Predictive factors of relapse and survival in childhood acute myeloid leukemia: Role of minimal residual disease

Expert Review of Anticancer Therapy

Volumn 11, Issue 9, 2011, Pages 1391-1401

  Rizzari, Carmelo ^a   Cazzaniga, Giovanni ^b   Coliva, Tiziana ^a   De Angelis, Chiara ^c   Conter, Valentino ^a,b,c  

^a SAN GERARDO HOSPITAL   (Italy)

^b Hematology Department   (Italy)

^c OSPEDALI RIUNITI   (Italy)

Author keywords

acute myeloid leukemia; childhood; minimal residual disease; prognostic impact

Indexed keywords

AML1 ETO FUSION PROTEIN; ANTHRACYCLINE; CBFB MYH11 FUSION PROTEIN; CLOFARABINE; CYTARABINE; DAUNORUBICIN; ETOPOSIDE; GEMTUZUMAB OZOGAMICIN; HYBRID PROTEIN; MERCAPTOPURINE; METHOTREXATE; RETINOIC ACID; SORAFENIB; UNCLASSIFIED DRUG; VALPROIC ACID;

ACUTE GRANULOCYTIC LEUKEMIA; CANCER CHEMOTHERAPY; CANCER DIAGNOSIS; CANCER SURVIVAL; CCAAT ENHANCER BINDING PROTEIN ALPHA GENE; CHILDHOOD CANCER; CHROMOSOME ABERRATION; DISEASE ASSOCIATION; DRUG EFFICACY; EVENT FREE SURVIVAL; FMS LIKE TYROSINE KINASE RECEPTOR 3 GENE; GENE MUTATION; GENE OVEREXPRESSION; GENETIC ASSOCIATION; HUMAN; IMMUNOPHENOTYPING; KARYOTYPE; LEUKEMIA RELAPSE; MINIMAL RESIDUAL DISEASE; MULTIPLE CYCLE TREATMENT; MUTATOR GENE; NUCLEOPHOSMIN GENE; OVERALL SURVIVAL; PREDICTION; PROGNOSIS; PROMYELOCYTIC LEUKEMIA; RETINOIC ACID RECEPTOR ALPHA GENE; REVIEW; WILMS TUMOR GENE;

HUMANS; LEUKEMIA, MYELOID, ACUTE; NEOPLASM, RESIDUAL; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; PROGNOSIS; RECURRENCE;

EID: 80053045882     PISSN: 14737140     EISSN: 17448328     Source Type: Journal    
DOI: 10.1586/era.11.37     Document Type: Review

References (93)

