scholarly journals Increased risk of infection in marrow transplant patients receiving methylprednisolone for graft-versus-host disease prevention

Blood ◽  
1994 ◽  
Vol 84 (4) ◽  
pp. 1328-1332 ◽  
Author(s):  
HG Sayer ◽  
G Longton ◽  
R Bowden ◽  
M Pepe ◽  
R Storb
Keyword(s):  
Graft Versus Host Disease ◽  
Cox Regression ◽  
Coagulase Negative Staphylococcus ◽  
Time Interval ◽  
Risk Of Infection ◽  
Host Disease ◽  
Cox Regression Analysis ◽  
Graft Versus Host ◽  
Increased Risk ◽  
To Receive

One hundred forty-seven patients with hematologic diseases and treated by allogeneic marrow transplants received graft-versus-host disease (GVHD) prevention with methotrexate and cyclosporine. In addition, 73 of the 147 patients were randomized to receive methylprednisolone during the first 35 days after transplant to improve GVHD prevention, whereas 74 patients were randomized not to receive methylprednisolone. The randomized trial enabled us to examine whether methylprednisolone increased the risk of infection after marrow grafting. Charts of study patients were analyzed retrospectively for infection events including bacteremia, septicemia, and fungemia. The randomization was stratified by diagnosis, patient age, genotypic HLA identity, and assignment to laminar airflow room isolation. All patients were given a short course of methotrexate (no longer than 11 days) and cyclosporine for no longer than 180 days after marrow transplantation. Methylprednisolone was begun on the day of marrow grafting at a dose of 1 mg/kg body weight intravenously in divided AM and PM doses through day 22. Methylprednisolone was administered at a dose of 0.5 mg/kg in divided doses from days 22 through 35, and then discontinued. Infections were analyzed for the time interval ending on day 65 after transplantation, which included the period of methylprednisolone administration and 1 month thereafter. Seventy-one episodes of first infection events were observed in patients receiving methylprednisolone compared with 47 episodes in patients not receiving the drug. Predominant infections were bacteremias, followed in descending order by fungemias and septicemias. The most prevalent organisms cultured were gram-positive bacteria, especially coagulase-negative Staphylococcus and Streptococcus species. Pseudomonas species were the most common gram negative bacteria, and the most prevalent fungus was Candida albicans. Multivariable Cox regression analysis showed that patients receiving methylprednisolone had a 1.5 times higher risk of infection (P = .03), with acute GVHD being another independent risk factor for infections (P = .005). Methylprednisolone, when added to GVHD prevention by methotrexate and cyclosporine, increases the risk of infection during the early posttransplantation period.

scholarly journals Increased risk of infection in marrow transplant patients receiving methylprednisolone for graft-versus-host disease prevention

Blood ◽  
1994 ◽  
Vol 84 (4) ◽  
pp. 1328-1332 ◽  
Author(s):  
HG Sayer ◽  
G Longton ◽  
R Bowden ◽  
M Pepe ◽  
R Storb
Keyword(s):  
Graft Versus Host Disease ◽  
Cox Regression ◽  
Coagulase Negative Staphylococcus ◽  
Time Interval ◽  
Risk Of Infection ◽  
Host Disease ◽  
Cox Regression Analysis ◽  
Graft Versus Host ◽  
Increased Risk ◽  
To Receive

Abstract One hundred forty-seven patients with hematologic diseases and treated by allogeneic marrow transplants received graft-versus-host disease (GVHD) prevention with methotrexate and cyclosporine. In addition, 73 of the 147 patients were randomized to receive methylprednisolone during the first 35 days after transplant to improve GVHD prevention, whereas 74 patients were randomized not to receive methylprednisolone. The randomized trial enabled us to examine whether methylprednisolone increased the risk of infection after marrow grafting. Charts of study patients were analyzed retrospectively for infection events including bacteremia, septicemia, and fungemia. The randomization was stratified by diagnosis, patient age, genotypic HLA identity, and assignment to laminar airflow room isolation. All patients were given a short course of methotrexate (no longer than 11 days) and cyclosporine for no longer than 180 days after marrow transplantation. Methylprednisolone was begun on the day of marrow grafting at a dose of 1 mg/kg body weight intravenously in divided AM and PM doses through day 22. Methylprednisolone was administered at a dose of 0.5 mg/kg in divided doses from days 22 through 35, and then discontinued. Infections were analyzed for the time interval ending on day 65 after transplantation, which included the period of methylprednisolone administration and 1 month thereafter. Seventy-one episodes of first infection events were observed in patients receiving methylprednisolone compared with 47 episodes in patients not receiving the drug. Predominant infections were bacteremias, followed in descending order by fungemias and septicemias. The most prevalent organisms cultured were gram-positive bacteria, especially coagulase-negative Staphylococcus and Streptococcus species. Pseudomonas species were the most common gram negative bacteria, and the most prevalent fungus was Candida albicans. Multivariable Cox regression analysis showed that patients receiving methylprednisolone had a 1.5 times higher risk of infection (P = .03), with acute GVHD being another independent risk factor for infections (P = .005). Methylprednisolone, when added to GVHD prevention by methotrexate and cyclosporine, increases the risk of infection during the early posttransplantation period.

