Risk Factors for the Development of Acute and National Institute of Health (NIH) Chronic Graft-Versus-Host Disease (GVHD).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 345-345
Author(s):  
Mary E.D. Flowers ◽  
Barry E. Storer ◽  
Stephanie J. Lee ◽  
Paulo Vidal Campregher ◽  
Afonso Celso Vigorito ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Study Cohort ◽  
Consensus Development ◽  
Donor Age ◽  
Multivariate Models ◽  
Unrelated Donors

Abstract Abstract 345 Background: In 2005, an NIH consensus development conference proposed new categories for manifestations of acute and chronic GVHD after allogeneic hematopoietic cell transplantation (HCT). A question not addressed by this NIH consensus development project was whether acute and chronic GVHD result from different pathogenic pathways or from a single pathogenic pathway. Purpose: To explore this question, we analyzed risk factors for grade 2-4 acute GVHD and for chronic GVHD according to NIH consensus criteria after allogeneic hematopoietic cell transplantation (HCT). Identification of different risk factors would support the hypothesis that acute and chronic GVHD result from different pathogenic pathways. Patients and Methods: The study cohort included 2941 recipients of a first related or unrelated allogeneic HCT with bone marrow or growth factor-mobilized blood cells after a myeloablative conditioning regimen for treatment of hematological malignancies between 07/01/1992 and 2005 in Seattle. Endpoints were grade 2-4 acute GVHD that was diagnosed at any time before or after day 100 and chronic GVHD that was diagnosed according to NIH criteria and required systemic treatment. Risks factors considered in multivariate Cox regression analyses were patient and donor age per decade, donor types, stem cell source, recipient/donor gender combination, use of rabbit antithymocyte globulin (ATG) in the conditioning regimen, prior infection of patient or donor with cytomegalovirus, chronic myeloid leukemia (CML) and myeloid malignancy. The multivariate models were also adjusted for year of transplant. The analysis was carried out as of 07/23/2009. Results: The median age of the study cohort was 40 (0.6-71) years. Of the 2941 patients, 1927 (66%) received bone marrow, 1284 (44%) had HLA-matched related donors, 957 (33%) had HLA-matched unrelated donors, and 700 (24%) had HLA-mismatched related or unrelated donors. The cumulative incidence of grade 2-4 acute GVHD was 80% at 6 months, and the cumulative incidence of NIH chronic GVHD at 2 years was 34%. 461 (16%) patients did not develop either grade 2-4 acute GVHD or NIH chronic GVHD. 922 patients (31.3%) had both grade 2-4 acute GVHD and NIH chronic GVHD. Among these 922 patients, 840 (91%) had acute GVHD before NIH chronic GVHD, 77 (8%) developed acute and NIH chronic GVHD at the same time, and 5 (0.5%) had acute GVHD after NIH chronic GVHD. The median time from HCT to onset of grade 2-4 acute GVHD was 20 days (3-711) days and the median time from HCT to onset of NIH chronic GVHD was 162 (66-2805) days. The two diseases had closely similar profiles of risk factors. In multivariate models, most factors showed concordant association with an increased (unrelated, HLA-mismatched donors, male recipients with female donors, mobilized blood cell graft, donor age) or decreased (ATG and CML) risk of acute GVHD and NIH chronic GVHD (figure), although the use of mobilized blood cells had a stronger association with chronic GVHD than with acute GVHD. Only one risk factor showed discordant association with grade 2-4 acute GVHD and NIH chronic GVHD. Older patient age was associated with a slightly increased risk of NIH chronic GVHD (HR 1.12 per decade; 95% CI 1.06-1.18; p < 0.0001) but with a slightly lower risk of acute GVHD (HR 0.96 per decade; 95% CI 0.93-0.99, p = 0.02). Conclusion: The close similarity of risk factor profiles for acute and chronic GVHD can not rule out the hypothesis that these diseases result from different pathogenic pathways. Disclosures: No relevant conflicts of interest to declare.

