A coded histologic study of hepatic graft-versus-host disease after human bone marrow transplantation

Shulman, Howard M.; Sharma, Pankaj; Amos, D. B.; Fenster, Laura; McDonald, George B.

doi:10.1002/hep.1840080305

Cited by 166 publications

(91 citation statements)

References 33 publications

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“…Although liver biopsy is useful for diagnosis, 2 patients had markedly elevated ALT and AST levels but did not show the histology of lobular hepatitis, likely reflecting the imperfect correlation between liver biopsy and serum ALT and AST levels. 4,5 Therefore, we included marked (more than 10 times UNL) elevation of serum aminotransferase levels in the definition of hepatitic GVHD.…”

Section: Discussionmentioning

confidence: 99%

“…Typical liver GVHD is characterized by lymphocytic infiltration of small bile ducts with nuclear pleomorphism and epithelial cell dropout. 4,5 The extent of both apoptosis and dropout cells serves to distinguish acute liver GVHD from the other causes of liver dysfunction. 4 Recently, an unusual form of liver GVHD has been described.…”

Section: Introductionmentioning

confidence: 99%

“…4,5 The extent of both apoptosis and dropout cells serves to distinguish acute liver GVHD from the other causes of liver dysfunction. 4 Recently, an unusual form of liver GVHD has been described. Strasser et al 6 report their observations in 14 patients in whom chronic GVHD of the liver was accompanied by marked elevations of serum aminotransferase levels, clinically resembling acute viral hepatitis.…”

Section: Introductionmentioning

confidence: 99%

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Hepatitic variant of graft-versus-host disease after donor lymphocyte infusion

Akpek

Boitnott

Lee

et al. 2002

Blood

101

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Graft-versus-host disease (GVHD) of the liver is characterized by bile duct damage and portal lymphocytic infiltrate. We report acute hepatitislike presentation of GVHD after donor lymphocyte infusion (DLI). Between April 1998 and September 2001, 73 patients received 94 DLI treatments. Liver GVHD developed after DLI in 22 (30%) patients whose median age was 43 years (range, 21 to 61 years). Onset of liver dysfunction was at 35 days (range, 11 to 406 days) after DLI. Fifteen patients underwent liver biopsy, and the diagnosis of liver GVHD was confirmed in 13 (87%) patients. After viral hepatitis and recent drug exposure were excluded, 11 (50%) patients were given a diagnosis of a hepatitic variant of GVHD based on histologic evidence of lobular hepatitis (n ‫؍‬ 5), elevation of maximum serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level more than 10 times the upper normal limit (n ‫؍‬ 9), or both. There was a significant difference in maximum ALT (P ‫؍‬ .002) and AST (P ‫؍‬ .01) level between the hepatitic-variant and classical GVHD groups. GVHD progressed in 14 (64%) patients, and 10 patients died after a median follow-up of 221 days (range, 31-1284 days). These observations suggest that GVHD that occurs after DLI may have distinct clinical features. Hepatiticvariant GVHD should be considered in the differential diagnosis in DLI recipients with unexplained hepatitis. (Blood. 2002; 100:3903-3907)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hepatitic variant of graft-versus-host disease after donor lymphocyte infusion

Akpek

Boitnott

Lee

et al. 2002

Blood

101

View full text Add to dashboard Cite

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“…[5][6][7][8][9] Mild and subclinical post-transplant ventilatory defects are commonly seen after SCT. [10][11][12] In contrast, severe airways obstruction (AO) after SCT is a major and clinically significant complication of chronic GVHD causing high morbidity and mortality.…”

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confidence: 99%

Discrepancy of clinical, radiographic and histopathologic findings in two children with chronic pulmonary graft-versus-host disease after HLA-identical sibling stem cell transplantation

Benesch

Kerbl

Schwinger

et al. 1998

Bone Marrow Transplant

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Summary:We report two children who presented with cough and shortness of breath 7-8 months after a matched sibling stem cell transplant (SCT) for chronic myelogenous leukemia and myelodysplastic syndrome, respectively. Pulmonary function tests (PFTs) revealed severe airways obstruction (AO). However, radiographic investigations showed no serious abnormalities in the early phase and open lung biopsy revealed only mild lymphocytic bronchiolitis and bronchiolitis obliterans consistent with pulmonary graft-versus-host disease (GVHD). Despite administration of bronchodilators and various immunosuppressive agents obstructive lung disease progressed to pulmonary failure in patient 1, whereas stabilization of the clinical course was observed in patient 2. Serial PFTs were the best predictor of the clinical course in contrast to radiographic and histologic findings. It is concluded that PFTs should be performed repeatedly in pediatric patients after allogeneic SCT with the aim of diagnosing GVHD-associated AO in the subclinical phase. Progressive post-transplant AO necessitates prompt initiation of intensive immunosuppressive therapy in order to stop the underlying immunopathologic process even in the absence of severe radiographic and histologic findings. Keywords: stem cell transplantation; graft-versus-host disease; airways obstruction; immunosuppressive therapy Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for various malignant and non-malignant diseases. [1][2][3][4] Results of SCT may be compromised by transplant-related mortality and graft-versus-host disease (GVHD). 1-5 Whereas the incidence of grades II-IV acute GVHD ranges from 30 to 70% in recent series, chronic GVHD occurs in approximately half of the patients. skin, liver, gastrointestinal tract and lungs. 5-9 Mild and subclinical post-transplant ventilatory defects are commonly seen after SCT. [10][11][12] In contrast, severe airways obstruction (AO) after SCT is a major and clinically significant complication of chronic GVHD causing high morbidity and mortality. 9,13-18 Although post-transplant AO is histologically often associated with bronchiolitis obliterans (BO), various other patterns of GVHD-related histopathologic changes of the lungs have been described. [18][19][20] Pulmonary function tests (PFTs) in patients with lung GVHD show abnormal ventilatory function either of the restrictive or the obstructive pattern or a combined ventilatory defect depending on the underlying histopathologic process. 16,17,20 However, clinical presentation of lung GVHD is uniform. Most patients have non-productive cough and shortness of breath or both as their initial symptoms. We present the clinical courses, radiographic and histopathologic findings and PFTs of two children with severe AO related to pulmonary GVHD. Case reports Patient 1A 14-year-old boy with Philadelphia chromosome-positive chronic myelogenous leukemia was referred for SCT after 6 months therapy with hydroxyurea and interferon alpha2c. Conditioning consisted of busulf...

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“…18 The limited/extensive GVHD classification was used for the clinical and histological grading of cGVHD of the liver. For histopathological grading, a modified scheme introduced by Shulman et al 19 was applied. The modifiedhistopathological GVHD grading scheme is shown in Table 2.…”

Section: Diagnosis Of the Liver Tissue Injurymentioning

confidence: 99%