4 4 2013 7 Organ Transplantation Vol. 4 No. 4 Jul. 2013 acute promyelocytic leukemia APL 2003 10 2012 12 1 APL Pubmed APL 52 acute myeloid leukemia AML -M 3 APL A 34 22 AML 18 4 26 38 d 8 18 AML APL 8 /18 44% t 15 17 A 22 AML 13 59% disseminated intravascular coagulation DIC APL APL 2 2 /8 11 79% 11 /14 P < 0. 05 APL 6 2 DIC AML APL APL APL A R617 A 1674-7445 2013 04-0003-08 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 510630 China Corresponding author CHEN Gui-hua Email 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 2012. Clinical data of the patient including clinical manifestations diagnosis treatment and prognosis were retrospectively analyzed. A scientific literature search was undertaken in the DOI 10.3969 /j.issn.1674-7445. 2013. 04. 003 2012ZX10002017 973 2009CB522404 U0932006 81000190 81172036 S2012040007964 12ykpy43 12ykpy47 510630 Email chgh1955@263.net
4. 197 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 15 17. 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 < 0. 05. 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- 2. 8 10 12 /L 2. 8 10 9 /L M 2 1 1 AML-M 3 0. 42 65 10 9 /L acute promyelocytic total bilirubin TB 200 μmol /L leukemia APL APL direct bilirubin DB 78 μmol /L activated partial thromboplastin time AML APTT 54. 9 s APL Child-Pugh B MELD 24 FK506 3 1 1. 1 2003 10 2012 12 FK506 1 APL 63 2008 4. 8 ~ 12. 3 ng /ml 2009 12 9 24 FK506 1. 5 mg 2 2012 12
198 4 1. 2 liver transplantation leukemia Pubmed CNKI 2 APL 2013 1 29 A 20 mg 2 2013 2 8 FAB 3 French-American-British Cooperative Group 1. 3 2 15 10 / SPSS 13. 0 73 U /L AST 82 U /L Fisher P < 0. 05 2 2. 1 APL 5 3 2012 6 5 2013 2 16 3. 9 10 9 /L 0. 59 1E 2 18 2012 12 4 2. 0 10 9 /L 1 mg 0. 44 2. 5 10 12 /L 5. 1 10 9 /L FK506 0. 83 123 10 9 /L ALT 50 U /L 2 1. 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. 5 ng /ml rhg-csf 300 μg 2. 2 34 106 g /L 3. 3 10 12 /L AML 22 0. 86 10 9 /L 0. 48 49 10 9 /L 22 AML 1 FK506 2. 9 ng /ml 3 0. 645 0. 2% ~ 2. 6% peroxidase POX 22 AML 18 4 APL 1A 1B 2013 1 29 1 AML-M 6 AML 30 APL 8 /18 44% fluorescence in situ hybridization 0. 65 Auer 1C POX 1D PML /RARα 3 3 1 2013 ALT A 2013 2 20 78 g /L 2013 6 2 4 8 1 3 26 38 d 8 t 15 17 A FISH
4. 199 22 AML 13 59% 2 disseminated coagulation DIC intravascular 2 1 AML APL APL 2 MMF 1 FK506 1 2 /8 25% 11 11 /14 79% APL APL P < 0. 05 FK506 CsA 6 2 DIC 5 /7 71% 19 P > 0. 05 11 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 2013 1 28 1C 1D 2013 1 30 1E 2013 2 16 1A 1C 1E HE - 1 000 1B 1D POX 1 000 1A 1 ~ 3 Auer 1B POX 1C 1A Auer 1D POX 1E
200 4 Table 1 1 Clinical characteristics of patients with de novo acute myeloid leukemia after liver transplantation FAB 1 63 2 Liu M et al 2 50 3 Bodó I et al 3 57 FK506 + FK506 + 52 M 3 t 15 17 85 M 3 t 15 17 A + 3 A + 22 + CsA + 24 M 3 t 15 17 A 4 Cho YU et al 4 62 FK506 + t 15 17 76 M A + 15 3 inv 16 5 Sato T et al 5 12 6 Sato T et al 5 4 7 Doti CA et al 6 50 8 Camós M et al 7 41 9 Camós M 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 Zhang GS et al 13 46 18 Cho YU et al 4 65 A + FK506 + 21 M 14 3 t 15 17 + + FK506 46 M 3 t 15 17 3 A + + + FK506 + A + OKT3 + 18 M 3 t 15 17 + DIC CsA + 24 M 3 t 15 17 A + 2 + 2 CsA + 1. 3 M 0 + + CsA + 42 M 6 1 + CsA + MMF + 24 M 1-5 - 17 CsA + 38 M 2 + 4 FK506 + FK506 + 79 M 4 NS + FK506 + 19 M 4 + 29 d CsA + ATG + 78 M 4 + + FK506 + MMF + FK506 + FK506 + MMF + + 4 M 5 + 46XY /47XY + 5 M 9 5 8 + 28 M 7 + + i 8 q10 + FLT3 /ITD AML M 0 85 d
