Restricted access

The inaugural NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for acute lymphoblastic leukemia (ALL) were developed as a result of meetings convened by a multi-disciplinary panel of experts in 2011. These NCCN Guidelines provide recommendations on the diagnostic evaluation and workup for ALL, risk assessment, risk-stratified treatment approaches based on the Philadelphia chromosome status and age (adults vs. adolescents/young adults), assessment of minimal residual disease, and supportive care considerations. It is recommended that patients be treated at specialized centers with expertise in the management of ALL.

  • 1

    Jabbour EJ, Faderl S, Kantarjian HM. Adult acute lymphoblastic leukemia. Mayo Clin Proc 2005;80:15171527.

  • 2

    National Cancer Institute. SEER Stat Fact Sheet: Acute Lymphocytic Leukemia. Bethesda, MD: 2011. Available at: http://seer.cancer.gov/statfacts/html/alyl.html. Accessed March 2012.

    • Search Google Scholar
    • Export Citation
  • 3

    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:1029.

  • 4

    Esparza SD, Sakamoto KM. Topics in pediatric leukemia--acute lymphoblastic leukemia. MedGenMed 2005;7:23.

  • 5

    Gaynon PS, Angiolillo AL, Carroll WL. Long-term results of the children’s cancer group studies for childhood acute lymphoblastic leukemia 1983-2002: a Children’s Oncology Group report. Leukemia 2010;24:285297.

    • Search Google Scholar
    • Export Citation
  • 6

    Pui CH, Evans WE. Acute lymphoblastic leukemia. N Engl J Med 1998;339:605615.

  • 7

    Pui CH, Pei D, Sandlund JT. Long-term results of St Jude Total Therapy Studies 11, 12, 13A, 13B, and 14 for childhood acute lymphoblastic leukemia. Leukemia 2010;24:371382.

    • Search Google Scholar
    • Export Citation
  • 8

    Annino L, Vegna ML, Camera A. Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study. Blood 2002;99:863871.

    • Search Google Scholar
    • Export Citation
  • 9

    Bassan R, Hoelzer D. Modern therapy of acute lymphoblastic leukemia. J Clin Oncol 2011;29:532543.

  • 10

    Kantarjian H, Thomas D, O’Brien S. Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer 2004;101:27882801.

    • Search Google Scholar
    • Export Citation
  • 11

    Larson RA, Dodge RK, Burns CP. A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood 1995;85:20252037.

    • Search Google Scholar
    • Export Citation
  • 12

    Linker C, Damon L, Ries C, Navarro W. Intensified and shortened cyclical chemotherapy for adult acute lymphoblastic leukemia. J Clin Oncol 2002;20:24642471.

    • Search Google Scholar
    • Export Citation
  • 13

    Rowe JM, Buck G, Burnett AK. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood 2005;106:37603767.

    • Search Google Scholar
    • Export Citation
  • 14

    Takeuchi J, Kyo T, Naito K. Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study. Leukemia 2002;16:12591266.

    • Search Google Scholar
    • Export Citation
  • 15

    Thomas X, Boiron JM, Huguet F. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol 2004;22:40754086.

    • Search Google Scholar
    • Export Citation
  • 16

    Pui CH, Relling MV, Downing JR. Acute lymphoblastic leukemia. N Engl J Med 2004;350:15351548.

  • 17

    Stock W. Adolescents and young adults with acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program 2010;2010:2129.

  • 18

    Faderl S, O’Brien S, Pui CH. Adult acute lymphoblastic leukemia: concepts and strategies. Cancer 2010;116:11651176.

  • 19

    Borowitz MJ, Chan JKC. B lymphoblastic leukaemia/lymphoma, not otherwise specified. In: Swerdlow SH, Campo E, Harris NL., eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (ed 4th). Lyon, France: IARC; 2008:168170.

    • Search Google Scholar
    • Export Citation
  • 20

    Borowitz MJ, Chan JKC. T lymphoblastic leukaemia/lymphoma. In: Swerdlow SH, Campo E, Harris NL., eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (ed 4th). Lyon, France: IARC; 2008 176178.

    • Search Google Scholar
    • Export Citation
  • 21

    Borowitz MJ, Chan JKC. B lymphoblastic leukaemia/lymphoma with recurrent genetic abnormalities. In: Swerdlow SH, Campo E, Harris NL., eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (ed 4th). Lyon, France: IARC; 2008:171175.

    • Search Google Scholar
    • Export Citation
  • 22

    Bassan R, Gatta G, Tondini C, Willemze R. Adult acute lymphoblastic leukaemia. Crit Rev Oncol Hematol 2004;50:223261.

  • 23

    Gokbuget N, Hoelzer D. Treatment of adult acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program 2006:133141.

  • 24

    Thomas DA, O’Brien S, Jorgensen JL. Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia. Blood 2009;113:63306337.

    • Search Google Scholar
    • Export Citation
  • 25

    Coustan-Smith E, Mullighan CG, Onciu M. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol 2009;10:147156.

    • Search Google Scholar
    • Export Citation
  • 26

    Armstrong SA, Look AT. Molecular genetics of acute lymphoblastic leukemia. J Clin Oncol 2005;23:63066315.

  • 27

    Seibel NL. Treatment of acute lymphoblastic leukemia in children and adolescents: peaks and pitfalls. Hematology Am Soc Hematol Educ Program 2008:374380.

    • Search Google Scholar
    • Export Citation
  • 28

    Burmeister T, Schwartz S, Bartram CR. Patients’ age and BCR-ABL frequency in adult B-precursor ALL: a retrospective analysis from the GMALL study group. Blood 2008;112:918919.

    • Search Google Scholar
    • Export Citation
  • 29

    Gleissner B, Gokbuget N, Bartram CR. Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. Blood 2002;99:15361543.

    • Search Google Scholar
    • Export Citation
  • 30

    Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med 2006;354:166178.

  • 31

    Arico M, Valsecchi MG, Camitta B. Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia. N Engl J Med 2000;342:9981006.

    • Search Google Scholar
    • Export Citation
  • 32

    Schultz KR, Pullen DJ, Sather HN. Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children’s Cancer Group (CCG). Blood 2007;109:926935.

