4 4 Organ Transplantation. Vol. 4 No. 4 Jul acute promyelocytic leukemia APL. acute myeloid leukemia AML -M 3 APL A

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1 Organ Transplantation Vol. 4 No. 4 Jul acute promyelocytic leukemia APL APL Pubmed APL 52 acute myeloid leukemia AML -M 3 APL A AML d 8 18 AML APL 8 /18 44% t A 22 AML 13 59% disseminated intravascular coagulation DIC APL APL 2 2 / % 11 /14 P < APL 6 2 DIC AML APL APL APL A R617 A Diagnosis and treatment of de novo acute promyelocytic leukemia after liver transplantation WANG Guo-ying * ZOU Yong LAI Wen-xing ZHANG Jian WANG Gen-shu LI Hua YANG Yang CHEN Gui-hua. * Liver Transplantation Center of the Third Affiliated Hospital Transplantation Research Institute Sun Yat-sen University Organ Transplantation Research Center of Guangdong Province Guangzhou China Corresponding author CHEN Gui-hua chgh1955@263.net Abstract Objective To investigate the diagnosis and treatment of de novo acute promyelocytic leukemia APL after liver transplantation. Methods One case developed APL among patients who were regularly followed up after liver transplantation in the Third Affiliated Hospital of Sun Yat-sen University from October 2003 to December Clinical data of the patient including clinical manifestations diagnosis treatment and prognosis were retrospectively analyzed. A scientific literature search was undertaken in the DOI /j.issn ZX CB U S ykpy43 12ykpy chgh1955@263.net

intravascular coagulation DIC APL APL 2 2 /8 11 79% 11 /14 P < 0.

2 domestic and foreign medical databases like Pubmed and Wanfang Medical Database. Clinical characteristics of patients with leukemia especially APL patients after liver transplantation were analyzed such as age gender primary disease the immunosuppression regimen the postoperative elapsed time the types of leukemia the types of chromosome mutations treatment prognosis and the cause of death. Results At 52 months after liver transplantation the patient was found a reduction in the number of peripheral white blood cells in the follow-up clinic without any sign symptom infection or bleeding tendency. After the failure of treatment of recombinant human granulocyte colony-stimulating factor the diagnosis of acute myeloid leukemia AML type M 3 APL was confirmed by bone marrow biopsy. After combined treatment of vitamin A acid and compound realgar natural indigo tablet main chemical component was arsenic disulfide the patient achieved complete remission. There were 34 reported cases of leukemia after liver transplantation in the literature including this case. Among them there were 22 cases of AML including 18 adults and 4 children. The median of postoperative elapsed time was 26 months range from 38 d to 8 years. The most common AML subtype was APL 8 /18 44% and all accompanied with abnormal karyotype t Therapeutic regimen consisted of vitamin A acid arsenic trioxide and chemotherapy drugs like daunorubicin or cytarabine. The overall mortality of AML patients was 59% 13 /22 and the main causes of death included disseminated intravascular coagulation DIC infection liver failure and heart failure. The deaths included 2 cases 2 /8 of APL and 11 cases 79% 11 /14 of the other types of AML where significant difference was observed P < Six APL patients achieved complete remission and the other two died of DIC and sepsis respectively. Conclusions The general prognosis of de novo AML after liver transplantation is not good but the prognosis of APL patients is better than that of the other types of AML. Early diagnosis and timely treatment is the key to improve the prognosis of APL after liver transplantation. Key words Vitamin A acid Arsenic disulfide Prognosis Liver transplantation Acute promyelocytic leukemia Acute myeloid leukemia acute myeloid leukemia AML 99 g /L 2 AML 1 AML /L /L M AML-M /L acute promyelocytic total bilirubin TB 200 μmol /L leukemia APL APL direct bilirubin DB 78 μmol /L activated partial thromboplastin time AML APTT s APL Child-Pugh B MELD 24 FK FK506 1 APL ~ ng /ml FK mg

elapsed time the types of leukemia the types of chromosome mutations treatment prognosis and the cause of death.

