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Review

Acute promyelocytic leukaemia:a review

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Pages 1379-1392 | Published online: 02 Mar 2005

Bibliography

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  • •Gives a good description of the pathogenesis of APL and understanding of the retinoic acid pathway.
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  • •Important study showing higher doses of daunorubicin are associated with a prolonged overall survival, DFS and CR rates.
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  • ••An important study of 11 patients, whichshowed tretinoin to be a safe and highly effective agent for inducing CR in patients with APL.
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  • •An important study of 110 patients, in which ATRA with or without chemotherapy gave a statistical improvement in CR rate and early mortality rate, as well as superior survival in newly diagnosed APL.
  • TALLMAN MS, ANDERSON JW, SCHIFFER CA et al.: All-trans-retinoic acid in acute promyelocytic leukemia. N. Engl. J. Med (1997) 337(15):1021–1028.
  • ••First randomised study to show that ATRAwith or without chemotherapy gives a statistical improvement in CR rate and early mortality rate, as well as superior survival in newly diagnosed APL.
  • SOIGNET SL, FLEISCHAUER A, POLYAK T et al.: All-Trans retinoic acid significantly increases 5 year survival in patients with acute promyelocytic leukemia: long term follow up of the New York Study. Cancer Chemother. Pharmacy] (1997) 40(Suppl.):S25–S29.
  • MANDELLI F, DIVIERO D, AVVISATI G et al.: Molecular remission in PML/RAR a-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Gruppo Italiano-Malattie Ematologiche Maligne dell'Adulto and Associazione Italiana di Ematologia ed Oncologia Pediatrica Cooperative Groups. Blood (1997) 90(3):1014–1021.
  • SHEN ZX, CHEN GQ, NI JH et al: Use of arsenic trioxide (As203) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood (1997) 89(9):3354–3360.
  • SOIGNET SL, MASLAK P, WANG ZG et al.: Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl. J. Med. (1998) 339(19):1341–1348.
  • ••First study to show that low doses of ATOcan induce complete remissions in patients with relapsed APL.
  • FENAUX P, CHASTANG C, CHEVRET S et al.: A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood (1999) 94(4):1192–1200.
  • •A large study, whose findings strongly suggest that the early addition of chemotherapy to ATRA and maintenance therapy combining continuous CT and intermittent ATRA can reduce the incidence of relapse in APL.
  • WARRELL RP, DE THE H, WANG ZY et al.: Acute promyelocytic leukemia. N. Engl. J. Med. (1993) 329(3):177–189.
  • •Fairly thorough review article of APL.
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  • LO COCO F, DIVIERO D, FALINI B et al.: Genetic diagnosis and molecular monitoring in the management of acute promyelocytic leukemia. Blood(1999) 94(1):12–22.
  • •Thorough review of molecular pathogenesis of APL and molecular monitoring.
  • GOLOMB HM, ROWLEY JD, VARDIMAN JW et al.: `Microgranulai acute promyelocytic leukemia: a distinct clinical, ultrastructural, and cytogenetic entity. Blood (1980) 55(2):253–259.
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  • DE THE H, LAVAU C, MARCHIO A et al.: The PML-PAR-a fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered PAR. Cell (1991) 66(4):675–684.
  • KAKIZUKA A, MILLER WH, UMISONO K et al.: Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses PAR-a with a novel putative transcription factor, PML. Cell (1991) 66(4):663–674.
  • MELNICK A, LICHT JD: Deconstructing a disease: PAR-a, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. Blood, (1999) 93(10):3167–3215.
  • ••A very good review of the understanding ofmolecular pathogenesis of APL.
  • DYCK JA, MAUL GG, MILLER WH, CHEN JD, KAKINZUKA A, EVANS RM: A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein. Cell (1994) 76(2):333–343.
  • KOKEN MH, PUVION-DUTILLUEL F, GUILLEMIN MC et al.: The t(15;17) translocation alters a nuclear body in a retinoic acid-reversible fashion. EMBO (1994) 13:1073–1083.