    • Search Google Scholar
    • Export Citation
  • 33

    Smith M, Arthur D, Camitta B. Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia. J Clin Oncol 1996;14:1824.

    • Search Google Scholar
    • Export Citation
  • 34

    Nachman J. Clinical characteristics, biologic features and outcome for young adult patients with acute lymphoblastic leukaemia. Br J Haematol 2005;130:166173.

    • Search Google Scholar
    • Export Citation
  • 35

    Hoelzer D, Thiel E, Loffler H. Intensified therapy in acute lymphoblastic and acute undifferentiated leukemia in adults. Blood 1984;64:3847.

    • Search Google Scholar
    • Export Citation
  • 36

    Hoelzer D, Thiel E, Loffler H. Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood 1988;71:123131.

    • Search Google Scholar
    • Export Citation
  • 37

    Moorman AV, Harrison CJ, Buck GAN. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood 2007;109:31893197.

    • Search Google Scholar
    • Export Citation
  • 38

    Pullarkat V, Slovak ML, Kopecky KJ. Impact of cytogenetics on the outcome of adult acute lymphoblastic leukemia: results of Southwest Oncology Group 9400 study. Blood 2008;111:25632572.

    • Search Google Scholar
    • Export Citation
  • 39

    Kamps WA, Bokkerink JP, Hakvoort-Cammel FG. BFM-oriented treatment for children with acute lymphoblastic leukemia without cranial irradiation and treatment reduction for standard risk patients: results of DCLSG protocol ALL-8 (1991–1996). Leukemia 2002;16:10991111.

    • Search Google Scholar
    • Export Citation
  • 40

    Moricke A, Reiter A, Zimmermann M. Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95 Blood 2008;111:44774489.

    • Search Google Scholar
    • Export Citation
  • 41

    Schrappe M, Reiter A, Ludwig WD. Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. German-Austrian-Swiss ALL-BFM Study Group. Blood 2000;95:33103322.

    • Search Google Scholar
    • Export Citation
  • 42

    Seibel NL, Steinherz PG, Sather HN. Early postinduction intensification therapy improves survival for children and adolescents with high-risk acute lymphoblastic leukemia: a report from the Children’s Oncology Group. Blood 2008;111:25482555.

    • Search Google Scholar
    • Export Citation
  • 43

    Stock W, La M, Sanford B. What determines the outcomes for adolescents and young adults with acute lymphoblastic leukemia treated on cooperative group protocols? A comparison of Children’s Cancer Group and Cancer and Leukemia Group B studies. Blood 2008;112:16461654.

    • Search Google Scholar
    • Export Citation
  • 44

    Bostrom BC, Sensel MR, Sather HN. Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children’s Cancer Group. Blood 2003;101:38093817.

    • Search Google Scholar
    • Export Citation
  • 45

    Mitchell CD, Richards SM, Kinsey SE. Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial. Br J Haematol 2005;129:734745.

    • Search Google Scholar
    • Export Citation
  • 46

    Pui CH. Central nervous system disease in acute lymphoblastic leukemia: prophylaxis and treatment. Hematology Am Soc Hematol Educ Program 2006:142146.

    • Search Google Scholar
    • Export Citation
  • 47

    Teuffel O, Kuster SP, Hunger SP. Dexamethasone versus prednisone for induction therapy in childhood acute lymphoblastic leukemia: a systematic review and meta-analysis. Leukemia 2011:12321238.

    • Search Google Scholar
    • Export Citation
  • 48

    Kantarjian HM, O’Brien S, Smith TL. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol 2000;18:547561.

    • Search Google Scholar
    • Export Citation
  • 49

    Koller CA, Kantarjian HM, Thomas D. The hyper-CVAD regimen improves outcome in relapsed acute lymphoblastic leukemia. Leukemia 1997;11:20392044.

    • Search Google Scholar
    • Export Citation
  • 50

    Hoelzer D, Ludwig WD, Thiel E. Improved outcome in adult B-cell acute lymphoblastic leukemia. Blood 1996;87:495508.

  • 51

    de Labarthe A, Rousselot P, Huguet-Rigal F. Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study. Blood 2007;109:14081413.

    • Search Google Scholar
    • Export Citation
  • 52

    Ottmann O, Dombret H, Martinelli G. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study. Blood 2007;110:23092315.

    • Search Google Scholar
    • Export Citation
  • 53

    Ottmann OG, Wassmann B, Pfeifer H. Imatinib compared with chemotherapy as front-line treatment of elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Cancer 2007;109:20682076.

    • Search Google Scholar
    • Export Citation
  • 54

    Ravandi F, O’Brien S, Thomas D. First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia. Blood 2010;116:20702077.

    • Search Google Scholar
    • Export Citation
  • 55

    Schultz KR, Bowman WP, Aledo A. Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a children’s oncology group study. J Clin Oncol 2009;27:51755181.

    • Search Google Scholar
    • Export Citation
  • 56

    Thomas DA, Faderl S, Cortes J. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 2004;103:43964407.

    • Search Google Scholar
    • Export Citation
  • 57

    Wassmann B, Pfeifer H, Goekbuget N. Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood 2006;108:14691477.

    • Search Google Scholar
    • Export Citation
  • 58

    Yanada M, Takeuchi J, Sugiura I. High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group. J Clin Oncol 2006;24:460466.

    • Search Google Scholar
    • Export Citation
  • 59

    Thomas DA, Faderl S, O’Brien S. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer 2006;106:15691580.

    • Search Google Scholar
    • Export Citation
  • 60

    Thomas DA, O’Brien S, Faderl S. Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome-negative precursor B-lineage acute lymphoblastic leukemia. J Clin Oncol 2010;28:38803889.

    • Search Google Scholar
    • Export Citation
  • 61

    Berg SL, Blaney SM, Devidas M. Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children’s Oncology Group. J Clin Oncol 2005;23:33763382.

    • Search Google Scholar
    • Export Citation
  • 62

    Cohen MH, Johnson JR, Justice R, Pazdur R. FDA drug approval summary: nelarabine (Arranon) for the treatment of T-cell lymphoblastic leukemia/lymphoma. Oncologist 2008;13:709714.