1. Campana D. Progress of minimal residual disease studies in childhood acute leukemia. Curr. Hematol. Malig. Rep. 5(3), 169-176 (2010).
2. Buccisano F, Maurillo L, Spagnoli A et al. Monitoring of minimal residual disease in acute myeloid leukemia. Curr. Opin. Oncol. 21(6), 582-588 (2009).
3. Grimwade D, Hills RK. Independent prognostic factors for AML outcome. Hematology Am. Soc. Hematol. Educ. Program. 2009, 385-395 (2009).
4. Meshinchi S, Arceci RJ. Prognostic factors and risk-based therapy in pediatric acute myeloid leukemia. Oncologist 12(3), 341-355 (2007). (Pubitemid 46562369)
5. Maurillo L, Buccisano F, Del Principe MI et al. Toward optimization of postremission therapy for residual disease-positive patients with acute myeloid leukemia. J. Clin. Oncol. 26(30), 4944-4951 (2008).
6. Langebrake C, Creutzig U, Dworzak M et al. Residual disease monitoring in childhood acute myeloid leukemia by multiparameter flow cytometry: the MRD-AML-BFM study group. J. Clin. Oncol. 24(22), 3686-3692 (2006). (Pubitemid 46630545)
7. Coustan-Smith E, Ribeiro RC, Rubnitz JE et al. Clinical significance of residual disease during treatment in childhood acute myeloid leukaemia. Br. J. Haematol. 123(2), 243-252 (2003). (Pubitemid 37305058)
8. Rubnitz JE. Childhood acute myeloid leukemia. Curr. Treat. Options Oncol. 9(1), 95-105 (2008).
9. Kaspers GJL, Zwaan CN. Pediatric acute myeloid leukemia: towards high-quality cure of all patients. Haematologica 92(11), 1519-1532 (2007). (Pubitemid 350144128)
10. Pession A, Basso G, Rizzari C et al. and on behalf of the AML Strategy & Study Committee of the Associazione Italiana di Ematologia e Oncologia pediatrica (AIEOP).Treatment and long-term results in children with acute myeloid leukaemia treated according to the AIEOP AML protocols. Leukemia 19, 2043-2053 (2005). (Pubitemid 41741596)
11. Bennett JM, Catovsky D, Daniel MT et al. Proposed revised criteria for the classification of acute myeloid-leukemia - a report of the French-American-British cooperative group. Ann. Intern. Med. 103(4), 620-625 (1985).
12. Vardiman JW, Thiele J, Arber DA et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114(5), 937-951 (2009).
13. Aversa F, Reisner Y, Martelli MF. The haploidentical option for high-risk haematological malignancies. Blood Cells Molecules Dis. 40(1), 8-12 (2008). (Pubitemid 350192297)
14. Klingebiel T, Reinhardt D, Bader P; EBMT Paediatric Diseases Working Party. Place of HSCT in treatment of childhood AML. Bone Marrow Transplant. 42, S7-S9 (2008).
15. Niewerth D, Creutzig U, Bierings MB, Kaspers GJL. A review on allogeneic stem cell transplantation for newly diagnosed pediatric acute myeloid leukemia. Blood 116(13), 2205-2214 (2010).
16. Aplenc R, Alonzo TA, Gerbing RB et al. Ethnicity and survival in childhood acute myeloid leukemia: a report from the Children's Oncology Group. Blood 108(1), 74-80 (2006). (Pubitemid 43990614)
17. Gamis AS. Acute myeloid leukemia and Down syndrome evolution of modern therapy - State of the art review. Pediatric Blood Cancer 44(1), 13-20 (2005). (Pubitemid 39602560)
18. Wheatley K, Burnett AK, Goldstone AH et al. A simple, robust, validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukaemia derived from the MRC AML 10 trial. Br. J. Haematol. 107(1), 69-79 (1999). (Pubitemid 29500811)
19. Creutzig U, Zimmerman M, Ritter J et al. Definition of a standard-risk group in children with AML. Br. J. Haematol. 104(3), 630-639 (1999). (Pubitemid 29119294)
20. Cheson BD, Bennett JM, Kopecky KJ et al. Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J. Clin. Oncol. 21(24), 4642-4649 (2003). (Pubitemid 46594039)
21. Reading CL, Estey EH, Huh YO et al. Expression of unusual immunophenotype combinations in acute myelogenous leukemia. Blood 81(11), 3083-3090 (1993). (Pubitemid 23162129)