scholarly journals Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate [see comments]

Blood ◽  
1992 ◽  
Vol 80 (7) ◽  
pp. 1838-1845 ◽  
Author(s):  
RA Nash ◽  
MS Pepe ◽  
R Storb ◽  
G Longton ◽  
M Pettinger ◽  
...  
Keyword(s):  
Risk Factors ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Malignant Disease ◽  
Acute Gvhd ◽  
Host Disease ◽  
Cox Regression Analysis ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Acute Graft

Abstract Previous studies of risk factors for acute graft-versus-host disease (GVHD) involved patients receiving predominantly single-agent prophylaxis. Therefore, a retrospective analysis was performed on 446 patients, from a single institution, who received transplants of marrow from HLA-identical siblings and the combination of cyclosporine (CSP) and methotrexate (MTX) to determine risk factors for acute GVHD associated with this more effective form of GVHD prophylaxis. The incidences of Grades II-IV and Grades III-IV (severe) acute GVHD were 35% and 16%, respectively. Increased clinical grades of acute GVHD in patients without advanced malignant disease were associated with a decreased survival. In a multivariate Cox regression analysis, risk factors associated with the onset of Grades II-IV acute GVHD were sex mismatch and donor parity (P = .001), increased dose of total body irradiation (TBI) (P = .001), and reduction to less than 80% of the scheduled dose of MTX (P = .02) or CSP (P = .02). The multivariate analysis indicated a relative risk of 1.37 for acute GVHD in a group defined as having advanced malignant disease at transplant; however, this difference failed to reach conventional levels of statistical significance (P = .07). Reduction of MTX and CSP occurred in up to 36% and 44% of patients, respectively, primarily because of renal or hepatic dysfunction. The periods of increased risk for the onset of acute GVHD were up to 1 week after a reduction of MTX and 2 weeks after a reduction in CSP. When only patients who developed Grades II-IV acute GVHD were considered, the more severe acute GVHD of Grades III-IV was associated with increased patient age of 40 years or greater (P = .05) and dose reductions of CSP (P = .008). Serologic status of patient and donor for cytomegalovirus (CMV), HLA antigens in the A and B loci, and isolation in a laminar air flow room during marrow transplantation, all previously identified as risk factors for acute GVHD, were not confirmed as risk factors in this study population. The toxicity of MTX and CSP and the development of acute GVHD from inadequate immunosuppression because of dose reduction warrants further trials with potentially less toxic immunosuppressive agents. Risk factors for acute GVHD should be considered in clinical management and in the design of clinical trials.

Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO)

Blood ◽  
2001 ◽  
Vol 98 (10) ◽  
pp. 2942-2947 ◽  
Author(s):  
Andrea Bacigalupo ◽  
Teresa Lamparelli ◽  
Paolo Bruzzi ◽  
Stefano Guidi ◽  
Paolo Emilio Alessandrino ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Antithymocyte Globulin ◽  
Advanced Disease ◽  
Chronic Gvhd ◽  
Host Disease ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Unrelated Donors ◽  
To Receive ◽  
Grade Iii

Abstract One hundred nine patients with hematologic malignancies, undergoing bone marrow transplants (BMT) from unrelated donors, were randomized in 2 consecutive trials to receive or not to receive antithymocyte globulin (ATG) in the conditioning regimen, as follows: (A) 54 patients (median age, 28 years; 39% with advanced disease) were randomized to no ATG (n = 25) versus 7.5 mg/kg rabbit ATG (Thymoglobulin; Sangstat, Lyon, France) (n = 29) ; (B) 55 patients (median age, 31 years, 71% with advanced disease) were randomized to no ATG (n = 28) versus 15 mg/kg rabbit ATG (n = 27). Grade III-IV graft-versus-host disease (GVHD) was diagnosed in 36% versus 41% (P = .8) in the first and in 50% versus 11% (P = .001) in the second trial. Transplant-related mortality (TRM), relapse, and actuarial 3-year survival rates were comparable in both trials. In fact, despite the reduction of GVHD in the second trial, a higher risk for lethal infections (30% vs 7%; P = .02) was seen in the arm given 15 mg/kg ATG. Extensive chronic GVHD developed overall more frequently in patients given no ATG (62% vs 39%;P = .04), as confirmed by multivariate analysis (P = .03). Time to 50 × 109/L platelets was comparable in the first trial (21 vs 24 days; P = .3) and delayed in the ATG arm in the second trial (23 vs 38 days;P = .02). These trials suggest that (1) 15 mg/kg ATG before BMT significantly reduces the risk for grade III-IV acute GVHD, (2) this does not translate to a reduction in TRM because of the increased risk for infections, and (3) though survival is unchanged, extensive chronic GVHD is significantly reduced in patients receiving ATG.