    • Search Google Scholar
    • Export Citation
  • 63

    DeAngelo DJ, Yu D, Johnson JL. Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. Blood 2007;109:51365142.

    • Search Google Scholar
    • Export Citation
  • 64

    Arico M, Schrappe M, Hunger SP. Clinical outcome of children with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia treated between 1995 and 2005. J Clin Oncol 2010;28:47554761.

    • Search Google Scholar
    • Export Citation
  • 65

    Ottmann OG, Druker BJ, Sawyers CL. A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias. Blood 2002;100:19651971.

    • Search Google Scholar
    • Export Citation
  • 66

    Wassmann B, Gokbuget N, Scheuring UJ. A randomized multicenter open label phase II study to determine the safety and efficacy of induction therapy with imatinib (Glivec, formerly STI571) in comparison with standard induction chemotherapy in elderly (>55 years) patients with Philadelphia chromosome-positive (Ph+/BCR-ABL+) acute lymphoblastic leukemia (ALL) (CSTI571ADE 10). Ann Hematol 2003;82:716720.

    • Search Google Scholar
    • Export Citation
  • 67

    Towatari M, Yanada M, Usui N. Combination of intensive chemotherapy and imatinib can rapidly induce high-quality complete remission for a majority of patients with newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia. Blood 2004;104:35073512.

    • Search Google Scholar
    • Export Citation
  • 68

    Tanguy-Schmidt A, de Labarthe A, Rousselot P. Long-term results of the imatinib GRAAPH-2003 Study in newly-diagnosed patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia [abstract]. Blood 2009;114:Abstract 3080.

    • Search Google Scholar
    • Export Citation
  • 69

    Thomas DA, O’Brien SM, Faderl S. Long-term outcome after hyper-CVAD and imatinib (IM) for de novo or minimally treated Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL) [abstract]. J Clin Oncol 2010;28:Abstract 6506.

    • Search Google Scholar
    • Export Citation
  • 70

    Burke MJ, Cao Q, Trotz B. Allogeneic hematopoietic cell transplantation (allogeneic HCT) for treatment of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL). Pediatr Blood Cancer 2009;53:12891294.

    • Search Google Scholar
    • Export Citation
  • 71

    Rives S, Estella J, Gomez P. Intermediate dose of imatinib in combination with chemotherapy followed by allogeneic stem cell transplantation improves early outcome in paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL): results of the Spanish Cooperative Group SHOP studies ALL-94, ALL-99 and ALL-2005. Br J Haematol 2011;154:600611.

    • Search Google Scholar
    • Export Citation
  • 72

    Cornelissen JJ, Carston M, Kollman C. Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors determining outcome. Blood 2001;97:15721577.

    • Search Google Scholar
    • Export Citation
  • 73

    Esperou H, Boiron JM, Cayuela JM. A potential graft-versus-leukemia effect after allogeneic hematopoietic stem cell transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: results from the French Bone Marrow Transplantation Society. Bone Marrow Transplant 2003;31:909918.

    • Search Google Scholar
    • Export Citation
  • 74

    Mizuta S, Matsuo K, Yagasaki F. Pre-transplant imatinib-based therapy improves the outcome of allogeneic hematopoietic stem cell transplantation for BCR-ABL-positive acute lymphoblastic leukemia. Leukemia 2011;25:4147.

    • Search Google Scholar
    • Export Citation
  • 75

    Fielding AK, Rowe JM, Richards SM. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood 2009;113:44894496.

    • Search Google Scholar
    • Export Citation
  • 76

    Bassan R, Rossi G, Pogliani EM. Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Northern Italy Leukemia Group protocol 09/00. J Clin Oncol 2010;28:36443652.

    • Search Google Scholar
    • Export Citation
  • 77

    Ribera JM, Oriol A, Gonzalez M. Concurrent intensive chemotherapy and imatinib before and after stem cell transplantation in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Final results of the CSTIBES02 trial. Haematologica 2010;95:8795.

    • Search Google Scholar
    • Export Citation
  • 78

    Chalandon Y, Thomas X, Hayette S. First results of the GRAAPH-2005 study in younger adult patients with de novo Philadelphia positive acute lymphoblastic leukemia [abstract]. Blood 2008;112:Abstract 12.

    • Search Google Scholar
    • Export Citation
  • 79

    Branford S, Rudzki Z, Walsh S. High frequency of point mutations clustered within the adenosine triphosphate-binding region of BCR/ABL in patients with chronic myeloid leukemia or Ph-positive acute lymphoblastic leukemia who develop imatinib (STI571) resistance. Blood 2002;99:34723475.

    • Search Google Scholar
    • Export Citation
  • 80

    Hofmann WK, Jones LC, Lemp NA. Ph(+) acute lymphoblastic leukemia resistant to the tyrosine kinase inhibitor STI571 has a unique BCR-ABL gene mutation. Blood 2002;99:18601862.

    • Search Google Scholar
    • Export Citation
  • 81

    Jones D, Thomas D, Yin CC. Kinase domain point mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia emerge after therapy with BCR-ABL kinase inhibitors. Cancer 2008;113:985994.

    • Search Google Scholar
    • Export Citation
  • 82

    Soverini S, Colarossi S, Gnani A. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin Cancer Res 2006;12:73747379.

    • Search Google Scholar
    • Export Citation
  • 83

    Bujassoum S, Rifkind J, Lipton JH. Isolated central nervous system relapse in lymphoid blast crisis chronic myeloid leukemia and acute lymphoblastic leukemia in patients on imatinib therapy. Leuk Lymphoma 2004;45:401403.

    • Search Google Scholar
    • Export Citation
  • 84

    Leis JF, Stepan DE, Curtin PT. Central nervous system failure in patients with chronic myelogenous leukemia lymphoid blast crisis and Philadelphia chromosome positive acute lymphoblastic leukemia treated with imatinib (STI-571). Leuk Lymphoma 2004;45:695698.

