensity conditioned (RIC) allogeneic SCT. Patients had high-risk features by age (median=62, range 21–74), donor source (matched related 34%, matched unrelated 50%, single-antigen mismatch 16%) and comorbidities (comorbidity index: low 55%, intermediate 34%, high 11%). Underlying diseases were AML (15), MDS (6), NHL (8), myelofibrosis (4), aplastic anemia, myeloma, CLL, Hodgkin, CML (1 each). Pts received fludarabine 120mg/m2 and IV busulfan 6.4 mg/kg followed by peripheral blood stem cells. In addition to standard GvHD prophylaxis with tacrolimus and methotrexate, MVC was given from day −2 to +30. Pharmacokinetic analysis on the first 13 pts identified 300 mg bid as the appropriate dose (Reshef, ASH 2010). MVC was well tolerated, and adverse events were similar to the expected toxicity observed in patients undergoing RIC SCT. The median time to ANC>500/μL was 15 d (range 10–27) and to platelets>20k/μL was 19 d (range 9–84). The median whole blood and T-cell donor chimerism at day 100 was 96.5% (range 0–100%) and 85% (range 0–100%) respectively. Median follow-up was 200 days (range 12–760). Among 35 evaluable patients, the cumulative incidences of any acute GvHD and grade III–IV acute GvHD at day 100 were 14.7 ± 6.2% and 2.9 ± 2.9%, respectively. Importantly, in the first 100 days, there were no cases of acute GvHD involving the liver or gut. At day 180, the rate of acute GvHD was 20.7 ± 7.1%, largely confined to the skin with low rates of GvHD in the liver (3 ± 3%) and gut (7.4 ± 5.3%). In evaluable pts who received a graft from their HLA-matched sibling (11), there was no GvHD before day 100 and only two cases of acute GvHD before day 180. We compared these results to a cohort of 38 well-matched consecutive patients treated at our institution with RIC SCT using an identical regimen but without MVC between 2009 and 2011. We observed a similar incidence of acute GvHD (all grades) at day 100 (14.7 ± 6.2 vs. 16 ± 6.1%; P=0.88), but a 64% decrease in the MVC group at day 180 (20.7 ± 7.1 vs. 45.4 ± 9%; P=0.03). The incidence rates of severe GvHD (grade III–IV) were 2.9 ± 2.9% in the MVC group vs. 5.5 ± 3.8% in the comparator group at day 100 (P=0.59) and 6.5 ± 4.5% vs. 18.1 ± 6.8% at day 180 (P=0.15). Treatment-related mortality in pts receiving MVC was low. At 1 year, non-relapse mortality rate was 7.6 ± 5.5% (control group: 15.7 ± 6.6%; P=0.35). Infectious complications were seen at a rate that is expected with RIC SCT. Recovery of lymphocyte counts and lymphocyte subsets was not impaired by MVC. We evaluated whether a protective effect against GvHD was associated with an increase in relapse. In the MVC group, the incidence of relapse was 34.2 ± 8.8% at day 180; this was not significantly different from the comparator group (43.9 ± 8.8%, P=0.44), implying preservation of the graft-versus-tumor effect with MVC. Rates of overall survival and relapse-free survival were similar in both groups. Pharmacodynamic testing revealed that sera from patients taking MVC prevented CCR5 internalization by RANTES and blocked T-cell chemotaxis in vitro, providing evidence for in vivo biological activity and supporting the hypothesized mechanism of action. In summary, inhibition of lymphocyte trafficking is a novel, specific and potentially effective strategy to reduce the incidence of acute GvHD. Disclosures: Off Label Use: Use of maraviroc in GvHD prophylaxis will be discussed. Frey:Pfizer: Speakers Bureau. Vonderheide:Pfizer: Research Funding. Porter:Pfizer: Research Funding.

scholarly journals First Results of a Prospective I/II Clinical Trial in Adult Patients Using TCR Alpha/Beta Depleted Stem Cell Transplantation from Matched Related and Unrelated Donors