  • WANG ZG, RUGGERO D, RONCHETTI S et al.: PML is essential for multiple apoptotic pathways. Nat. Genet. (1998) 20(3):266–272.
  • ZHONG S, SALOMONI P, PANDOLFI PP: The transcriptional role of PML and the nuclear body. Nat. Cell Biol. (2000) 2(5):E85–E90.
  • HE LZ, GUIDEZ F, TRIBIOLI C et al.: Distinct interactions of PML-PAR-a and PLZF-PAR-a with co-repressors determine differential responses to RA in APL. Nat. Genet. (1998) 18(2):126–135.
  • PEREZ A, KASTNER P, SETHI S, LUTZ Y, REIBEL C, CHAMBON P: PMLRAR homodimers: distinct DNA binding properties and heteromeric interactions with RXR. EMBO (1993) 12(8):3171–3182.
  • ZHONG S, MULLER S, RONCHETTI S, FREEMONT PS, DEJEAN A, PANDOLFI PP: Role of SUMO-1-modified PML in nuclear body formation. Blood (2000) 95(9):2748–2752.
  • ALTUCCI L, GRONEMEYER H: The promise of retinoids to fight against cancer. Nat. Rev Cancer (2001) 1(3):181–193.
  • ••An excellent review of the therapeuticeffect of retinoids and an explanation of the different mechanisms of action in APL.
  • BACHLEITNER-HOFMANN T, KEES M, GISSLINGER H et al.: Arsenic trioxide: acute promyelocytic leukemia and beyond. Leuk. Lymphoma (2002) 43(8):1535–1540.
  • ZHAO WL, CHEN SJ, SHEN Y et al.: Treatment of acute promyelocytic leukemia with arsenic trioxide: clinical and basic studies. Leuk. Lymphoma (2001) 42(6):1265–1273.
  • GRIGNANI F, TESTA U, ROGAIA D et al.: Effects on differentiation by the promyelocytic leukemia PML/RAR-a protein depend on the fusion of the PML protein dimerization and PAR-a DNA binding domains. EMBO (1996) 15(18):4949–4958.
  • LIU TX, ZHANG JW, TAO Jet al.: Gene expression networks underlying retinoic acid-induced differentiation of acute promyelocytic leukemia cells. Blood (2000) 96(4):1496–1504.
  • CHEN Z, BRAND NJ, CHEN A et al.: Fusion between a novel Kruppel-like zinc finger gene and the retinoic acid receptor-a locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia. EMBO (1993) 12(3):1161–1167.
  • ARNOULD C, PHILIPPE C, BOURDON V, GREGOIRE MJ, BERGER R, JONVEAUX P: The signal transducer and activator of transcription STAT5b gene is a new partner of retinoic acid receptor-a in acute promyelocytic-like leukaemia. Hum. MM. Genet. (1999) 8(9):1741–1749.
  • GIANNI M, PONZANELLI I, MOLOGNI L et al.: Retinoid-dependent growth inhibition, differentiation and apoptosis in acute promyelocytic leukemia cells. Expression and activation of caspases. Cell Death Differ. (2000) 7(5):447–460.
  • KAMBHAMPATI S, VERMA A, LI YZ, PARMAR S, SASSANO A, PLATANIAS L: Signalling pathways activated by all-trans-retinoic acid in acute promyelocytic leukemia cells. Leuk. Lymphoma (2003) (Submitted).
  • •Recent update on signal transduction induced by ATRA in APL.
  • HUANG W, SUN GL, LI XS et al.: Acute promyelocytic leukemia: clinical relevance of two major PML-PAR-a isoforms and detection of minimal residual disease by retrotranscriptase/polymerase chain reaction to predict relapse. Blood (1993) 82(4):1264–1269.
