132 VARIABLE INTENSITY CONDITIONING IS ASSOCIATED WITH LESS TRANSPLANT-RELATED MORTALITY THAN NONMYELOABLATIVE CONDITIONING IN UNRELATED AND RELATED ALLOGENEIC TRANSPLANT RECIPIENTS

2005 ◽  
Vol 53 (1) ◽  
pp. S276.4-S276
Author(s):  
C. L. Bigelow ◽  
S. Elkins ◽  
C. L. Hardy ◽  
J. C. Files
Keyword(s):  
Transplant Recipients ◽  
Allogeneic Transplant ◽  
Variable Intensity ◽  
Related Mortality

Less Treatment Related Mortality with Variable Intensity Conditioning Than Non-Myeloablative Conditioning in Unrelated and Related Adult Allogeneic Transplant Recipients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5051-5051
Author(s):  
Carolyn L. Bigelow ◽  
Stephanie Elkins ◽  
Cheryl L. Hardy ◽  
Joe Clark Files
Keyword(s):  
Acute Gvhd ◽  
Transplant Recipients ◽  
Allogeneic Transplant ◽  
Myeloablative Conditioning ◽  
Variable Intensity ◽  
Group 2 ◽  
One Year ◽  
Treatment Related Mortality ◽  
Related Mortality ◽  
Group 1

Abstract For the past four years our adult allogeneic transplant program has employed two alternative approaches to standard recipient conditioning, the use of non-myeloablative “mini” conditioning and variable intensity conditioning. We now report a retrospective comparison of relapse, day +100 and one year survival, engraftment and grades I-II and III-IV acute GVHD in unrelated as well as related recipients in these two preparative regimen groups. Patients with a variety of malignancies were not randomized to receive either non-myeloablative (Group 1) or variable intensity (Group 2) conditioning. Twenty patients with a median age of 49 (range 27–64, Group 1) and 17 patients also with a median age of 49 (range 24–58, Group 2) received either marrow or peripheral blood stem cells, usually with a 6/6 match grade; one recipient in Group 2 received a cord blood transplant (4/6 match). Group 1 regimen consisted of fludarabine 30 mg/m2 x 3d and TBI 200 cGY. Group 2 regimen consisted of Campath 20 mg/d either 5 or 3 days, fludarabine x 5d and melphalan 140 mg/m2 x 1d. GVHD prophylaxis was the same in both groups (standard dose cyclosporine or tacrolimus and MMF.) All patients received an adequate CD34+ cell dose and none of the products was manipulated. Relapse rate was 37% in Group 1 and 53% in Group 2. Day+100 survival and one year survival were 55% and 20%, respectively, in Group 1 vs 69% and 33% in Group 2. Only one patient in Group 2 had acute GVHD, grades I-II; none had grades III-IV. However, in Group 1, 6 patients had grades I-II and 8 had grades III-IV (40%). Graft failure occurred in five patients in Group 1, while no patients in Group 2 experienced it. We conclude, first, that in our program the application of variable intensity conditioning has been quite successful in unrelated transplant recipients, as well as in related. Second, significant treatment related mortality in the form of graft failure and acute GVHD occurred less frequently in recipients who received this conditioning than in those receiving non-myeloablative conditioning. This regimen requires some further modification to enhance its tumoricidal properties; however, its treatment-related toxicity is minimal and allows us to offer this therapy to patients with co-morbid conditions and older age.

Emergence of Cunninghamella As a Pathogenic Invasive Mold Infection in Allogeneic Transplant Recipients

2013 ◽  
Vol 13 (5) ◽  
pp. 622-628 ◽  
Author(s):  
Lynne Strasfeld ◽  
Luis Espinosa-Aguilar ◽  
James L. Gajewski ◽  
Peter Stenzel ◽  
Agustin Pimentel ◽  
...  
Keyword(s):  
Transplant Recipients ◽  
Allogeneic Transplant

scholarly journals Optimizing Outcomes Beyond Day +100: Process for Identifying and Managing High-Risk Allogeneic Transplant Recipients

2017 ◽  
Vol 23 (3) ◽  
pp. S451-S452
Author(s):  
Sheila Serafino ◽  
Navneet S. Majhail ◽  
Julie Curtis ◽  
Laura Bernhard ◽  
Sharon Caroniti ◽  
...  
Keyword(s):  
High Risk ◽  
Transplant Recipients ◽  
Allogeneic Transplant

scholarly journals Comparison of pediatric allogeneic transplant outcomes using myeloablative busulfan with cyclophosphamide or fludarabine

2018 ◽  
Vol 2 (11) ◽  
pp. 1198-1206 ◽  
Author(s):  
Andrew C. Harris ◽  
Jaap J. Boelens ◽  
Kwang Woo Ahn ◽  
Mingwei Fei ◽  
Allistair Abraham ◽  
...  
Keyword(s):  
Allogeneic Transplant ◽  
Transplant Outcomes ◽  
Key Points ◽  
Related Mortality

Key Points Children receiving BuFlu for nonmalignant conditions experienced less toxicity than those receiving BuCy, but survival was comparable. Children with malignancy had shorter postrelapse survival with BuFlu than BuCy; transplant-related mortality and relapse were similar.