22. van Rhenen A, Feller N, Kelder A et al. High stem cell frequency in acute myeloid leukemia at diagnosis predicts high minimal residual disease and poor survival. Clin. Cancer Res. 11(18), 6520-6527 (2005). (Pubitemid 41338990)
23. Frascella E, Rondelli R, Pigazzi M et al. Clinical features of childhood acute myeloid leukaemia with specific gene rearrangements. Leukemia 18(8), 1427-1429 (2004). (Pubitemid 39136754)
24. von Neuhoff C, Reinhardt D, Sander A et al. Prognostic impact of specific chromosomal aberrations in a large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM 98. J. Clin. Oncol. 28(16), 2682-2689 (2010).
25. Harrison CJ, Hills RK, Moorman AV et al. Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council treatment trials AML 10 and 12. J. Clin. Oncol. 28(16), 2674-2681 (2010).
26. Mrozek K, Marcucci G, Paschka P, Whitman SP, Bloomfield CD. Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification? Blood 109(2), 431-448 (2007). (Pubitemid 46105936)
27. Gilliland DG, Griffin JD. The roles of FLT3 in hematopoiesis and leukemia. Blood 100(5), 1532-1542 (2002). (Pubitemid 34925124)
28. Meshinchi S, Woods WG, Stirewalt DL et al. Prevalence and prognostic significance of Flt3 internal tandem duplication in pediatric acute myeloid leukemia. Blood 97(1), 89-94 (2001). (Pubitemid 32061246)
29. Arrigoni P, Beretta C, Silvestri D et al. FLT3 internal tandem duplication in childhood acute myeloid leukaemia: association with hyperleucocytosis in acute promyelocytic leukaemia. Br. J. Haematol. 120(1), 89-92 (2003). (Pubitemid 36056913)
30. Meshinchi S, Stirewalt DL, Alonzo TA et al. Activating mutations of RTK/RAS signal transduction pathway in pediatric acute myeloid leukemia. Blood 102(4), 1474-1479 (2003). (Pubitemid 36988059)
31. Meshinchi S, Alonzo TA, Stirewalt DL et al. Clinical implications of FLT3 mutations in pediatric AML. Blood 108(12), 3654-3661 (2006).
32. Green CL, Koo KK, Hills RK, Burnett AK, Linch DC, Gale RE. Prognostic significance of CEBPA mutations in a large cohort of younger adult patients with AML: impact of double CABPA mutations and the interaction with FLT3 and NPM1 mutations. Haematologica 94, 1069 (2009).
33. Wouters BJ, Lowenberg B, Erpelinck- Verschueren CAJ, van Putten WLJ, Valk PJM, Delwel R. Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood 113(13), 3088-3091 (2009).
34. Leroy H, Roumier C, Huyghe P, Biggio V, Fenaux P, Preudhomme C. CEBPA point mutations in hematological malignancies. Leukemia 19(3), 329-334 (2005). (Pubitemid 40409478)
35. Ho PA, Alonzo TA, Gerbing RB et al. Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group. Blood 113(26), 6558-6566 (2009).
36. Falini B, Martelli MP, Pileri SA, Mecucci C. Molecular and alternative methods for diagnosis of acute myeloid leukemia with mutated NPM1: flexibility may help. Haematologica 95(4), 529-534 (2010).
37. Mullighan CG, Kennedy A, Zhou X et al. Pediatric acute myeloid leukemia with NPM1 mutations is characterized by a gene expression profile with dysregulated HOX gene expression distinct from MLL-rearranged leukemias. Leukemia 21, 2000-2009 (2007). (Pubitemid 47299976)
38. Cazzaniga G, Dell'Oro MG, Mecucci C et al. Nucleophosmin mutations in childhood acute myelogenous leukemia with normal karyotype. Blood 106(4), 1419-1422 (2005). (Pubitemid 41129610)
39. Brown P, Alonzo T, Gerbing R et al. High level expression of wild type FLT3 is associated with poor outcome and selective sensitivity to FLT3 inhibitors in childhood acute myeloid leukemia: a Children's Oncology Group Study. Blood 112(11), 60-60 (2008).
40. Hollink I, Zwaan CM, Zimmermann M et al. Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML. Leukemia 23(2), 262-270 (2009).
41. Hollink I, van den Heuvel-Eibrink MM, Zimmermann M et al. Clinical relevance of Wilms tumor 1 gene mutations in childhood acute myeloid leukemia. Blood 113(23), 5951-5960 (2009).