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2164-2164
Author(s):  
Moniek De Witte ◽  
Anna Van Rhenen ◽  
Geerte Van Sluis ◽  
Rick Admiraal ◽  
Lotte van der Wagen ◽  
...  
Keyword(s):  
Research Funding ◽  
Immune Reconstitution ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Myeloablative Conditioning ◽  
Post Transplant ◽  
Kaplan Meier ◽  
Unrelated Donors ◽  
Male Patients ◽  
Grade Iii

Abstract Introduction: We report the first analysis of a multicenter prospective single-arm phase I/II study that assesses the safety and feasibility of transplantation of TCRalpha/beta depleted stem cells from matched related or unrelated donors using the CliniMACS plus System (Miltenyi Biotec, Germany) in combination with a non-myeloablative conditioning in adult patients (trial nr NL48606.000.14). The conditioning regimen consisted of ATG (Thymoglobulin®) 1.5mg/kg i.v. days -12 to -9; fludarabine i.v. 40 mg/m2 days -5 to -2 and busulfan i.v. (Busivex®) days -5 to -2 (cumulative AUC of 80-90mg*h/L), followed by 28 days of mycophenolic acid. All 35 subjects were eligible to address the primary endpoint which is the incidence of acute GVHD at day 100. Results: 2 centers enrolled 10 female and 25 male patients (median age 59 years, range 19 - 69 years), including 9 AML, 4 ALL, 2 CML, 5 MM, 1 NHL, 10 MDS, 4 MPN. Diseases were in CR (n=17), VGPR (n=1), PR (n=5) or non-remission (n=12). 4 subjects had one or more previous allogeneic SCTs. Donors included 4 MRD, 24 10/10 matched MUD and 7 9/10 matched MUD. 8 male patients received stem cells of female donors. The median number of CD34+ cells and αβ TCR cells/kg was 6.1x 10^6 (range, 1.9-10) and 14.5x10^3 (range, 0-136), respectively. One primary graft failure was observed. Primary engraftment of ANCs > 500 cells/μL was reached at a median of 14 days (range 9 - 48 days) and of platelets > 20 at a median of 17 days (range 10 - 99) days. The median time of follow-up of this first analysis was 190 days (range 110-400 days). 3/35 patients developed acute GVHD grade III-IV during the first 100 days, 9/35 patients developed acute GVHD grade II-IV and 16/35 patients grade I-IV at day 100. At day 100 the cumulative incidence (CI) of CMV was 31%, of EBV 36% and of BK cystitis 20%. The combined CI of CMV/EBV/BK infections with a CTC-AE grade III-V was 53% at day 100. Immune reconstitution was rapid with a median of 227 (range 34 - 1626) CD3+ cells/µl on day 100 but varied substantially between patients. The median numbers of CD3/CD4+ and CD3/CD8+ at day 100 post transplant were 60 (range 30 - 120) and 124 (range 5 - 1450) cells/µl. The median numbers of NK were 289 (range 32-1140) at day 30 and 128 (range 24 - 1228) cells/µl at day 100 post transplant. The median numbers of γδ T cells were 38 (range 4-143) at day 30 and 50 (range 8-556) cells/µl at day 100 post transplant. 26 out of 35 patients were alive, 2 patients died of a relapse, 2 of GVHD and 5 of infectious complications. Kaplan Meier estimates of the OS are 88% (+/- 6%) at day 100 and 68% (+/- 9%) at 1Y. Kaplan Meier estimates of the EFS are 77% (+/- 7%) at day 100 and 52% (+/- 10%) at 1Y. 2 patients developed a relapse before day 100 and 5 patients before 1Y. It is noted that the outcome of 5 patients with MM was very poor in this cohort (3 patients developed a relapse and 2 patients died of complications). Conclusion: Allo-SCT of αβ T cell depleted PBMCs form matched related or unrelated donors, in combination with early ATG and a non-myeloablative conditioning regimen, resulted in favorable rates of primary engraftment (34/35), a CI of aGVHD II-IV of 26% with only minimal immuno-suppression and an encouraging early disease control (Fig 1). OS survival was mainly impacted by NRM (Fig 1), by which the majority of complications were of infectious nature. While all patients with MM suffered from NRM or relapse, all other disease categories had a rather favorable outcome. Reducing inter-individual variations in immune reconstitution early after transplantation will be key to further improve outcomes. Disclosures Minnema: Amgen: Consultancy; Takeda: Consultancy; Celgene: Consultancy, Research Funding; Janssen: Consultancy; Servier: Consultancy. Kuball:Novartis: Research Funding; Miltenyi Biotec: Research Funding; Gadeta (www.gadeta.nl): Consultancy, Equity Ownership, Patents & Royalties: on gd T cells and receptors and isolation strategies, Research Funding.