scholarly journals Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate [see comments]

Blood ◽  
1992 ◽  
Vol 80 (7) ◽  
pp. 1838-1845 ◽  
Author(s):  
RA Nash ◽  
MS Pepe ◽  
R Storb ◽  
G Longton ◽  
M Pettinger ◽  
...  
Keyword(s):  
Risk Factors ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Malignant Disease ◽  
Acute Gvhd ◽  
Host Disease ◽  
Cox Regression Analysis ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Acute Graft

Previous studies of risk factors for acute graft-versus-host disease (GVHD) involved patients receiving predominantly single-agent prophylaxis. Therefore, a retrospective analysis was performed on 446 patients, from a single institution, who received transplants of marrow from HLA-identical siblings and the combination of cyclosporine (CSP) and methotrexate (MTX) to determine risk factors for acute GVHD associated with this more effective form of GVHD prophylaxis. The incidences of Grades II-IV and Grades III-IV (severe) acute GVHD were 35% and 16%, respectively. Increased clinical grades of acute GVHD in patients without advanced malignant disease were associated with a decreased survival. In a multivariate Cox regression analysis, risk factors associated with the onset of Grades II-IV acute GVHD were sex mismatch and donor parity (P = .001), increased dose of total body irradiation (TBI) (P = .001), and reduction to less than 80% of the scheduled dose of MTX (P = .02) or CSP (P = .02). The multivariate analysis indicated a relative risk of 1.37 for acute GVHD in a group defined as having advanced malignant disease at transplant; however, this difference failed to reach conventional levels of statistical significance (P = .07). Reduction of MTX and CSP occurred in up to 36% and 44% of patients, respectively, primarily because of renal or hepatic dysfunction. The periods of increased risk for the onset of acute GVHD were up to 1 week after a reduction of MTX and 2 weeks after a reduction in CSP. When only patients who developed Grades II-IV acute GVHD were considered, the more severe acute GVHD of Grades III-IV was associated with increased patient age of 40 years or greater (P = .05) and dose reductions of CSP (P = .008). Serologic status of patient and donor for cytomegalovirus (CMV), HLA antigens in the A and B loci, and isolation in a laminar air flow room during marrow transplantation, all previously identified as risk factors for acute GVHD, were not confirmed as risk factors in this study population. The toxicity of MTX and CSP and the development of acute GVHD from inadequate immunosuppression because of dose reduction warrants further trials with potentially less toxic immunosuppressive agents. Risk factors for acute GVHD should be considered in clinical management and in the design of clinical trials.

scholarly journals 1075. Absolute Lymphocyte Count as a Predictor of Cytomegalovirus (CMV) Infection and Recurrence in Hematopoietic Stem Cell Transplant (HSCT) Recipients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S565-S565
Author(s):  
Joanne Reekie ◽  
Marie Helleberg ◽  
Christina Ekenberg ◽  
Mark P Khurana ◽  
Isabelle P Lodding ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Lymphocyte Count ◽  
Absolute Lymphocyte Count ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Acute Graft

