scholarly journals Prevalence and Risk Factors of Antibodies to Class I and II Human Leukocyte Antigens in Haploidentical Allograft Candidates: A Prospective Study on 3805 Subjects

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2880-2880
Author(s):  
Ning Ma ◽  
Lan-Ping Xu ◽  
Xiaohui Zhang ◽  
Yu Wang ◽  
Huan Chen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lymphoblastic Leukemia ◽  
Class Ii ◽  
Class I ◽  
Hla Antibodies ◽  
Hematological Diseases ◽  
Factors Associated ◽  
Elder Patients ◽  
Hla Dq ◽  
Main Factors

Abstract The aim of this study is to investigate the prevalence and risk factors of anti-human leukocyte antigen (HLA) antibodies in haploidentical candidates. This study was completed at Peking University People's Hospital, Beijing China. We performed a prospective analysis of patients with hematological diseases concerning the prevalence and risk factors of anti-HLA antibodies. Patients were enrolled between July 2015 - December 2019. Serum was collected for PRAs test within 1 month before haploidentical transplantation. The risk factors, such as age, sex, total transfusion, red blood cell (RBC) transfusion, platelet (PLT) transfusion, pregnancy, disease duration and diagnosis were collected. Univariate and multivariate logistic regression analyses were performed to evaluate the risk factors of anti-HLA antibodies. Six hundred and eighty (17.9%) patients were positive for panel reactive antibodies (PRA)-class I, 360 (9.5%) for class II, 768 (20.2%) class I or II, and 272 (7.1%) positive for class I and II both. Multivariate analysis indicated that female was related to higher risk of having PRAs for class I (P = 0.011), class I or II (P = 0.009), anti-HLA-A (P = 0.015), anti-HLA-DP (P = 0.048) and also for having higher mean fluorescence intensity (MFI) (2000 or more) of PRAs in class I (P = 0.020) and class I or II (P = 0.005). Compared to patients with myelodysplastic syndrome (MDS), patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), aplastic anemia (AA) had a lower incidence for PRAs in class I, class II, class I or II, class I and II, anti-HLA-A. anti-HLA-B, anti-HLA-C, anti-HLA-DQ, anti-HLA-DR, anti-HLA-DP (Table 1). Prior pregnancy was a risk factor for PRAs (P < 0.001), and no previous pregnancy group having lower MFI of PRAs in class I (P = 0.001) and class I or II (P = 0.004). PLT transfusion (more than 4 times) rleted with a higher prevalence of PRAs (P < 0.001), and also had a higher MFI of PRAs in class II (P < 0.001), class I and II (P < 0.001). Patients with RBC transfusion (more than 3 times) had a higher prevalence of PRAs in class I (P = 0.001), class II (P = 0.029), class I or II (P < 0.001), anti-HLA-A (P = 0.001), anti-HLA-B (P < 0.001), anti-HLA-C (P = 0.007), anti-HLA-DQ (P < 0.001) and anti-HLA-DR (P = 0.011). In addition, diseases duration (8 months or more) was also associated with higher MFI of PRAs in class I (P = 0.023) and class I or II (P = 0.004). Subgroup analysis showed that 11.7% of pediatric patients were positive for PRAs in class I; 19.2% of adults, 17.9% of elder patients; 12.4% of males; 26.1% of females; 21.0% of patients with AML; 10.5% of patients with acute lymphoblastic leukemia (ALL); 18.9% of patients with AA; 30.3% of patients with MDS; 16.6% of patients with other hematological diseases. The positive rate of class II PRAs in children was 4.3%; 11.1% for adults; 9.5% for elder patients; 5.5% for males; 15.4% for females; 11.4% for patients with AML; 5.2% for patients with ALL; 10.3% for patients with AA; 17.2% for patients with MDS; 6.6% of patients with other hematological diseases. Multivariate analysis showed that, in children, PLT transfusion and diagnosis were the two main risk factors of PRAs in class I and class II (P < 0.001, P = 0.017). In adults, diagnosis (P = 0.003), transfusion (P < 0.001) and pregnancy (P < 0.001) were the three main factors associated with PRAs in class I and transfusion (P < 0.001) and pregnancy (P < 0.001) were the two main factors associated with PRAs in class II. In males, PLT transfusion (P < 0.001) and diagnosis (P < 0.001) were the two main factors associated with PRAs in class I and class II. In ALL subgroup, gender (P = 0.026, P = 0.048), pregnancy (P < 0.001) and transfusion (P < 0.001) were the three main factors associated with PRAs in class I and II. In AA subgroup, gender (P = 0.004) and PLT transfusion (P < 0.001) were risk factors for class I PRAs, pregnancy (P = 0.008) and PLT transfusion (P = 0.003) were risk factors for class II PRAs. In elder patients, females, AML, MDS and other diseases subgroup, transfusion and pregnancy were the two main factors associated with PRAs in class I and class II. Our results indicated that female sex, diagnosis, pregnancy, transfusion, disease duration were independent risk factors of anti-HLA antibodies in haploidentical allograft candidates, which provided evidence for best haploidentical donor selection. The risk factors of anti-HLA antibodies were different among total patients and those of cases in different subgroups. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Prevalence and Significance of Pre-Formed Anti-HLA Antibodies in Hematopoietic Stem Cell Transplant Recipients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1174-1174
Author(s):  
Darshan Gautam Gandhi ◽  
Jennifer Holter ◽  
Mohamad Khawandanah ◽  
Robert B. Epstein ◽  
Julie Stoner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Failure ◽  
Hla Antigens ◽  
Class Ii ◽  
Class I ◽  
Hla Antibodies ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Antibody Levels