  • MILLER WH, KAKIZUKA A, FRANKEL SR et al.: Reverse transcription polymerase chain reaction for the rearranged retinoic acid receptor a clarifies diagnosis and detects minimal residual disease in acute promyelocytic leukemia. Proc. Nati Acad. ScL USA (1992) 89(7)2694–2698.
  • CASTAIGNE S, BALITRAND N, DE THE H, DEJEAN A, DEGOS L, CHOMIENNE C: A PML/retinoic acid receptor-a fusion transcript is constantly detected by RNA-based polymerase chain reaction in acute promyelocytic leukemia. Blood (1992) 79(12):3110–3115.
  • GRIMWADE, D: The pathogenesis of acute promyelocytic leukaemia: evaluation of the role of molecular diagnosis and monitoring in the management of the disease. &J. Haematol (1999) 106(3):591–613.
  • LO COCO F, DIVERIO D, D'ADAMO F et al.: PML/RAR-a rearrangement in acute promyelocytic leukaemias apparently lacking the t(15;17) translocation. Eur. Haematol (1992) 48(3):173–176.
  • IKEDA K, SASAKI K, TASAKA T et al: Detection of PML-retinoic acid receptor-a fusion transcripts in acute promyelocytic leukemia with trisomy 8 but without t(15;17). Am. J. Hematol (1994) 45(3):212–216.
  • HIORNS LR, MINT, SWANSBURY GJ, ZELENT A, DYER MJ, CATOVSKY D: Interstitial insertion of retinoic acid receptor-a gene in acute promyelocytic leukemia with normal chromosomes 15 and 17. Blood(1994) 83(10):2946–2951.
  • GRIMWADE D, HOWE K, LANGABEUR S et al.: Establishing the presence of the t(15;17) in suspected acute promyelocytic leukaemia: cytogenetic, molecular and PML immunofluorescence assessment of patients entered into the M.R.C. ATRA trial. M.R.C. Adult Leukaemia Working Party. Br. Haematol (1996) 94(3):557–573.
  • GRIMWADE D, GORMAN P, DUPREZ E et al.: Characterization of cryptic rearrangements and variant translocations in acute promyelocytic leukemia. Blood (1997) 90(12):4876–4885.
  • DYCK JA, WARELL RP, EVANS PM, MILLER WH: Rapid diagnosis of acute promyelocytic leukemia by immunohistochemical localization of PML/RAR-a protein. Blood (1995) 86(3):862–867.
  • FALINI B, FLENGHI L, FAGIOLI M et al.: Immunocytochemical diagnosis of acute promyelocytic leukemia (M3) with the monoclonal antibody PG-M3 (anti-PML). Blood(1997) 90(10):4046–4053.
  • FENAUX P, CHOMIENNE C, DEGOS L et al.: Acute promyelocytic leukemia: biology and treatment. Semin. Oncol (1997) 24(1):92–102.
  • WIERNIK PH, TALLMAN MS: Diagnosis and treatment of acute promyelocytic leukemia In: Neoplastic diseases of the blood, (3-d edn.), Wiernik PH, Dutcher JP, Kyle RA (Eds), Churchill Livingstone, New York, USA (1996):533–580.
  • LO COCO F, NERVI C, AVVISATI G, MANDELLI F: Acute promyelocytic leukemia: a curable disease. Leukemia (1998) 12(12):1866–1880.
  • FRANKEL SR, POWELL BL: Current approaches to promyelocytic leukemia. In: Diagnostic and Therapeutic Advances in Hematological Malignancies, Gordon L, Tallman MS (Eds), (1999) Kluwer, Boston, USA (1999):125–153.
  • ASOU N, ADACHI K, TAMURA J et al: Analysis of prognostic factors in newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Japan Adult Leukemia Study Group." Clin. Oncol (1998) 16(1):78–85.
  • •A multi-centre study of 196 patients, which shows that age, haemorrhagic diathesis, and initial leukocyte count are prognostic factors for APL, treated with ATRA followed by intensive chemotherapy.
