The Clinical Spectrum of Acute GVHD: Beyond Day 100.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5377-5377
Author(s):  
Daniel R. Couriel ◽  
Rima Saliba ◽  
Shubhra Gosh ◽  
Marcos De Lima ◽  
Sergio Giralt ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Gvhd ◽  
Current Knowledge ◽  
Chronic Gvhd ◽  
Clinical Manifestations ◽  
Disease Status ◽  
Response To Therapy ◽  
Preparative Regimen ◽  
Prognostic Implications ◽  
The Difference

Abstract Objective: To assess the clinical and prognostic implications of the timing of acute GVHD (aGVHD). Introduction: Traditionally, the syndrome of acute GVHD has been chronologically defined as GVHD occurring before day 100. It has become increasingly clear that this syndrome can occur after day 100, which raises the question of historical misclassification of aGVHD occurring after day 100 (“late aGVHD”) as chronic GVHD. On the other hand, timing of GVHD could have prognostic implications and the case in hyperacute forms of GVHD are an example. In this study, we redifine aGVHD based on clinical manifestations and we evaluate risk factors as well as clinical and prognostic differences between late aGVHD and GVHD before day 100 (“classic aGVHD”). Methods: Retrospective evaluation of records and database on all matched sibling transplants (n= 128) performed at UT MDACC from 1/00 to 2/02. Results: A total of 47 patients (37%) had “classic” aGVHD and another 67 (52%) were classified as chronic GVHD (cGVHD) in our database. Upon review of medical records, 30/67 patients (45%) were found to have late aGVHD, and the remainder true cGVHD. Of these 30 patients, 9 had aGVHD progressing through day 100 and were reclassified as classic aGVHD. The remainder 21 had newly diagnosed late aGVHD. We evaluated risk factors for developing late aGVHD in patients who were alive at day 100. Only a later engraftment (ANC>500 beyond day 12) was associated with a higher incidence of late aGVHD, while age, gender, malignancy, disease status at transplant, type of preparative regimen (nonmyeloablative versus others), bone marrow vs peripheral blood or CD3,4 or 8 infused did not impact the incidence of late acute GVHD. Compared to classic aGVHD, the late group had a significantly higher proportion of grade 2–4 GVHD (85 vs 61%, p= 0.03) with similar grade 3–4 aGVHD (29 vs 27%, p= 0.5). Skin and GI involvement, as well as isolated elevation of the alkaline phosphatase were more common manifestations of late aGVHD. There was a trend to better response (CR/PR) to first line immunosuppression in patients with late aGVHD (81 vs 63%, p= 0.13), but this was not statistically significant. The overall survival (OS) and non-relapse mortality (NRM) since the diagnosis of GVHD were substantially better in patients with late aGVHD (OS 70 vs 29%, p= 0.01; NRM 16 vs 39%, p= 0.06). Finally, the NRM of patients with chronic GVHD prior to reclassifying patients with late aGVHD (n= 67) was 28% at 2 years. When patients with late aGVHD were excluded, the NRM at 2 years for the remainder 37 patients with chronic GVHD was 20% (p= 0.3). Conclusions: 1- The current chronological definition of acute GVHD may lead to misclassification of late aGVHD as chronic GVHD. This could have implications in interpreting the current knowledge and literature on GVHD, 2- There was a trend to higher NRM in the chronic GVHD group prior to reclassifying cases of late aGVHD, althought the difference was not statistically significant, 3-Patients with late aGVHD share similarities with those with classic aGVHD, although there seems to be a trend to better response to therapy and better survival in patients developing aGVHD beyond day 100. Thus, timing of aGVHD may affect its outcome.

scholarly journals Predictors of death from chronic graft-versus-host disease after bone marrow transplantation

Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1428-1435 ◽  
Author(s):  
JR Wingard ◽  
S Piantadosi ◽  
GB Vogelsang ◽  
ER Farmer ◽  
DA Jabs ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hazard Ratio ◽  
Actuarial Survival ◽  
Host Disease ◽  
Late Morbidity