Incidence, Risk Factors and Outcomes of Sclerotic Chronic Graft-Versus-Host Disease (GVHD) Phenotype After Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 322-322
Author(s):  
Yoshihiro Inamoto ◽  
Barry Storer ◽  
Effie W. Petersdorf ◽  
Paul A. Carpenter ◽  
Stephanie J. Lee ◽  
...  
Keyword(s):  
Risk Factors ◽  
Malignant Disease ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Factors Associated ◽  
Increased Risk ◽  
Unrelated Donors ◽  
Recurrent Malignancy

Abstract Abstract 322 Background: A sclerotic GVHD phenotype represents one of the most severe late complications of allogeneic hematopoietic cell transplantation (HCT), sharing some clinical similarities with systemic sclerosis. The incidence and risk factors of sclerotic chronic GVHD and its association with major transplant outcomes are not well established. Patients and methods: We analyzed 986 consecutive patients who received systemic therapy for chronic GVHD after a first allogeneic HCT performed between 2000 – 2008 in Seattle for malignant and nonmalignant diseases. Chronic GVHD was diagnosed by the NIH consensus criteria. Sclerotic GVHD was defined when manifestations of cutaneous sclerosis, fasciitis or joint contracture were first documented in the medical record. Multivariate Cox regression analyses accounted for patient and donor age per decade, donor type, HLA matching, ABO matching, diagnosis and disease risk, stem cell source, patient gender, intensity of conditioning regimen, use of total body irradiation (TBI) or rabbit antithymocyte globulin in the conditioning regimen, and GVHD prophylaxis. Risk factors considered at the onset of chronic GVHD were prior acute GVHD, prior severe (stage 3 and 4) skin acute GVHD, eosinophilia, thrombocytopenia, progressive onset, extent of skin involvement, and bronchiolitis obliterans. Overall mortality (OM), nonrelapse mortality (NRM; malignant disease only) and recurrent malignancy (malignant disease only) were compared between patients with and without sclerotic features using time-dependent Cox models. Results: Of the 986 patients, median age was 47 (0–78) years, 776 (79%) were Caucasian, 950 (96%) had malignant diseases, 407 (41%) had HLA-matched related donors, 356 (36%) had HLA-matched unrelated donors, and 223 (23%) had HLA-mismatched related or unrelated donors. The median time from HCT to chronic GVHD was 5.3 (2.5–46) months; 73 patients (7%) presented with sclerotic features at initial diagnosis and 142 patients (14%) developed sclerosis after the onset of chronic GVHD. The cumulative incidence of sclerotic GVHD was 20% (95%CI, 18–23) at 36 months after onset of chronic GVHD, and median onset of sclerosis was 7.9 months after onset of chronic GVHD (Figure). In multivariate models (Table), factors associated with an increased risk of sclerotic GVHD were mobilized blood cell graft, female recipient, TBI >450cGy, and prior severe skin acute GVHD. Factors associated with a decreased risk of sclerotic GVHD were HLA-mismatched donors and ABO major mismatch. Risks of OM, NRM and recurrent malignancy in patients with sclerotic features did not differ statistically from patients without sclerotic features (hazard ratio (HR) 0.97, 95% CI 0.7–1.3, p=0.83; HR 0.94, 95% CI 0.6–1.4, p=0.78; HR 0.73, 95% CI 0.5–1.2, p=0.17, respectively). Conclusion: Sclerotic GVHD is an underestimated phenotype of chronic GVHD. Female predominance in sclerotic chronic GVHD is similar to that in systemic sclerosis. Risks of major transplant outcomes do not differ statistically between patients with and without sclerotic chronic GVHD phenotype. Mechanisms that account for the decreased risk of sclerosis associated with HLA and ABO mismatching and for the increased risk associated with prior severe skin acute GVHD warrant future investigation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Risk Factors for Adverse Outcomes Following Haploidentical Hematopoietic Cell Transplantation with Posttransplant Cyclophosphamide: A Two-Center Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4889-4889
Author(s):  
Viviane De Jesus Torres Lima ◽  
Anderson Felipe Felipe Da Silva ◽  
Andreza Alice Feitosa Ribeiro ◽  
Mariana Nassif Kerbauy ◽  
Lucila Kerbauy ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Disease Risk ◽  
Risk Index ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Adverse Outcomes ◽  
Very High