scholarly journals Exploring why patients with cancer consult GPs: a 1-year data extraction

BJGP Open ◽  
2019 ◽  
Vol 3 (4) ◽  
pp. bjgpopen19X101663 ◽  
Author(s):  
Heidi Lidal Fidjeland ◽  
Ingvild Vistad ◽  
Svein Gjelstad ◽  
Mette Brekke
Keyword(s):  
Electronic Medical Records ◽  
Medical Records ◽  
Data Extraction ◽  
Survival Rates ◽  
Main Diagnosis ◽  
Consultation Rate ◽  
Patients With Cancer ◽  
Explorative Study ◽  
The Mean

BackgroundSurvival rates of patients with cancer are increasing owing to improvements in diagnostics and therapies. The traditional hospital-based follow-up model faces challenges because of the consequent increasing workload, and it has been suggested that selected patients with cancer could be followed up by GPs.The hypothesis of the study was that, regardless of the hospital-based follow-up care, GPs see their patients with cancer both for cancer-related problems as well as for other reasons. Thus, a formalised follow-up by GPs would not mean too large a change in GPs’ workloads.AimTo explore to what extent patients with cancer consult their GPs, and for what reasons.Design & settingA 1-year explorative study was undertaken, based on data from 91 Norwegian GPs from 2016–2017.MethodThe data were electronically extracted from GPs' electronic medical records (EMR).ResultsData were collected from 91 GPs. There were 11 074 consultations in total, generated by 1932 patients with cancer. The mean consultation rate was higher among the patients with cancer compared with Norwegian patients in general. In one-third of the consultations, cancer was the main diagnosis. Apart from cancer, cardiovascular and musculoskeletal diagnoses were common. Patients with cancer who had multiple diagnoses or psychological diagnoses did not consult their GP significantly more often than patients with cancer without such comorbidity.ConclusionThis study confirms that patients with cancer consult their GP more often than other patients, both for cancer-related reasons and for various comorbidities. A formalised follow-up by GPs would probably be feasible, and GPs should prepare for this responsibility.

Prospective, Biological Randomized Study of T-Cell Depleted Nonmyeloablative Allogeneic Transplantation From HLA-Matched Related, Unrelated or Haploidentical Donors for Patients with Hematologic Malignancies

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3541-3541
Author(s):  
Junya Kanda ◽  
Gwynn D. Long ◽  
Cristina Gasparetto ◽  
Mitchell E. Horwitz ◽  
Keith M. Sullivan ◽  
...  
Keyword(s):  
Research Funding ◽  
Acute Gvhd ◽  
Residual Disease ◽  
Fungal Infections ◽  
Randomized Study ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Rank Test ◽  
Log Rank Test ◽  
Grade Iii