Abstract Abstract 1174 Poster Board I-196 Introduction: The presence of sensitization to HLA antigens has been an important consideration in solid organ transplantation. It is considered a standard process to check for donor-specific allogeneic (allo) antibodies (DSA) and monitor formation of such antibodies post-transplant which could predict early and late graft failure. Most of the current data regarding the importance of anti-HLA (human leukocyte antigen) antibodies is available from renal transplant where presence of HLA antibodies is clearly associated with an increased risk of early graft loss up to the magnitude of 21%. It is routine to perform desensitization to alleviate these antibodies in an effort to enhance their chances of engraftment. The role of and approach to prior sensitization in the hematopoietic stem cell transplantation (HSC) setting is far less clear. This is of unique importance as a wider range of donor cell sources and transplant applications are utilized to treat hematologic diseases. Many of our patients have had multiple transfusions in the past, been pregnant or have had prior HLA mismatched allograft, all of which predispose to development of anti-HLA antibodies. Here we analyze the prevalence of Class I and Class II antibodies as a primary goal and also see if they correlate with graft survival. Methods: 52 patients were followed between July 2008 and July 2009 with hematologic malignancies including leukemia's, lymphoma's, multiple myeloma and others. 37/52 underwent transplantation of which 14 were unrelated donor (URD), 5 cord blood (CB) and 8 sibling (sib) transplants. Donors with corresponding HLA were excluded. Post-transplantation with day 100 antibody testing was performed in eligible patients. Antibody determination was done by testing the patients' sera with a panel of fluorescent beads coated with single HLA antigens using a solid-phase Luminex™ platform. Cut-point of 1500 [mean fluorescence intensity (MFI) ≥ 1500 defined as positive] was used for performing statistical analyses. The prevalence of positive antibody levels was compared among the transplant groups using a Fisher's exact test. Level of expression of antibodies was evaluated with MFI <500 considered negative, 500-1500 weak, 1500-3000 intermediate and >3000 strong. High resolution HLA typing was performed. Results: Class I antibodies were positive in 24 out of 52 total (46%) with 95% CI: 32% to 61%.14/37 (38%) who underwent transplantation (95% CI: 22% to 55%), 12/27 (44%) undergoing allo transplant, CB (20%), sib (38%), and URD (57%) were positive. The prevalence did not differ significantly among the transplant groups (p=0.3). Class II antibodies were positive in 8 out of 52 total (15%) with 95% CI: 7% to 28%. 5/37 (14%) who underwent transplantation (95% CI: 5% to 29%), 4/27 (15%) undergoing allo transplant, Sib (0%), CB (20%) and URD (21%) were positive. The prevalence did not differ significantly among the transplant groups (p=0.6). In females, 18/28 (64%) were positive for Class I or Class II antibodies of which 5/6 (83%) underwent URD transplants. Persistent antibody levels were detected in 3 of 4 patients tested at day 100 post transplant. Conclusions: Based on this limited pilot study we conclude that there is a high prevalence of anti-HLA antibodies present in recipients at the time of HSC transplantation. However detection of such antibodies did not jeopardize engraftment from various donor sources when HLA donor specific reactions are excluded. Bray et al showed higher incidence of graft failure associated with DSA. Takanashi et al showed that in CB transplants, antibodies were not significant unless the corresponding HLA was present in the CB unit. Based on these studies, we excluded donors with corresponding HLA. All but one patient, in whom donor specific anti-HLA antibodies were identified, achieved sustained marrow engraftment. The long term implications of antibody evolution and specificity to sustained marrow engraftment, graft vs. host and graft vs. tumor effects remain to be clarified. A larger prospective study will need to be conducted to definitely evaluate these relationships including our own which is currently under way. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Impact of Hypomethylating Agents and BCL-2 Inhibitor on HLA Expression on THP-1 Cells