Abstract Chronic graft-v-host disease (chronic GVHD) is a frequent cause of late morbidity and death after bone marrow transplantation (BMT). The actuarial survival after onset of chronic GVHD in 85 patients was 42% (95%Cl = 29%, 54%) at 10 years. Baseline characteristics present at the onset of chronic GVHD (before therapy) in 85 patients were reviewed to determine which were risk factors for death. In a multivariate proportional hazards analysis, three baseline factors emerged as independent predictors of death: progressive presentation (chronic GVHD following acute GVHD without resolution of acute GVHD; hazard ratio of 4.1, 95% Cl = 2.1 to 7.8), lichenoid changes on skin histology (hazard ratio of 2.2, 95% Cl = 1.1 to 4.3), and elevation of serum bilirubin greater than 1.2 mg/dL (hazard ratio = 2.1, 95% Cl = 1.1 to 4.1). Actuarial survival of 23 chronic GVHD patients with none of these risk factors was 70% at 6 years (95% Cl = 38%, 88%). Thirty-eight patients with one of these risk factors had a projected 6-year survival of 43% (95% Cl = 21%, 63%). The 29 patients with any combination of two or more of these factors had a projected 6-year survival of only 20% (95% Cl = 8%, 37%). Identification of baseline risk factors should facilitate design of trials of chronic GVHD therapies and assignment of high-risk patients to more aggressive innovative therapeutic regimens.

scholarly journals Epidemiology of Atrial Fibrillation in the 21st Century

2020 ◽  
Vol 127 (1) ◽  
pp. 4-20 ◽  
Author(s):  
Jelena Kornej ◽  
Christin S. Börschel ◽  
Emelia J. Benjamin ◽  
Renate B. Schnabel
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Current Knowledge ◽  
Population Level ◽  
Targeted Prevention ◽  
Global Epidemic ◽  
The Public ◽  
Health Dimension ◽  
Prognostic Implications ◽  
Review Current

Accompanying the aging of populations worldwide, and increased survival with chronic diseases, the incidence and prevalence of atrial fibrillation (AF) are rising, justifying the term global epidemic. This multifactorial arrhythmia is intertwined with common concomitant cardiovascular diseases, which share classical cardiovascular risk factors. Targeted prevention programs are largely missing. Prevention needs to start at an early age with primordial interventions at the population level. The public health dimension of AF motivates research in modifiable AF risk factors and improved precision in AF prediction and management. In this review, we summarize current knowledge in an attempt to untangle these multifaceted associations from an epidemiological perspective. We discuss disease trends, preventive opportunities offered by underlying risk factors and concomitant disorders, current developments in diagnosis and risk prediction, and prognostic implications of AF and its complications. Finally, we review current technological (eg, eHealth) and methodological (artificial intelligence) advances and their relevance for future prevention and disease management.

Iron Overload Strongly Correlates with Acute Graft-Versus-Host-Disease of the Liver and Treatment Related Mortality after Allogeneic Hematopoetic Cell Transplantation (HCT).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1812-1812
Author(s):  
Ann-Kathrin Eisfeld ◽  
Ralph Burkhardt ◽  
Daniel Teupser ◽  
Sabine Schroeder ◽  
Rainer Krahl ◽  
...  
Keyword(s):  
Risk Factors ◽  
Iron Overload ◽  
Retrospective Analysis ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hfe Gene ◽  
Strongly Correlated ◽  
Body Iron ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Risk factors for morbidity and treatment related mortality (TRM) following HCT have been well defined in retrospective analysis and prospective validations. These include disease-, recipient- and donor-specific characteristics, but not treatment related factors. Considering that patients undergoing HCT usually receive multiple blood transfusions (BT) and that mutations of the HFE gene are common in the European population, we asked the question if iron overload and HFE mutations were risk factors for complications following HCT. Patients and methods: From January 2001 to December 2004, 265 consecutive patients (142 m/123 f; median age 47 y) received HCT at the University of Leipzig. Patients suffered from acute leukaemia (n=113; 43%), chronic leukaemia (n=75; 28%), lymphoma (n=37; 14%), multiple myeloma (n=21; 8%), and others (n=19; 7%). Preparative regimen consisted of Cyclophosphamid 120 mg/kg and 12 Gy TBI in 145 (55%) patients. The remaining 120 (45%) patients were conditioned with Fludarabin 30 mg/m2/day for 3 days and 2 Gy TBI. HCT was performed from matched related donors in 85 (32%) and matched unrelated donors (MUD) in 180 (68%) patients. Patients and donors were screened for mutant HFE genes by PCR using LightCycler, Roche. Serum ferritin (reference values 30–400 ng/ml) was measured at a median of 1 month after HCT. At the time of measurement, patients had to be in good clinical condition with normal C-reactive protein. Results: Elevated iron stores were present in 86% of patients (median ferritin 1697 ng/ml). At a median of 25 (range 7–55) months after HCT, 92 (35%) patients have died from relapse (n= 27; 29%) or TRM (n= 65; 71%). TRM occurred at a median of 4 months after HCT. Median ferritin in patients who died (measured at a median of 3 months prior to death) and in surviving patients were 3815 and 1146 ng/ml respectively (p<0.0001). The median number of BT at HCT in the 2 groups were 34, and 16 unit respectively (p<0.0001). MUD, CMV-serological status and the gender of the donor did not correlate with TRM. In multivariate analysis, ferritin and BT strongly correlated with TRM (p<0.0001). Mutant HFE genes were found in 98 (37%) patients prior to HCT [heterozygous (het; n=82, 84%), compound (n=9; 9%), homozygous (homo; n=7; 7%). Similarly, 99 (37%) donors showed mutant HFE genes [het, n=86 (87%), compound, n=8 (8%), and homo, n=5 (5%)]. After HCT, all patients expressed donor HFE genotype. HFE genotype of patients and donors did not correlate with TRM. Acute GvHD > grade II was significantly more in pts who died (p=0.0002). Acute GvHD of the liver strongly correlated with excess body iron (p=0.009). Interestingly, chronic GvHD of the skin and liver tended to be more frequent in patients with mutant HFE genes prior to HCT (p=0.03). Conclusions: This is, to our knowledge, the first retrospective analysis where excess body iron and the number of BT at HCT strongly correlated with acute GvHD of the liver and TRM after HCT. These data must be confirmed in prospective studies. Whether morbidity and TRM after HCT can be reduced by iron chelation needs to be evaluated.