Abstract Introduction Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for several malignant hematologic diseases. As only 30% of patients will have a matched related donor, alternative donors play a significant role in HCT. Luznik et al pioneered the use of posttransplant cyclophosphamide (PTCy) based GVHD prophylaxis in haploidentical transplantation (haplo-HCT), which greatly expanded the pool of donors and nearly revolutionized the field. Despite the increasing use of haplo-HCT with PTCy, some questions remain, namely the selection of the best donor, graft source and conditioning regimen, and risk factors for adverse outcomes. Methods Retrospective study conducted at two Brazilian centers. All patients with hematologic malignancies who underwent first HCT between 2010 and 2021, haploidentical with posttransplant cyclophosphamide, were included. The objective was to identify risk factors for adverse outcomes following haploidentical HCT with PTCy. Independent variables are detailed in table 1. Acute GVHD was graded according to the MAGIC criteria and chronic GVHD was diagnosed according to the NIH consensus criteria. Survival and cumulative incidence curves were built with the Kaplan-Meier and Gray methods, and compared with the logrank and Gray tests, respectively. Multivariate analyses were carried out with Cox models. GVHD, as an independent variable, was included as a time-dependent covariate. Results A total of 103 patients were included (table 1). In brief, median age was 39 y/o and most patients were male (58%); 71 patients had low or intermediate disease risk index, while 29 had high or very high-risk disease. Bone marrow was the preferred stem-cell (72%, followed by peripheral blood stem-cells - 28%) and reduced-intensity, the most frequent conditioning regimen (43%). Median follow-up for the whole cohort was 2.6 years. Overall survival at 2 years was 51.7% (95CI 42.4-63.0%, figure 1). Multivariable analyses are in table 2. Risk factors for death were age at transplant (HR = 1.03 for each year; 95CI 1.01-1.05; p = 0.002), high or very high disease risk index (HR = 2.73; 95CI 1.52-4.90; p = 0.0008), and compared with low or intermediate, and mother as the donor (HR = 3.50; 95CI 1.44-8.47; p = 0.006). Progression-free survival at 2 years was 45.8% (95CI 36.6-57.2%). In multivariate analysis (table 2), progression-free survival was significantly poorer for older patients (HR = 1.02; 95CI 1.01-1.04; p = 0.009), high or very high disease risk index (HR = 2.29; 95CI 1.30-4.04; p = 0.004), compared with low or intermediate, and mother as a donor (HR = 3.15; 95CI 1.37-7.22; p = 0.007; figure 2). Two-year relapse rate was 22.2% (95CI 15.2-32.5%). Risk factors for relapse (table 2) were high or very high disease risk index (HR = 3.55; 95CI 1.44-8.74; p = 0.006), compared with low or intermediate, and mother as the donor (HR = 2.85; 95CI 1.12-7.25; p = 0.007). Two-year non-relapse mortality was 32.0% (23.9-42.9%). The only risk factor we found was age at transplantation (HR = 1.03 for each year; 95CI 1.01-1.05; p = 0.02; table 2). We found no effect of GVHD, acute or chronic, on relapse, nor on non-relapse mortality. Rates of grades II-IV and III-IV acute GVHD and 2y-chronic GVHD were 30.4% (95CI 22.7-40.8%), 6.9% (95CI 3.4-14.1%) and 19.8% (95CI 13.2-29.7%), respectively. The only risk factor (table 2) identified for grades II-IV acute GVHD was tacrolimus (HR = 0.36; 95CI 0.14-0.95; p = 0.04) compared with cyclosporine. We have not carried out multivariate analysis for grades III-IV acute GVHD due to the low number of events (only 7). In multivariable analysis (table 2), peripheral blood graft was a risk factor for chronic GVHD (HR = 3.72; 95CI 1.53-9.01; p = 0.004; figure 3), compared with bone marrow, while tacrolimus was protective (HR = 0.27; 95CI 0.11-0.68; p = 0.005), compared with cyclosporine. Conclusion Our results show that mother as the donor was an important risk factor for poorer OS, PFS and relapse, and mothers might not the best choice of donor. Tacrolimus was protective for both grades II-IV aGVHD and for cGVHD, suggesting that tacrolimus may be more effective than cyclosporine in preventing GVHD. PBSC was a risk factor for cGVHD without any impact on relapse, and this result does not support the systematic use of PBSC in detriment of BM. As expected, age at transplant negatively impacted OS, PFS and NRM as well as high/very high DRI led to poorer OS, PFS and relapse. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Treosulfan-Based Reduced Toxicity Regimen Prior to Allogeneic Hematopoietic Cell Transplantation in Non-Malignant Disorders.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5245-5245
Author(s):  
Jerzy Wojnar ◽  
Sebastian Giebel ◽  
Miroslaw Markiewicz ◽  
Malgorzata Krawczyk-Kulis ◽  
Iwona Wylezol ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Hematological Toxicity ◽  
Haemorrhagic Cystitis ◽  
Hematopoietic Disorders ◽  
One Year ◽  
Reduced Toxicity