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3990-3990
Author(s):  
Benjamin Peton ◽  
Melissa Valerio ◽  
Michiko Taniguchi ◽  
Ivan Rodriguez ◽  
Ebtsesam Nafie ◽  
...  
Keyword(s):  
Immune Escape ◽  
Hla Class I ◽  
Surface Expression ◽  
Class Ii ◽  
Hla Class Ii ◽  
Class I ◽  
Hypomethylating Agents ◽  
Hla Dr ◽  
Hla Dq ◽  
Ifn Γ

Abstract Note: BP, MV and LG, KG contributed equally Background Relapsed acute myeloid leukemia (AML) remains the most common reason for allogeneic hematopoietic cell transplant (HCT) failure. Thus, understanding AML immune escape mechanism is important for improving the odds of curing HCT patients with AML. Downregulation of HLA Class I and II expression by AML is one of the potential immune escape mechanisms. Therefore, treatment to restore HLA surface expression is crucial to prevent and treat relapse. Endogenous cytokines, such as IFN-γ, have been shown to stimulate HLA expression but are poorly tolerated by patients. However, two hypomethylating agents (HMA), decitabine (Dec) and azacitadine (Aza), that are routinely used in AML treatment are known to augment HLA expression. For AML, HMAs are often combined with venetoclax (Ven), a drug that blocks the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein. Thus, while HMAs have been reported to increase HLA expression, what is unknown is whether these agents impact individual HLA loci differently and whether Ven has any impact on HLA expression. To address these questions, we treated the THP-1 cell line with Dec, Aza or Ven and measured changes in cell-surface expression of HLA proteins by flow cytometry using locus-specific HLA mAbs. Methods THP-1 cells were incubated with IFN-γ (500 U/mL), Aza (2µM), Dec (5µM), or Ven (30nM) for 48 hours (drug concentrations were determined by earlier titration experiments). THP-1 cells are a monocytic cell line, derived from the peripheral blood of a childhood case of acute monocytic leukemia (M5 subtype), that express HLA Class I and HLA-DR but not HLA-DQ or -DP under basal conditions, although they are inducible by IFN-γ. Thus, the induction of HLA Class II expression by IFN-γ serves as a positive control. Isotype controls were included to measure background. Data is presented as the difference in MFI (delta MFI) between cells treated with a drug and those treated with diluent only. Results Treatment of THP-1 cells with either IFN-γ or Dec led to increases in Class I HLA-A, -B & -C (Figure 1) compared to untreated cells (a mean fold increase of 1.4 and 1.2, respectively). Notably, Aza did not stimulate additional HLA-C expression and induced less of an increase in HLA-A & -B expression (an increase of 1.1-fold) than IFN-γ or Dec. Treatment of THP-1 cells by Ven did not induce a change in HLA Class I expression. For Class II, IFN-γ or Dec increased HLA-DR, -DQ and -DP expression in comparison to untreated cells (Figure 1). IFN-γ induced greater HLA-DR expression compared to Dec (an increase of 2.3-fold and 1.5-fold, respectively), and both stimulated similar increases in HLA-DQ (increases of 1.5-fold and 1.4-fold, respectively) & -DP (increases of 1.9-fold and 1.5-fold, respectively). However, treatment of cells with either Aza or Ven did not lead to changes in HLA Class II expression. Discussion Previous studies have illustrated the ability of IFN-γ to induce HLA Class II expression in THP-1 cells, however, data for Dec to induce HLA Class II expression was unconfirmed. We report differences in the degree to which IFN-γ and Dec are capable of stimulating HLA-DR with IFN-γ being more potent. The inability of Aza to induce HLA Class II expression in THP-1 cells may be related to the differing drug activating pathways of the two HMAs. Indeed, there are conflicting reports as to whether Aza can stimulate HLA Class II expression. Though Ven treatment of THP-1 cells did not impact HLA expression, because it is given with HMAs, it remains to be seen what effect these drugs may have on HLA expression when administered together. Additional studies to confirm these observations in patient-derived AML blasts are ongoing. Conclusion We report that HMAs increased expression of HLA-A, -B, & -C loci and Dec but not Aza stimulated HLA-DR, -DQ, and -DP expression in THP-1 cells. Given these data, Dec may be superior in increasing HLA Class II expression post-HCT. Figure 1 Figure 1. Disclosures Marcucci: Abbvie: Other: Speaker and advisory scientific board meetings; Agios: Other: Speaker and advisory scientific board meetings; Novartis: Other: Speaker and advisory scientific board meetings. Al Malki: Neximmune: Consultancy; CareDx: Consultancy; Jazz Pharmaceuticals, Inc.: Consultancy; Rigel Pharma: Consultancy; Hansa Biopharma: Consultancy.