Abstract Abstract 3541 We have previously shown that SCT from HLA-haploidentical related donors (HAPLO) after nonmyeloablative conditioning is feasible with a low incidence of grade III-IV acute GVHD or treatment-related mortality (TRM) (Rizzieri et al. JCO 2007). We now report our comparative study in patients who received SCT from a 6/6 HLA-matched related (MRD), 8–10/8 HLA-matched unrelated (MUD), or HAPLO donor, after nonmyeloablative conditioning. Methods: Patients with chemosensitive relapse or high risk disease with minimal residual disease at study entry were eligible. The conditioning regimen consisted of fludarabine, 40 mg/m2 for 4 days; melphalan, 140 mg/m2 for 1 day; and alemtuzumab, 20 mg for 4 days for patients with lymphoid or myelomatous diseases. Fludarabine and alemtuzumab at the same doses with busulfan, 130 mg/m2 for 2 days was used for patients with myeloid diseases. Mycophenolate mofetil was used for GVHD prophylaxis. Donor lymphocyte infusions were performed in 15 MRD patients and 4 HAPLO patients. Disease-free survival (DFS) and overall survival (OS) rates after SCT were estimated using the Kaplan–Meier method, and univariate comparisons were performed using the log-rank test. Cox proportional-hazards regression was used to evaluate variables that potentially affected the survival rates. Results: The lymphoid cohort included 52 patients with ALL (n = 6), lymphoma (n = 42), or myeloma (n = 4), whereas the myeloid cohort included 46 patients with AML/MDS (n = 40), and myeloproliferative disorder (MPD) (n = 6). The median subject age was 56.5 (range, 20–73) years with a median follow-up of 15 months among survivors. A total of 29, 40, and 29 patients received transplants from MRD, MUD, and HAPLO, respectively. All 29 patients engrafted after HCT from MRD. One of 40 patients who received SCT from MUD had a primary graft failure (GF), with 2 secondary GF and 1 early relapse. Two of them were rescued by subsequent nonmyeloablative SCT from the same MUD or new HAPLO donor. Among 28 HAPLO patients evaluable for engraftment, 8 had a primary GF, 6 of these had myeloid disease; 2 additional patients had donor cell recovery but without full recovery of normal blood counts. Three of the 8 were rescued with subsequent nonmyeloablative SCT from the same donor. The transplant regimen resulted in 11% TRM at day 100. Grade III-IV acute GVHD rates were 0/29 (0%), 4/40 (10%), and 5/29 (17%) in patients who received a transplant from a MRD, MUD, or HAPLO, respectively. CMV reactivation occurred in 57% of patients and 6% developed CMV disease. Other infectious complications included polyomavirus in 24% of patients, bacteria in 23%, respiratory viruses in 13%, and fungal infections in 7%. The common causes of death were progressive disease (30% for all cause of death) and infections (32%). The 1-year DFS rate after SCT from MRD, MUD, and HAPLO was 55% (95% CI, 33–73%), 39% (22–56%), and 34% (16–53%), respectively (Log-rank test, P = 0.094) (Figure 1); the corresponding 1-year OS rate was 66% (43–82%), 39% (21–55%), and 34% (16–53%), respectively (Log-rank test, P = 0.012) (Figure 2). Multivariate analysis revealed that SCT from MUD/HAPLO, compared with that from MRD, was the only adverse factor that affected the OS rate (HR for MUD, 2.62 (95% CI, 1.15–5.96), P = 0.022; HR for HAPLO, 3.17 (1.36–7.37), P = 0.007), but the OS rate after SCT from HAPLO did not significantly differ from that after SCT from MUD (P = 0.560). Other variables (recipient age, conditioning regimen, and disease status at transplant) were not significantly associated with the outcome. Conclusions: The results show the feasibility of this approach with this regimen and the clinical outcomes in patients who received transplants from HAPLO are comparable to patients who received transplants from MUD. Development of strategies to improve immune recovery remains a current challenge. Disclosures: Off Label Use: Alemtuzumab for conditioning in allogeneic stem cell transplantation. Horwitz:Genzyme: Honoraria, Research Funding. Chao:Genzyme: Research Funding. Rizzieri:Genzyme: Speakers Bureau.

scholarly journals Comparison of Outcomes between HSCT Donor Sources for Pediatric Patients with Hematologic Malignancies