    • Search Google Scholar
    • Export Citation
  • 85

    Pfeifer H, Wassmann B, Hofmann WK. Risk and prognosis of central nervous system leukemia in patients with Philadelphia chromosome-positive acute leukemias treated with imatinib mesylate. Clin Cancer Res 2003;9:46744681.

    • Search Google Scholar
    • Export Citation
  • 86

    Takayama N, Sato N, O’Brien SG. Imatinib mesylate has limited activity against the central nervous system involvement of Philadelphia chromosome-positive acute lymphoblastic leukaemia due to poor penetration into cerebrospinal fluid. Br J Haematol 2002;119:106108.

    • Search Google Scholar
    • Export Citation
  • 87

    O’Hare T, Walters DK, Stoffregen EP. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res 2005;65:45004505.

    • Search Google Scholar
    • Export Citation
  • 88

    Shah NP, Tran C, Lee FY. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 2004;305:399401.

  • 89

    Talpaz M, Shah NP, Kantarjian H. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 2006;354:25312541.

    • Search Google Scholar
    • Export Citation
  • 90

    Lilly MB, Ottmann OG, Shah NP. Dasatinib 140 mg once daily versus 70 mg twice daily in patients with Ph-positive acute lymphoblastic leukemia who failed imatinib: results from a phase 3 study. Am J Hematol 2010;85:164170.

    • Search Google Scholar
    • Export Citation
  • 91

    Porkka K, Koskenvesa P, Lundan T. Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia. Blood 2008;112:10051012.

    • Search Google Scholar
    • Export Citation
  • 92

    Foa R, Vitale A, Guarini A. Dasatinib monotherapy effective and feasible as firstline treatment of adult Ph+ acute lymphoblastic leukemia (ALL) patients. Final results of the GIMEMA LAL1205 study [abstract]. Blood 2008;112(Suppl 11):Abstract 305.

    • Search Google Scholar
    • Export Citation
  • 93

    Foa R, Vitale A, Vignetti M. Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 2011;118:65216528.

    • Search Google Scholar
    • Export Citation
  • 94

    Delannoy A, Delabesse E, Lheritier V. Imatinib and methylprednisolone alternated with chemotherapy improve the outcome of elderly patients with Philadelphia-positive acute lymphoblastic leukemia: results of the GRAALL AFR09 study. Leukemia 2006;20:15261532.

    • Search Google Scholar
    • Export Citation
  • 95

    Vignetti M, Fazi P, Cimino G. Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive patients with acute lymphoblastic leukemia without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) LAL0201-B protocol. Blood 2007;109:36763678.

    • Search Google Scholar
    • Export Citation
  • 96

    Fielding AK, Richards SM, Chopra R. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood 2007;109:944950.

    • Search Google Scholar
    • Export Citation
  • 97

    Oriol A, Vives S, Hernandez-Rivas JM. Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group. Haematologica 2010;95:589596.

    • Search Google Scholar
    • Export Citation
  • 98

    Tavernier E, Boiron JM, Huguet F. Outcome of treatment after first relapse in adults with acute lymphoblastic leukemia initially treated by the LALA-94 trial. Leukemia 2007;21:19071914.

    • Search Google Scholar
    • Export Citation
  • 99

    Thomas DA, Kantarjian H, Smith TL. Primary refractory and relapsed adult acute lymphoblastic leukemia: characteristics, treatment results, and prognosis with salvage therapy. Cancer 1999;86:12161230.

    • Search Google Scholar
    • Export Citation
  • 100

    Hu Y, Liu Y, Pelletier S. Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia. Nat Genet 2004;36:453461.

    • Search Google Scholar
    • Export Citation
  • 101

    Hofmann WK, Komor M, Wassmann B. Presence of the BCR-ABL mutation Glu255Lys prior to STI571 (imatinib) treatment in patients with Ph+ acute lymphoblastic leukemia. Blood 2003;102:659661.

    • Search Google Scholar
    • Export Citation
  • 102

    Pfeifer H, Wassmann B, Pavlova A. Kinase domain mutations of BCR-ABL frequently precede imatinib-based therapy and give rise to relapse in patients with de novo Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood 2007;110:727734.

    • Search Google Scholar
    • Export Citation
  • 103

    Redaelli S, Piazza R, Rostagno R. Activity of bosutinib, dasatinib, and nilotinib against 18 imatinib-resistant BCR/ABL mutants. J Clin Oncol 2009;27:469471.

    • Search Google Scholar
    • Export Citation
  • 104

    Verstovsek S, Golemovic M, Kantarjian H. AMN107, a novel aminopyrimidine inhibitor of p190 Bcr-Abl activation and of in vitro proliferation of Philadelphia-positive acute lymphoblastic leukemia cells. Cancer 2005;104:12301236.

    • Search Google Scholar
    • Export Citation
  • 105

    Kantarjian H, Giles F, Wunderle L. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med 2006;354:25422551.

    • Search Google Scholar
    • Export Citation
  • 106

    Ottmann OG, Larson RA, Kantarjian HM. Nilotinib in patients (pts) with relapsed/refractory Philadelphia Chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who are resistant or intolerant to imatinib [abstract]. Blood 2007;110:Abstract 2815.

    • Search Google Scholar
    • Export Citation
  • 107

    Muller MC, Cortes JE, Kim DW. Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations. Blood 2009;114:49444953.

    • Search Google Scholar
    • Export Citation
  • 108

    Soverini S, Colarossi S, Gnani A. Resistance to dasatinib in Philadelphia-positive leukemia patients and the presence or the selection of mutations at residues 315 and 317 in the BCR-ABL kinase domain. Haematologica 2007;92:401404.

    • Search Google Scholar
    • Export Citation
  • 109

    Soverini S, Martinelli G, Colarossi S. Presence or the emergence of a F317L BCR-ABL mutation may be associated with resistance to dasatinib in Philadelphia chromosome-positive leukemia. J Clin Oncol 2006;24:e5152.

    • Search Google Scholar
    • Export Citation
  • 110

    Soverini S, Hochhaus A, Nicolini FE. BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet. Blood 2011;118:12081215.