3 liver transplantation leukemia Pubmed CNKI 2 APL A 20 mg FAB 3 French-American-British Cooperative Group / SPSS U /L AST 82 U /L Fisher P < APL /L E /L 1 mg /L /L FK /L ALT 50 U /L AST 14 U /L /L recombinant human granulocyte colony stimulating factor rhg-csf 3 d /L ~ /L /L 1 FK506 1 mg /L ~ 3. 5 ng /ml rhg-csf 300 μg g /L /L AML /L /L 22 AML 1 FK ng /ml % ~ 2. 6% peroxidase POX 22 AML 18 4 APL 1A 1B AML-M 6 AML 30 APL 8 /18 44% fluorescence in situ hybridization Auer 1C POX 1D PML /RARα ALT A g /L d 8 t A FISH

5 AST 14 U /L 2013 3 8 5 14 10 9 /L recombinant human granulocyte colony stimulating factor rhg-csf 3 d 1. 9 10 9 /L ~ 5. 2 10 9 /L 3. 5 10 9 /L 1 FK506 1 mg 1. 4 10 9 /L2013 1 18 2 2. 5 ~ 3.

4 AML 13 59% 2 disseminated coagulation DIC intravascular 2 1 AML APL APL 2 MMF 1 FK /8 25% /14 79% APL APL P < FK506 CsA 6 2 DIC 5 /7 71% 19 P > FK506 1 MMF 7 CsA MMF FK506 4 /11 36% Fig. 1 1 Analysis of the bone marrow aspirate smears from this patient with acute promyelocytic leukemia after liver transplantation 1A 1B C 1D E A 1C 1E HE B 1D POX A 1 ~ 3 Auer 1B POX 1C 1A Auer 1D POX 1E

1 1 Analysis of the bone marrow aspirate smears from this patient with acute promyelocytic leukemia after liver

5 200 4 Table 1 1 Clinical characteristics of patients with de novo acute myeloid leukemia after liver transplantation FAB Liu M et al Bodó I et al 3 57 FK506 + FK M 3 t M 3 t A + 3 A CsA + 24 M 3 t A 4 Cho YU et al 4 62 FK506 + t M A inv 16 5 Sato T et al Sato T et al Doti CA et al Camós M et al Camós M et al Camós M et al O'Boyle KP et al Jiang N et al Wozniak LJ et al Doti CA et al Thalhammer- Scherrer R et al Mannelli F et al Zhang GS et al Cho YU et al 4 65 A + FK M 14 3 t FK M 3 t A FK506 + A + OKT M 3 t DIC CsA + 24 M 3 t A CsA M CsA + 42 M CsA + MMF + 24 M CsA + 38 M FK506 + FK M 4 NS + FK M d CsA + ATG + 78 M FK506 + MMF + FK506 + FK506 + MMF M XY /47XY + 5 M M i 8 q10 + FLT3 /ITD AML M 0 85 d

et al 7 61 10 Camós M et al 7 51 11 O'Boyle KP et al 8 69 12 Jiang N et al 1 9 45 13 Wozniak LJ et al 10 7 14 Doti CA et al 6 36 15 Thalhammer- Scherrer R et al 11 71 16 Mannelli F et al 12 28 17

6 FAB 19 Kourelis TV et al Cruz E et al 15 NS NS 21 Srinivasan P et al 16 NS NS MMF + 96 FK506 + NS NS NS 1 - NS 24 NS NS NS 3 - NS NS NS NS NS Ho CM et al 17 NS NS NS NS NS NS NS NS OKT3 T CD3 ATG 2 PML /RARα AML Fig. 2 Polymerase chain reaction products of PML / RARα fusion gene in this patient with acute promyelocytic leukemia after liver transplantation AML APL APL 393 bp FK506 marker 3 Epstein-Barr virus EBV B 19 AML rhg-csf AML 6 DIC rhg-csf FISH AML APL AML-M 3 AML % ~ 2. 6% AML 5 AML APL AML 13

2 Polymerase chain reaction products of PML / RARα fusion gene in this patient with acute promyelocytic leukemia after liver