Outcomes of c Hematopoietic Stem Cell Transplantation (HCT) after Non-Myeloablative Conditioning in Relapsed, Refractory, or Transformed Indolent Non-Hodgkin Lymphoma (NHL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3124-3124 ◽  
Author(s):  
Andrew R. Rezvani ◽  
Brenda M. Sandmaier ◽  
Barry Storer ◽  
Michael Maris ◽  
Edward Agura ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Status ◽  
Aggressive Lymphoma ◽  
Optimal Timing ◽  
Unrelated Donor ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Allogeneic Hct ◽  
Grade 3

Abstract Sixty-two patients (pts) with chemotherapy-refractory indolent or transformed NHL were treated at 10 centers with allogeneic HCT from related (n=34) and unrelated (n=28) donors after 2 Gy total body irradiation with or without fludarabine. Diagnoses included follicular lymphoma (FL) (n=54, including 10 with grade 3 FL), small lymphocytic lymphoma (n=6), and marginal zone lymphoma (n=2). Median age was 54 years (range 33–66 years), and median time from diagnosis to HCT was 4.4 years (range 0.5–18.5 years). Sixteen pts had histologically documented transformation to diffuse aggressive lymphoma prior to HCT. Twenty-seven pts (44%) had failed autologous HCT. Disease status at the time of HCT was complete response (CR, n=16), partial response (PR, n=22), refractory (n=13), untested relapse (n=9), or unknown (n=2). Eleven of the 28 unrelated donor/recipient pairs (39%) had HLA mismatches: 2 at a single allele, 7 at a single antigen, and 2 at an antigen and an allele. One pt had non-fatal graft rejection from a 1-antigen-mismatched unrelated donor. Median follow-up of survivors after HCT was 36.6 months (range 2.3–60 months). Responses (CR [n=18] and PR [n=7]) were seen in 25 of 44 (57%) pts with evaluable disease prior to HCT, while 5 had stable disease, 9 progressed, and 5 were not evaluable due to early non-relapse mortality (NRM) on d27–d108. Two of 16 pts (13%) transplanted in CR relapsed; one was treated with donor lymphocyte infusion and achieved a persistent CR. The incidences of acute GVHD grades II–IV, III–IV, and chronic GVHD were 63%, 19%, and 53%, respectively. At 3 years, the risks of relapse/progression and NRM were 19% and 42%, respectively. There was a trend toward increased mortality with unrelated donors (HR 1.87 [0.9–3.7, p=0.08]). Progression-free and overall survival (PFS and OS) were significantly better in the non-transformed group (see tables 1 and 2). Table 1. Outcomes Non-transformed Transformed Relapse 6/46 (13%) 6/16 (38%) NRM 20/46 (43%) 6/16 (38%) 3-year OS 24/46 (52%) 4/16 (25%) 3-year PFS 20/46 (43%) 4/16 (25%) Table 2. Hazard Ratios (HR) for Transformed vs. Non-Transformed Pts HR (95% CI) p All-cause Mortality 2.39 (1.2–4.9) 0.02 Relapse/progression 4.75 (1.5–15) 0.01 Grade 3+ acute GVHD 1.84 (0.5–6.3) 0.35 Extensive chronic GVHD 1.96 (0.8–5.0) 0.18 Figure Figure Allogeneic HCT after non-myeloablative conditioning can produce durable responses and prolonged survival in pts with refractory indolent or transformed NHL. Pts transplanted before histologic transformation had significantly better outcomes. Future efforts will focus on reducing NRM and identifying optimal timing of HCT.