    • Search Google Scholar
    • Export Citation
  • 111

    Cortes JE, Kim D- W, Pinilla-Ibarz J. Initial findings from the PACE trial: a pivotal phase 2 study of ponatinib in patients with CML and Ph+ ALL resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation [abstract]. Blood 2011;118:Abstract 109.

    • Search Google Scholar
    • Export Citation
  • 112

    Khoury HJ, Cortes JE, Gambacorti-Passerini C. Activity of bosutinib by baseline and emergent mutation status in Philadelphia chromosome-positive leukemia patients with resistance or intolerance to other tyrosine kinase inhibitors [abstract]. Blood 2011;118:Abstract 110.

    • Search Google Scholar
    • Export Citation
  • 113

    Khoury HJ, Cortes JE, Kantarjian HM. Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. Blood 2012;119:34033412.

    • Search Google Scholar
    • Export Citation
  • 114

    Ishida Y, Terasako K, Oshima K. Dasatinib followed by second allogeneic hematopoietic stem cell transplantation for relapse of Philadelphia chromosome-positive acute lymphoblastic leukemia after the first transplantation. Int J Hematol 2010;92:542546.

    • Search Google Scholar
    • Export Citation
  • 115

    Millot F, Cividin M, Brizard F. Successful second allogeneic stem cell transplantation in second remission induced by dasatinib in a child with Philadelphia chromosome positive acute lymphoblastic leukemia. Pediatr Blood Cancer 2009;52:891892.

    • Search Google Scholar
    • Export Citation
  • 116

    Collins RH Jr, Goldstein S, Giralt S. Donor leukocyte infusions in acute lymphocytic leukemia. Bone Marrow Transplant 2000;26:511516.

  • 117

    Kolb HJ, Schattenberg A, Goldman JM. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood 1995;86:20412050.

    • Search Google Scholar
    • Export Citation
  • 118

    Keil F, Kalhs P, Haas OA. Relapse of Philadelphia chromosome positive acute lymphoblastic leukaemia after marrow transplantation: sustained molecular remission after early and dose-escalating infusion of donor leucocytes. Br J Haematol 1997;97:161164.

    • Search Google Scholar
    • Export Citation
  • 119

    Matsue K, Tabayashi T, Yamada K, Takeuchi M. Eradication of residual bcr-abl-positive clones by inducing graft-versus-host disease after allogeneic stem cell transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Bone Marrow Transplant 2002;29:6366.

    • Search Google Scholar
    • Export Citation
  • 120

    Yazaki M, Andoh M, Ito T. Successful prevention of hematological relapse for a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic bone marrow transplantation by donor leukocyte infusion. Bone Marrow Transplant 1997;19:393394.

    • Search Google Scholar
    • Export Citation
  • 121

    Tiribelli M, Sperotto A, Candoni A. Nilotinib and donor lymphocyte infusion in the treatment of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) relapsing after allogeneic stem cell transplantation and resistant to imatinib. Leuk Res 2009;33:174177.

    • Search Google Scholar
    • Export Citation
  • 122

    Yoshimitsu M, Fujiwara H, Ozaki A. Case of a patient with Philadelphia-chromosome-positive acute lymphoblastic leukemia relapsed after myeloablative allogeneic hematopoietic stem cell transplantation treated successfully with imatinib and sequential donor lymphocyte infusions. Int J Hematol 2008;88:331335.

    • Search Google Scholar
    • Export Citation
  • 123

    Relling MV, Hancock ML, Rivera GK. Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. J Natl Cancer Inst 1999;91:20012008.

    • Search Google Scholar
    • Export Citation
  • 124

    Boissel N, Auclerc MF, Lheritier V. Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. J Clin Oncol 2003;21:774780.

    • Search Google Scholar
    • Export Citation
  • 125

    de Bont JM, Holt Bvd, Dekker AW. Significant difference in outcome for adolescents with acute lymphoblastic leukemia treated on pediatric vs adult protocols in the Netherlands. Leukemia 2004;18:20322035.

    • Search Google Scholar
    • Export Citation
  • 126

    Hallbook H, Gustafsson G, Smedmyr B. Treatment outcome in young adults and children >10 years of age with acute lymphoblastic leukemia in Sweden: a comparison between a pediatric protocol and an adult protocol. Cancer 2006;107:15511561.

    • Search Google Scholar
    • Export Citation
  • 127

    Ramanujachar R, Richards S, Hann I. Adolescents with acute lymphoblastic leukaemia: outcome on UK national paediatric (ALL97) and adult (UKALLXII/E2993) trials. Pediatr Blood Cancer 2007;48:254261.

    • Search Google Scholar
    • Export Citation
  • 128

    Barry E, DeAngelo DJ, Neuberg D. Favorable outcome for adolescents with acute lymphoblastic leukemia treated on Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium Protocols. J Clin Oncol 2007;25:813819.

    • Search Google Scholar
    • Export Citation
  • 129

    Nachman JB, La MK, Hunger SP. Young adults with acute lymphoblastic leukemia have an excellent outcome with chemotherapy alone and benefit from intensive postinduction treatment: a report from the children’s oncology group. J Clin Oncol 2009;27:51895194.

    • Search Google Scholar
    • Export Citation
  • 130

    Pui CH, Campana D, Pei D. Treating childhood acute lymphoblastic leukemia without cranial irradiation. N Engl J Med 2009;360:27302741.

  • 131

    Pui CH, Pei D, Campana D. Improved prognosis for older adolescents with acute lymphoblastic leukemia. J Clin Oncol 2011;29:386391.

  • 132

    Ribera JM, Oriol A, Sanz MA. Comparison of the results of the treatment of adolescents and young adults with standard-risk acute lymphoblastic leukemia with the Programa Espanol de Tratamiento en Hematologia pediatric-based protocol ALL-96. J Clin Oncol 2008;26:18431849.

    • Search Google Scholar
    • Export Citation
  • 133

    DeAngelo DJ, Dahlberg S, Silverman LB. A multicenter phase II study using a dose intensified pediatric regimen in adults with untreated acute lymphoblastic leukemia [abstract]. Blood 2007;110:Abstract 587.