scholarly journals Infection-Related Mortality in Recipients of a Kidney Transplant in Australia and New Zealand

2019 ◽  
Vol 14 (10) ◽  
pp. 1484-1492 ◽  
Author(s):  
Samuel Chan ◽  
Elaine M. Pascoe ◽  
Philip A. Clayton ◽  
Stephen P. McDonald ◽  
Wai H. Lim ◽  
...  
Keyword(s):  
New Zealand ◽  
T Cell ◽  
General Population ◽  
Kidney Transplant ◽  
Older Age ◽  
Competing Risk ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Female Sex ◽  
Related Mortality

Background and objectivesThe burden of infectious disease is high among kidney transplant recipients because of concomitant immunosuppression. In this study the incidence of infectious-related mortality and associated factors were evaluated.Design, setting, participants, & measurementsIn this registry-based retrospective, longitudinal cohort study, recipients of a first kidney transplant in Australia and New Zealand between 1997 and 2015 were included. Cumulative incidence of infectious-related mortality was estimated using competing risk regression (using noninfectious mortality as a competing risk event), and compared with age-matched, populated-based data using standardized incidence ratios.ResultsAmong 12,519 patients, (median age 46 years, 63% men, 15% diabetic, 6% Indigenous ethnicity), 2197 (18%) died, of whom 416 (19%) died from infection. The incidence of infection-related mortality during the study period (1997–2015) was 45.8 (95% confidence interval [95% CI], 41.6 to 50.4) per 10,000 patient-years. The incidence of infection-related mortality reduced from 53.1 (95% CI, 45.0 to 62.5) per 10,000 person-years in 1997–2000 to 43.9 (95% CI, 32.5 to 59.1) per 10,000 person-years in 2011–2015 (P<0.001) Compared with the age-matched general population, kidney transplant recipients had a markedly higher risk of infectious-related death (standardized incidence ratio, 7.8; 95% CI, 7.1 to 8.6). Infectious mortality was associated with older age (≥60 years adjusted subdistribution hazard ratio [SHR], 4.16; 95% CI, 2.15 to 8.05; reference 20–30 years), female sex (SHR, 1.62; 95% CI, 1.19 to 2.29), Indigenous ethnicity (SHR, 2.87; 95% CI, 1.84 to 4.46; reference white), earlier transplant era (2011–2015: SHR, 0.39; 95% CI, 0.20 to 0.76; reference 1997–2000), and use of T cell–depleting therapy (SHR, 2.43; 95% CI, 1.36 to 4.33). Live donor transplantation was associated with lower risk of infection-related mortality (SHR, 0.53; 95% CI, 0.37 to 0.76).ConclusionsInfection-related mortality in kidney transplant recipients is significantly higher than the general population, but has reduced over time. Risk factors include older age, female sex, Indigenous ethnicity, T cell–depleting therapy, and deceased donor transplantation.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_08_27_CJN03200319.mp3

Age-Adjusted Recipient Pre-Transplant Telomere Length and Treatment Related Mortality After Hematopoietic Stem Cell Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 490-490
Author(s):  
Régis Peffault de Latour ◽  
Rodrigo T. Calado ◽  
Marc Busson ◽  
Jeffrey Abrams ◽  
Marie Robin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Telomere Length ◽  
Hematopoietic Stem Cell ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Control Group ◽  
Transplant Recipients ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Related Mortality