  • BURNETT AK, GRIMWADE D, SALOMON E, WHEATLEY K, GOLDSTONE AH: Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the randomized MRC trial. Blood (1999) 93(12):4131–4143.
  • •A large, randomised study that evaluated the role of extended therapy with ATRA and presenting white count as a prognostic factor.
  • TALLMAN MS, ANDERSEN JW, SCHIFFER CA et al.: All-trans retinoic acid in acute promyelocytic leukemia: long term outcome results and prognostic factor analysis from intergroup protocol 0129. Blood (1999) 94 (10 Suppl. 1):698a (Abstract).
  • CHOU WC, TANG JL, YAO M et al.: Clinical and biological characteristics of acute promyelocytic leukemia in Taiwan: a high relapse rate in patients with high initial and peak white blood cell counts during all-trans retinoic acid treatment. Leukemia (1997) 11(7):921–928.
  • OHNO R, KANAMARU A, MIYAKAWI S et al.: The JALSG APL92 Study for newly diagnosed acute promyelocytic leukemia(APL) Analysis of prognostic factors to increase cure rate in the next stud. Blood (1999) 94:2262a (Abstract).
  • SANZ MA, LO COCO F, MARTIN G et al.: Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood (2000) 96(4):1247–1253.
  • ••A combination of data from two largestudies, that shows the omission of nonanthracycline drugs from the consolidation regimen is not associated with reduced antileukemic efficacy, and a simple predictive model may be used for risk-adapted therapy in this disease.
  • MORENO I, MARTIN G, BOLUFER P et al.: Incidence and prognostic value of FLT3 internal tandem duplication and D835 mutations in acute myeloid leukemia. Haematologica (2003) 88(1):19–24.
  • KOTTARIDIS PD, GALE RE, FREW ME et al.: The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood (2001) 98(6):1752–1759.
  • THIEDE C, STEUDEL C, MOHR B et al.: Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood (2002) 99(12):4326–4335.
  • SCHNITTGER S, SCHOCH C, DUGAS M et al.: Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood (2002) 100(1):59–66.
  • SLACK JL, ARTHUR DC, LAWRENCE D: Secondary cytogenetic changes in acute promyelocytic leukemia-prognostic importance in patients treated with chemotherapy alone and association with the intron 3 breakpoint of the PML gene: a Cancer and Leukemia Group B study. Clin. °nail (1997) 15(5):1786–1795.
  • HERNANDEZ JM, MARTIN G, GUTIERREZ NC et al: Additional cytogenetic changes do not influence the outcome of patients with newly diagnosed acute promyelocytic leukemia treated with an ATRA plus anthracycline based protocol. A report of the Spanish group PETHEMA. Haematologica (2001) 86(8):807–813.
  • DE BOTTON S, CHEVRET S, SANZ M et al.: Additional chromosomal abnormalities in patients with acute promyelocytic leukaemia (APL) do not confer poor prognosis: results of APL 93 trial. Br. Haematol. (2000) 111(3):801–806.
  • HIORNS LR, SWANSBURY GJ, MEHTAJ et al.: Additional chromosome abnormalities confer worse prognosis in acute promyelocytic leukaemia. Br. Haematol. (1997) 96(2):314–321.
  • XU L, ZHAO WL, XIONG SM et al: Molecular cytogenetic characterization and clinical relevance of additional, complex and/or variant chromosome abnormalities in acute promyelocytic leukemia. Leukemia (2001) 15(9):1359–1368.
  • MURRAY CK, ESTEY E, PAIETTA E et al.: CD56 expression in acute promyelocytic leukemia: a possible indicator of poor treatment outcome? Clin. Omni (1999) 17(1):293–297.
  • FERRARA F, MORABITO F, MARTINO B et al: CD56 expression is an indicator of poor clinical outcome in patients with acute promyelocytic leukemia treated with simultaneous all-trans-retinoic acid and chemotherapy. J Clin. Omni (2000) 18(6):1295–1300.