7 % DIC N Engl J Med APL 4 Cho YU Chi HS Park CJ et al. Two cases of post-liver APL APL 25% 79% transplant acute myeloid leukemia in Korean adults review of bibliographies and comparison with post-renal P < transplant acute myeloid leukemia J. Ann Hematol CsA % FK506 36% 5 Sato T Kobayashi R Iguchi A et al. Acute A APL orthotopic liver transplantation in two Japanese girls J. Leuk Lymphoma A APL 6 Doti CA Gondolesi GE Sheiner PA et al. Leukemia DIC after liver transplant J. Transplantation APL 7 Camós M Esteve J Rimola A et al. Increased APL A retinoic acid incidence of acute myeloid leukemia after liver syndrome RAS A APL transplantation description of three new cases and review of the literature J. Transplantation A APL A 8 O'Boyle KP Murigeppa A Jain D et al. Probable 6 venoocclusive disease after treatment with gemtuzumab 3 2 DIC 6 ozogamicin in a patient with acute myeloid leukemia and APL a history of liver transplantation for familial hemochromatosis J. Med Oncol Jiang N Zhang T Wang GS et al. Acute leukemia after liver transplantation a new AML-M 2 case report and review of the literature J. Chin J Pract Surg 2010 A J AML 10 Wozniak LJ Yang HM Lassman CR et al. Extramedullary acute myelocytic leukemia following liver AML APL APL APL Pediatr Gastroenterol Nutr Thalhammer-Scherrer R Wieselthaler G Knoebl P et DIC al. Post-transplant acute myeloid leukemia PT-AML J. Leukemia Jiang N Li H Wang GS et al. Acute leukemia a rare but fatal complication after liver transplantation J. Leuk Res Liu M Liu J Liu L et al. A case report of acute myeloid leukemia after liver transplantation J. Acta Haematol Bodó I Peters M Radich JP et al. Donor-derived acute promyelocytic leukemia in a liver-transplant recipient J. promyelocytic leukemia after living donor partial transplantation for VOD with immunodeficiency J. 12 Mannelli F De Simone P Gianfaldoni G et al. Atypical acute leukemia early after liver transplantation J. Transplant Proc Zhang GS Dai CW Peng HL et al. Myelodysplastic syndrome with transformation to acute monocytic leukemia with FLT3-ITD mutation following orthotopic liver transplantation J. Leuk Res Kourelis TV Boruchov A Hull D et al. Acute myeloid J

Ann Hematol CsA 2008 87 6 513-514. 71% FK506 36% 5 Sato T Kobayashi R Iguchi A et al. Acute A APL orthotopic liver transplantation in two Japanese girls J. Leuk Lymphoma 2005 46 7 1057-1060.

8 leukemia following solid organ transplantation case report and comprehensive review J. Conn Med Cruz E Ascher NL Roberts JP et al. High incidence of recurrence and hematologic events following liver transplantation for Budd-Chiari syndrome J. Clin Transplant Srinivasan P Rela M Prachalias A et al. Liver transplantation for Budd-Chiari syndrome J. Transplantation Ho CM Ho MC Shau WY et al. Isolated increase in serum alkaline phosphatase after liver transplantation risk factors and outcomes analysis J. Int J Surg Saigal S Norris S Muiesan P et al. Evidence of differential risk for posttransplantation malignancy based on pretransplantation cause in patients undergoing liver transplantation J. Liver Transpl Kanegane H Nomura K Miyawaki T et al. Biological aspects of Epstein-Barr virus EBV -infected lymphocytes in chronic active EBV infection and associated malignancies J. Crit Rev Oncol Hematol from page Razak F Anand SS Shannon H et al. Defining obesity cut points in a multiethnic population J. Circulation Miyake T Kumagi T Hirooka M et al. Body mass index is the most useful predictive factor for the onset of nonalcoholic fatty liver disease a community-based retrospective longitudinal cohort study J. J Gastroenterol Browning JD Szczepaniak LS Dobbins R et al. Prevalence of hepatic steatosis in an urban population in the United States impact of ethnicity J. Hepatology The Chinese National Workshop on Fatty Liver and Alcoholic Liver Disease for the Chinese Liver Disease. Guidelines for management of nonalcoholic fatty liver disease an updated and revised edition J. Chin J Hepatol J Feldstein AE Wieckowska A Lopez AR et al. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis a multicenter validation study J. Hepatology Xia MF Gao X. Progress in noninvasive diagnosis of nonalcoholic fatty liver disease J. Chin J Endocrinol Metab J Koneru B Dikdan G. Hepatic steatosis and liver transplantation current clinical and experimental perspectives J. Transplantation

Liver transplantation for Budd-Chiari syndrome J. Transplantation 2002 73 6 973-977. 17 Ho CM Ho MC Shau WY et al.

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