    • Search Google Scholar
    • Export Citation
  • 134

    Huguet F, Leguay T, Raffoux E. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol 2009;27:911918.

    • Search Google Scholar
    • Export Citation
  • 135

    GlaxoSmithKline. Prescribing Information. ARRANON (nelarabine) Injection. 2009. Available at: http://us.gsk.com/products/assets/us_arranon.pdf. Accessed June 2011.

    • Search Google Scholar
    • Export Citation
  • 136

    Winter SS, Devidas M, Wood B. Nelarabine may be safely incorporated into a phase III study for newly diagnosed T-lineage acute lymphoblastic leukemia: a report from the Children’s Oncology Group [abstract]. Blood 2010;116:Abstract 865.

    • Search Google Scholar
    • Export Citation
  • 137

    Ribera JM, Oriol A, Bethencourt C. Comparison of intensive chemotherapy, allogeneic or autologous stem cell transplantation as post-remission treatment for adult patients with high-risk acute lymphoblastic leukemia. Results of the PETHEMA ALL-93 trial. Haematologica 2005;90:13461356.

    • Search Google Scholar
    • Export Citation
  • 138

    Goldstone AH, Richards SM, Lazarus HM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood 2008;111:18271833.

    • Search Google Scholar
    • Export Citation
  • 139

    Cornelissen JJ, van der Holt B, Verhoef GE. Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison. Blood 2009;113:13751382.

    • Search Google Scholar
    • Export Citation
  • 140

    Ram R, Gafter-Gvili A, Vidal L. Management of adult patients with acute lymphoblastic leukemia in first complete remission: systematic review and meta-analysis. Cancer 2010;116:34473457.

    • Search Google Scholar
    • Export Citation
  • 141

    Yanada M, Matsuo K, Suzuki T, Naoe T. Allogeneic hematopoietic stem cell transplantation as part of postremission therapy improves survival for adult patients with high-risk acute lymphoblastic leukemia: a metaanalysis. Cancer 2006;106:26572663.

    • Search Google Scholar
    • Export Citation
  • 142

    Marks DI, Paietta EM, Moorman AV. T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Blood 2009;114:51365145.

    • Search Google Scholar
    • Export Citation
  • 143

    Maury S, Huguet F, Leguay T. Adverse prognostic significance of CD20 expression in adults with Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia. Haematologica 2010;95:324328.

    • Search Google Scholar
    • Export Citation
  • 144

    Nguyen K, Devidas M, Cheng SC. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children’s Oncology Group study. Leukemia 2008;22:21422150.

    • Search Google Scholar
    • Export Citation
  • 145

    Einsiedel HG, von Stackelberg A, Hartmann R. Long-term outcome in children with relapsed ALL by risk-stratified salvage therapy: results of trial acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Munster Group 87. J Clin Oncol 2005;23:79427950.

    • Search Google Scholar
    • Export Citation
  • 146

    Tallen G, Ratei R, Mann G. Long-term outcome in children with relapsed acute lymphoblastic leukemia after time-point and site-of-relapse stratification and intensified short-course multidrug chemotherapy: results of trial ALL-REZ BFM 90. J Clin Oncol 2010;28:23392347.

    • Search Google Scholar
    • Export Citation
  • 147

    Malempati S, Gaynon PS, Sather H. Outcome after relapse among children with standard-risk acute lymphoblastic leukemia: Children’s Oncology Group study CCG-1952. J Clin Oncol 2007;25:58005807.

    • Search Google Scholar
    • Export Citation
  • 148

    Genzyme Corporation Prescribing Information. Clolar (clofarabine) Injection for Intravenous Use. 2010. Available at: http://www.clolar.com/~/media/Files/Clolar/prescribing-information.pdf. Accessed January 2012.

    • Search Google Scholar
    • Export Citation
  • 149

    Jeha S, Gaynon PS, Razzouk BI. Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. J Clin Oncol 2006;24:19171923.

    • Search Google Scholar
    • Export Citation
  • 150

    Locatelli F, Testi AM, Bernardo ME. Clofarabine, cyclophosphamide and etoposide as single-course re-induction therapy for children with refractory/multiple relapsed acute lymphoblastic leukaemia. Br J Haematol 2009;147:371378.

    • Search Google Scholar
    • Export Citation
  • 151

    Pigneux A, Sauvezie M, Vey N. Clofarabine combinations in adults with refractory/relapsed acute lymphoblastic leukemia (ALL): a GRAALL report [abstract]. Blood 2011;118:Abstract 2586.

    • Search Google Scholar
    • Export Citation
  • 152

    Schiller G, Lee M, Territo M. Phase II study of etoposide, ifosfamide, and mitoxantrone for the treatment of resistant adult acute lymphoblastic leukemia. Am J Hematol 1993;43:195199.

    • Search Google Scholar
    • Export Citation
  • 153

    Weiss MA, Aliff TB, Tallman MS. A single, high dose of idarubicin combined with cytarabine as induction therapy for adult patients with recurrent or refractory acute lymphoblastic leukemia. Cancer 2002;95:581587.

    • Search Google Scholar
    • Export Citation
  • 154

    Faderl S, Thomas DA, O’Brien S. Augmented hyper-CVAD based on dose-intensified vincristine, dexamethasone, and asparaginase in adult acute lymphoblastic leukemia salvage therapy. Clin Lymphoma Myeloma Leuk 2011;11:5459.

    • Search Google Scholar
    • Export Citation
  • 155

    Kantarjian H, Thomas D, Jorgensen J. Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. Lancet Oncol 2012;13:403411.

    • Search Google Scholar
    • Export Citation
  • 156

    O’Brien S, Thomas DA, Ohanian M. Inotuzumab ozogamycin (I0), a CD22 monoclonal antibody conjugated to calecheamicin, is active in refractory-relapse acute lymphocytic leukemia (R-R ALL) [abstract]. Blood 2011;118:Abstract 875.

    • Search Google Scholar
    • Export Citation
  • 157

    Topp MS, Goekbuget N, Zugmaier G. Anti-CD19 BiTE blinatumomab induces high complete remission rate in adult patients with relapsed B-precursor ALL: updated results of an ongoing phase II trial [abstract]. Blood 2011;118:Abstract 252.

