Acute lymphoblastic leukemia

New England Journal of Medicine

Volumn 339, Issue 9, 1998, Pages 605-615

  Pui, Ching Hon ^a,b,c   Evans, William E ^a,b  

^a UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^b UNIVERSITY OF TENNESSEE COLLEGE OF MEDICINE   (United States)

^c ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; ASPARAGINASE; CYCLOPHOSPHAMIDE; CYTARABINE; DEXAMETHASONE; DOXORUBICIN; EPIPODOPHYLLOTOXIN; ETOPOSIDE; GLUCOCORTICOID; IFOSFAMIDE; MERCAPTOPURINE; METHOTREXATE; TIOGUANINE; VINCRISTINE;

ACUTE LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; ADULT; BRAIN METASTASIS; CANCER COMBINATION CHEMOTHERAPY; CHILD; CHILDHOOD LEUKEMIA; GENOTYPE; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMAN; IMMUNOPHENOTYPING; LEUKEMIA CELL; MAJOR CLINICAL STUDY; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT;

DISEASE-FREE SURVIVAL; DNA-BINDING PROTEINS; GENE REARRANGEMENT; HUMANS; LEUKEMIA, LYMPHOCYTIC, ACUTE; MYELOID-LYMPHOID LEUKEMIA PROTEIN; NEOPLASM, RESIDUAL; ONCOGENE PROTEINS, FUSION; PROGNOSIS; PROTO-ONCOGENES; RISK ASSESSMENT; TRANSCRIPTION FACTORS;

EID: 0032572912     PISSN: 00284793     EISSN: None     Source Type: Journal    
DOI: 10.1056/NEJM199808273390907     Document Type: Review

References (105)

