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.

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

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.

scholarly journals Mast Cell Involvement in Fibrosis in Chronic Graft-Versus-Host Disease

2021 ◽  
Vol 22 (5) ◽  
pp. 2385
Author(s):  
Ethan Strattan ◽  
Gerhard Carl Hildebrandt
Keyword(s):  
Wound Healing ◽  
Mast Cell ◽  
Mast Cells ◽  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Fibrotic Disease ◽  
Acute Leukemias ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Allogeneic hematopoietic stem cell transplantation (HSCT) is most commonly a treatment for inborn defects of hematopoiesis or acute leukemias. Widespread use of HSCT, a potentially curative therapy, is hampered by onset of graft-versus-host disease (GVHD), classified as either acute or chronic GVHD. While the pathology of acute GVHD is better understood, factors driving GVHD at the cellular and molecular level are less clear. Mast cells are an arm of the immune system that are known for atopic disease. However, studies have demonstrated that they can play important roles in tissue homeostasis and wound healing, and mast cell dysregulation can lead to fibrotic disease. Interestingly, in chronic GVHD, aberrant wound healing mechanisms lead to pathological fibrosis, but the cellular etiology driving this is not well-understood, although some studies have implicated mast cells. Given this novel role, we here review the literature for studies of mast cell involvement in the context of chronic GVHD. While there are few publications on this topic, the papers excellently characterized a niche for mast cells in chronic GVHD. These findings may be extended to other fibrosing diseases in order to better target mast cells or their mediators for treatment of fibrotic disease.

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

scholarly journals Acute and chronic graft versus host disease after hematopoietic stem cell transplant

JBMTCT ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 53-66
Author(s):  
Vaneuza A. M. Funke ◽  
Maria Claudia Rodrigues Moreira ◽  
Afonso Celso Vigorito
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Primary Therapy ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Graft versus host disease is one of the main complications of Hematopoietic stem cell, in­volving about 50% to 80% of the patients. Acute GVHD clinical manifestations and therapy is discussed, as well as new NIH criteria for the diagnosis and classification of chronic GVHD. Therapy for both refractory chronic and acute GVHD is an important field of discussion once there is no superiority for the majority of the agents after primary therapy has failed. Hence, this review is meant to be a useful tool of consultation for clinicians who are dealing with this complex complication.

scholarly journals Ruxolutinib in Steroid Refractory Graft Versus Host Disease (SR-GVHD): Systemic Literature Review

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5682-5682
Author(s):  
Mostafa F. Mohammed Saleh ◽  
Shahrukh K. Hashmi
Keyword(s):  
Adverse Events ◽  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Infectious Complications ◽  
Systemic Review ◽  
Close Monitoring ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Steroid Refractory

Background: Graft versus host disease (GVHD) is a main cause of morbidity and mortality in patients having undergone allogeneic hematopoietic stem cell transplantation (HSCT). About 30-40% of patients have steroid‐refractory GVHD (SR‐GVHD) after the first‐line use of high doses of corticosteroids with a poor prognosis .Ruxolitinib is a promising treatment for SR-GVHD. However, data regarding optimum dosing, response rates and associated adverse events are scarce. Herein, we provide the first systemic review of literature for the use ruxolutinib in GVHD. Methods: A Medline (PubMed), google scholar, OVID and Cochrane Database of Systematic Reviews search using key words "Ruxolutinib and GVHD", "Ruxolutinib and SR-GVHD" was undertaken in June 2019. Only peer reviewed databases were searched and search was restricted to human studies of acute and chronic GVHD only. Results: 16 publications, as listed in Table 1. Only one was a prospective trial, all others were retrospective studies, case series (5), and case reports (2). Overall response, ranged 45% - 100%, complete response was noted in 5.2% -80% patients. Time to response was variable from 1-12 weeks. Cytopenias and infectious complications were frequently reported with dose reduction or interruptions needed in most studies. Maintained responses were reported in a small proportion after ruxolutinib discontinuation. Conclusion Ruxolutinib has promising efficacy in SR-GVHD , however cytopenias and infectious complications reported frequently mandate close monitoring. Results of ongoing prospective trials could provide answers for optimum dosing and response assessment, and management of related adverse events. Table Disclosures No relevant conflicts of interest to declare.

scholarly journals Uva1 Phototherapy in the Management of Sclerodermatous Graft-Versus-Host Disease (Gvhd): a report of two cases / Uva1 fototerapija u lečenju sklerodermatoznog oblika hronične Gvhd: Prikaz dva slučaja

2009 ◽  
Vol 1 (4) ◽  
pp. 147-152 ◽  
Author(s):  
Hiva Fassihi ◽  
Kamran Iqbal ◽  
Trish Garibaldinos ◽  
Robert Sarkany ◽  
Julia Scarisbrick ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Skin Diseases ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Allogeneic Hsct ◽  
Graft Versus Host ◽  
Uva1 Phototherapy ◽  
Matched Sibling