Busulfan Fludarabine Vs. Busulfan Cyclophosphamide As a Preparative Regimen Prior to Allogeneic Hematopoietic Cell Transplantation – Systematic Review and Meta-analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3872-3872
Author(s):  
Sharon Ben Barouch ◽  
Omri Cohen ◽  
Liat Vidal ◽  
Irit Avivi ◽  
Ron Ram
Keyword(s):  
Systematic Review ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Meta Analysis ◽  
Chronic Gvhd ◽  
All Cause Mortality ◽  
Preparative Regimen ◽  
Grade 3 ◽  
Neutrophil Engraftment

Abstract Background: Both busulfan-cyclophosphamide (BuCy) and the reduced toxicity regimen busulfan-fludarabine (BuFlu) are considered myeloablative preparative regimens given prior to allogeneic hematopoietic cell transplantation (HCT). A comprehensive literature evaluation of BuFlu vs. BuCy is lacking and the question of the preferable regimen is still debatable. Objectives: We aimed to compare the efficacy and safety of BuFlu (intervention arm) vs. BuCy (comparable arm) as preparative regimens in patients given allografts. Methods: Systematic review and meta-analysis of all randomized controlled trials (RCTs) and non-randomized comparative trials of patients given BuFlu vs. BuCy as preparative regimens prior to allografts. Electronic search in the Cochrane Library, MEDLINE and conference proceedings was conducted up-to July 2014. Primary outcomes were all-cause mortality at 100 days and at the end of study. Secondary outcomes were time to neutrophil engraftment, primary & secondary rejection, risk for grade 3-4 mucositis, sinusoidal obstruction syndrome (SOS), microbiology documented infection, overall and grade 3-4 acute graft vs. host disease (GVHD), overall and extensive chronic GVHD, non-relapse mortality at 100 day and at the end of study, and relapse risk. For dichotomous data, relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled. For continuous variables we calculated weighted mean difference (WMD). Results: Our search yielded 14 trials recruiting 1578 patients. Three trials were RCTs and 11 were either one arm intervention trials compared to historical controls or retrospective studies. There were no differences in all-cause mortality at 100 days and end of study ( RR 0.85; 95% CI 0.56-1.30, 9 trials and RR 0.77; 95% CI 0.59-1.02, 12 trials, respectively), Figure, with similar results in sensitivity analyses including only RCTs and only studies in which patients' age and status of disease at HCT were well matched. Both primary and secondary rejections were comparable between the two regimens. Time to neutrophil engraftment was 1-day longer in patients given the BuCy regimen (WMD 0.84; 95% CI 0.37-1.31, 6 trials). Both the risks for SOS and microbiology documented infections were lower in the BuFlu patients (RR 0.34; 95% CI 0.19-0.62, 8 trials and RR 0.79; 95% CI 0.64-0.97, 2 trials, respectively). Grade 3-4 mucositis was comparable between the two groups. There was a lower incidence of grade 2-4 acute GVHD in patients given FluBu (RR 0.67; 95% CI 0.46-0.99, 10 trials), however this was no longer true in sensitivity analysis including only RCTs. There were no differences between the two arms in grade 3-4 acute GVHD, overall and extensive chronic GVHD, non-relapse mortality at 100 days and at the end of study and relapse risk. Conclusions: While toxicity profile of BuFlu regimen is safer than the classic BuCy regimen, this does not translate into composite transplantation outcomes. Patients at higher risk for SOS may benefit from the BuFlu regimen; however additional RCTs are required to identify other subgroups of patients who will benefit from a tailored-preparative regimen approach. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria

Blood ◽  
2011 ◽  
Vol 117 (11) ◽  
pp. 3214-3219 ◽  
Author(s):  
Mary E. D. Flowers ◽  
Yoshihiro Inamoto ◽  
Paul A. Carpenter ◽  
Stephanie J. Lee ◽  
Hans-Peter Kiem ◽  
...  
Keyword(s):  
Risk Factors ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Human Leukocyte ◽  
National Institutes Of Health ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Abstract Risk factors for grades 2-4 acute graft-versus-host disease (GVHD) and for chronic GVHD as defined by National Institutes of Health consensus criteria were evaluated and compared in 2941 recipients of first allogeneic hematopoietic cell transplantation at our center. In multivariate analyses, the profiles of risk factors for acute and chronic GVHD were similar, with some notable differences. Recipient human leukocyte antigen (HLA) mismatching and the use of unrelated donors had a greater effect on the risk of acute GVHD than on chronic GVHD, whereas the use of female donors for male recipients had a greater effect on the risk of chronic GVHD than on acute GVHD. Total body irradiation was strongly associated with acute GVHD, but had no statistically significant association with chronic GVHD, whereas grafting with mobilized blood cells was strongly associated with chronic GVHD but not with acute GVHD. Older patient age was associated with chronic GVHD, but had no effect on acute GVHD. For all risk factors associated with chronic GVHD, point estimates and confidence intervals were not significantly changed after adjustment for prior acute GVHD. These results suggest that the mechanisms involved in acute and chronic GVHD are not entirely congruent and that chronic GVHD is not simply the end stage of acute GVHD.