Abstract Graft rejection is a major cause of failure after alloHCT in non-malignant hematopoietic disorders including severe aplastic anemia (SAA) and paroxysmal nocturnal hemaoglobinuria (PNH). For patients with high risk of this complication we introduced a novel conditioning regimens, based on treosulfan - an alkylating agent possesing both immuno- and myeloablative properties. Between 2003–2006, eleven patients (age: 23(14–35) years) with SAA (n=6) or PNH (n=5) were treated in a single institution with alloHSCT from either HLA-identical sibling (n=3) or an unrelated volunteer (n=8). For patients with SAA conditioning regimen consisted of treosulfan 10 g/m2/d on days -7, -6, cyclophosphamide 40 mg/kg/d on d. -5, -4, -3, -2, and anti-thymocyte globulin (ATG) 2 mg/kg/d on d. -3, -2, -1. PNH patients received treosulfan 14 g/m2/d on days -6, -5, -4, fludarabine 30 g/m2 on d. -6, -5, -4, -3, -2, and (ATG) 2 mg/kg/d on d. -3, -2, -1. Bone marrow was used as a source of stem cells in 5 patients and peripheral blood - in 6 cases. Graft-vs.-host disease (GVHD) prophylaxis consisted of Cyclosporin A and short-course Methotrexate. All patients engrafted with the median time to neutrophil >0.5×10e9/L and platelet >50×10e9/L recovery of 16 (14–22) days and 21.5 (12–29) days, respectively. Complete donor chimerism was achieved on day +30 in all cases. None of the patients developed grade III-IV acute GVHD, two patients experienced grade II acute GVHD. At one year the cumulative incidence of extensive chronic GVHD equaled 22%. No severe organ toxicity was observed. With the median follow-up of 19 months, the disease-free survival at 2.5 years was 91%. A single PNH patient died of haemorrhagic cystitis. We conclude that treosulfan-based preparative regimens are well-tolerated and allow stable engraftment in SAA and PNH patients. The use of treosulfan allows intensification of the conditioning without providing an additional non-hematological toxicity.

One Antigen HLA-Mismatched Related and 8/8 Allele Matched Unrelated Donors Are Associated with Similar Survival after Hematopoietic Cell Transplantation for Acute Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 965-965
Author(s):  
David Valcarcel ◽  
Fangyu Kan ◽  
Tao Wang ◽  
Stephanie J. Lee ◽  
Stephen R Spellman ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Unrelated Donor ◽  
Free Survival ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
Related Donor ◽  
Disease Free

Abstract Patients in need of an allogenetic hematopoietic cell transplant but who lack an HLA genotypically identical sibling donor, are faced with the decision to consider a single HLA antigen mismatched related donor, or a search for a suitable 8/8 matched unrelated donor. We compared the outcomes of adult patients (≥18 years old) receiving a transplant for the treatment of AML or ALL in first or second remission from either a one-antigen mismatched related donor (MMRD group, N=89) reported to the CIBMTR or an 8/8 HLA-A, B, C and DRB1 allele matched unrelated donor (UD group, N=700) facilitated by the NMDP between 1995–2005. MMRD group was typed by serological or DNA-based methods for HLA-A, -B and –DR with all results verified by lab report review. The UD group was retrospectively typed for HLA-A, B, C and DRB1 by high resolution typing methods. Most received myeloablative conditioning regimens (77%), calcineurin inhibitor-based GVHD prophylaxis (100%) and T cell replete grafts (100%). 13% received ATG with the conditioning regimen. Median follow-up was 54 and 38 months in the MMRD and UD groups, respectively. The MMRD group was younger (median age 35 vs 43, p=0.002), had more ALL patients with low-risk cytogenetics (43% vs 18%, p=0.005), had older donors (median age: 38 vs 34, p=0.047), were more likely to receive methotrexate for GVHD prophylaxis (89% vs 77%, p=0.014) and were more likely to be transplanted prior to 2001 (62% vs 24%; p<0.001). There were no differences in patient or donor gender, diagnosis, disease-status, cytogenetic-risk of AML, time from diagnosis to transplant, stem cell source, conditioning regimen, use of ATG and Karnofsky index. Univariate comparisons (MMRD vs. UD) showed: 3-year OS (42% vs 44%, p=0.647), 3-year DFS (41% vs 41%, p=0.931), 3-year TRM (39% vs 31%, p=0.136), 3-year incidence of relapse (20% vs 28%, p=0.094), grade III–IV acute GVHD by 100 days (22% vs. 15%, p=0.147), chronic GVHD by 1 year (35% vs 47%, p=0.029). All multivariate analyses were adjusted for patient and transplant characteristics and are shown in the table below. In summary, transplants utilizing one-antigen mismatched related and 8/8 allele-matched unrelated donors did not significantly differ in overall survival or disease free survival, but chronic GVHD was more frequent after UD transplantation. Outcome RR (MMRD vs. UD) 95% CI p-value Survival 0.99 0.73–1.34 0.94 Disease-free survival 1.06 0.80–1.41 0.69 Treatment related mortality 1.14 0.77–1.69 0.52 Relapse 0.81 0.50–1.30 0.38 Acute GVHD III–IV 1.53 0.91–2.57 0.11 Chronic GVHD 0.58 0.39–0.85 0.006