scholarly journals Class II HLA Epitope Level Mismatch Can Predict Chronic Graft-Versus-Host Disease and Survival Following Haploidentical Transplant Using Post-Transplant Cyclophosphamide

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 311-311
Author(s):  
Scott R Solomon ◽  
Michael T Aubrey ◽  
Cheri Anobile ◽  
Xu Zhang ◽  
Brian M Freed ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Hla Class I ◽  
Class Ii ◽  
Class I ◽  
Transplant Outcome ◽  
Graft Versus Host ◽  
Hla Dr ◽  
Hla Dq ◽  
The Impact

Abstract Post-transplant cyclophosphamide (PTCy) has improved the outcomes and expanded the use of haploidentical hematopoietic cell transplantation (haplo-HCT). Unlike many other allogeneic HCT settings, the impact of HLA disparity on graft-versus-host disease (GVHD) and transplant outcome in this setting remains unclear. HLAMatchmaker is a computer algorithm that assesses HLA compatibility at the structural level by determining what and how many functional epitopes (eplets), defined as patches of polymorphic residues within a radius of 3.0-3.5 Ångstroms, are shared between donor and recipient. It has been useful in the identification of acceptable mismatches (mm) for alloimmunized kidney transplant candidates. In order to determine the effects of HLA class I (HLA-A, B, C) and II (HLA-DR, DQ, DP) epitope mm on transplant outcome, we retrospectively analyzed 208 consecutive donor-recipient pairs receiving haplo-HCT with PTCy for hematologic malignancy. The impact of epitope mm (GVH direction) on GVHD and survival endpoints was evaluated by Cox multivariate analysis (MVA), controlling for other significant patient, donor and transplant-related factors. Median (range) recipient and donor age was 52 (19-75) and 38 (15-73) years respectively. Patients were transplanted for AML (34%), MDS/MPS/CML (20%), ALL (17%), NHL/HD/CLL (25%). PBSC was used as the stem cell source in 66% of patients, and conditioning intensity was myeloablative in 41%. The donor was a child, sibling, or parent in 47%, 38%, and 14% respectively. Median (range) follow-up for surviving patients was 33 (7-130) months. HLA class I epitope mm had no effect on GVHD or survival. In contrast, increased HLA class II epitope mm (>16) was significantly correlated to an increased frequency of chronic GVHD (figure 1). In MVA, higher degree of class II epitope mm was associated with chronic GVHD, total (HR 1.91, p=0.012) and moderate-to-severe (HR 2.37, p=0.006). The positive effect of increased class II epitope mm on chronic GVHD was driven mostly by HLA-DQ epitope mm (HR 1.7 for >7 vs. ≤7, p=0.047) with a non-significant contribution from HLA-DP (HR 1.36 for >2 vs. ≤2, p=0.24). In contrast, increased HLA-DR epitope mm had a protective effect on chronic GVHD (HR 0.52 for >7 vs. ≤7, p=0.021). Epitope mm was not significantly associated with acute GVHD, grade 2-4 or 3-4. There was also no effect of allele-level mm at any HLA loci on acute or chronic GVHD. We next tested the impact of class I and II epitope mm on survival, including the individual impact of HLA-DR, -DQ and -DP epitope mm. Although class I epitope mm had no impact in univariate analysis, a higher number of class II epitope mm (>16) was correlated with better overall survival and the effect was primarily driven by HLA-DQ epitope mm (figure 2). To better assess the impact of class II epitope mm on survival, we analyzed this variable in the context of a previously published MVA (Solomon et al. Biol Blood Marrow Transplant. 2018;24:789-798). Controlling for other significant variables (age, race, CMV status, donor relationship, HLA-DR mm, nonpermissive HLA-DP mm, KIR receptor-ligand mm and KIR haplotype), only increased HLA-DQ epitope mm (>7) was independently associated with decreased non-relapse (HR 0.34, p=0.021) and overall mortality (HR 0.60, p=0.039). These results indicate a significant effect of class II epitope mm on chronic GVHD and survival following haplo-HCT with PTCy. Higher level of class II epitope mm and HLA-DQ epitope mm is associated with increased chronic GVHD incidence, whereas HLA-DR epitope mm is protective. Higher HLA-DQ epitope mm is independently associated with better survival, when controlling for the presence of HLA-DR allele-level mm or a nonpermissive HLA-DP mm, which have been shown previously to improve survival. Class II HLA epitope level matching provides important prognostic information in the setting of haplo-HCT and PTCy, which is not reflected by conventional allele-level matching. Disclosures Solh: Amgen: Speakers Bureau; Celgene: Speakers Bureau; ADC Therapeutics: Research Funding.