42. Cilloni D, Renneville A, Hermitte F et al. Real-time quantitative polymerase chain reaction detection of minimal residual disease by standardized WT1 assay to enhance risk stratification in acute myeloid leukemia: a European LeukemiaNet study. J. Clin. Oncol. 27(31), 5195-5201 (2009).
43. Willasch A, Gruhn B, Coliva T et al. Standardization of WT1 mRNA quantitation for MRD monitoring in childhood AML and implications of WT1 gene mutations: a European multicenter study. Eur. J. Pediatrics 169(3), 392-392 (2010).
44. Jacobsohn DA, Tse WT, Chaleff S et al. High WT1 gene expression before haematopoietic stem cell transplant in children with acute myeloid leukaemia predicts poor event-free survival. Br. J. Haematol. 146(6), 669-674 (2009).
45. Lapillonne H, Renneville A, Auvrignon A et al. High WT1 expression after induction therapy predicts high risk of relapse and death in pediatric acute myeloid leukemia. J. Clin. Oncol. 24(10), 1507-1515 (2006). (Pubitemid 46638771)
46. Gaidzik VI, Schlenk RF, Moschny S et al. Prognostic impact of WT1 mutations in cytogenetically normal acute myeloid leukemia: a study of the German-Austrian AML Study Group. Blood 113(19), 4505-4511 (2009).
47. Farr C, Gill R, Katz F, Gibbons B, Marshall CJ. Analysis of RAS gene-mutations in childhood myeloid-leukemia. Br. J. Haematol. 77(3), 323-327 (1991).
48. Renneville A, Roumier C, Biggio V et al. Cooperating gene mutations in acute myeloid leukemia: a review of the literature. Leukemia 22(5), 915-931 (2008). (Pubitemid 351709343)
49. Abdel-Wahab O, Mullally A, Hedvat C et al. Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood 114(1), 144-147 (2009).
50. Gregory J, Feusner J. Acute promyelocytic leukemia in childhood. Curr. Oncol. Rep. 11(6), 439-445 (2009).
51. Lo-Coco F, Ammatuna E, Montesinos P, Sanz M. Acute promyelocytic leukemia: Recent advances in diagnosis and management. Semin. Oncol. 35(4), 401-409 (2008).
52. Testi AM, Biondi A, Lo Coco F et al. GIMEMA-AIEOP AIDA protocol for the treatment of newly diagnosed acute promyelocytic leukemia (APL) in children. Blood 106(2), 447-453 (2005). (Pubitemid 40981236)
53. Ortega JJ, Madero L, Martin G et al. Treatment with all-trans retinoic acid and anthracycline mono chemotherapy for children with acute promyelocytic leukemia: a multicenter study by the PETHEMA group. J. Clin. Oncol. 23(30), 7632-7640 (2005). (Pubitemid 46291827)
54. Mathews V, George B, Chendamarai E et al. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: long-term follow-up data. J. Clin. Oncol. 28(24), 3866-3871 (2010).
55. Thirugnanam R, George B, Chendamarai E et al. Comparison of clinical outcomes of patients with relapsed acute promyelocytic leukemia induced with arsenic trioxide and consolidated with either an autologous stem cell transplant or an arsenic trioxide-based regimen. Biol. Blood Marrow Transplant. 15(11), 1479-1484 (2009).
56. Rubnitz JE, Inaba H, Dahl G et al. Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial. Lancet Oncol. 11(6), 543-552 (2010).
57. Pession A, Masetti R, Putti C et al. AIEOP LAM 2002/01 protocol: preliminary results. Haematologica 93, S23 (2008).
58. Campana D. Status of minimal residual disease testing in childhood haematological malignancies. Br. J. Haematol. 143(4), 481-489 (2008).
59. Goulden N, Virgo P, Grimwade D. Minimal residual disease directed therapy for childhood acute myeloid leukaemia: the time is now. Br. J. Haematol. 134(3), 273-282 (2006). (Pubitemid 43990789)
60. Shook D, Coustan-Smith E, Ribeiro RC, Rubnitz JE, Campana D. Minimal residual disease quantitation in acute myeloid leukemia. Clin. Lymphoma Myeloma 9, S281-S285 (2009).
61. Szczepanski T, Orfao A, van der Velden VH, San Miguel JF, van Dongen JJ. Minimal residual disease in leukaemia patients. Lancet Oncol. 2(7), 409-417 (2001). (Pubitemid 33585945)