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4611-4611
Author(s):  
Lauren Longo ◽  
Filippo Milano ◽  
Colleen Delaney ◽  
Marie Bleakley ◽  
Lauri S Burroughs ◽  
...  
Keyword(s):  
Research Funding ◽  
Pediatric Patients ◽  
Acute Gvhd ◽  
Disease Risk ◽  
Conditioning Regimen ◽  
Hematologic Malignancies ◽  
Advisory Committees ◽  
Equity Ownership ◽  
Grade Iii ◽  
Donor Source

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for pediatric patients with hematologic malignancies. Historically, matched sibling donors (MSD) have been the preferred donor source given ease of availability and lower rates of graft-versus-host-disease (GVHD). However, only 30% of patients have a MSD and relapse rates are high after MSD HSCT, raising the question of best donor choice. As conditioning regimens evolve, GVHD management improves and supportive care advances, it is important to evaluate the role of donor source on short and long-term clinical outcomes to inform donor selection. We performed a single-center retrospective analysis comparing post-HSCT outcomes in a cohort of pediatric patients undergoing MSD, matched unrelated donor (MUD), and umbilical cord blood (CB) transplants from 2006 to 2018. Methods: A retrospective analysis was performed on an IRB-approved protocol through Fred Hutchinson Cancer Research Center. 232 patients were included who received MSD (n=56), MUD (n=89) or CB (n=87) transplants. Of note, 24 CB patients received expanded CB cells in addition to unmanipulated unit(s). GVHD prophylaxis in all patients consisted of a calcineurin inhibitor and MMF or methotrexate. The vast majority received a high-intensity conditioning regimen (86%, 96%, and 82% respectively for MSD, MUD and CB). Overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method. Probabilities of non-relapse mortality (NRM), relapse, and acute GVHD were evaluated using cumulative incidence (CI) estimates with appropriate competing risks. The Cox regression model was used for adjusted analysis for age, year of transplant, sex, CMV status, MRD status, disease risk, and conditioning regimen. Results: Patient/treatment/donor demographics are shown in Table 1. Median follow-up was 2.6, 3.7 and 3.1 years for MSD, MUD and CB respectively. Patient diagnosis, disease risk, gender, age, and CMV serology were balanced between groups. CI of engraftment was similar as well, with only one graft failure in the MUD group (Fig 1). Median time to platelet recovery was significantly faster in MUD and MSD groups as compared to the CB group (p<0.0001; p<0.0001). There was no difference in unadjusted 5 year OS (Fig 2) and NRM (Fig 3) between groups. Five-year DFS was significantly higher in CB v. MSD (71% v. 54%, p=0.03) but not between CB v. MUD (71% v. 61%, p=0.18) or between MSD and MUD (p=0.38) (Fig 4). The CI of relapse at 5 years was 20% for CB patients, significantly lower than that of MSD recipients (49%, p=0.003) and not different from MUD (32%, p=0.11) (Fig 5). After adjusted analysis, the risk of DFS failures was higher among recipients of MSD than CB [HR: 1.88 (CI 95%: 1.01-3.47), p=0.04]. When CB versus MUD groups were compared, there was a trend of higher risk of DFS failures in the MUD group [HR: 1.28 (CI 95%: 0.96-1.66), p=0.09]. No difference was observed in risk of DFS failures between MSD versus MUD groups [HR:0.77 (CI 95%: 0.44-1.4), p=0.43]. Incidence of grade II-IV acute GVHD was 90% (95%CI: 82-95%), 75% (95%CI: 61-84%) and 88% (95%CI: 80-94%), for CB, MSD and MUD, respectively (p=0.25). Incidence of grade III-IV acute GVHD was 33% (95%CI: 23-43%) for CB, 9% (95%CI: 3-18%) for MSD, and 11% (95%CI: 5-18%) for MUD. Incidence of grade III-IV was significantly higher for the CB group compared to the other groups (p=0.001); however, nearly 60% of CB recipients with grade III-IV acute GVHD were diagnosed before engraftment had occurred and in retrospect met criteria for pre-engraftment syndrome. Among surviving patients, 23 CB recipients developed chronic GVHD (26% - 15 mild, 4 moderate, 4 severe) as compared to 14 MSD patients (25% - 13 mild, 1 moderate) and 40 MUD patients (45% - 27 mild, 11 moderate, 2 severe). Conclusions: Our data demonstrate no difference in unadjusted OS between MSD, MUD and CB recipients. Importantly, despite this equivalence, 5-year DFS was significantly better in the CB v. MSD group, reflecting the lower relapse rate observed in CB patients and seen previously by us and others. CB continues to be viewed as an "alternative" donor for HSCT due to the low stem cell dose in a CB graft resulting in delayed neutrophil recovery, primary graft failure and increased NRM. However, this was not observed herein, supporting the use of CB for pediatric HSCT perhaps especially in patients at high risk of post-transplant relapse. Disclosures Milano: ExCellThera: Research Funding; Amgen: Research Funding. Delaney:Nohla Therapeutics: Employment, Equity Ownership; Biolife Solutions: Membership on an entity's Board of Directors or advisory committees. Bleakley:HighPass Biotherapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.