scholarly journals HLA CLASS I AND CLASS II ASSOCIATIONS IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA 91

1997 ◽  
Vol 41 (5) ◽  
pp. 761-761
Author(s):  
N Constantinidou ◽  
S Polychronopoulou ◽  
P Georgi ◽  
J P Panagiotou ◽  
S Haidas
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Hla Class I ◽  
Class Ii ◽  
Class I ◽  
Childhood Acute Lymphoblastic Leukemia

scholarly journals A Study in the Clinical Characteristics of Stenotrophomonas Maltophilia Bacteremia in Hematological Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4631-4631
Author(s):  
Haiyan Bao ◽  
Jia Chen ◽  
Xiaojin Wu ◽  
Xiao Ma ◽  
Chengcheng Fu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Respiratory Failure ◽  
Stenotrophomonas Maltophilia ◽  
Clinical Characteristics ◽  
Univariate Analysis ◽  
P Value ◽  
Hematological Diseases ◽  
Factors Associated

Abstract Introduction: Stenotrophomonas maltophilia is an important nosocomial pathogen, particularly in immunocompromised patients, especially in patients with hematologic diseases. Methods: We reviewed the clinical characteristics and prognosis of patients with S. maltophilia bacteremia over a five-year period from January 2010 to December 2014. Species identification was performed using the automated Vitek 2 compact system (bioMe rieux). Results: The incidence of S. maltophilia bacteremia was 25.1 per 10 000 admissions in our study. Thirty-four patients (median age: 34 years; 64.7% males) with S. maltophilia bacteremia were analyzed. The S. maltophilia bacteremia related 30-day mortality was 44.1%. Risk factors associated with mortality in patients with S. maltophilia infection in the univariate and multivariate analysis were represented in Tables I and II. In the univariate analysis, risk factors included T>39.0¡æ, septic shock, respiratory failure and non-remission after treatment for primary hematological diseases (P <0.05). In the multivariate analysis, respiratory failure and non-remission status after treatment forhematological diseases were independent prognostic factors for mortality. In vitro susceptibility was higher to ciprofloxacin(82.4%), ceftazidime(70.6%), sulbactam and cefoperazone(58.8%), which was shown in Table III. Conclusion: Combination regimens with ciprofloxacin and ceftazidime, or sulbactam and cefoperazone could be alternative treatment. Novel antibiotics are required for treatment of S. maltophilia infection, as well as infection control practices of environmental reserves, rapid detection of pathogens, risk stratification strategy and appropriate treatment for primary hematologic malignancies, which might conjointly contribute to better survival outcome of S. maltophilia bacteremia. Univariate analysis of prognostic factors associated with mortality from S. maltophilia bacteremia Table 1. Factor Mortality HR 95%CI P-value Withfactor Withoutfactor T>39.0¡æ 75% 16.7% 2.490 1.318-4.704 0.005 Septic shock 90.0% 25.0% 2.544 1.473-4.393 0.001 Respiratory failure 100% 20.8% 4.672 2.366-9.225 0.000 Treatment outcome for hematological diseases Remission 10.0% 85.7% 0.247 0.116-0.526 0.000 HR, hazard ratio; CI, confidence interval; HSCT, Hematopoietic stem cell transplantation Table 2. Multivariate analysis of prognostic factors associated with mortality from S. maltophilia bacteremia Factor HR 95%CI P-value Respiratory failure 2.688 1.297-5.569 0.008 Remission after treatment for hematological diseases 0.367 0.153-0.879 0.025 HR, hazard ratio; CI, confidence interval Table 3. Susceptibility pattern of the 34 patients with Stenotrophomonas maltophilia bacteremia Antimicrobial agents S (%) I (%) Ceftazidime 24(70.6%) 1(2.9%) Cefoperazone 19(44.1%) 6(17.6%) Sulbactam and Cefoperazone 20(58.8%) 5(14.7%) Piperacillin 7(20.6%) 6(17.6%) Piperacillin-Tazobactam 11(32.3%) 7(20.6%) Amikacin 6(17.6%) 0(0%) Ciprofloxacin 28(82.4%) 1(2.9%) S, susceptible; I, intermediately susceptible. Disclosures No relevant conflicts of interest to declare.