  • GUGLIELMI C, MARTELLI MP, DIVERIO D et al.: Immunophenotype of adult and childhood acute promyelocytic leukaemia: correlation with morphology, type of PML gene breakpoint and clinical outcome. A cooperative Italian study on 196 cases. Br. Haematol. (1998) 102(4):1035–1041.
  • AVVISATI G, MANDELLI F, PETTI MC et al.: Idarubicin (4-demethoxydaunorubicin) as single agent for remission induction of previously untreated acute promyelocytic leukemia: a pilot study of the Italian cooperative group GIMEMA. Haematol. (1990) 44(4):257–260.
  • PAIETTA E, ANDERSEN J, RACEVSKISJ et al: Significantly lower P-glycoprotein expression in acute promyelocytic leukemia than in other types of acute myeloid leukemia: immunological, molecular and functional analyses. Leukemia (1994) 8(6):968–973.
  • MICHIELI M, DAMIANI D, ERMACORA A et al.: P-glycoprotein (PGP), lung resistance-related protein (LRP) and multidrug resistance-associated protein (MRP) expression in acute promyelocytic leukaemia. Br. Haematol. (2000) 108(4):703–709.
  • TAKESHITA A, SHINJO K, NAITO K et al.: Role of P-glycoprotein in all-trans retinoic acid (ATRA) resistance in acute promyelocytic leukaemia cells: analysis of intracellular concentration of ATRA. Haematol. (2000) 108(1):90–92.
  • DEGOS L, CHOMIENNE C, DANIEL MT et al.: Treatment of first relapse in acute promyelocytic leukaemia with all-trans retinoic acid. Lancet (1990) 336(8728):1440–1441.
  • VAJDAT L, MASLAK P, MLLER WH et al.: Early mortality and the retinoic acid syndrome in acute promyelocytic leukemia: impact of leukocytosis, low-dose chemotherapy, PMN/RAR-a isoform, and CD13 expression in patients treated with all-trans retinoic acid. Blood (1994) 84(11):3843–3849.
  • TALLMAN MS, ANDERSEN JW, SCHIFFER CA et al: Clinical description of 44 patients with acute promyelocytic leukemia who developed the retinoic acid syndrome. Blood (2000) 95(1):90–95.
  • •This reports the incidence, clinical course, and outcome of patients with newly diagnosed APL who developed the RAS treated on the Intergroup Protocol 0129.
  • DE BOTTON S, DOMBRET H, SANZ M et al: Incidence, clinical features, and outcome of all trans-retinoic acid syndrome in 413 cases of newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood (1998) 92(8):2712–2718.
  • ••The first large study to show that theoccurrence of ATRA syndrome was associated with lower EFS and survival.
  • SANZ MA, MARTIN G, RAYON C et al: A modified AIDA protocol with anthracycline-based consolidation results in high antileukemic efficacy and reduced toxicity in newly diagnosed PML/RAR-a-positive acute promyelocytic leukemia. PETHEMA group. Blood (1999) 94(9):3015–3021.
  • FENAUX P, TERTIAN G, CASTAIGNE S et al: A randomized trial of amsacrine and rubidazone in 39 patients with acute promyelocytic leukemia. J. Clin. Oncol. (1991) 9(9):1556–1561.
  • ESTEY E, THALL PF, PIERCE S, KANTARJIAN H, KEATING M: Treatment of newly diagnosed acute promyelocytic leukemia without cytarabine. Clin. Oncol. (1997) 15(2):483–490.
  • •This study shows that omission of cytarabine (Ara-C) from treatment of newly diagnosed APL, allows administration of more anthracycline leading to similar CR rates with combination therapy.
  • ESTEY EH, GILES FJ, BERAN M et al: Experience with gemtuzumab ozogamicin (IVIylotarg) and all-trans retinoic acid in untreated acute promyelocytic leukemia. Blood (2002) 99(11):4222–4224.