scholarly journals Non-Infectious Pulmonary Toxicity after Allogeneic Hematopoietic Cell Transplantation (HCT): A Center for International Blood and Marrow Transplant Research (CIBMTR) Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-8
Author(s):  
Sagar S. Patel ◽  
Kwang Woo Ahn ◽  
Manoj Khanal ◽  
Caitrin Fretham ◽  
Celalettin Ustun ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lower Risk ◽  
Research Funding ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Multivariable Analysis ◽  
Marrow Transplant ◽  
Smoking History ◽  
Platelet Recovery ◽  
Increased Risk

Introduction Early non-infectious pulmonary toxicity (NIPT) is a significant HCT complication and comprises diffuse alveolar hemorrhage (DAH), idiopathic pneumonia syndrome (IPS), and cryptogenic organizing pneumonia (COP) with an overall incidence ranging 1-10%. Treatment options are primarily immunosuppressive therapy and supportive care with limited efficacy. Mortality in IPS, for example, approaches 60-80% (PMID: 21531955). Therefore, to better identify potentially high-risk patients (pts) we performed a registry-based analysis of the incidence, risk factors, and outcomes of early NIPT after HCT. Methods This retrospective study included adult pts undergoing allogenic HCT for hematologic malignancies and non-malignant disorders as reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) (2008-2017). Data analyses were divided into four common disease categories (AML/ALL, CML/MDS/MPN, NHL/CLL/PCD, and non-malignant diseases) to minimize statistical interactions in the multivariate model. The primary outcome was the incidence of and risk factors for individual NIPT and a composite of the three NIPT (IPS, DAH, COP); the secondary outcome was overall survival (OS). Multivariable Cox proportional hazards regression models were developed to identify the risk factors for NIPT and OS. In addition to baseline pre-transplant covariates, post-transplant neutrophil recovery (>500/mcL x 3 consecutive days), platelet recovery (>20k/mcL x 3 consecutive days, without transfusion in 7 previous days) and grade 2-4 acute GVHD were included as time-dependent covariates in the multivariable models. Results Characteristics of 21,587 adult pts are shown in Table 1. Median age at HCT was 54 years, 59% were male, and 39% had KPS <90. Median follow-up was 49 months. Per the HCT-Comorbidity Index (HCT-CI), 15% and 24% of pts had a severe (FEV1 and/or DLCO≤65%, dyspnea at rest, requiring supplemental oxygen) and moderate (FEV1 and/or DLCO 66-80%, dyspnea on slight activity) pulmonary comorbidity, respectively. Pre-transplant, 3% of pts had a history of mechanical ventilation, 5% had a history of pulmonary fungal infection, and 40% reported a smoking history. Most pts had a matched sibling or unrelated donor (68%) and received peripheral blood graft (71%). Myeloablative conditioning was used in 49% pts, and 39% received total body irradiation (TBI). Table 2 shows the cumulative incidence of early NIPT amongst pts in the four disease categories. Multivariable analysis in the AML/ALL group identified TBI-based conditioning, grade 2-4 acute GVHD, HCT-CI score of 1-3, and prior autologous HCT were associated with increased risk of NIPT, while platelet recovery decreased the risk of NIPT. In the CML/MDS/MPN group, smoking history, grade 2-4 acute GVHD and HCT-CI scores of 2-5+ were associated with increased risk of NIPT, while non-TBI and non-myeloablative TBI conditioning and platelet recovery were associated with a lower risk. In the NHL/HD/CLL/PCD group, a higher risk of NIPT was seen with severe pulmonary comorbidity pre-HCT and chronic GVHD, while platelet recovery and non-TBI regimens were associated with a lower risk. In the non-malignant disease group, both neutrophil and platelet recovery were associated with a lower risk of NIPT. Furthermore, the multivariable analysis for OS (Table 2) showed across all disease groups, NIPT increased the risk of mortality (vs. no NIPT; HR of 4.3 in AML/ALL, 4.1 in CML/MDS/MPN, 3.5 in NHL/CLL/PCD, 6.8 in non-malignant diseases; p<0.0001). Conclusions This large registry-based analysis of allogeneic HCT pts highlights several risk factors for the development of early NIPT including smoking history, severe pulmonary comorbidity, myeloablative TBI conditioning, and acute and/or chronic GVHD. Identification of these risk factors can enhance appropriate selection of pts prior to HCT. We also found that post-transplant, platelet and neutrophil recovery was associated with a reduced risk of NIPT. Furthermore, early NIPT is associated with a several-fold higher mortality risk in the current era despite significant advances in supportive care. Future studies are needed to optimize risk factors such as conditioning regimen and graft source selection to reduce the risk of early NIPT. Disclosures Ustun: Kadmon: Honoraria. Hamilton:Syndax Pharmaceuticals: Consultancy, Honoraria. Majhail:Anthem, Inc.: Consultancy; Incyte: Honoraria; Nkarta Therapeutics: Honoraria; Mallinckrodt: Honoraria. Sorror:Jazz Pharmaceutical: Other: Honorarium for Advisory role. . Stadtmauer:Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Novartis, Onyx Pharmaceuticals, an Amgen subsidiary, Takeda Oncology: Consultancy. Pasquini:Bristol Myers Squibb: Consultancy; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Other; Novartis: Research Funding; Kite: Research Funding.