Abstract Background Cytomegalovirus (CMV) is a serious complication following Hematopoietic Stem Cell Transplant (HSCT) and can lead to serious organ disease and mortality. This study aimed to investigate the association between absolute lymphocyte count (ALC) and CMV to determine whether ALC could help to identify those at an increased risk of CMV infection and recurrence Methods Adults undergoing HSCT between 2011 and 2016 at Rigshospitalet, Denmark were included. Cox proportional hazards models investigated risk factors, including ALC, for CMV infection in the first year post-transplant and recurrent CMV infection 6 months after clearance and stopping CMV treatment for the first infection. For the primary outcome ALC was investigated as a time-updated risk factor lagged by 7 days, and for recurrent CMV, ALC measured at the time at the time of stopping treatment for the first CMV infection was investigated (+/- 7 days). Results Of the 352 HSCT recipients included, 57% were male, 40% received myeloablative conditioning, 42% had high risk (D-R+) CMV IgG serostatus at transplant and the median age was 56 (IQR 43-63). 143 (40.6%) patients had an episode of CMV DNAemia a median of 47 days after transplant (IQR 35-62). A lower current ALC (≤ 0.3 x109/L) was associated with a higher risk of CMV infection in univariate analysis compared to a high current ALC (> 1 x109/L). However, this association was attenuated after adjustment, particularly for acute graft versus host disease (Figure). 102 HSCT recipients were investigated for risk of recurrent CMV of which 41 (40.2%) had a recurrent CMV episode a median of 27 days (IQR 16-50) after stopping CMV treatment for the first infection. A lower ALC (≤ 0.3 x109/L) at the time of stopping CMV treatment was associated with a significantly higher risk of recurrent CMV after adjustment (Figure). A higher peak viral load (> 1500 IU/ml) during the first episode of CMV infection was also associated with an increased risk of recurrent CMV (aHR 2.47, 95%CI 1.00-6.10 compared to < 750 IU/ml). Association between absolute lymphocyte count (ALC) and risk of CMV infection and recurrent CMV within 6 months. **First CMV infection multivariable model also adjusted for sex, CMV serostatus, age, year of transplant, Charlson Comorbidity Index, Anti-thymocyte globulin (ATG) given, HLA donor-recipient matching, and acute graft versus host disease (time-updated) *Recurrent CMV infection multivariable model also adjusted for conditioning regimen, sex, CMV serostatus, age, year of transplant Anti-thymocyte globulin (ATG) given, HLA donor-recipient matching, and acute graft versus host disease and peak CMV viral load during the first CMV infection Conclusion A lower ALC at the time of stopping treatment for the first CMV infection was associated with an increased risk of recurrent CMV and could be used to help guide decisions for augmented CMV surveillance and clinical awareness of CMV disease symptoms in these patients. Disclosures All Authors: No reported disclosures

Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 3683-3686 ◽  
Author(s):  
Samar Kulkarni ◽  
Ray Powles ◽  
Jennie Treleaven ◽  
Unell Riley ◽  
Seema Singhal ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Pneumococcal Infection ◽  
Pneumococcal Infections ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Penicillin Prophylaxis

Abstract Incidences of and risk factors for Streptococcus pneumoniaesepsis (SPS) after hematopoietic stem cell transplantation were analyzed in 1329 patients treated at a single center between 1973 and 1997. SPS developed in 31 patients a median of 10 months after transplantation (range, 3 to 187 months). The infection was fatal in 7 patients. The probability of SPS developing at 5 and 10 years was 4% and 6%, respectively. Age, sex, diagnosis, and graft versus host disease (GVHD) prophylaxis did not influence the development of SPS. Allogeneic transplantation (10-year probability, 7% vs 3% for nonallogeneic transplants; P = .03) and chronic GVHD (10-year probability, 14% vs 4%; P = .002) were associated with significantly higher risk for SPS. All the episodes of SPS were seen in patients who had undergone allograft or total body irradiation (TBI) (31 of 1202 vs 0 of 127;P = .07). Eight patients were taking regular penicillin prophylaxis at the time of SPS, whereas 23 were not taking any prophylaxis. None of the 7 patients with fatal infections was taking prophylaxis for Pneumococcus. Pneumococcal bacteremia was associated with higher incidences of mortality (6 of 15 vs 1 of 16;P = .04). We conclude that there is a significant long-term risk for pneumococcal infection in patients who have undergone allograft transplantation, especially those with chronic GVHD. Patients who have undergone autograft transplantation after TBI-containing regimens also appear to be at increased risk. These patients should receive lifelong pneumococcus prophylaxis. Consistent with increasing resistance to penicillin, penicillin prophylaxis does not universally prevent SPS, though it may protect against fatal infections. Further studies are required to determine the optimum prophylactic strategy in patients at risk.

scholarly journals Adverse events in second- and third-line treatments for acute and chronic graft-versus-host disease: systematic review

2020 ◽  
Vol 11 ◽  
pp. 204062072097703
Author(s):  
Vladica M. Velickovic ◽  
Emily McIlwaine ◽  
Rongrong Zhang ◽  
Tim Spelman
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Pharmaceutical Management ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Third Line