The Use of Bone Marrow Graft for Hematopoietic Stem Cell Transplantation From Matched Unrelated Donors After Reduced Intensity Conditioning Regimen Improves Survival : Analysis of the Societe Française De Greffe De Moelle Et De Therapie Cellulaire.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 873-873
Author(s):  
Andrea Toma ◽  
Marie-Lorraine Balère-Appert ◽  
Jean-Michel Boiron ◽  
Pierre Bordigoni ◽  
Gerard Socie ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multivariate Analysis ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Reduced Intensity Conditioning Regimen ◽  
Unrelated Donors ◽  
Grade Ii

Abstract Abstract 873 The use of peripheral blood stem cells (PBSC) for hematopoietic stem cell transplantation (HSCT) is associated with a higher risk of chronic graft versus host disease (GvHD) but its impact on survival is not clear since it may favor a greater graft versus leukemia (GvL) effect. However, in the context of HSCT from unrelated donors (UD), the balance between GvH and GvL may differ from the context of sibling donors and thus the use of PBSC may be deleterious. In this retrospective study, we analyzed 103 patients from the french registry who received a graft from an UD after a reduced intensity conditioning regimen (RIC) to evaluate the role of various parameters including the source of stem cells on the outcome. Seventy-one D/R pairs (69%) were 10/10 HLA match at the allelic level. Mismatches concerned 5, 6, 15, 2 and 7 D/R pairs for HLA-A, -B, -C, -DRB1 and -DQB1, respectively. The median age was 46 years (18-67). All patients had hematologic malignancies: AL (n=35), MM (n=18), CLL (n=5), NHL (n=11), HD (n=9), CML (n=12), MDS (n=9), and MPS (n=4). 39% of the patients were in an advanced phase of the disease at time of HSCT. The conditioning regimen was Fluda/TBI 2Gys for 26 patients, Bu/Fluda/ATG for 24 patients, Fluda/Melph for 16 patients and others for 37 patients. Overall, anti-thymocytes globulins (ATG) were part of the conditioning regimen for 77% of patients. The source of stem cells was PBSC for 65 patients and bone marrow (BM) for 38 patients. The median follow up of the cohort is 61,3 months (1,2-113,7). The results showed that 95% of patients engrafted. Five patients did not engraft (4 in the BM group and 1 in the PBSC group). Acute GvHD grade II to IV and grade III/IV occurred in 47% and 19% of patients, respectively. The risk of developing chronic GvHD was 49% at 2 years. Overall survival (OS) was 36% at five years. The median disease free survival (DFS) was 55 months among the 36 patients alive. We performed univariate and multivariate analysis of factors susceptible to impact on GvHD and survival. The multivariate analysis included the impact of HLA mismatch, disease status, diagnosis, source of stem cells, patient's and donor's ages. This multivariate analysis performed on the global population shows a trend towards an improved OS with the use of BM instead of PBSC. However, when focusing the multivariate analysis on the 71 patients transplanted with a 10/10 match donor, the most potent factor influencing the outcome is the use of BM which is associated with an improved OS (p=0.03) and DFS (p=0.02), less acute GvHD grade II-IV (p=0.05), or grade III/IV (p=0.05) and less chronic GvHD (p=0.05). These results suggest that the use of BM as the source of stem cells should be reconsidered in the context of matched UD after RIC transplantation. 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.

Risk Factors and Outcomes of Klebsiella Pneumoniae Infection before and after Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4502-4502
Author(s):  
Eleni Gavriilaki ◽  
Ioanna Sakellari ◽  
Thomas Chatziconstantinou ◽  
Despina Mallouri ◽  
Ioannis Batsis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Klebsiella Pneumoniae ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Secondary Prophylaxis ◽  
Post Transplant ◽  
Before And After