scholarly journals Use of Partially Mismatched Related Donors Extends Access to Allogeneic Marrow Transplant

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3864-3872 ◽  
Author(s):  
P. Jean Henslee-Downey ◽  
Sunil H. Abhyankar ◽  
Rudolph S. Parrish ◽  
Asim R. Pati ◽  
Kamar T. Godder ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Status ◽  
Marrow Transplant ◽  
Successful Outcome ◽  
High Dose ◽  
Allogeneic Bone ◽  
Significant Difference

Most patients requiring allogeneic bone marrow transplant (allo-BMT) do not have an HLA-matched sibling donor. A phenotypically matched unrelated donor graft has been made available for approximately 50% of Caucasians and less than 10% of ethnic and racial minorities in need. However, almost all patients have a readily available partially mismatched related donor (PMRD). We summarize our experience with 72 patients who ranged from 1 to 50 years of age (median, 16 years) and who were recipients of a PMRD allo-BMT from haploidentical family members following conditioning therapy using total body irradiation (TBI) and multiagent, high-dose chemotherapy. T-cell depletion and post-BMT immunosuppression were combined for graft-versus-host disease (GVHD) prophylaxis. The probability of engraftment was 0.88 at 32 days. Six of 10 patients who failed to engraft achieved engraftment after secondary transplant. Grade II to IV acute GVHD was seen in 9 of 58 (16%) evaluable patients; extensive chronic GVHD was seen in 4 of 48 (8%) evaluable patients. There was a statistically significant difference in 2-year survival probability between low-risk and high-risk patients (0.55 v 0.27, P = .048). Prognostic factors that affected outcomes in multivariate analysis were (1) a lower TBI dose and 3-antigen rejection mismatch decreased stable engraftment (P = .005 and P = .002, respectively); (2) a higher T-cell dose increased acute GVHD (P = .058); (3) a higher TBI dose increased chronic GVHD (P = .016); and (4) a high-risk disease category increased treatment failure from relapse or death (P = .037). A PMRD transplant can be performed with acceptable rates of graft failure and GVHD. Using sequential immunomodulation, the disease status at the time of transplant is the only prognostic factor significantly associated with long-term successful outcome after PMRD allo-BMT. When allogeneic rather than autologous BMT is indicated, progression in disease status before transplant can be avoided using a PMRD with equal inclusion of all ethnic or racial groups.

scholarly journals Analysis of Risk Factors Determining Incidence and Outcome of Infections in Children and Adults after Hematopoietic Cell Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3364-3364
Author(s):  
Jan Styczynski ◽  
Krzysztof Czyzewski ◽  
Sebastian Giebel ◽  
Jowita Fraczkiewicz ◽  
Malgorzata Salamonowicz ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Leukemia ◽  
Bacterial Infections ◽  
Acute Gvhd ◽  
Viral Infections ◽  
Chronic Gvhd ◽  
Multivariable Analysis ◽  
Risk Of Death ◽  
Increased Risk ◽  
Cmv Reactivation