  • •A small study, showing that initial induction therapy with combination of ATRA and Mylotare" leads to high CR rates comparable to combination of ATRA with chemotherapy.
  • BARBUI T, FALANGA A: The management of bleeding and thrombosis in leukemia. In: Leukemia, (6h edn.), Henderson ES, Greaves MF (Eds), Philadelphia, PA, USA. (1996):291.
  • TALLMAN MS, HAKIMIAN D, KWAAN HC, RICKLES FR: New insights into the pathogenesis of coagulation dysfunction in acute promyelocytic leukemia. Leak. Lymphoma (1993) 11(1-2):27–36.
  • •An excellent review of coagulopathy in APL.
  • FENAUX P, LE DELEY MC, CASTAIGNE S et al.: Effect of all transretinoic acid in newly diagnosed acute promyelocytic leukemia. Results of a multicenter randomized trial. European APL 91 Group. Blood (1993) 82(11):3241–3249.
  • •An important study reconfirming role of ATRA in induction therapy for APL.
  • DI BONA E, AVVISATI G, CASTAMAN G et al.: Early haemorrhagic morbidity and mortality during remission induction with or without all-trans retinoic acid in acute promyelocytic leukaemia. Br. Haematol. (2000) 108(4):689–695.
  • FALANGA A, IACOVIELLO L, EVANGELISTA V et al.: Loss of blast cell procoagulant activity and improvement of hemostatic variables in patients with acute promyelocytic leukemia administered all-trans-retinoic acid. Blood (1995) 86(3):1072–1081.
  • DOMBRET H, SCROBOHACI ML, GHORRA P et al.: Coagulation disorders associated with acute promyelocytic leukemia: corrective effect of all-trans retinoic acid treatment. Leukemia (1993) 7(1):2–9.
  • KAWAI Y, WANTABE K, KIZAKI M et al.: Rapid improvement of coagulopathy by all-trans retinoic acid in acute promyelocytic leukemia. Am. Hematol (1994) 46(3):184–188.
  • BARBUI T, FINAZZI G, FALANGA A: The impact of all-trans-retinoic acid on the coagulopathy of acute promyelocytic leukemia. Blood (1998) 91(9):3093–3102.
  • FALANGA A, CONSONNI R, MARCHETTI M et al: Cancer procoagulant in the human promyelocytic cell line NB4 and its modulation by all-trans-retinoic acid. Leukemia (1994) 8(1):156–159.
  • KOYAMA T, HIROSAWA S, KAWAMATA N, TOHDA S, AOKI N: All-trans retinoic acid upregulates thrombomodulin and downregulates tissue-factor expression in acute promyelocytic leukemia cells: distinct expression of thrombomodulin and tissue factor in human leukemic cells. Blood (1994) 84(9):3001–3009.
  • ISHII H, HORIE S, KIZAKI K, KAZAMA M: Retinoic acid counteracts both the downregulation of thrombomodulin and the induction of tissue factor in cultured human endothelial cells exposed to tumor necrosis factor. Blood (1992) 80(10):2556–2562.
  • FRANKEL SR, EARDLEY A, HELLER G et al.: All-trans retinoic acid for acute promyelocytic leukemia. Results of the New York Study. Ann. Intern. Med. (1994) 120(4):278–286.
  • •This study emphasises on the role of post remission consolidation with ATRA in patients with APL, and described the `retinoic acid syndrome'.
  • FRANKEL SR, EARDLEY A, LAUWERS G, WEISS M, WARRELL RP: The `retinoic acid syndrome' in acute promyelocytic leukemia. Ann. Intern. Med. (1992) 117(4):292–296.
  • ••This study described RAS for the first timeand role of high dose dexarnethasone for its treatment.
  • KO BS, TANG JL, CHEN YC et al.: Extramedullary relapse after all-trans retinoic acid treatment in acute promyelocytic leukemia-the occurrence of retinoic acid syndrome is a risk factor. Leukemia (1999) 13(9):1406–1408.
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