BACKGROUNDAutoimmune hemolytic anemia (AIHA) is an uncommon complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) which has only been reported in a few cases. We here aimed to explore its mechanism.

METHODSWe retrospectively analyzed 296 patients who underwent allo-HSCT in our center from July 2010 to July 2012. Clinical manifestations were carefully reviewed and the response to currently available treatment approaches were evaluated. The survival and risk factors of AIHA patients after allo-HSCT were further analyzed.

RESULTSTwelve patients were diagnosed with AIHA at a median time of 100 days (15-720 days) after allo-HSCT. The incidence of AIHA after allo-HSCT was 4.1%. IgG antibody were detected in ten patients and IgM antibody in two patients. The two cold antibody AIHA patients had a better response to steroid corticoid only treatment and the ten warm antibody AIHA patients responded to corticosteroid treatment and adjustment of immunosuppressant therapy. Rituximab was shown to be effective for AIHA patients who failed conventional therapy. Survival analysis showed that the combination of AIHA in allo-HSCT patients hinted at poor survival. Cytomegalovirus (CMV) infection, graft-versus-host disease (GVHD) and histocompatibility leukocyte antigen (HLA) mismatch seemed to increase the risk of developing AIHA.

CONCLUSIONSPatients who develop AIHA after allo-HSCT have poor survival compared to non-AIHA patients. Possible risk factors of AIHA are CMV infection, GVHD, and HLA mismatch. Rituximab is likely to be the effective treatment choice for the refractory patients.

Adolescent ; Adrenal Cortex Hormones ; therapeutic use ; Adult ; Anemia, Hemolytic, Autoimmune ; diagnosis ; drug therapy ; etiology ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Child ; Child, Preschool ; Female ; Graft vs Host Disease ; diagnosis ; drug therapy ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Rituximab ; Transplantation, Homologous ; adverse effects ; Young Adult

This study was purposed to explore the correlation of regenerating Islet-derived 3-alpha(Reg3α) protein level in plasma with the diagnosis and prognosis of the gastrointestinal acute graft-versus-host disease (GI-aGVHD) after all-HSCT, 103 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) were observed in our hospital from December 2011 to December 2012. Peripheral blood samples were routinely collected at 9 d before allo-HSCT, 0 d, 14 d, 28 d after allo-HSCT as well as in aGVHD and at the 1 and 4 weeks after aGVHD therapy. The plasma concentrations of Reg3α were measured by using ELISA kit. The results indicated that among the 103 patients, 17 cases never developed aGVHD symptoms (no-aGVHD), 27 cases presented with non-aGVHD associated diarrhea, 10 cases presented with isolated skin aGVHD, 17 cases developed grades I-II GI-aGVHD, 32 cases with grades III-IV GI-aGVHD. The plasma concentrations of Reg3α in group of patients with GI-aGVHD and group of non-aGVHD diarrhea were 111.5 (54.7-180.2) and 23.9 (14.5-89.5) ng/ml respectively with significant difference (P < 0.001). The plasma concentrations of Reg3α in 17 patients of grades III-IV GI-aGVHD who experienced a complete or partial response and 7 patients who had no response to therapy at 4 weeks were 137.2(51.7-205.4) and 679.4(122.3-896.8) ng/ml respectively with the significant difference (P = 0.028). All of the patients who had no response to therapy died of aGVHD associated multiple organ failure. The area under the ROC curve was 0.902 when plasma concentration of Reg3α was set at 87.73 ng/ml. The sensitivity was 81.48% and the specificity was 82.86% when the critical value was used in diagnosis of grades III-IV GI-aGVHD. The probability of grades III-IV GI-aGVHD had statistical difference above and below 87.73 ng/ml after allo-HSCT (P < 0.001). It is concluded that the increase of plasma Reg3α level after transplantation suggests the incidence of grades III-IV GI-aGVHD. The high level of plasma Reg3α protein in patients with grades III-IV GI-aGVHD after the immunosuppressive treatment for four weeks indicates a poor prognosis. The plasma concentrations of Reg3α can be used as a specific biomarker of GI-aGVHD.
Adolescent ; Adult ; Antigens, Neoplasm ; blood ; Biomarkers, Tumor ; blood ; Female ; Graft vs Host Disease ; diagnosis ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Intestinal Diseases ; diagnosis ; etiology ; Lectins, C-Type ; blood ; Male ; Middle Aged ; Pancreatitis-Associated Proteins ; Plasma ; Prognosis ; Transplantation, Homologous ; Young Adult

