Allogeneic hematopoietic stem cell transplantation for acute leukemia with Gilbert's syndrome
© Yu et al; licensee BioMed Central Ltd. 2011
Received: 4 February 2011
Accepted: 9 March 2011
Published: 9 March 2011
Acute leukemia with coexisting Gilbert's syndrome treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rarely reported. Here we described a case whose transaminase levels were almost normal, although transient hyperbilirubinemia repeatedly happened during chemotherapy.
To the editor:
After 3 cycles of chemotherapy, the patient received transplantation from his HLA-identical sibling sister who was also diagnosed to have GS. The conditioning regimen included fludarabine and busulfan. Hematopoietic engraftment was observed on day +11. In the absence of GVHD, the levels of transaminase and bilirubin were almost normal within 100 days post-transplantation (Figure 1). The patient received G-CSF mobilized donor peripheral lymphocyte transfusion on days + 60 and +90, respectively. He developed skin rash and abnormal liver function on day +123 (Figure 1), consistent with grade II acute GVHD. After one month treatment with Methylprednisolone, tacrolimus and methotrexate, his liver dysfunction gradually returned to normal. At the last follow-up on day +510, his liver function was still normal, and he remained leukemia free.
GS is a common condition; its prevalence has been described in 3-10% of the general population . With mild symptoms and reversible indirect hyperbilirubinemia, most cases of GS remain undiagnosed and they may become evident after exercise, stress, drug administration, prolonged fasting or inter-current diseases . Several drugs have been reported to induce hyperbilirubinemia to GS patients, such as paracetamol, nilotinib, and pazopanib [3, 4]. In our case, hyperbilirubinemia happened to the patient after each cycle of the chemotherapy, but it did not occur during the conditioning and within 100 days post-transplantation. This suggests that anthracyclines and/or cytarabine might be an inhibitor of UGT1A1 enzyme.
Some reports suggest that GS might be a risk factor of cancer [5, 6]. GS with coexisting hematological malignancies including AML has been reported in individuals, but the incidence of hematological malignancy in GS is still unknown . Among these cases, just like ours, non-hemolytic low-grade indirect hyperbilirubinemia after chemotherapy occurred repeatedly, but it did not effect the treatment of hematologic malignancies. In clinical practice, hyperbilirubinemia is suggestive of hemolysis, drug-induced liver damage or other conditions, but GS is not very frequently considered . In our case, we initially attributed hyperbilirubinemia to drug-induced liver damage in the first two cycles of chemotherapy.
To our knowledge, there is little description of the onset of hyperbilirubinemia in GS patients who received HSCT. Ruiz-Arguelles GJ, et al.  reported seven cases of acute leukemia with coexisting GS, of which 3 patients accepted chemotherapy alone, 3 cases treated by allo-HSCT and one received auto-PBSCT. All seven patients developed indirect hyperbilirubinemia during the course of their treatment. No patients died from the liver dysfunction. In our case, transaminase and bilirubin levels were almost normal during the conditioning and within 100 days after transplantation, although indirect hyperbilirubinemia repeatedly happened during chemotherapy with daunorubicin, idarubicin, and cytarabine prior to HSCT. This may suggest that fludarabine and busulfan had low liver toxicity in GS patients . It could also be possible that phenytoin, an inducer of UGT1A1 activity used during the conditioning, prevented hyperbilirubinemia . It has been reported that UGT1A1 inducers, including phenobarbital, rifampin and phenytoin, were used in the diagnosis and treatment of GS [8, 9].
QFL, MD, Ph.D, Department of Hematology, Nanfang Hospital, Southern Medical University; Member of the Asian-Pacific Society of Hematology; Member of Blood Branch of the Chinese Medical Association; Member of the Chinese hematopoietic stem cell transplant group; Standing Committee member of Chinese Anti-Cancer Association of Professional Committee of Hematology Branch; editor of more than 10 journals.
List of abbreviations
Allogeneic hematopoietic stem cell transplantation
acute myeloid leukemia
uridine 5'-diphosphoglucose glucuronosyl transferase
human leukocyte antigen
pneumocystis carinii pneumonia.
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