Abstract 16546: Pre-Pregnancy Body Mass Index and Risk of Peripartum Cardiomyopathy and Heart Failure in the Years Following Delivery

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yuliya Mints ◽  
Asya Lyass ◽  
Michelle D Schmiegelow ◽  
morten schou ◽  
Gunnar H Gislason ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Body Mass Index ◽  
Body Mass ◽  
Class Ii ◽  
Elevated Risk ◽  
Peripartum Cardiomyopathy ◽  
Class I ◽  
Increased Risk

Introduction: Peripartum cardiomyopathy (PPCM) is a form of systolic heart failure that occurs during pregnancy or in the early post-partum period. Obesity is known to be associated with other forms of heart failure in young adults, however it is unclear if it is also a risk factor for the development of PPCM. Objectives: To investigate the association of body mass index (BMI) with PPCM and heart failure in the years following childbirth. Methods: We conducted a retrospective review of pregnant women in the Danish National Patient Registry between 2004 - 2017. Baseline characteristics and other risk factors were obtained at the first prenatal visit (occurring at 8-11 weeks post-conception). Women were followed until the end of the study period, emigration, or death. Logistic regression was performed, adjusting for age as well as other known risk factors for PPCM. Cox proportional hazards analysis was used to assess the long-term risk of development of heart failure. Results: There were 403,820 pregnancies evaluated in 300,892 women, with an average age of 29 years. The average BMI was 24.4 kg/m2, with 21.6% classified as overweight (BMI 25 - 30 kg/m2) and 12.8% as obese (BMI > 30 kg/m2). The rate of PPCM was 0.1 per 1,000 in normal weight and overweight groups, and 0.3 per 1,000 in the obese women. After adjustment for age, ethnicity, smoking status, gestational diabetes, and presence of preeclampsia, there was a statistically significant increased risk of the development of PPCM up to 6 months after childbirth in patients who had class I (odds ratio [OR] 2.25, 95% CI 1.08-4.68) but not class II/III obesity (OR 1.63, 95% CI 0.60-4.43). This elevated risk persisted during long term follow up, with hazard ratios of 2.43 (95% CI 1.55 - 3.80) in women with class I obesity and 3.20 (95% CI 1.93 - 5.30) in women with class II/III obesity. Conclusions: High early pregnancy BMI is associated with elevated risk of development of peripartum cardiomyopathy even after adjustment for traditional risk factors. This risk of heart failure persists for several years after childbirth.

Clinical Experience of Transfusion of Plasma from HLA Immunized Donors

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4317-4317
Author(s):  
Fleur M Aung ◽  
Benjamin Lichtiger
Keyword(s):  
Whole Blood ◽  
Blood Donors ◽  
Hla Class I ◽  
Class Ii ◽  
Hla Class Ii ◽  
Biologically Active ◽  
Class I ◽  
Antibody Testing ◽  
Hla Antibodies ◽  
Male Donor