scholarly journals Who Is the Best Donor for the Second Transplant?: HLA Discrepancy between Graft and Host Rather Than That Graft and First Donor May Impact the Second Transplant Outcome from the JSHCT

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4635-4635
Author(s):  
Yoshinobu Maeda ◽  
Tomotaka Ugai ◽  
Eisei Kondo ◽  
Kazuhiro Ikegame ◽  
Makoto Murata ◽  
...  
Keyword(s):  
Research Funding ◽  
Acute Gvhd ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Immunological Responses ◽  
Increased Risk ◽  
Significant Difference ◽  
Otsuka Pharmaceutical ◽  
Risk Of Relapse ◽  
Grade Iii

Abstract For patients with malignant hematological diseases that relapse after allogeneic hematopoietic stem cell transplantation (HSCT), a second HSCT is thought to be a curative option. A second donor is usually searched for due to HLA discrepancy between the graft and the host. However, it is unclear whether HLA discrepancy between the graft and the first donor has an impact on the outcome of second HSCT. To address this issue, we focused on second HSCT patients who had received first HSCT from an HLA-mismatched (MM) donor and compared the effects of HLA discrepancy between graft and first donor with those between graft and host. We retrospectively analyzed 646 patients receiving second HSCT between 1994 and 2016 after an initial HLA-MM transplantation. With regard to the graft versus host results, the one-allele mismatch (1 MM) group (relative risk [RR], 1.88; 95% confidence interval [CI], 0.79-4.45; p=0.163) and more than one-allele mismatch group (≥ 2 MM) (RR, 1.84; 95% CI, 0.75-4.51; p=0.182) had higher risks of grade III-IV acute GVHD compared to the HLA-matched (0 MM) group, although the results were not significant. In contrast, almost no difference in risk of acute GVHD was found among the 0, 1, and ≥ 2 MM group with respect to graft vs. first donor. Furthermore, with regard to graft vs. host, the ≥ 2 MM group showed a significantly higher risk of treatment-related mortality (TRM) (RR, 1.90; 95% CI, 1.04-3.50; p=0.038) compared to the 0 MM group. In contrast, the risk of relapse was slightly lower in the ≥ 2 MM group (RR, 068; 95% CI, 0.44-1.06; p=0.086). Consequently, no significant difference in OS was found among the three groups. In the analysis of each HLA allele MM, B allele MM between graft and host was associated with an increased risk of grade III-IV acute GVHD (RR 2.87; 95% CI, 1.42-5.79; p=0.003) and DR allele MM between graft and host was associated with a lower risk of relapse (RR, 0.75; 95% CI, 0.58-0.95; p=0.018) and higher risk of TRM (RR, 1.44; 95% CI, 1.03-2.00; p=0.033). In contrast, with regard to graft vs. first donor, there were no significant differences in relapse, TRM, or OS among the three groups, and also analysis of each HLA allele MM indicated no associations with relapse, TRM, or OS. These findings suggested that HLA discrepancy between graft and host, rather than