62. Boeckx N, Willemse MJ, Szczepanski T et al. Fusion gene transcripts and Ig/TCR gene rearrangements are complementary but infrequent targets for PCR-based detection of minimal residual disease in acute myeloid leukemia. Leukemia 16(3), 368-375 (2002). (Pubitemid 34223696)
63. Yin JAL, Grimwade D. Minimal residual disease evaluation in acute myeloid leukaemia. Lancet 360(9327), 160-162 (2002). (Pubitemid 34786209)
64. Gabert J, Beillard E, van der Velden VHJ et al. Standardization and quality control studies of 'real-time' quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia - a Europe Against Cancer Program. Leukemia 17(12), 2318-2357 (2003). (Pubitemid 38072573)
65. van der Velden VHJ, Hochhaus A, Cazzaniga G, Szczepanski T, Gabert J, van Dongen JJM. Detection of minimal residual disease in hematologic malignancies by real-time quantitative PCR: principles, approaches, and laboratory aspects. Leukemia 17(6), 1013-1034 (2003). (Pubitemid 36722231)
66. Viehmann S, Teigler-Schlegel A, Bruch J, Langebrake C, Reinhardt D, Harbott J. Monitoring of minimal residual disease (MRD) by real-time quantitative reverse transcription PCR (RQ-RT-PCR) in childhood acute myeloid leukemia with AML1/ETO rearrangement. Leukemia 17(6), 1130-1136 (2003). (Pubitemid 36722244)
67. Kondo M, Kudo K, Kimura H et al. Real-time quantitative reverse transcription-polymerase chain reaction for the detection of AML1-MTG8 fusion transcripts in t(8;21)-positive acute myelogenous leukemia. Leukemia Res. 24(11), 951-956 (2000).
68. Krauter J, Heil G, Ganser A. The AML1/ MTG8 fusion transcript in t(8;21) positive AML and its implication for the detection of minimal residual disease; malignancy. Hematology 5(5), 369-381 (2001). (Pubitemid 32273272)
69. Schnittger S, Weisser M, Schoch C, Hiddemann W, Haferlach T, Kern W. New score predicting for prognosis in PML-RARA(+), AML1-ETO+, or CBFB- MYH11(+) acute myeloid leukemia based on quantification of fusion transcripts. Blood 102(8), 2746-2755 (2003). (Pubitemid 37248843)
70. Guieze R, Renneville A, Cayuela JM et al. Prognostic value of minimal residual disease by real-time quantitative PCR in acute myeloid leukemia with CBFB- MYH11 rearrangement: the French experience. Leukemia 24(7), 1386-1388 (2010).
71. Corbacioglu A, Scholl C, Schlenk RF et al. Prognostic impact of minimal residual disease in CBFB-MYH11-positive acute myeloid leukemia. J. Clin. Oncol. 28(23), 3724-3729 (2010).
72. Beretta C, Gaipa G, Rossi V et al. Development of a quantitative-PCR method for specific FLT3/ITD monitoring in acute myeloid leukemia. Leukemia 18(8), 1441-1444 (2004). (Pubitemid 39136759)
73. Kottaridis PD, Gale RE, Langabeer SE, Frew ME, Bowen DT, Linch DC. Studies of FLT3 mutations in paired presentation and relapse samples from patients with acute myeloid leukemia: implications for the role of FLT3 mutations in leukemogenesis, minimal residual disease detection, and possible therapy with FLT3 inhibitors. Blood 100(7), 2393-2398 (2002).
74. Bachas C, Schuurhuis GJ, Hollink I et al. High-frequency type I/II mutational shifts between diagnosis and relapse are associated with outcome in pediatric AML: implications for personalized medicine. Blood 116(15), 2752-2758 (2010).
75. Gorello P, Cazzaniga G, Alberti F et al. Quantitative assessment of minimal residual disease in acute myeloid leukemia carrying nucleophosmin (NPM1) gene mutations. Leukemia 20(6), 1103-1108 (2006). (Pubitemid 43797304)
76. Schnittger S, Weiss T, Haferlach C, Kern W, Haferlach T. Prognostic impact of FLT3 mutation load in NPM1 mutated AML. Blood 114(22), 341-341 (2009).
77. Boissel N, Renneville A, Biggio V et al. Prevalence, clinical profile, and prognosis of NPM mutations in AML with normal karyotype. Blood 106(10), 3618-3620 (2005). (Pubitemid 41609201)