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with an increased risk of graft- versus-host disease (GvHD), a strong prognostic predictor of early mortality within the first 2 years following allo-HSCT. The objective of this study was to describe the harm outcomes reported among patients receiving second- and third-line treatment as part of the management for GvHD via a systematic literature review. Methods: A total of 34 studies met the systematic review inclusion criteria, reporting adverse events (AEs) across 12 different second- and third-line therapies. Results: A total of 14 studies reported AEs across nine different therapies used in the treatment of acute GvHD (aGvHD), 17 studies reported AEs of eight different treatments for chronic GvHD (cGvHD) and 3 reported a mixed population. Infections were the AE reported most widely, followed by haematologic events and laboratory abnormalities. Reported infections per patient were lower under extracorporeal photopheresis (ECP) for aGvHD (0.267 infections per patient over 6 months) relative to any of the therapies studied (ranging from 0.853 infections per patient per 6 months under etanercept up to 1.998 infections per patient on inolimomab). Conclusion: The reported incidence of infectious AEs in aGvHD and grade 3–5 AEs in cGvHD was lower on ECP compared with pharmaceutical management.

Allogeneic HY Antibodies 3 Months Following Sex-Mismatched HCT Predicts Chronic Graft-Versus-Host Disease and Non-Relapse Mortality

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 147-147
Author(s):  
Hideki Nakasone ◽  
Lu Tian ◽  
Takakazu Kawase ◽  
Bita Sahaf ◽  
Rakesh Popli ◽  
...  
Keyword(s):  
B Cell ◽  
Graft Versus Host Disease ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Cumulative Number ◽  
Clinical Factors ◽  
Roc Curve Analysis ◽  
Host Disease ◽  
Graft Versus Host ◽  
Increased Risk

Abstract Background B-cells play a significant role in chronic graft-versus-host disease (cGVHD). Male patients with female donors (F→M) are at a higher risk of developing cGVHD. B cell responses against minor histocompatibility antigens encoded on the Y chromosome, called H-Y antigens, develop following F→M HCT patients in association with cGVHD (Miklos, Blood. 2005 & Sahaf, PNAS. 2013). Here we present our novel HY microarray and use this sensitive technology to determine temporal development of HY antibody (Ab) preceding cGVHD. Multivariate analyses demonstrate that HY-Ab detection 3 months (3m) post HCT predicts cGHVD incidence and non-relapse mortality (NRM). Methods We studied 136 adult male recipients of F→M HCT between 2005 and 2012 who survived without relapse for at least 3m post-HCT with 3m plasma available. Median patient age was 53 (21-74). Related donors were transplanted in 85 (63%) and 128 (94%) were PBSC grafts. Reduced intensity conditioning accounted for 61 (45%) and anti-thymocyte globulin (ATG) was used in 71 (52%). Thirty-one patients (23%) experienced grade II-IV acute GVHD. We measured IgG against six HY antigens (DBY, UTY, ZFY, SMCY, EIF1AY, and RBS4Y) from plasma collected 3m post-HCT using a novel proteomic microarray here presented for the first time. The cut-off value for seropositivity was defined as the third quartile + 2x the interquartile range, determined from plasma of 60 male donors. HY-score was defined as the cumulative number of HY antigen targeted by Abs at 3m post-HCT. Results The frequencies of HY antigen-specific Ab are presented in Table 1, showing that SMCY and UTY were most frequently detected and overall, 78 (57%) had developed allo-Ab against any of these 6 HY antigens. Each HY-Ab was significantly associated with the development of cGVHD and DBY was greatest. LASSO analysis suggested that DBY, UTY, and ZFY were the most predictive for the development of cGVHD (Table 1). Univariate analysis failed to identify associations between clinical features and the development of HY-Ab at 3m. The detection of HY-Ab gradually increased within the 1st year post HCT and seropositivity for each HY-IgG (except RPS4Y) persisted. Considering each HY-IgG response by principal component analysis, a higher HY-score was associated with an increased risk for the development of cGVHD and NRM, after adjusting for usual alloHCT clinical factors (Table 2). In addition, the severity of cGVHD was significantly associated with the HY-score: the proportion of severe/moderate cGVHD was 33% in 0, 30% in 1, 60% in 2-3, and 70% in 4-6 (P<0.01). Receiver operating characteristic (ROC) curve analysis revealed that HY-score in combination with clinical factors enhanced the predictive potential for the development of cGVHD [area under the curve (AUC): 0.76], in comparison with either of only HY-score (AUC: 0.66) or clinical factors (AUC: 0.69). Conclusion Here, we show that HY Ab detection 3m following sex-mismatch HCT actually predicts the development of cGVHD, independently from clinical risk factors. In addition, the combination of HY-score and clinical factors had a greater predictive potential than clinical factors alone for the development of cGVHD in F→M HCT. HY-Ab development 3m post HCT may stratify cGVHD risk and support B-cell-depletion therapy beginning 3 months or earlier to prevent cGVHD development. Disclosures: No relevant conflicts of interest to declare.

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