    • Search Google Scholar
    • Export Citation
  • 158

    Topp MS, Kufer P, Gokbuget N. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol 2011;29:24932498.

    • Search Google Scholar
    • Export Citation
  • 159

    Hahn T, Wall D, Camitta B. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute lymphoblastic leukemia in adults: an evidence-based review. Biol Blood Marrow Transplant 2006;12:130.

    • Search Google Scholar
    • Export Citation
  • 160

    Eapen M, Raetz E, Zhang MJ. Outcomes after HLA-matched sibling transplantation or chemotherapy in children with B-precursor acute lymphoblastic leukemia in a second remission: a collaborative study of the Children’s Oncology Group and the Center for International Blood and Marrow Transplant Research. Blood 2006;107:49614967.

    • Search Google Scholar
    • Export Citation
  • 161

    Burger B, Zimmermann M, Mann G. Diagnostic cerebrospinal fluid examination in children with acute lymphoblastic leukemia: significance of low leukocyte counts with blasts or traumatic lumbar puncture. J Clin Oncol 2003;21:184188.

    • Search Google Scholar
    • Export Citation
  • 162

    Lazarus HM, Richards SM, Chopra R. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E2993. Blood 2006;108:465472.

    • Search Google Scholar
    • Export Citation
  • 163

    Reman O, Pigneux A, Huguet F. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis and/or at first relapse: results from the GET-LALA group. Leuk Res 2008;32:17411750.

    • Search Google Scholar
    • Export Citation
  • 164

    Sancho JM, Ribera JM, Oriol A. Central nervous system recurrence in adult patients with acute lymphoblastic leukemia: frequency and prognosis in 467 patients without cranial irradiation for prophylaxis. Cancer 2006;106:25402546.

    • Search Google Scholar
    • Export Citation
  • 165

    Children’s Oncology Group. Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers. 2008. Available at: http://www.survivorshipguidelines.org/. Accessed January 2012.

    • Search Google Scholar
    • Export Citation
  • 166

    Mortuza FY, Papaioannou M, Moreira IM. Minimal residual disease tests provide an independent predictor of clinical outcome in adult acute lymphoblastic leukemia. J Clin Oncol 2002;20:10941104.

    • Search Google Scholar
    • Export Citation
  • 167

    Neale GA, Coustan-Smith E, Stow P. Comparative analysis of flow cytometry and polymerase chain reaction for the detection of minimal residual disease in childhood acute lymphoblastic leukemia. Leukemia 2004;18:934938.

    • Search Google Scholar
    • Export Citation
  • 168

    Kerst G, Kreyenberg H, Roth C. Concurrent detection of minimal residual disease (MRD) in childhood acute lymphoblastic leukaemia by flow cytometry and real-time PCR. Br J Haematol 2005;128:774782.

    • Search Google Scholar
    • Export Citation
  • 169

    Coustan-Smith E, Sancho J, Behm FG. Prognostic importance of measuring early clearance of leukemic cells by flow cytometry in childhood acute lymphoblastic leukemia. Blood 2002;100:5258.

    • Search Google Scholar
    • Export Citation
  • 170

    Coustan-Smith E, Sancho J, Hancock ML. Clinical importance of minimal residual disease in childhood acute lymphoblastic leukemia. Blood 2000;96:26912696.

    • Search Google Scholar
    • Export Citation
  • 171

    Cave H, van der Werff ten Bosch J, Suciu S. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia. European Organization for Research and Treatment of Cancer--Childhood Leukemia Cooperative Group. N Engl J Med 1998;339:591598.

    • Search Google Scholar
    • Export Citation
  • 172

    Coustan-Smith E, Behm FG, Sanchez J. Immunological detection of minimal residual disease in children with acute lymphoblastic leukaemia. Lancet 1998;351:550554.

    • Search Google Scholar
    • Export Citation
  • 173

    Stow P, Key L, Chen X. Clinical significance of low levels of minimal residual disease at the end of remission induction therapy in childhood acute lymphoblastic leukemia. Blood 2010;115:46574663.

    • Search Google Scholar
    • Export Citation
  • 174

    Conter V, Bartram CR, Valsecchi MG. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood 2010;115:32063214.

    • Search Google Scholar
    • Export Citation
  • 175

    Basso G, Veltroni M, Valsecchi MG. Risk of relapse of childhood acute lymphoblastic leukemia is predicted by flow cytometric measurement of residual disease on day 15 bone marrow. J Clin Oncol 2009;27:51685174.

    • Search Google Scholar
    • Export Citation
  • 176

    Panzer-Grumayer ER, Schneider M, Panzer S. Rapid molecular response during early induction chemotherapy predicts a good outcome in childhood acute lymphoblastic leukemia. Blood 2000;95:790794.

    • Search Google Scholar
    • Export Citation
  • 177

    Ko RH, Ji L, Barnette P. Outcome of patients treated for relapsed or refractory acute lymphoblastic leukemia: a Therapeutic Advances in Childhood Leukemia Consortium study. J Clin Oncol 2010;28:648654.

    • Search Google Scholar
    • Export Citation
  • 178

    Coustan-Smith E, Gajjar A, Hijiya N. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia after first relapse. Leukemia 2004;18:499504.

    • Search Google Scholar
    • Export Citation
  • 179

    Paganin M, Zecca M, Fabbri G. Minimal residual disease is an important predictive factor of outcome in children with relapsed ‘high-risk’ acute lymphoblastic leukemia. Leukemia 2008;22:21932200.

    • Search Google Scholar
    • Export Citation
  • 180

    Bruggemann M, Raff T, Flohr T. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood 2006;107:11161123.

    • Search Google Scholar
    • Export Citation
  • 181

    Holowiecki J, Krawczyk-Kulis M, Giebel S. Status of minimal residual disease after induction predicts outcome in both standard and high-risk Ph-negative adult acute lymphoblastic leukaemia. The Polish Adult Leukemia Group ALL 4-2002 MRD Study. Br J Haematol 2008;142:227237.