Adolescent ; Adult ; Female ; Graft vs Host Disease ; diagnosis ; etiology ; prevention & control ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Risk Factors ; Young Adult

OBJECTIVETo analyze the specificity, sensitivity and receiver operating characteristic (ROC) curve of plasma elafin for diagnosis of skin acute graft-versus-host disease (aGVHD), and to explore its clinical diagnostic value.

METHODSIncidence of skin aGVHD from fifty-three patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) were observed prospectively in Guangdong General Hospital from Apr 2010 to Aug 2011. The plasma concentrations of elafin were detected by enzyme-linked immunosorbent assay (ELISA). Skin biopsies were taken from 28 patients with skin rash, and elafin expression in the skin was detected by immunohistochemistry. Positive expression was defined as significant staining of at 50% of the depth of the epidermis, excluding the granular cell layer and the acrosyringium.

RESULTSAmong 28 patients with skin rash, twenty-five were considered as skin aGVHD by clinical diagnosis, seventeen were confirmed as skin aGVHD by pathological biopsy. 11 cases were elafin positive by immunohistochemical staining. Elafin protein was overexpressed in aGVHD skin tissue (P = 0.001). Plasma concentrations of elafin were significantly higher in patients with skin aGVHD (positive) group than in those without skin aGVHD (negative) group (P = 0.005), among which there being no statistically significant difference in plasma elafin level between patients with grade I skin aGVHD group and negative group(P = 0.971), but being statistically significant difference compared patients with grade II-IV skin aGVHD group with those with grade I skin aGVHD group (P = 0.02) and with negative group (P = 0.008). Using the pathological diagnosis as the gold standard, the estimated specificity and the sensitivity of clinical diagnosis criteria were 27.3% and 100%, respectively, and those of tissue elafin protein level were 100% and 64.7%, respectively. The area under the ROC curve was 0.909 (0.797 - 1.021) when plasma concentrations of elafin was used in diagnosis of skin aGVHD. The sensitivity was 82.4% and the specificity was 81.8 % when the critical value was set at 1456.043 µg/L.

CONCLUSIONPlasma concentration of elafin is significantly higher at the onset of skin aGVHD. It can be used as biochemical marker of skin aGVHD and has higher value in diagnosis of skin aGVHD.

Adolescent ; Adult ; Elafin ; blood ; Female ; Graft vs Host Disease ; blood ; diagnosis ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; ROC Curve ; Sensitivity and Specificity ; Skin Diseases ; blood ; diagnosis ; etiology ; Young Adult

PURPOSE: This study was performed in order to evaluate the incidence and characteristics of cytomegalovirus (CMV) infection in children with acute leukemia according to donor source and graft type. MATERIALS AND METHODS: We retrospectively identified children with acute leukemia who had received allogeneic hematopoietic cell transplantation at Samsung Medical Center in Korea from October 1998 to December 2009. RESULTS: In total, 134 recipients were identified. The patients were classified into the following three groups: unrelated cord blood (CB, n=36), related bone marrow or peripheral blood stem cells (RD, n=41), and unrelated bone marrow or peripheral blood stem cells (UD, n=57). The 365-day cumulative incidence of CMV antigenemia was not significantly different among the three groups (CB 67% vs. RD 49% vs. UD 65%, p=0.17). However, CB recipients had the highest median value of peak antigenemia (CB 160/2x10(5) leukocytes vs. RD 7/2x10(5) leukocytes vs. UD 19/2x10(5) leukocytes, p<0.01) and the longest duration of CMV antigenemia than the other stem cell source recipients (CB 87 days vs. RD 17 days vs. UD 28 days, p<0.01). In addition, the 730-day cumulative incidence of CMV disease was the highest in the CB recipients (CB 36% vs. RD 2% vs. UD 5%, p<0.01). Thirteen CB recipients developed CMV disease, in which five of them had more than one organ involvement. Two patients, who were CB recipients, died of CMV pneumonia. CONCLUSION: This study suggests that CB recipients had both longer and higher cumulative incidences of CMV infection. Therefore, a more aggressive and effective strategy of CMV management should be considered in CB recipients.
Acyclovir/therapeutic use ; Adolescent ; Antiviral Agents/therapeutic use ; Child ; Child, Preschool ; Cyclosporine/therapeutic use ; Cytomegalovirus Infections/*diagnosis/drug therapy/etiology ; Female ; Graft vs Host Disease/diagnosis/drug therapy/etiology ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Immunosuppressive Agents/therapeutic use ; Infant ; Leukemia/therapy ; Male ; Retrospective Studies ; Young Adult