Introduction: Carbapenemase-producing (KPC) Klebsiella pneumoniae (Kp) infections have emerged as a major healthcare concern worldwide. Although infections are recognized as a major contributor of morbidity and mortality before and after allogeneic hematopoietic cell transplantation (HCT), the burden of Kp infections has not been extensively evaluated. Therefore, we aimed to determine risk factors and outcomes of these infections in HCT recipients. Methods: We retrospectively studied consecutive patients with Kp colonization and/or infection before and/or after HCT performed in 2008-2018. Patients were transplanted according to standard operating procedures of our JACIE-accredited center. Colonization was defined as the isolation of the microorganism from any non-sterile body site in the absence of clinical signs or symptoms of disease. Patients with colonization or infection pre-transplant received secondary prophylaxis pre and during transplant. Nurses, visitors and staff were carefully trained on infection control measures such as contact precautions and intensified hygienic measures in patients with pre-transplant isolation. Statistical analysis included the following factors: age, gender, disease phase at transplant (early, intermediate or advanced), donor, pre-transplant and post-transplant Kp infections and colonizations, KPC-Kp, severe acute and extensive chronic GVHD, relapse, treatment-related mortality (TRM) and overall survival (OS). Results: We studied 52 patients with a median age of 42 (range 17-42). Colonizations were detected in 9 patients pre-transplant (17%) and 29 post-transplant (56%); whereas infections in 23 pre- and 28 post-transplant (44% and 54%, respectively). KPC-Kp was isolated in 12 patients (29%). With a median follow-up of 23.5 months (range 1-99), cumulative incidence (CI) of severe acute GVHD was 44.5% and severe chronic GVHD 56.7%. Two-year CI of TRM was 14.3% and was independently predicted by the isolation of KPC-Kp (p=0.040, Figure 1A) and chronic GVHD (p<0.001). Among pre-transplant and transplant factors, acute GVHD was associated only with pre-transplant Kp infections (p=0.049). Pre-transplant infections were also associated with post-transplant infections (p=0.010), despite secondary prophylaxis. Overall survival was associated with disease phase at transplant (p=0.017), post-transplant infections (p=0.034) and acute GVHD (p=0.013). In the multivariate model, only post-transplant Kp infections independently predicted OS (beta=9.042, p=0.008, Figure 1B). Conclusions: Our study highlights the significant impact of Kp infections on TRM and OS of HCT recipients. In our population of patients with Kp colonization and/or infection, the burden of GVHD was high. Acute GVHD was linked with pre-transplant Kp infections, suggesting that disruption of intestinal microbiota may be an underlying predisposing condition. Secondary prophylaxis did not improve rates of post-transplant infections, but allowed the performance of HCT with an acceptable TRM rate. Our data suggest that additional interventions need to be further investigated to address the major problem of Kp infections in HCT. Figure 1 Disclosures No relevant conflicts of interest to declare.

A Retrospective Comparison of Tacrolimus Vs. Cyclosporine for Immunosuppression After Allogeneic Hematopoietic Cell Transplantation with G-CSF-Mobilized Blood Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2319-2319
Author(s):  
Yoshihiro Inamoto ◽  
Mary E.D. Flowers ◽  
Frederick R. Appelbaum ◽  
Paul A. Carpenter ◽  
H. Joachim Deeg ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Blood Cells ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Unrelated Donors ◽  
Total Body

Abstract Abstract 2319 Background: Graft-versus-host disease (GVHD) is a common immunologic complication after allogeneic hematopoietic cell transplantation (HCT). Cyclosporine or tacrolimus in combination with other agents represent widely accepted standards of care as immunosuppressive regimens after HCT. Results of open-label randomized prospective phase III studies have indicated that the risk of grades II-IV acute GVHD after bone marrow transplantation with related or unrelated donors is lower with the use of tacrolimus as compared to cyclosporine, in combination with methotrexate. The current study was carried out to compare results with tacrolimus versus cyclosporine after HCT with G-CSF-mobilized blood cells. Patients and methods: The study cohort included 510 consecutive patients who received a first G-CSF-mobilized blood cell graft from related or unrelated donors after high-intensity conditioning for treatment of hematological malignancies between 7/1/2003 and 2009 at our center. All patients received ursodeoxycholic acid from 2 weeks before conditioning until 90 days after HCT to prevent hepatic complications, and all patients received immunosuppression with either tacrolimus or cyclosporine in combination with methotrexate after HCT. Endpoints included grades II-IV acute GVHD, grades III-IV acute GVHD, chronic GVHD, end of treatment for chronic GVHD, overall survival, disease-free survival, recurrent malignancy and nonrelapse mortality. Multivariate Cox regression models were used to evaluate hazard ratios for these endpoints with tacrolimus as compared to cyclosporine. The models were adjusted for patient age, donor type, recipient and donor gender combination, disease type, disease risk category, use of total body irradiation in the conditioning regimen, and year of HCT. The analysis was carried out as of July, 2010. Results: The median age of patients was 47 (range, 1 to 66) years. Diagnosis at HCT was acute myeloid leukemia in 200 (39%) patients, acute lymphoblastic leukemia in 73 (14%), chronic myeloid leukemia in 49 (10%), myelodysplastic syndrome or myeloproliferative disorders in 160 (31%) and other lymphoid malignancies in 28 (5%). Total body irradiation was used for conditioning in 168 (33%) patients. Of the 510 patients, 277 (54%) had HLA-matched related donors, 203 (40%) had HLA-matched unrelated donors, and 30 (6%) had HLA-mismatched related or unrelated donors. Outcomes according to immunosuppression with tacrolimus or cyclosporine are shown in Table 1. Multivariate analysis showed no statistically significant differences between tacrolimus and cyclosporine for any of the endpoints tested (Table 2), although the results showed a trend suggesting that the risk of non-relapse mortality might be lower with tacrolimus as compared to cyclosporine. Conclusion: In this retrospective analysis, tacrolimus offered no statistically significant advantage over cyclosporine for preventing grades II-IV acute GVHD after HCT with G-CSF-mobilized blood cells, and results for other outcomes also showed no statistically significant differences. Although our data support the hypothesis that either regimen could be an acceptable standard of care for immunosuppression, the number of patients analyzed in this study is not sufficient to completely exclude clinically meaningful differences in outcomes with the two regimens. Disclosures: Off Label Use: Tacrolimus and cyclosporine for immunosuppression after allogeneic hematopoietic cell transplantation.

