Graft-versus-host disease (GVHD)-specific survival and duration of systemic immunosuppressive treatment in patients who developed chronic GVHD following allogeneic haematopoietic cell transplantation

2003 ◽  
Vol 122 (4) ◽  
pp. 637-644 ◽  
Author(s):  
Jung-Hee Lee ◽  
Je-Hwan Lee ◽  
Seong-Jun Choi ◽  
Shin Kim ◽  
Miee Seol ◽  
...  
Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 755-755
Author(s):  
Olga Sala-Torra ◽  
Paul J. Martin ◽  
Barry Storer ◽  
Mohamed Sorror ◽  
Rainer F. Storb ◽  
...  

Abstract We have previously described serious graft-versus-host disease (GVHD) as a highly undesirable outcome after allogeneic hematopoietic cell transplantation (HCT). Serious GVHD encompasses death, lengthy hospitalization, major disability, or recurrent major infections related to either acute or chronic GVHD. In a previous study, we found a 25% incidence of serious GVHD among 171 consecutive patients who had HCT after non-myeloablative (NMA) conditioning between January 1998 and May 2002. To put this observation into perspective, we applied the same criteria for serious GVHD in a cohort of 264 consecutive patients who had HCT after myeloablative (MA) conditioning during the same period of time and compared results with those of the previous study. The overall incidence of serious GVHD was 17% (44/264) in the MA group, compared to 25% (43/171) in the NMA group. There were no statistically significant differences in the incidence of grades III–IV GVHD, extensive chronic GVHD or nonrelapse mortality between the two groups (Table). Patients in the NMA group were older and had higher comorbidity scores than those in the MA group. In the univariate analysis, the hazard ratio (HR) of serious GVHD for the NMA group compared to the MA group was 1.71 (95% C.I., 1.1–2.6) (p = 0.01). After adjusting for patient age, patient and donor gender, donor type, HLA-mismatch, aggressive versus indolent malignancy at HCT, remission versus relapse at HCT, myeloid versus non–myeloid malignancy, HCT co–morbidity index, and prior donor lymphocyte infusion, the HR of serious GVHD was 1.50 (95% C.I., 0.8–2.7) (p = 0.17). After censoring for recurrent or progressive malignancy after HCT, the cumulative incidence of serious GVHD at 3 years was 21% for the NMA group and 14% for the MA group, and the HR was 1.33 (95% C.I., 0.7–2.6) (p = 0.40). Reasons for categorization of GVHD as serious (i.e., death, lengthy hospitalization, major disability, or recurrent major infections) were similar between the MA and NMA cohorts. Among the 44 patients with serious GVHD in the MA group, 19 (43%) had serious acute GVHD, and 25 (57%) had serious chronic GVHD. Among the 43 patients with serious GVHD in the NMA group, 20 (46%) had serious acute GVHD, and 30 (70%) had serious chronic GVHD. Among the 264 MA patients, 28 (11%) had grade III–IV acute GVHD and 147 (56%) had extensive chronic GVHD that did not meet the criteria for serious GVHD, compared to 7 (4%) and 84 (49%) of the 171 NMA patients, respectively. We conclude that the type of pretransplant conditioning regimen does not have a large effect on the incidence of serious GVHD after HCT. Assessment of serious GVHD provides additional useful information to acute GVHD grades and the classification of limited and extensive chronic GVHD in describing overall GVHD-related outcomes after HCT. MA NMA Outcome, n (%) n = 264 n = 171 Serious GVHD 44 (17) 43 (25) Grades III–IV acute GVHD 54 (20) 27 (16) Extensive chronic GVHD 174 (66) 114 (68) 2-year nonrelapse mortality 66 (25) 43 (25)


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4534-4534
Author(s):  
Michael Koldehoff ◽  
Ahmet H Elmaagacli ◽  
Reinhild Klein ◽  
Dietrich Beelen

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.


Blood ◽  
2016 ◽  
Vol 127 (11) ◽  
pp. 1502-1508 ◽  
Author(s):  
Marco Mielcarek ◽  
Terry Furlong ◽  
Paul V. O’Donnell ◽  
Barry E. Storer ◽  
Jeannine S. McCune ◽  
...  

Key Points With conventional immunosuppression, the incidence of chronic GVHD is higher after transplantation of mobilized blood compared with marrow. Administration of cyclophosphamide after mobilized blood cell transplantation is associated with a low incidence of chronic GVHD.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1238-1238
Author(s):  
Susanne Auffermann-Gretzinger ◽  
Lars Eger ◽  
Martin Bornhaeuser ◽  
Christian Thiede ◽  
Knuth Schaekel ◽  
...  

Abstract Both number and origin of dendritic cells (DC) in the blood have been associated with acute graft-versus-host disease (aGvHD), graft-verus-leukemia effect, relapse and graft failure after human allogeneic haematopoietic cell transplantation (aHCT). Aim of this study was the systematic simultaneous investigation of skin and blood DC subtypes, the analysis of their host/recipient origin after HCT and the correlation of DC kinetics with treatment, outcome and incidence of aGVD and its treatment in 31 recipients of allogeneic HCT. Epidermal shave biopsies and peripheral blood samples were collected from patients pre and at defined time points following aHCT, DC from skin and blood isolated and examined by FACS and quantitative PCR for Short Tandem Repeat markers. A significant reduction in number of skin and blood DC subtypes was observed already before start of conditioning chemotherapy in patients compared to healthy volunteers. A majority of donor derived epidermal Langerhans Cells (median 95%, range 53–100%) and also dermal DC (median 94%, range 39–100%) was found in all examined patients even early after transplant independent from chemotherapy regimen, graft, occurrence of skin GvHD or time point after transplantation. Numbers of both skin DC subsets remained low for months post HCT. Reconstitution kinetics of CD 11c+ preDC1 and CD 123+ preDC2 blood DC were similar to each other and pre transplant numbers were reached again around day +112 post transplant. Recipients of grafts containing higher T cell numbers had lower preDC1 counts on day +28. PreDC2 reconstitution was negatively affected by steroid treatment. Patients with aGvHD tended to have more preDC1 on day +28 and lower numbers of both preDC subsets on day 56 post transplant. Residual host blood DC were rare at all time points (median &lt;3% at all investigated timepoints range 2–97%). The kinetics of DC reconstitution at different sites might become an important diagnostic tool to predict the occurrence of acute and chronic GvHD and to monitor the efficacy of prophylactic and therapeutic interventions.


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