This study was purposed to investigate the clinical features and related factors influencing prognosis of patients with severe intestinal graft-versus-host disease (siGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). 710 patients received allo-HSCT in Beijing Dao-Pei hospital from Jan 2007 to Jan 2011 were enrolled in this study. A total of 34 patients with siGVHD out of 710 patients were analyzed retrospectively, and the univariate analysis for related factors influencing prognosis were carried out by using SPSS 19.0 software. The results showed that the incidence of siGVHD was 4.79%, its medium occurrence time was 29 (18 - 210) days after allo-HSCT. 18 out of 34 patients with siGVHD received colonoscopy, among them 6 patients were complicated with viral enteritis. The deep ulcers could be found under colonoscope. Histopathologic examination revealed the viral inclusion bodies or positive viral antigen. Methylprednisolone (MP), cyclosporine A (CsA) or tacrolimus combined CD25 monoclonal antibody and oral budesonide were used for treatment of siGVHD. 29 out of 34 cases achieved complete response (CR) with CR rate of 85.29%, overall survival rate was 58.82% (20/34). 9 out of 29 cases achieving CR died of other complications. The univariate analysis of the related factor indicated the hyperacute GVHD is the adverse factor influencing overall survival of patients with siGVHD. It is concluded that early colonoscopy is an effective way for definitive diagnosis of siGVHD. The combined treatment including MP, CsA or tacrolimus, CD25 monoclonal antibody and oral budesonide shows a significant curative effects. Intensive treatment of complications in late period of GVHD can enhance the overall survival rate.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Gastrointestinal Tract ; Graft vs Host Disease ; diagnosis ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

PURPOSE: In this study, we analyzed a cohort of children with chronic graft-versus-host disease (GvHD) according to the NIH consensus classification (NCC) in order to observe whether global assessment at diagnosis correlates with GvHD-specific endpoints. We then studied the clinical course of these patients, specifically with regards to episodes of GvHD exacerbation requiring treatment escalation. MATERIALS AND METHODS: Recipients of either allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT) from January 2006 to August 2008 at the Department of Pediatrics, The Catholic University of Korea were evaluated for chronic GvHD, which was diagnosed according to the NCC. The course of chronic GvHD in these patients was then followed. RESULTS: Of 59 evaluable patients, 23 developed chronic GvHD for a cumulative incidence of 39.3%. Upon multivariate analysis, previous acute GvHD (> or =grade II) had a significant impact on chronic GvHD incidence. With a median duration of systemic treatment for chronic GvHD of 501 days, no significant relationship was found between initial global severity of chronic GvHD and either duration of immunosuppressive treatment or final clinical response to treatment. Fifteen patients (65%) experienced at least one episode of chronic GvHD exacerbation during the period of follow-up, with a median of four exacerbations in the subgroup of patients who experienced such events. Lung GvHD resulted in the highest number of exacerbations per diagnosed patient, followed by oral GvHD. CONCLUSION: Analysis of this small cohort indicates that global assessment as proposed by the NCC may have limited correlations with GvHD-specific endpoints, possibly due to the favorable response of children to treatment.
Adolescent ; Bone Marrow Transplantation/adverse effects ; Child ; Child, Preschool ; Chronic Disease ; Cohort Studies ; Consensus Development Conferences, NIH as Topic ; Female ; Graft vs Host Disease/classification/*diagnosis/drug therapy/etiology ; Humans ; Immunosuppressive Agents/administration & dosage ; Infant ; Male ; National Institutes of Health (U.S.) ; Peripheral Blood Stem Cell Transplantation/adverse effects ; Prognosis ; Republic of Korea ; Risk Factors ; United States