scholarly journals Risk Factors for the Development of Cutaneous Melanoma after Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 249-249
Author(s):  
Megan Herr ◽  
Rochelle E. Curtis ◽  
Margaret A. Tucker ◽  
Heather R. Tecca ◽  
Eric A. Engels ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Skin Involvement ◽  
Melanoma Risk ◽  
Allogeneic Hct ◽  
Melanoma Diagnosis ◽  
Conditioning Regimens

Abstract Introduction Advances in clinical practice for allogeneic hematopoietic cell transplantation (HCT), a potentially curative treatment most frequently indicated for hematologic malignancies, have led to substantial improvements in prognosis. HCT survivors are at risk for a number of post-transplant complications, including the development of new malignancies. Although cutaneous melanoma risk is known to be increased after HCT, no previous study has comprehensively investigated risk factors in order to identify patients at highest risk for melanoma development. The purpose of this study was to identify risk factors for developing melanoma after allogeneic HCT, specifically evaluating the relationship between melanoma and conditioning regimens as well as factors associated with immunosuppression and immune dysfunction. Methods We conducted a nested case-control study of melanoma within a cohort of 21,590 patients receiving a first allogeneic HCT during 1985-2012, as reported to the Center for International Blood and Marrow Transplant Research. Data on patient and transplant characteristics derived from standardized reports pre-HCT, 100 days and 6 months post-HCT, and annually thereafter or until death. The cohort was restricted to non-Hispanic Caucasians because melanoma is rare among other racial/ethnic groups. Among cases with a melanoma diagnosis reported by transplant centers (N=140), 82 (59%) were confirmed by pathology report review. Four controls were matched to each case on age at HCT (±3 years), sex, primary disease, and time since HCT (without a melanoma diagnosis). Conditional logistic regression was utilized to assess risk factors associated with melanoma development after allogeneic HCT. Multivariable models were adjusted for ambient ultraviolet radiation (UVR), estimated based on residence at the time of HCT, because of the known association between UVR and melanoma. Exploratory analyses were conducted to assess melanoma risk by age and time to melanoma development. Results Among the 140 melanoma cases, the median age at HCT was 46 years (range, 1-73 years), 56% were male, and median time from HCT to melanoma was 4 years (range <1-24 years). Patients were most frequently transplanted for chronic myeloid leukemia (24%) followed by acute myeloid leukemia (18%), acute lymphoblastic leukemia (18%), and non-Hodgkin lymphoma (12%). Multivariable analysis showed that melanoma risk was statistically significantly increased among HCT survivors who received myeloablative conditioning regimens with total body irradiation [odds ratio (OR), 95% confidence interval (95%CI): 1.8, 1.0-3.2] or reduced intensity conditioning regimens containing melphalan (OR, 95%CI: 2.6, 1.1-6.0) or fludarabine (OR, 95%CI: 2.7, 1.0-7.3) compared with those receiving a busulfan-containing myeloablative conditioning regimen; acute graft-versus-host disease (GvHD) with stage 2+ skin involvement (OR, 95%CI: 1.9, 1.2-3.1) versus no acute GvHD; chronic GvHD without skin involvement (OR, 95%CI: 1.9, 1.0-3.6) versus no chronic GvHD; and occurrence of keratinocytic carcinoma (OR, 95%CI: 2.4, 1.2-4.8; median time from keratinocyte carcinoma to melanoma: cases=3.5 years, controls=2.8 years). In exploratory analyses of these factors by patient subgroup, melanoma risks associated with acute GvHD stage 2+ skin involvement were especially increased among individuals of younger age at HCT (age<40 years: OR, 95%CI: 3.2, 1.4-7.4) but not among those of older age at HCT. In the multivariable model, no significant associations were observed with other patient and transplant characteristics, including graft source and ex-vivo or in-vivo T-cell depletion. Conclusion In the largest study to date of melanoma risk factors following allogeneic HCT, we report novel associations with specific conditioning regimens, occurrence of acute and chronic GvHD, and occurrence of keratinocyte carcinoma. Our results emphasize the importance of adherence to current surveillance guidelines for HCT recipients, specifically routine skin examination, heightened skin cancer awareness, and photoprotection recommendations, particularly for those survivors at highest risk. Disclosures No relevant conflicts of interest to declare.