Abstract Transfusion-related acute lung injury (TRALI) is a serious complication of plasma-containing blood components. Studies have implicated HLA antibodies along with biologically active lipids in stored blood in the pathogenesis of TRALI. We reviewed the HLA Antibody testing of our whole blood donors during a three month period who were tested for HLA Class I and HLA Class II antibodies by the DONORSCREEN-HLA Class I and Class II ELISA from GTI Diagnostics @ Waukesha, WI. The testing for HLA Antibodies in our donors was implemented as both HLA Class I and HLA Class II antibodies have been implicated in TRALI. The goal was to quarantine the plasma from these donors in order to reduce the exposure to patients to plasma from HLA Immunized Donors. Of 4056 whole blood donors, there were twenty-two donors of which 21 female and one male who tested positive for either HLA Class I or HLA Class II antibodies whose plasma was transfused. Of the twenty two donors, twenty one were females and one was male. Of the twenty one females, fifteen tested positive for HLA Class I antibodies and seven tested positive for HLA Class II antibodies. The single male donor tested positive for HLA Class II antibodies. The cause of the HLA immunization of these donors was unknown (as to whether they were caused by multiparity or blood transfusions). The plasma from the HLA Immunized female donors were transfused to ten female patients and eleven male patients. The plasma from the male donor was transfused to a male patient. All of the plasma from the HLA immunized donors was pooled with other plasma products in pools ranging from three to eight. All of the plasma products were irradiated and transfused via Fenwal Sepacell Reduction Filter for Red cells and all of the patients were premedicated prior to transfusion. One male and one female patient received plasma on two occasions from two donors both of whom were positive for HLA Class I antibodies. The twenty two patients consisted of four with hematological malignancies, one with a lymphoid malignancy and seventeen with malignancies of solid organs. Three of the patients had received an autologous transplant and one had received an allogeneic unrelated transplant. None of the patients had received IVIG therapy. The transfusions reactions reported for the three months of this review was also reviewed. None of the patient that received the HLA immunized plasma products was reported to have suffered a transfusion reaction. Although we did not meet our goal of reserving 100% of our plasma products from HLA immunized donors as recovered plasma, we discovered that the plasma products that were transfused from the HLA immunized donors were not associated with transfusion reactions in our patient population. The reason for not meeting our goal was the test results for the HLA Class I and HLA Class II antibodies were received after the plasma products were released for transfusion, due to logistical limitations in the performance of the testing. Although the number is small, we feel that the results may be significant in light of the current thinking of accepting only male donors for plasma products.

scholarly journals Class I and class II anti-hla antibodies after implantation of cryopreserved allograft material in pediatric patients

2000 ◽  
Vol 119 (2) ◽  
pp. 324-330 ◽  
Author(s):  
John A. Hawkins ◽  
John P. Breinholt ◽  
Linda M. Lambert ◽  
Thomas C. Fuller ◽  
Tracie Profaizer ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Class Ii ◽  
Class I ◽  
Hla Antibodies

scholarly journals Risk factors associated with the development of moderate to severe chronic graft-versus-host disease after non-myeloablative conditioning allogeneic stem cell transplantation in patients with AML or MDS

Human Cell ◽  
2019 ◽  
Vol 33 (1) ◽  
pp. 243-251 ◽  
Author(s):  
Laurence M. C. Kok ◽  
Laura Bungener ◽  
Geertruida H. de Bock ◽  
Anouschka Biswana ◽  
Geertiena van der Wal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Hla Antibodies ◽  
Host Disease ◽  
Graft Versus Host ◽  
Factors Associated

AbstractModerate to severe chronic graft-versus-host disease (cGVHD) is associated with high morbidity, hospital dependency and poor quality of life. In this study, we analyzed a well-defined consecutive series of 98 patients with acute myelogenous leukemia/myelodysplastic syndrome (AML/MDS) who received allogeneic stem cell transplantation with non-myeloablative (NMA) conditioning to determine risk factors associated with the severity of cGVHD. cGVHD was defined according to the 2005 National Institute of Health consensus criteria. Transfusions before transplantation, presence of HLA antibodies, composition of the graft (CD3+, CD19+, CD34+ cells), sibling or matched unrelated donor, female donor to male recipient, CMV serology and the development of acute GVHD (aGVHD), were considered potential risk factors. Multivariate Cox regression analysis identified the number of CD19+ 106/kg (HR 2.79; 95% CI 1.35–5.74), CD3+ 106/kg (HR 2.18; 95% CI 1.04–4.59) infused cells and the presence of patient HLA antibodies before transplantation (HR 2.34; CI 1.11–4.95) as significant risk factors for the development of moderate to severe cGVHD. In summary, we identified in a small, but well-defined cohort, 3 risk factors associated with the severity of cGVHD that should be validated in a larger multi-center study.

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