1. Parker SL, Tong T, Bolden S, Wingo PA. Cancer statistics, 1997. CA Cancer J Clin 1997;47:5-27. [Erratum, CA Cancer J Clin 1997;47:68.]
2. Cortes JE, Kantarjian HM. Acute lymphoblastic leukemia: a comprehensive review with emphasis on biology and therapy. Cancer 1995;76:2393-417.
3. Laport GF, Larson RA. Treatment of adult acute lymphoblastic leukemia. Semin Oncol 1997;24:70-82.
4. Pui C-H. Acute lymphoblastic leukemia. Pediatr Clin North Am 1997; 44:831-46.
5. Groupe Français de Cytogénétique Hématologique. Cytogenetic abnormalities in adult acute lymphoblastic leukemia: correlations with hematologic findings and outcome: a collaborative study of the Groupe Français de Cytogénétique Hématologique. Blood 1996;87:3135-42. [Erratum, Blood 1996;88:2818.]
6. Chessells JM, Hall E, Prentice HG, Durrant J, Bailey CC, Richards SM. The impact of age on outcome in lymphoblastic leukaemia: MRC UKALL X and XA compared: a report from the MRC Paediatric and Adult Working Parties. Leukemia 1998;12:463-73.
7. Copelan EA, McGuire EA. The biology and treatment of acute lymphoblastic leukemia in adults. Blood 1995;85:1151-68.
8. Pui C-H, Behm FG, Crist WM. Clinical and biologic relevance of immunologic marker studies in childhood acute lymphoblastic leukemia. Blood 1993;82:343-62.
9. Pui C-H. Childhood leukemias. N Engl J Med 1995;332:1618-30.
10. Kishimoto T, Goyert S, Kikutani H, et al. CD antigens 1996. Blood 1997;89:3502.
11. Pui C-H, Raimondi SC, Head DR, et al. Characteristics of childhood acute leukemia with multiple myeloid and lymphoid markers at diagnosis and at relapse. Blood 1991;78:1327-37.
12. Larson RA, Dodge RK, Burns CP, et al. A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 8811. Blood 1995;85:2025-37.
13. Uckun FM, Sather HN, Gaynon PS, et al. Clinical features and treatment outcome of children with myeloid antigen positive acute lymphoblastic leukemia: a report from the Children's Cancer Group. Blood 1997;90:28-35.
14. Campana D, Pui C-H. Detection of minimal residual disease in acute leukemia: methodologic advances and clinical significance Blood 1995;85: 1416-34.
15. Look AT. Oncogenic transcription factors in the human acute leukemias. Science 1997;278:1059-64.
16. Pui C-H, Crist WM. Biology and treatment of acute lymphoblastic leukemia. J Pediatr 1994;124:491-503.
17. Schorin MA, Blattner S, Gelber RD, et al. Treatment of childhood acute lymphoblastic leukemia: results of Dana-Farber Cancer Institute/ Children's Hospital Acute Lymphoblastic Leukemia Consortium Protocol 85-01. J Clin Oncol 1994;12:740-7.
18. Reiter A, Schrappe M, Ludwig W-D, et al. Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients: results and conclusions of the multicenter trial ALL-BFM 86. Blood 1994;84:3122-33.
19. Soussain C, Patte C, Ostronorf M, et al. Small noncleaved cell lymphoma and leukemia in adults: a retrospective study of 65 adults treated with the LMB pediatric protocols. Blood 1995;85:664-74.
20. Hoelzer D, Ludwig W-D, Thiel E, et al. Improved outcome in adult B-cell acute lymphoblastic leukemia. Blood 1996;87:495-508.
21. Reiter A, Schrappe M, Ludwig W-D, et al. Favorable outcome of B-cell acute lymphoblastic leukemia in childhood: a report of three consecutive studies of the BFM group. Blood 1992;80:2471-8.
22. Patte C. Non-Hodgkin's lymphoma. Eur J Cancer 1998;34:359-63.
23. Nachman J, Sather HN, Buckley JD, et al. Young adults 16-21 years of age at diagnosis entered on Childrens Cancer Group acute lymphoblastic leukemia and acute myeloblastic leukemia protocols: results of treatment Cancer 1993;71:Suppl:3377-85.
24. Pui C-H, Boyett JM, Hancock ML, Pratt CB, Meyer WH, Crist WM. Outcome of treatment for childhood cancer in black as compared with white children: the St. Jude Children's Research Hospital experience, 1962 through 1992. JAMA 1995;273:633-7.
25. Smith M, Arthur D, Camitta B, et al. Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia. J Clin Oncol 1996;14:18-24.
26. Pui C-H, Kane JR, Crist WM. Biology and treatment of infant leukemias. Leukemia 1995;9:762-9.
27. Rubnitz JE, Link MP, Shuster JJ, et al. Frequency and prognostic significance of HRX rearrangements in infant acute lymphoblastic leukemia: a Pediatric Oncology Group study. Blood 1994;84:570-3.
28. Behm FG, Raimondi SC, Frestedt JL, et al. Rearrangement of the MLL gene confers a poor prognosis in childhood acute lymphoblastic leukemia, regardless of presenting age. Blood 1996;87:2870-7.
29. Rubnitz JE, Downing JR, Pui C-H, et al. TEL gene rearrangement in acute lymphoblastic leukemia: a new genetic marker with prognostic significance. J Clin Oncol 1997;15:1150-7.
30. Borkhardt A, Cazzaniga G, Viehmann S, et al. Incidence and clinical relevance of TEL/AML1 fusion genes in children with acute lymphoblastic leukemia enrolled in the German and Italian multicenter therapy trials Blood 1997;90:571-7.
31. Gajjar A, Ribeiro R, Hancock ML, et al. Persistence of circulating blasts after 1 week of multiagent chemotherapy confers a poor prognosis in childhood acute lymphoblastic leukemia. Blood 1995;86:1292-5.
32. Gaynon PS, Desai AA, Bostrom BC, et al. Early response to therapy and outcome in childhood acute lymphoblastic leukemia: a review. Cancer 1997;80:1717-26.
33. Coustan-Smith E, Behm FG, Sanchez J, et al. Immunological detection of minimal residual disease in children with acute lymphoblastic leukaemia. Lancet 1998;351:550-4.
34. Cavé H, van der Werff ten Bosch J, Suciu S, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia N Engl J Med 1998;339:591-8.
35. Hunger SP, Fall MZ, Camitta BM, et al. E2A-PBX1 chimeric transcript status at end of consolidation is not predictive of treatment outcome in childhood acute lymphoblastic leukemias with a t(1;19)(q23;p13): a Pediatric Oncology Group study. Blood 1998;91:1021-8.
36. Kaspers GJL, Veerman AJP, Pieters R, et al. In vitro cellular drug resistance and prognosis in newly diagnosed childhood acute lymphoblastic leukemia. Blood 1997;90:2723-9.