This study was aimed to investigate the role of sequence similar matching (SSM) method in prediction of GVHD after HLA unmatched allogeneic hematopoietic stem cell transplantation (allo-HSCT). The data from 23 patients undergoing HLA unmatched allo-HSCT were analyzed and calculated by SSM method. The results showed that the incidence of acute and severe GVHD were significantly less in the allo-HSCT cases with total SSM value less than 55. In conclusion, the SSM method can be used to predict GVHD in the HLA-unmatched allogeneic hematopoietic stem cell transplantation.
Adolescent ; Adult ; Child ; Female ; Graft vs Host Disease ; diagnosis ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Histocompatibility Testing ; methods ; Humans ; Male ; Middle Aged ; Transplantation, Homologous ; adverse effects ; Young Adult

Chimerism testing permits early prediction and documentation of successful engraftment, and also facilitates detection of impending graft rejection. In this study, we serially monitored chimerism status by short tandem repeat-based PCR in nucleated cells (NC), T cells and natural killer (NK) cells after myeloablative allogeneic stem cell transplantation (SCT). Four patients with myeloid malignancies showed discrepant chimerism results among those three fractions. Three patients had mixed chimerism (MC) of donor/host T cells at a time point around the onset of chronic graft-versus-host disease (GVHD). In two patients with disease relapse, MC of NK cells preceded a morphological relapse or NK cells showed a higher percentage of patient cells compared to NC. Therefore, our study shows that chimerism analysis in lineage-specific cells might be useful in predicting clinical outcome after allogeneic SCT in certain patients.
Adult ; *Chimerism ; Graft vs Host Disease/*diagnosis/etiology ; Humans ; Killer Cells, Natural/cytology/immunology ; Male ; Microsatellite Repeats/*genetics ; Middle Aged ; Polymerase Chain Reaction ; Predictive Value of Tests ; Stem Cell Transplantation ; T-Lymphocytes/cytology/immunology ; Transplantation, Homologous

OBJECTIVETo analyze experimental results of Graft-versus-host disease (GVHD) after liver transplantation.

METHODS13 cases of GVHD out of the 1013 liver transplantation between 2002-2008 were analysed. Routine blood test, liver function and microorganisms test were done in all of the 13 cases, bone marrow test was done in 5 cases, liver pathological test was done in 5 cases, cytokines were analyzed in 4 cases, chimerism test was done in 6 cases.

RESULTSLeukocytes were reduced to various degree in all 13 cases, and were extremely low in 8 cases. Hematopoiesis was repressed in 4 cases. Normal liver function was found in 9 cases. Bacterium were found in blood, bile, wound secrete juice, excrement, phlegm of 10 cases. The pathological characteristics was in accordance with GVHD in 5 cases. The levels of IL-1 alpha, IL-1 beta, IL-2, IL-4 were low or undetectable. IL-10 was decreased in 4 cases but increased in 1 case. MCP-1, VEGF, IL-6, EGF, IL-8 were increasing or remained at high level during GVHD. TNF alpha was slightly increased. IFN gamma was only slightly changed before GVHD.

CONCLUSIONChimerism is a reliable but not unique evidence of GVHD.

Acute Disease ; Adult ; Aged ; Bacterial Infections ; etiology ; Bone Marrow Diseases ; blood ; etiology ; Bone Marrow Examination ; Cause of Death ; Chimerism ; Cytokines ; blood ; Female ; Graft vs Host Disease ; blood ; diagnosis ; etiology ; mortality ; Humans ; Interleukins ; blood ; metabolism ; Leukopenia ; blood ; etiology ; Liver Transplantation ; adverse effects ; Male ; Middle Aged ; Retrospective Studies ; Transplantation, Autologous ; Tumor Necrosis Factor-alpha ; metabolism