A 38-year-old male patient with ulcerative colitis was treated with mesalazine enteric- coated tablets 2 g twice daily, and developed pruritus, dark urine and jaundice approximately 8 months later. Laboratory tests revealed severe liver function abnormalities, showing alanine aminotransferase (ALT) 1 251 U/L, aspartate aminotransferase (AST) 1 102 U/L, γ-glutamyl transferase (GGT) 615 U/L, alkaline phosphatase (ALP) 715 U/L, total bile acid (TBA) 244.72 μmol/L, total bilirubin (TBil) 456.9 μmol/L, direct bilirubin (DBil) 350.6 μmol/L and indirect bilirubin (IBil) 106.3 μmol/L. Abdominal CT showed no significant abnormalities. Mesalazine was discontinued, and hepatoprotective therapy was initiated with magnesium isoglycyrrhizinate, ademetionine 1,4-butanedisulfonate, acetylcysteine, and ursodeoxycholic acid. Viral hepatitis, Wilson′s disease, and hemochromatosis were ruled out in further investigations and liver biopsy. Severe drug-induced liver injury (DILI) caused by mesalazine was suspected, but autoimmune hepatitis (AIH) could not be entirely excluded. The hepatoprotective treatments were continued, and the patient′s liver function was improved significantly, showing ALT 48 U/L, AST 35 U/L, GGT 144 U/L, ALP 202 U/L, TBA 24.72 μmol/L, TBil 71.8 μmol/L, DBil 62.3 μmol/L and IBil 9.5 μmol/L by day 24 of treatments. Later, he was treated only with ursodeoxycholic acid and bicyclol. The patient′s liver function normalized approximately one and a half months later. However, the patient self-reinitiated mesalazine several days thereafter, and the liver function tests showed ALT 155 U/L and AST 80 U/L after about 2 months of resumed use. Mesalazine was discontinued again, and his liver function returned to normal within 1 week with supportive treatments. AIH was excluded, DILI induced by mesalazine was considered at last.

A 38-year-old male patient with ulcerative colitis was treated with mesalazine enteric- coated tablets 2 g twice daily, and developed pruritus, dark urine and jaundice approximately 8 months later. Laboratory tests revealed severe liver function abnormalities, showing alanine aminotransferase (ALT) 1 251 U/L, aspartate aminotransferase (AST) 1 102 U/L, γ-glutamyl transferase (GGT) 615 U/L, alkaline phosphatase (ALP) 715 U/L, total bile acid (TBA) 244.72 μmol/L, total bilirubin (TBil) 456.9 μmol/L, direct bilirubin (DBil) 350.6 μmol/L and indirect bilirubin (IBil) 106.3 μmol/L. Abdominal CT showed no significant abnormalities. Mesalazine was discontinued, and hepatoprotective therapy was initiated with magnesium isoglycyrrhizinate, ademetionine 1,4-butanedisulfonate, acetylcysteine, and ursodeoxycholic acid. Viral hepatitis, Wilson′s disease, and hemochromatosis were ruled out in further investigations and liver biopsy. Severe drug-induced liver injury (DILI) caused by mesalazine was suspected, but autoimmune hepatitis (AIH) could not be entirely excluded. The hepatoprotective treatments were continued, and the patient′s liver function was improved significantly, showing ALT 48 U/L, AST 35 U/L, GGT 144 U/L, ALP 202 U/L, TBA 24.72 μmol/L, TBil 71.8 μmol/L, DBil 62.3 μmol/L and IBil 9.5 μmol/L by day 24 of treatments. Later, he was treated only with ursodeoxycholic acid and bicyclol. The patient′s liver function normalized approximately one and a half months later. However, the patient self-reinitiated mesalazine several days thereafter, and the liver function tests showed ALT 155 U/L and AST 80 U/L after about 2 months of resumed use. Mesalazine was discontinued again, and his liver function returned to normal within 1 week with supportive treatments. AIH was excluded, DILI induced by mesalazine was considered at last.

OBJECTIVETo observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.

METHODSTwenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n = 11), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n = 9).

RESULTSFive patients in Group A were in hematologic relapse. After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively. One achieved partial remission and died of interstitial pneumonia; and the other one showed no response. Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia, and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion. All 9 patients in group B were in hematologic relapse. Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon. And the other one with AML showed no response to the therapy.

CONCLUSIONDonor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse. Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL) effect than DDL infusion.

Adolescent ; Adult ; Bone Marrow Transplantation ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Hematopoietic Stem Cell Mobilization ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia ; therapy ; Male ; Middle Aged ; Recurrence