Abstract BACKGROUND: Recent EBMT analysis showed that infections are responsible for 21% of deaths after allo-HCT and 11% after auto-HCT. However, the risk, types and outcome of infections vary between age groups. The aim of the study is the direct comparison of risk factors of incidence and outcome of infections in children and adults. PATIENTS AND METHODS: We analyzed risk factors for the incidence and outcome of bacterial, fungal, and viral infections in 650 children and 3200 adults who received HCT between 2012-2015. The risk factors were determined by multivariable logistic regression analysis. RESULTS: A total number of 395/650 (60.8%) children and 1122/3200 (35.0%) adults were diagnosed for microbiologically confirmed infection, including 345/499 (69.1%) and 679/1070 (63.5%), respectively after allo-HCT, and 50/151 (33.1%) and 443/2130 (20.8%) respectively, after auto-HCT. At 2 years after HCT, the incidences of microbiologically documented bacterial infection were 36.0% and 27.6%, (p<0.001) for children and adults, respectively. Incidences of proven/probable invasive fungal disease (IFD) were 8.4% and 3.7% (p<0.001), respectively; and incidences of viral infection were 38.3%, and 13.5% (p<0.001), respectively. Overall, 31/650 (4.8%) children and 206/3200 adults (6.4%) have died after these infections. The distribution of deaths was different in children (35.5% bacterial, 48.4% fungal, 16.1% viral) and adults (61.7% bacterial, 24.7% fungal, 13.6% viral). BACTERIAL INFECTIONS: In multivariable analysis, the risk of infections was higher after allo-HCT (HR=1.8; p<0.001). In allo-HCT patients, the risk was higher in children (HR=2.1; p<0.001), in patients with acute leukemia (HR=1.6; p<0.001), matched unrelated (MUD) vs matched family-donor (MFD) HCT (HR=1.6; p<0.001), mismatched unrelated (MMUD) vs MFD HCT (HR=2.0; p<0.001), myeloablative vs reduced-intensity conditioning (RIC) (HR=1.3; p<0.001), delayed (>21d) hematological recovery (HR=3.3; p<0.001), acute GVHD before infection (HR=1.7; p<0.001), and chronic GVHD before infection (HR=1.4; p=0.014). In auto-HCT patients, the risk was higher in children (HR=1.7; p<0.001), and in patients with delayed hematological recovery (HR=2.8; p<0.001). In patients with multiple myeloma (MM) the risk was decreased (HR=0.7; p=0.005). FUNGAL INFECTIONS: The risk of proven/probable IFD was higher after allo-HCT (HR=5.4; p<0.001). In allo-HCT patients, the risk was higher in children (HR=3.9; p<0.001), in patients with acute leukemia (HR=3.8; p<0.001), MUD vs MFD HCT (HR=1.5; p=0.013), MMUD vs MFD HCT (HR=2.5; p<0.001), delayed hematological recovery (HR=3.3; p<0.001), acute GVHD before infection (HR=1.5; p=0.021), and chronic GVHD before infection (HR=2.2; p<0.001). In auto-HCT patients, the risk was higher in children (HR=1.8; p=0.025). Patients with MM were at decreased risk of IFD (HR=0.6; p=0.005). VIRAL INFECTIONS: In multivariable analysis, the risk of infections was higher after allo-HCT (HR=6.1; p<0.001). In allo-HCT patients, the risk was higher in children (HR=1.3; p=0.010), in patients with acute leukemia (HR=1.7; p<0.001), MUD vs MFD HCT (HR=2.0; p<0.001), MMUD vs MFD HCT (HR=3.3; p<0.001), myeloablative vs RIC (HR=1.8; p=0.050), acute GVHD before infection (HR=1.5; p<0.001) and chronic GVHD before infection (HR=2.7; p=0.014). Among auto-HCT patients, diagnosis of MM brought decreased risk of viral infections (HR=0.5; p<0.001). DEATH FROM INFECTION: In allo-HCT patients, adults (HR=3.3; p<0.001), recipients of MMUD-HCT (HR=3.8; p<0.001), patients with acute leukemia (HR=1.5; p=0.023), chronic GVHD before infection (HR=3.6; p=0.014), CMV reactivation (HR=1.4; p=0.038) and with duration of infection treatment >21 days (HR=1.4; p=0.038) were associated with increased risk of death from infection. Among patients with bacterial infections, the risk was higher in G- infections (HR=1.6; p=0.031). Among auto-HCT patients, no child died of infection. In adults, the risk of death was higher if duration of treatment of infection was >21 days (HR=1.7; p<0.001). In patients with MM the risk was decreased (HR=0.4; p<0.001). CONCLUSIONS: The profile of infections and related deaths varies between children and adults. MMUD transplants, diagnosis of acute leukemia, chronic GVHD, CMV reactivation and prolonged infection are relative risk factors for death from infection after HCT. Disclosures Kalwak: Sanofi: Other: travel grants; medac: Other: travel grants.

scholarly journals A Study of Predictors of Clinical Outcomes and Healthcare Utilization in Children with Sickle Cell Disease Undergoing Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 528-528 ◽  
Author(s):  
Prakash Satwani ◽  
Ruta Brazauskas ◽  
Staci D. Arnold ◽  
Naya He ◽  
Yimei Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Outcomes ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Disease ◽  
Adjusted Cost ◽  
Factors Associated ◽  
Gvhd Prophylaxis ◽  
Donor Type ◽  
Hospital Days