78. Inoue K, Ogawa H, Sonoda Y et al. Aberrant overexpression of the Wilms tumor gene (WT1) in human leukemia. Blood 89(4), 1405-1412 (1997). (Pubitemid 27080005)
79. Trka J, Kalinova M, Hrusak O et al. Real-time quantitative PCR detection of WT1 gene expression in children with AML: prognostic significance, correlation with disease status and residual disease detection by flow cytometry. Leukemia 16(7), 1381-1389 (2002).
80. Ostergaard M, Olesen LH, Hasle H, Kjeldsen E, Hokland P. WT1 gene expression: an excellent tool for monitoring minimal residual disease in 70% of acute myeloid leukaemia patients - results from a single-centre study. Br. J. Haematol. 125(5), 590-600 (2004). (Pubitemid 38747961)
81. Freeman SD, Jovanovic JV, Grimwade D. Development of minimal residual disease-directed therapy in acute myeloid leukemia. Semin. Oncol. 35(4), 388-400 (2008).
82. Garg M, Moore H, Tobal K, Yin JAL. Prognostic significance of quantitative analysis of WT1 gene transcripts by competitive reverse transcription polymerase chain reaction in acute leukaemia. Br. J. Haematol. 123(1), 49-59 (2003). (Pubitemid 37222757)
83. Dworzak MN, Gaipa G, Ratei R et al. Standardization of flow cytometric minimal residual disease evaluation in acute lymphoblastic leukemia: multicentric assessment is feasible. Cytometry Part B Clinical Cytometry, 74B(6), 331-340 (2008).
84. Langebrake C, Teigler-Schlegel A, Creutzig U et al. Immunophenotypic differences between diagnosis and relapse in childhood AML: implications for MRD monitoring. Cytometry Part B Clinical Cytometry 63B, 1-9 (2005). (Pubitemid 40096838)
85. Baer MR, Stewart CC, Dodge RK et al. High frequency of immunophenotype changes in acute myeloid leukemia at relapse: implications for residual disease detection (Cancer and Leukemia Group B Study 8361).Blood 97(11), 3574-3580 (2001).
86. Sievers EL, Lange BJ, Alonzo TA et al. Immunophenotypic evidence of leukemia after induction therapy predicts relapse: results from a prospective Children's Cancer Group study of 252 patients with acute myeloid leukemia. Blood 101(9), 3398-3406 (2003). (Pubitemid 36857920)
87. Rosenberg AR, Leisenring W, Sanders JE et al. Sub-morphologic evidence of disease prior to stem cell transplantation correlates with inferior post transplant outcome in childhood acute myeloid leukemia. Blood 114(22), 139-139 (2009).
88. van der Velden VHJ, van der Sluijs- Geling A, Gibson BES et al. Clinical significance of flowcytometric minimal residual disease detection in pediatric acute myeloid leukemia patients treated according to the DCOG ANLL97/MRC AML12 protocol. Leukemia 24(9), 1599-1606 (2010).
89. Sanz MA, Grimwade D, Tallman MS et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 113(9), 1875-1891 (2009).
90. Grimwade D, Jovanovic JV, Hills RK et al. Prospective minimal residual disease monitoring to predict relapse of acute promyelocytic leukemia and to direct pre-emptive arsenic trioxide therapy. J. Clin. Oncol. 27(22), 3650-3658 (2009).
91. Diverio D, Rossi V, Avvisati G et al. Early detection of relapse by prospective reverse transcriptase-polymerase chain reaction analysis of the PML/RAR a fusion gene in patients with acute promyelocytic leukemia enrolled in the GIMEMA-AIEOP multicenter 'AIDA' trial. Blood 92(3), 784-789 (1998). (Pubitemid 28355460)
92. Lo-Coco E, Ammatuna E. Front line clinical trials and minimal residual disease monitoring in acute promyelocytic leukemia. In: Acute Promyelocytic Leukemia: Molecular Genetics, Mouse Models and Targeted Therapy. Springler-Verlag Berlin Heidelberg, Germany, 145-156 (2007). (Pubitemid 47400337)
93. Esteve J, Escoda L, Martin G et al. Outcome of patients with acute promyelocytic leukemia failing to front-line treatment with all-trans retinoic acid and anthracycline-based chemotherapy (PETHEMA protocols LPA96 and LPA99): benefit of an early intervention. Leukemia 21(3), 446-452 (2007).