between graft and first donor may induce transplant-related immunological responses in second HSCT leading to an increase in TRM. In conclusion, HLA-MM donor is an option after initial HLA-MM transplantation, however, TRM remains a challenge, particularly with a ≥ 2 MM donor regarding to graft versus host. In this study, the biological effects of HLA discrepancy between the graft and the first donor on the outcome appeared negligible, and our findings shed light on the role of nonhematopoietic APCs on transplant-related immunological responses. Figure. Figure. Disclosures Nakamae: Otsuka Pharmaceutical Co., Ltd.: Consultancy, Honoraria, Research Funding. Ichinohe:Mundipharma: Honoraria; Eisai Co.: Research Funding; Ono Pharmaceutical Co.: Research Funding; Alexion Pharmaceuticals: Honoraria; Zenyaku Kogyo Co.: Research Funding; Kyowa Hakko Kirin Co.: Research Funding; CSL Behring: Research Funding; Novartis.: Honoraria; Takeda Pharmaceutical Co.: Research Funding; Taiho Pharmaceutical Co.: Research Funding; Chugai Pharmaceutical Co.: Research Funding; Astellas Pharma: Research Funding; Repertoire Genesis Inc.: Research Funding; Sumitomo Dainippon Pharma Co.: Research Funding; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; JCR Pharmaceuticals: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Pfizer: Research Funding; Nippon Shinyaku Co.: Research Funding; MSD: Research Funding; Otsuka Pharmaceutical Co.: Research Funding. Kanda:Ono: Consultancy, Honoraria, Research Funding; Shionogi: Consultancy, Honoraria, Research Funding; Nippon-Shinyaku: Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Kyowa-Hakko Kirin: Consultancy, Honoraria, Research Funding; Taiho: Research Funding; Pfizer: Research Funding; Taisho-Toyama: Research Funding; MSD: Research Funding; Novartis: Research Funding; Tanabe-Mitsubishi: Research Funding; Chugai: Consultancy, Honoraria, Research Funding; Otsuka: Research Funding; Dainippon-Sumitomo: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Eisai: Consultancy, Honoraria, Research Funding; Sanofi: Research Funding; CSL Behring: Research Funding; Asahi-Kasei: Research Funding; Celgene: Consultancy, Honoraria; Mochida: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Takara-bio: Consultancy, Honoraria.

The Use of Anti-Thymocyte Globulin Is Associated with Increased Chance of Survival Free from Relapse and Graft-Versus-Host Disease after Allogeneic Peripheral Blood Stem Cell Transplantation for Adults with Philadelphia-Negative Acute Lymphoblastic Leukemia: An Analysis By the Acute Leukemia Working Party of the EBMT

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 666-666
Author(s):  
Sebastian Giebel ◽  
Myriam Labopin ◽  
Wlodzimierz Mendrek ◽  
Gerard Socie ◽  
Liisa Volin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Acute Gvhd ◽  
Lymphoblastic Leukemia ◽  
Conditioning Regimen ◽  
Advisory Committees ◽  
Graft Versus Host ◽  
Grade Ii ◽  
Grade Iii