Abstract Chronic graft-versus-host disease (GVHD) is a frequent complication after allogeneic hematopoietic stem cell transplantation (HSCT). Approximately 10% of patients with GVHD develop sclerodermatous changes, which can cause significant morbidity and are often refractory to standard systemic immunosuppression. We present two cases of sclerodermatous GVHD. The first is a 39-year-old man, who had a matched sibling, undergoing allogeneic HSCT for severe aplastic anemia. The second patient is a 7-year-old boy, who had an allogeneic HSCT from his HLA-identical mother for acute myeloid leukemia (AML). Both patients presented with widespread sclerotic changes, resulting in joint contractures and significant functional difficulties. Studies have shown UVA1 phototherapy to be a promising and well tolerated treatment modality in patients with sclerotic skin diseases. Both of our patients were treated with UVA1, which resulted in a significant skin softening, improvement in joint mobility and quality of life. UVA1 appears to be an effective treatment for refractory sclerodermatous GVHD; however, long-term clinical studies in larger groups are needed to accurately evaluate its efficacy and safety.

scholarly journals Methotrexate for the Treatment of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Amr Nassar ◽  
Ghada Elgohary ◽  
Tusneem Elhassan ◽  
Zubeir Nurgat ◽  
Said Y. Mohamed ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Corticosteroid Treatment ◽  
Complete Response ◽  
Primary Treatment ◽  
Lower Grade ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Pooled Data

Glucocorticoids have been the primary treatment of graft-versus-host disease (GVHD) over the past decade. Complete responses to steroid therapy are usually expected in almost one-third of aGVHD cases and partial response is anticipated in another one-third of patients. However, for those patients not responding to corticosteroid treatment, there is no standard second-line therapy for acute or chronic GVHD. Methotrexate (MTX) for treatment of steroid refractory GVHD has been evaluated in a number of studies. Results from peer-reviewed original articles were identified and the pooled data analyzed. Despite several limitations in data collection and analysis, weekly administration of methotrexate at a median dose of 7.5 mg/m2seems to be safe with minimal toxicities in the context of both aGVHD and cGVHD treatments. The observed overall response (OR) in patients with aGVHD to MTX treatment in the published studies was 69.9%, with complete response (CR) in 59.2% and PR in 10.6%. In cGVHD the OR was 77.6%, with CR reported in 49.6% and PR in 28% of patients. Predictors of better responses were lower grade GVHD, cutaneous involvement, and isolated organ involvement. MTX as a steroid sparing agent might reduce long-term complications and improve the quality of life of GVHD affected individuals.

Single Nucleotide Polymorphism (SNP) Approach of Multiple Candidate Pathways Predicting the Risk of Acute / Chronic Graft-Versus-Host Disease or Transplant Outcomes Following Allogeneic Hematopoietic Stem Cell Transplantation: Potential Involvement of Nuclear Factor Kappa-B (NFKB), Platelet-Derived Growth Factor (PDGF) and Transforming Growth Factor-Beta (TGF-β) Pathway with Chronic Graft-Versus-Host Disease Graft-Versus-Host Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2221-2221
Author(s):  
Dong Hwan (Dennis) Kim ◽  
Jina Yun ◽  
Jee Hyun Kong ◽  
Chul Won Jung ◽  
Ahmed Galal ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Growth Factor ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Transforming Growth Factor ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Cytokine Activation