Abstract Abstract 490 Telomeres are highly conserved protective terminal chromosomal structures consisting of hundreds of repeated TTAGGG hexamers and associated shelterin proteins. Telomeres shorten with every cell cycle, and telomere attrition has a fundamental role in cell senescence. Telomeres of leukocytes are shorter in transplant recipients than in their donors. Dyskeratosis congenita, a congenital aplastic anemia caused by mutations in the telomerase complex genes, is associated with treatment related mortality (TRM) after hematopoietic stem cell transplantation (HSCT). We hypothesized that age-adjusted pre-transplant telomere length might generally predict TRM after HSCT. Between 2000 and 2005, 178 consecutive patients underwent HSCT from HLA-identical sibling donor after myeloablative conditioning regimen (including TBI in 57 patients), mainly for hematological malignancies (n= 153) in our center. The stem cell source was bone marrow (BM) in 128 cases and peripheral blood (PB) in 50 cases. Median age at transplant was 32 years (range 3–65). Graft-versus-host disease (GvHD) prophylaxis mostly consisted of cyclosporine and methotrexate (n=149, 84%). Before HSCT, blood lymphocytes were obtained from each of the donor-recipient pair. Telomere length was assessed by real time quantitative PCR. We first determined the normal age distribution of telomere length using a group of 173 healthy French hematopoietic stem cell donors (f=-0.00833*age+1.522) as a control group. We then calculated the pre-transplant recipient age-adjusted telomere length in comparison to controls. After age adjustment, we categorized the population in quartiles (shortest telomeres for quartile 1) and analyzed the outcome post HSCT using competing risk in univariate and multivariate analyses (Fine and Gray). The mean telomere length in transplant recipients (1.05) was shorter than in the control group (1.23, p= 0.0001). After age-adjustment, patients' distribution was similar among all four quartiles except for disease severity (more high risk disease was present among patients with the shortest telomeres). The median follow-up was 51 months (range, 1 – 121 months). All patients engrafted. The median time to achieve absolute neutrophils count >500/ul was 18 days (range 4–45) and median time to platelet count >20.000/ul was 17 days (range 7–58). Cumulative incidence (CI) of acute GvHD grade II-IV was 45% (95% confidence interval [95CI] 37%–53%) and of chronic GvHD was 41% at 36 months (95CI 33%–49%). Thirty-four patients relapsed: CI: 22% at 5 years (95CI 16%–28%). There was no correlation between telomere length and engraftment, acute or chronic GvHD or relapse. The overall survival was 62% at 5 years (95CI 54%–70%). During the study, 37 patients died due to TRM. TRM rate inversely correlated with telomere length. In the first quartile, the 5-year CI of TRM was 33% (95CI 2%–22%), 20% (95CI, 8%–32%) in the second quartile; 20% (95CI, 8%–32%) in the third quartile; and 12% in the fourth quartile (95CI, 2%–22%) (p=0.06). When quartiles 2, 3 and 4 were pooled, the increased TRM in first quartile was statistically significant (p = 0.017) (Figure 1). In multivariate analysis using competing risk regression, (including age-adjusted telomeres length, disease stage, age, TBI and source of stem cells), age of the recipients (HR: 1.1, 95% CI [.0–1.1, p=0.0001] and age-adjusted telomeres [HR: 0.4, 95% CI [0.2–0.8, p=0.01]) were independently associated with TRM. The same two factors remained significant in subset analysis of patients with malignant diseases (n=154) (p= 0.0004, HR: 1.1 and p=0.018, HR: 0.43, respectively). No association was found between donor telomere length and outcome post HSCT. In conclusion, age-adjusted recipient pre-transplant telomere length is an independent biological marker of TRM after HSCT from related donors using a myeloablative conditioning regimen and cyclosporine-based GvHD prophylaxis. Disclosures: Peffault de Latour: Alexion: Consultancy, Research Funding.

Interim analysis of the largest prospective trial to date in adult CD20-positive post-transplant lymphoproliferative disorder (PTLD): Introducing risk-stratified sequential treatment (RSST).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8030-8030 ◽  
Author(s):  
Ralf Ulrich Trappe ◽  
Daan Dierickx ◽  
Petra Reinke ◽  
Ruth Neuhaus ◽  
Franck Morschhauser ◽  
...  
Keyword(s):  
High Risk ◽  
Overall Response Rate ◽  
Prospective Trial ◽  
Low Risk ◽  
Sequential Treatment ◽  
Tumor Control ◽  
Transplant Recipients ◽  
Risk Patients ◽  
Related Mortality

8030 Background: The prospective, multicenter international phase II PTLD-1 trial of sequential treatment (ST, 4 cycles of weekly rituximab followed by 4 cycles of CHOP-21 + G-CSF) in adult CD20-positive PTLD demonstrated excellent efficacy (90% overall response rate, ORR) and safety (11% treatment-related mortality, TRM). As the response to rituximab predicted overall survival (OS), the trial was amended in 2007 introducing risk-stratified sequential treatment (RSST) according to the response to rituximab (NCT00590447). Methods: Following rituximab on days 1, 8, 15 and 22, RSST consisted of 4 3-weekly courses of rituximab monotherapy for patients (pts) in complete remission (CR, low risk) while all others (high risk) received 4 cycles of R-CHOP-21 + G-CSF. Key exclusion criteria were CNS involvement, HIV infection, severe organ dysfunction not related to PTLD, and ECOG > 2. Primary endpoint was ORR. This is an analysis of the first 91 patients treated with RSST. Results: 79/91 pts had monomorphic, 12 polymorphic PTLD. 41/91 pts were kidney, 27 liver, 12 heart, 7 lung or heart+lung, 3 heart+kidney and 1 kidney+pancreas transplant recipients. Median age at diagnosis was 60 years (range 20-82). 73/91 pts had late PTLD and 39/85 PTLDs were EBV-associated. 1 pt died before initiation of treatment; 5 pts discontinued treatment after 4 cycles rituximab. TRM of RSST was 7/90 (8%) including 5 deaths with unknown remission status. ORR was thus 74/80 (93%, 95%CI: 84-97%; CR: 62/80 [78%]). 24/90 pts (27%) achieved CR with 4 cycles of rituximab. After a median follow up of >3 years, relapse rate in low risk pts was not increased by rituximab consolidation in RSST compared to CHOP consolidation in ST (3/23 vs. 5/14, p=0.104]). In patients in PD after rituximab, R-CHOP was more effective than CHOP in achieving CR (15/23 vs. 3/11, p=0.038). OS at 3 years was higher with RSST (70%, 95% CI: 60-82%) compared to ST (61%, 95%CI 49-72%) but this difference was not significant. Conclusions: With RSST 27% of pts were classified as low risk and achieved durable tumor control without chemotherapy while R-CHOP seems more efficient than CHOP in in high risk patients.

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