    • Search Google Scholar
    • Export Citation
  • 182

    Patel B, Rai L, Buck G. Minimal residual disease is a significant predictor of treatment failure in non T-lineage adult acute lymphoblastic leukaemia: final results of the international trial UKALL XII/ECOG2993. Br J Haematol 2010;148:8089.

    • Search Google Scholar
    • Export Citation
  • 183

    Vidriales MB, Perez JJ, Lopez-Berges MC. Minimal residual disease in adolescent (older than 14 years) and adult acute lymphoblastic leukemias: early immunophenotypic evaluation has high clinical value. Blood 2003;101:46954700.

    • Search Google Scholar
    • Export Citation
  • 184

    Bassan R, Spinelli O, Oldani E. Improved risk classification for risk-specific therapy based on the molecular study of minimal residual disease (MRD) in adult acute lymphoblastic leukemia (ALL). Blood 2009;113:41534162.

    • Search Google Scholar
    • Export Citation
  • 185

    Raff T, Gokbuget N, Luschen S. Molecular relapse in adult standard-risk ALL patients detected by prospective MRD monitoring during and after maintenance treatment: data from the GMALL 06/99 and 07/03 trials. Blood 2007;109:910915.

    • Search Google Scholar
    • Export Citation
  • 186

    Dworzak MN, Froschl G, Printz D. Prognostic significance and modalities of flow cytometric minimal residual disease detection in childhood acute lymphoblastic leukemia. Blood 2002;99:19521958.

    • Search Google Scholar
    • Export Citation
  • 187

    Bruggemann M, Schrauder A, Raff T. Standardized MRD quantification in European ALL trials: proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18-20 September 2008. Leukemia 2010;24:521535.

    • Search Google Scholar
    • Export Citation
  • 188

    Campana D. Minimal residual disease in acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program 2010;2010:712.

  • 189

    Goodman JL, Winston DJ, Greenfield RA. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med 1992;326:845851.

    • Search Google Scholar
    • Export Citation
  • 190

    Marr KA, Seidel K, Slavin MA. Prolonged fluconazole prophylaxis is associated with persistent protection against candidiasis-related death in allogeneic marrow transplant recipients: long-term follow-up of a randomized, placebo-controlled trial. Blood 2000;96:20552061.

    • Search Google Scholar
    • Export Citation
  • 191

    Slavin MA, Osborne B, Adams R. Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation--a prospective, randomized, double-blind study. J Infect Dis 1995;171:15451552.

    • Search Google Scholar
    • Export Citation
  • 192

    Hughes WT, Rivera GK, Schell MJ. Successful intermittent chemoprophylaxis for Pneumocystis carinii pneumonitis. N Engl J Med 1987;316:16271632.

    • Search Google Scholar
    • Export Citation
  • 193

    Lindemulder S, Albano E. Successful intermittent prophylaxis with trimethoprim/sulfamethoxazole 2 days per week for Pneumocystis carinii (jiroveci) pneumonia in pediatric oncology patients. Pediatrics 2007;120:e4751.

    • Search Google Scholar
    • Export Citation
  • 194

    Mattano LA Jr, Sather HN, Trigg ME, Nachman JB. Osteonecrosis as a complication of treating acute lymphoblastic leukemia in children: a report from the Children’s Cancer Group. J Clin Oncol 2000;18:32623272.

    • Search Google Scholar
    • Export Citation
  • 195

    te Winkel ML, Pieters R, Hop WC. Prospective study on incidence, risk factors, and long-term outcome of osteonecrosis in pediatric acute lymphoblastic leukemia. J Clin Oncol 2011;29:41434150.

    • Search Google Scholar
    • Export Citation
  • 196

    Vora A. Management of osteonecrosis in children and young adults with acute lymphoblastic leukaemia. Br J Haematol 2011;155:549560.

  • 197

    Asselin BL. The three asparaginases. Comparative pharmacology and optimal use in childhood leukemia. Adv Exp Med Biol 1999;457:621629.

    • Search Google Scholar
    • Export Citation
  • 198

    Pieters R, Hunger SP, Boos J. L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase. Cancer 2011;117:238249.

    • Search Google Scholar
    • Export Citation
  • 199

    Stock W, Douer D, Deangelo DJ. Prevention and management of asparaginase/pegasparaginase-associated toxicities in adults and older adolescents: recommendations of an expert panel. Leuk Lymphoma 2011;52:22372253.

    • Search Google Scholar
    • Export Citation
  • 200

    Avramis VI, Sencer S, Periclou AP. A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: a Children’s Cancer Group study. Blood 2002;99:19861994.

    • Search Google Scholar
    • Export Citation
  • 201

    Wang B, Relling MV, Storm MC. Evaluation of immunologic crossreaction of antiasparaginase antibodies in acute lymphoblastic leukemia (ALL) and lymphoma patients. Leukemia 2003;17:15831588.

    • Search Google Scholar
    • Export Citation
  • 202

    Zalewska-Szewczyk B, Gach A, Wyka K. The cross-reactivity of anti-asparaginase antibodies against different L-asparaginase preparations. Clin Exp Med 2009;9:113116.

    • Search Google Scholar
    • Export Citation
  • 203

    Willer A, Gerss J, Konig T. Anti-Escherichia coli asparaginase antibody levels determine the activity of second-line treatment with pegylated E coli asparaginase: a retrospective analysis within the ALL-BFM trials. Blood 2011;118:57745782.

    • Search Google Scholar
    • Export Citation
  • 204

    Vrooman LM, Supko JG, Neuberg DS. Erwinia asparaginase after allergy to E. coli asparaginase in children with acute lymphoblastic leukemia. Pediatr Blood Cancer 2010;54:199205.

    • Search Google Scholar
    • Export Citation
  • 205

    EUSA Pharma (USA), Inc. Prescribing Information. Asparaginase Erwinia chrysanthemi ERWINAZE™ For Injection, Intramuscular Use. 2011. Available at: http://www.erwinaze.com/pdf/PI_18-Nov2011.pdf. Accessed February 2012.

    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 390 295 15
PDF Downloads 104 82 3
EPUB Downloads 0 0 0