Abstract Abstract 2221 Poster Board II-198 Background: Acute graft-versus-host disease (GVHD) was known to be involved in the Th1 cytokine activation and alloreactive T-cell cytotoxicity, while the pathogenesis of chronic GVHD is yet revealed fully although in which Th2 cytokine activation or transforming growth factor (TGF) mediated pathway was suggested to be involved. The current study is a hypothesis generating study in order to identify potential predictive surrogate associated with the risk of acute or chronic GVHD in addition with transplant outcomes after allogeneic hematopoietic stem cell transplantation (HSCT). Methods: The current study was performed to identify genetic surrogates predicting the risk of acute / chronic GVHD, relapse free survival, non-relapse mortality and overall survival in 394 pairs transplanted at the Princess Margaret Hospital, Toronto, ON, Canada. In addition, the predictive markers for organ specific incidence of acute / chronic GVHD were also evaluated (i.e. for skin/liver/gut acute GVHD or skin, eye, oral, lung or liver chronic GVHD). Total of 261 single nucleotide polymorphisms (SNPs) in 56 genes were determined for donor/recipients' genotypes using MALDI-TOF based platform, involving in the pathways of 1) cytokines (i.e. IL1A, IL1B and its receptor, IL1R1, IL2 & IL2RA, IL4 & IL4R, IL6 & IL6R, IL8, IL10 & IL10RA, RB, IL12A/BandIL12RB1, IFNG & IFNGR1/2, TNFTI/II/II), 2) NFKB (NFKB1/2/A, NFKBIA/B, IKB, IKK1, IKBKB, RelB), 3) apoptosis (FAS, TRAIL & TRAILR1), 4) endothelium nitric oxide regulation (EDN1, NOS1/2A/3), 5) PDGF (PDGFB/C/D & PDGFRA/B), 6) TGF-β (TGFB1/2 & TGFBR1/2/3, TGFRB1), 7) Toll-like receptor (TLR4/5), 8) NOD2/CARD15 and 9) prostaglandin-endoperoxide synthase (PTGS1/2). The candidate genotypes have been selected by choosing the SNPs in non-synonymous SNPs in exon region with minor allele frequency of > 0.05 to 0.1. Results: Followings are the lists of recipients' and donors' genotypes with p-value<0.05 thus associating with clinical outcomes following allogeneic HSCT: In summary, the risk of chronic GVHD was significantly associated with SNP of the genes involved in the pathway of NFKB, PDGF, TGF-β, and some of cytokines (esp. type II, IL6 & IL4), while that of acute GVHD associates with the genotypes in the pathway of TNF and apoptosis. In addition, survival after allogeneic transplantation was associated with the genotypes in NOS (nitric oxide synthase, endothelial nitric oxide synthesis pathway), IL-2 and TGF pathway. Conclusion: Because of complex nature of GVHD pathogenesis, multiple candidate pathway SNPs has been explored targeting SNPs in the pathway of cytokines, NFKB, apoptosis, endothelium nitric oxide regulation, NOD2/CARD15, PDGF, PTGS1/2, TGF-β and TLR. Different involvements were noted of TGF-β, PDGF or NFKB with chronic GVHD versus TNF and apoptosis-associated SNPs with acute GVHD. Further study will help us to reach more clear conclusion which genotype is the predictor of the risk of GVHD. Disclosures: No relevant conflicts of interest to declare.

Incidence and Outcome of Auto/Alloimmune Hepatitis with Hepatic Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4534-4534
Author(s):  
Michael Koldehoff ◽  
Ahmet H Elmaagacli ◽  
Reinhild Klein ◽  
Dietrich Beelen
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Abstract Abstract 4534 Auto/alloimmune hepatitis (AIH) is an inflammatory liver disease characterized histological by a dense mononuclear cell infiltrate in the portal tract and serological by the presence of non-organ and liver-specific antibodies, high transaminases and increased levels of IgG. The relation between allogeneic hematopoietic stem cell transplantation (HSCT) and auto/alloimmune disease is complex. To examine this association, we retrospectively studied 1,636 allogeneic patients (median age 43, range 18–73 years) between May 1996 and December 2008. Among these patients, 311 (19%) developed hepatic graft-versus-host disease (GvHD) (162 pts had a hepatic GvHD of grade > II). We followed 25 patients (11 male, 14 female) in whom GvHD of the liver presented with marked elevation of serum aminotransferases, clinically resembling acute hepatitis and auto/antibodies characteristics for AIH. The median age at transplant was 35 (range, 18–54) years. Onset of liver dysfunction was at 286 days (range, 55–2766) after HSCT. Median peak serum was 312 (range 105–1750) U/L for alanine aminotransferase, 629 (133-2410) U/L for gamma-glutamyl transferase and 1.74 (0.5-23.4) mg/dl for bilirubin. The autoantibody profiles of AIH were 60% for anti-nuclear antibody, 44% for antibodies to liver-kidney microsomes, 24% for antibodies to smooth-muscle antigens, 28% for anti-mitochondrial antibody, 16% for antibodies to actin, 8% for antibodies to nucleoli, and 4% for other autoantibodies. AIH had a higher prevalence in younger and in female patients. AIH occurred in 92% in patients, who were transplanted with G-CSF mobilized and peripherally collected stem cells (PSC), but in only 8% in patients with bone marrow (BM) source (p<0.02), comparing all transplanted patients (1326 PSC, 310 BM). Stem cell grafts from matched sibling donor or matched unrelated donor were similar in the two groups. Acute GvHD of grade> II occurred more frequently in the groups with AIH (15/25 vs. 649/1636, p<0.002), and chronic GvHD (11 limited, 14 extensive) was ascertained in all AIH patients vs. 49.8% in all transplanted patients (p<0.0001). Three patients with AIH died from pulmonary bleeding, chronic GvHD, and relapse, whereas 22 patients with AIH are still alive (88%) at a median survival time of 2570 days. In conclusion, our evaluation confirms a strong association between G-CSF mobilized PSC, chronic GvHD and the development of AIH. Disclosures: No relevant conflicts of interest to declare.

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