Transplant-Related Mortality in Patients ≥50 Years of Age Is No Lower after Transplantation from Young Fully Matched Unrelated Donors (MUD) Than from Matched Siblings When All Patients Are Given the FLUBUP Regimen with Thymoglobulin.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3159-3159
Author(s):  
James A. Russell ◽  
M. Ahsan Chaudhry ◽  
Diana M. Quinlan ◽  
A. Robert Turner ◽  
Loree M. Larratt ◽  
...  
Keyword(s):  
Blood Cells ◽  
Antithymocyte Globulin ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Low Risk ◽  
Donor Age ◽  
Once Daily ◽  
Unrelated Donors ◽  
Matched Sibling ◽  
Related Mortality

Abstract There are reports indicating that older patients (pts) may have better outcomes after stem cell transplantation (SCT) from young fully matched unrelated donors (MUD) than from matched siblings (MRD) perhaps because of donor age. In some of these studies MUD and MRD recipients may have been treated differently, for example with more intense GVHD prophyaxis for MUD SCT such as antithymocyte globulin (ATG). We have compared outcomes of SCT pts receiving myeloablative fludarabine & busulfan based conditioning (FLUBUP) between 05/99 and 05/05. Only 10/10 (HLA–A, −B, C, DR & DQ) matched SCT were considered. Recipients of MRD SCT were ≥50 years old, MUD SCT recipients were unselected for age but their donors were ≤30 years old. All pts received fludarabine 50mg/m2 on days −6 to −2 and IV busulfan (Busulfex, PDL Pharma) at a myeloablative dose of 3.2 mg/kg once daily days −5 to −2 inclusive (FLUBUP) +/− TBI 200cGy x 2 on day −1 or 0. Prophylaxis for GVHD was cyclosporine A, methotrexate with folinic acid and Thymoglobulin (Genzyme) 4.5 mg/kg in divided doses over 3 consecutive days pretransplant finishing D0.[table 1]These data demonstrate that TRM for older SCT pts given the FLUBUP regimen with ATG is similar to that for adults in general transplanted from young MUD. When using these protocols in older pts there is usually no justification for the expense and inconvenience of using a young MUD in preference to a matched sibling. Patient, donor & SCT characteristics and outcomes Unrelated Related p * at 5 years Number 41 63 Patient age median (range) 44 (16–61) 55 (50–65) <0.0001 Donor age median (range) 24 (19–30) 52 (37–71) <0.0001 Low risk (Acute leukemia CR1/2, CML CP1) 22 (54%) 14 (22%) 0.0015 CMV+ve recipient or donor 31 (76%) 53 (84%) ns Female to male SCT 8 (20%) 18 (29%) ns Blood cells 20 (49%) 56 (89%) <0.0001 CD 34+ cell dose x 10e6 median (range) 5.35 (0.91–15.47) 4.23 (0.83–13.52) 0.08 TBI (not TRM risk factor) 19 (46%) 10 (16%) 0.0014 Acute GVHD II–IV 21±7% 16±5% ns Acute GVHD III–IV 10±5% 5±3% ns Chronic GVHD 64±7% 61±9% ns Pts≥50 TRM * 26±15% (n = 12) 16±5% ns Low risk TRM 5±5% 0% ns High risk TRM 31±12% 23±7% ns BCT TRM 10±7% 19±6% ns All pts TRM 16±6% 16±5% ns

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