Abstract BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-SCT) is considered a standard of care for adults with high risk Philadelphia-negative acute lymphoblastic leukemia (Ph-neg ALL). During the last decade mobilized peripheral blood stem cells (PBSCT) has become predominant source of graft for allo-SCT. However, as compared to bone marrow, PBSCT is associated with increased risk of chronic graft-versus-host disease (cGVHD). Attempts to reduce the cGVHD rate include the addition of anti-thymocyte globulin (ATG) to the conditioning regimen. The goal of this registry-based, retrospective study was to analyze the effect of ATG on results of allo-PBSCT in adults with Ph-neg ALL. PATIENTS AND METHODS: 682 patients, aged 18-74 years, with Ph-neg ALL, treated with un-manipulated allo-PBSCT in first complete remission between 1997-2014 were included in the analysis. Conditioning regimen was myeloablative in 550 (81%) cases. Among 339 transplantations from matched sibling donors, ATG was used in 57 (22%) cases. In the 8/8 HLA-matched unrelated setting 204/343 (78%) patients were treated with ATG. Survival free from grade III-IV acute GVHD, cGVHD and relapse (GRFS) was the primary study end-point. RESULTS: In a univariate analysis the use of ATG was associated with increased probability of GRFS at 3 years (46% vs 38%, p=0.02) as well as decreased incidence of the overall cGVHD (34% vs. 51%, p=0.0001) and extensive cGVHD (12% vs. 25%, p<0.0001). No significant difference could be demonstrated with regard to the incidence of grade II-IV acute GVHD (30% vs. 33%, p=0.41), grade III-IV acute GVHD (8% vs. 11%, p=0.12), relapse (28% vs. 26%, p=0.38) and non-relapse mortality (NRM, 15% vs. 17%, p=0.21) as well as probability of leukemia-free survival (LFS, 57% vs. 57%, p=0.89) and overall survival (OS, 65% vs. 65%, p=0.54). In a multivariate model adjusted for other potential risk factors, the use of ATG was associated with reduced risk of grade II-IV aGVHD (HR=0.64, p=0.007), grade III-IV aGVHD (HR=0.52, p=0.03), overall cGVHD (HR=0.61, p=0.001), extensive cGVHD (HR=0.4, p<0.0001), and NRM (HR=0.62, p=0.04). No significant effect was found with regard to the incidence of relapse (p=0.27), LFS (p=0.7) and OS (p=0.16). GRFS was significantly increased with the use of ATG (HR=0.74; p=0.009). Among other factors a chance of GRFS was significantly decreased with increasing patient age (HR=1.1 for each 10 years, p=0.02), transplantations with reduced-intensity conditioning (HR=1.61, p=0.0009) and positive recipient CMV serological status (HR=1.3, p=0.02). CONCLUSIONS: Patients with Ph-neg ALL treated with allo-PBSCT benefit from the use ATG in terms of survival free from GVHD and relapse. The use of ATG should therefore be recommended in this setting. Further studies are needed to explore potential role of the ATG brand and dose. Disclosures Masszi: Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Maertens:Merck Sharp & Dohme: Consultancy, Honoraria, Research Funding, Speakers Bureau; Astellas: Consultancy, Speakers Bureau; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy.

A brief intervention to improve rates and quality of physical examinations for admissions to acute adult psychiatry units

2019 ◽  
Vol 27 (6) ◽  
pp. 641-644
Author(s):  
Usama Munir ◽  
Adnan Younus ◽  
Vlasios Brakoulias
Keyword(s):  
Physical Examination ◽  
Electronic Medical Records ◽  
Brief Intervention ◽  
Retrospective Review ◽  
Medical Records ◽  
Breath Sounds ◽  
Adult Psychiatry ◽  
Physical Examinations ◽  
The Mean

Objective: To determine the frequency and quality of physical examinations within 24 h of admission to an acute adult psychiatry unit, and whether a brief intervention involving feedback to clinicians could lead to improvement. Method: Retrospective review of the electronic medical records followed by four brief feedback sessions and email correspondence, followed by a further review of the medical records 1 month later. Results: The proportion of patients receiving a physical examination increased from 36/71 (50.7%) in the initial audit to 41/64 (64.1%) in the re-audit. The mean score of the quality of physical examinations improved from 7.5 to 9.3 (out of 15). The greatest improvement on re-audit occurred in the documentation of additional cardiac sounds (33.9% increase), additional breath sounds (17.7% increase), breath sounds (17.1% increase), cardiac sounds (14.2% increase) and bowel sounds (12.5% increase). Conclusion: This audit supports the use of brief peer-led feedback to improve the rates and quality of physical examinations.

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