4. 201 FAB 19 Kourelis TV et al 14 58 20 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 72 22 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 34 22 AML APL AML-M 3 AML 2 6-7 0. 2% ~ 2. 6% 18 2 2 AML 5 AML APL 3 18-22 AML 13
202 4 59% DIC N Engl J Med 1999 341 11 807-813. 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 < 0. 05 transplant acute myeloid leukemia 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. A APL 6 Doti CA Gondolesi GE Sheiner PA et al. Leukemia DIC after liver transplant J. Transplantation 2001 72 10 1643-1646. 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 2004 77 2 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 2003 20 4 379-384. 9 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 2 30 11 946-948.. 1 J. 2010 AML 10 Wozniak LJ Yang HM Lassman CR et al. Extramedullary acute myelocytic leukemia following liver AML APL APL APL Pediatr Gastroenterol Nutr 2011 53 3 346-349. 11 Thalhammer-Scherrer R Wieselthaler G Knoebl P et DIC al. Post-transplant acute myeloid leukemia PT-AML J. Leukemia 1999 13 3 321-326. 1 Jiang N Li H Wang GS et al. Acute leukemia a rare but fatal complication after liver transplantation J. Leuk Res 2009 33 10 1349-1351. 2 Liu M Liu J Liu L et al. A case report of acute myeloid leukemia after liver transplantation J. Acta Haematol 2013 129 4 225-228. 3 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 311-313. 30 11 946-948. 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 2009 41 9 3945-3946. 13 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 2006 30 7 908-910. 14 Kourelis TV Boruchov A Hull D et al. Acute myeloid J
4. 203 leukemia following solid organ transplantation case report and comprehensive review J. Conn Med 2012 76 3 151-154. 15 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 2005 19 4 501-506. 16 Srinivasan P Rela M Prachalias A et al. Liver transplantation for Budd-Chiari syndrome J. Transplantation 2002 73 6 973-977. 17 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 2013 11 1 92-95. 18 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 2002 8 5 482-487. 19 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 2002 44 3 239-249. 2013-06 - 10 195 from page 195 6 Razak F Anand SS Shannon H et al. Defining obesity cut points in a multiethnic population J. Circulation 2007 115 16 2111-2118. 7 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 2013 48 3 413-422. 8 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 2004 40 6 1387-1395. 9 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 2010 18 3 163-166. 2010 J. 2010 18 3 163-166. 10 Feldstein AE Wieckowska A Lopez AR et al. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis a multicenter validation study J. Hepatology 2009 50 4 1072-1078. 11 Xia MF Gao X. Progress in noninvasive diagnosis of nonalcoholic fatty liver disease J. Chin J Endocrinol Metab 2010 26 7 623-626.. J. 2010 26 7 623-626. 12 Koneru B Dikdan G. Hepatic steatosis and liver transplantation current clinical and experimental perspectives J. Transplantation 2002 73 3 325-330. 2013-05 - 13.