Abstract Introduction: Current advances in allogeneic hematopoietic cell transplant (alloHCT) may warrant a paradigm shift in managing children with sickle cell disease (SCD). This study characterizes the clinical outcomes and health care utilization (HCU) of alloHCT for pediatric SCD. We hypothesize that early alloHCT will have improved clinical outcomes, and decreased HCU. Methods: The Center for International Blood and Marrow Transplant Research database was used to identify children 21 years or less with alloHCT for SCD in the United States. Patient data included comprehensive research forms (CRF) from 2000-13 and transplant essential data (TED) forms from 2000-11. CRFs provided clinical risk factors associated with overall survival, graft failure, grade III-IV acute GVHD, and GVHD related event free survival (GREFS) - the survival free of graft failure, chronic GVHD, or death. Risk factors included age, gender, performance status, year of alloHCT, prior SCD complications and therapy, CMV status, donor type, conditioning regimen, and GVHD prophylaxis. Due to low event rates and sample size, only univariate analysis of risk factors was performed. TED data was merged with Pediatric Health Information System (PHIS) inpatient data using a probabilistic merging algorithm to determine risk factors and clinical outcomes associated with HCU. Available PHIS adjusted cost data was used to determine the total adjusted cost for all inpatient admissions per patient per hospital day. To standardize these costs, the total adjusted cost per 30 hospital days was calculated for each patient and used as the primary HCU outcome. HCU outcomes were analyzed for the alloHCT year, day 0 to day +365. Results: CRF data for 161 patients showed an overall survival at 2 years of 90% (95% confidence intervals [CI] 85-95%): 96% (95% CI 89-100%) for related and unrelated cord blood transplant (CBT), 94% (95% CI 86-98%) matched siblings (MSD), and 74% (95% CI 54-90%) matched unrelated donors (MUD, p=0.002). All deaths occurred among children with pre-alloHCT complications of SCD, and deaths were due to organ failure (37.5%), infections (25%), GVHD (6.25%). Risk of death was significantly higher for children ≥10 years old (HR 21, p=0.003) and MUD compared to MSD (HR 5.88, p=0.005) but lower with cyclosporine A (CSA) GVHD prophylaxis versus FK506 (HR 0.33, p=0.031). 75% of deaths occurred before day +42. Cumulative acute GVHD incidence at day 100 was 14% (95% CI 9-20%)and was associated with age ≥10yrs (HR 2.63, p=0.035). Chronic GVHD incidence was 31% (95% CI 23-38%) at 2yrs, and factors associated were age ≥10yrs (HR 1.92, p=0.034), MUD vs MSD (HR 2.53, p=0.017), and CSA vs FK506 prophylaxis (HR 0.48, p=0.018). Chronic GVHD risk increased significantly after 2006 (HR 2.81, p=0.018). The 2yr GREFS was 64% (95% CI 56-71%). Age ≥10yrs (HR 2.2, p=0.005), MUD (vs MSD, HR 3.00, p=0.002) and CSA prophylaxis (vs FK506, HR 0.49, p=0.011) were significantly associated with this outcome. Among the 175 patients with combined TED and PHIS data, the median total adjusted cost was $117,393 per 30 hospital days per patient (range: $36,244-$515,640) during the alloHCT year with a median of 53 hospital days per patient (range: 16-304). Age ≥10yrs and HCU were not significantly associated (p=0.775). MSD had the lowest HCU compared to CBT and unrelated transplants (p<0.001). CBT and peripheral blood stem cells were associated with higher HCU compared to bone marrow (p=0.004). Increased HCU was associated with prior stroke (p=0.0004) and pain crises (p=0.0094) but not acute chest syndrome (p=0.2913). Overall SCD complication and severity indices correlated with increased HCU (p=0.052, p=0.0219, respectively). Conclusions: AlloHCT outcomes in children with SCD were linked to age and donor type suggesting that early alloHCT before age 10 years is preferred. Specifically, SCD severity and MUD alloHCT are associated with poorer outcomes and increased HCU. This supports the recommendation of early alloHCT, prior to onset of SCD complications, for children with SCD and an available MSD. Donor source and type had a significant impact on both outcomes and HCU. CBT outcomes were similar to MSD bone marrow; yet CBT had higher HCU suggesting additional analysis is needed to determine if the clinical benefit outweighs the cost. Further analysis is also needed to better understand and mitigate risk factors associated with poor outcomes and increased HCU following MUD alloHCT. Disclosures Arnold: Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program: Other: award. Hahn:NIH/NHLBI: Research Funding; Novartis: Equity Ownership.

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