37. Uckun FM. Severe combined immunodeficient mouse models of human leukemia. Blood 1996;88:1135-46.
38. Kumagai M, Manabe A, Pui C-H, et al. Stroma-supported culture in childhood B-lineage acute lymphoblastic leukemia cells predicts treatment outcome. J Clin Invest 1996;97:755-60.
39. Ribeiro RC, Broniscer A, Rivera GK, et al. Philadelphia chromosome-positive acute lymphoblastic leukemia in children: durable responses to chemotherapy associated with low initial white blood cell counts. Leukemia 1997;11:1493-6.
40. Schrappe M, Aricò M, Harbott J, et al. Ph+ childhood acute lymphoblastic leukemia: good initial steroid response allows early prediction of a favorable treatment outcome. Blood (in press).
41. Pui C-H, Carroll AJ, Raimondi SC, et al. Clinical presentation, karyotypic characterization, and treatment outcome of childhood acute lymphoblastic leukemia with a near-haploid or hypodiploid <45 line Blood 1990;75:1170-7.
42. Pui C-H, Frankel LS, Carroll AJ, et al. Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t(4;11)(q21;q23): a collaborative study of 40 cases. Blood 1991;77:440-7.
43. Conter V, Schrappe M, Aricó M, et al. Role of cranial radiotherapy for childhood T-cell acute lymphoblastic leukemia with high WBC count and good response to prednisone. J Clin Oncol 1997;15:2786-91.
44. Mahmoud HH, Rivera GK, Hancock ML, et al. Low leukocyte counts with blast cells in cerebrospinal fluid of children with newly diagnosed acute lymphoblastic leukemia. N Engl J Med 1993;329:314-9.
45. Dinarello CA, Bunn PA Jr. Fever. Semin Oncol 1997;24:288-98.
46. Hughes WT, Rivera GK, Schell MJ, Thornton D, Loft L. Successful intermittent chemoprophylaxis for Pneumocystis carinii pneumonitis. N Engl J Med 1987;316:1627-32.
47. Masson E, Synold TW, Relling MV, et al. Allopurinol inhibits de novo purine synthesis in lymphoblasts of children with acute lymphoblastic leukemia. Leukemia 1996;10:56-60.
48. Pui C-H, Relling MV, Lascombes F, et al. Urate oxidase in prevention and treatment of hyperuricemia associated with lymphoid malignancies Leukemia 1997;11:1813-6.
49. Bunin NJ, Pui C-H. Differing complications of hyperteukocytosis in children with acute lymphoblastic or acute nonlymphoblastic leukemia. J Clin Oncol 1985;3:1590-5.
50. Nelson SC, Bruggers CS, Kurtzberg J, Friedman HS. Management of leukemic hyperleukocytosis with hydration, urinary alkalinization, and allopurinol: are cranial irradiation and invasive cytoreduction necessary? Am J Pediatr Hematol Oncol 1993;15:351-5.
51. Rivera GK, Raimondi SC, Hancock ML, et al. Improved outcome in childhood acute lymphoblastic leukemia with reinforced early treatment and rotational combination chemotherapy. Lancet 1991;337:61-6.
52. Niemeyer CM, Gelber RD, Tarbell NJ, et al. Low-dose versus high-dose methotrexate during remission induction in childhood acute lymphoblastic leukemia (Protocol 81-01 update). Blood 1991;78:2514-9.
53. Gaynon PS, Steinherz PG, Bleyer WA, et al. Improved therapy for children with acute lymphoblastic leukemia and unfavorable presenting features: a follow-up report of the Childrens Cancer Group Study CCG-106. J Clin Oncol 1993;11:2234-42.
54. Bostrom B, Gaynon PS, Sather H, et al. Dexamethasone (DEX) decreases central nervous system (CNS) relapse and improves event-free survival (EFS) in lower risk acute lymphoblastic leukemia (ALL). Proc Am Soc Clin Oncol 1998;17:527A.
55. Veerman AJP, Hählen K, Kamps WA, et al. High cure rate with a moderately intensive treatment regimen in non-high-risk childhood acute lymphoblastic leukemia: results of protocol ALL VI from the Dutch Childhood Leukemia Study Group. J Clin Oncol 1996;14:911-8.
56. Rohatiner AZ, Bassan R, Battista R, et al. High dose cytosine arabinoside in the initial treatment of adults with acute lymphoblastic leukaemia. Br J Cancer 1990;62:454-8.
57. Mahoney DH Jr, Shuster JJ, Nitschke R, et al. Intermediate-dose intravenous methotrexate with intravenous mercaptopurine is superior to repetitive low-dose oral methotrexate with intravenous mercaptopurine for children with lower-risk B-lineage acute lymphoblastic leukemia: a Pediatric Oncology Group phase III trial. J Clin Oncol 1998;16:246-54.
58. Chessells JM, Bailey C, Richards SM. Intensification of treatment and survival in all children with lymphoblastic leukaemia: results of UK Medical Research Council trial UKALL X. Lancet 1995;345:143-8.
59. Hoelzer D, Thiel E, Ludwig WD, et al. The German multicentre trials for treatment of acute lymphoblastic leukemia in adults: the German Adult ALL Study Group. Leukemia 1992;6:Suppl 2:175-7.
60. Evans WE, Crom WR, Abromowitch M, et al. Clinical pharmacodynamics of high-dose methotrexate in acute lymphoblastic leukemia: identification of a relation between concentration and effect. N Engl J Med 1986;314:471-7.
61. Evans WE, Relling MV, Rodman JH, Crom WR, Boyett JM, Piu C-H. Conventional compared with individualized chemotherapy for childhood acute lymphoblastic leukemia. N Engl J Med 1998;338:499-505.
62. Childhood ALL Collaborative Group. Duration and intensity of maintenance chemotherapy in acute lymphoblastic leukaemia: overview of 42 trials involving 12 000 randomised children. Lancet 1996;347:1783-8.
63. Tubergen DG, Gilchrist GS, O'Brien RT, et al. Improved outcome with delayed intensification for children with acute lymphoblastic leukemia and intermediate presenting features: a Childrens Cancer Group phase III trial J Clin Oncol 1993;11:527-37.
64. Nachman JB, Sather HN, Sensel MG, et al. Augmented post-induction therapy for children with high-risk acute lymphoblastic leukemia and a slow response to initial therapy. N Engl J Med 1998;338:1663-71.
65. Cortes J, O'Brien SM, Pierce S, Keating MJ, Freireich EJ, Kantarjian HM. The value of high-dose systemic chemotherapy and intrathecal therapy for central nervous system prophylaxis in different risk groups of adult acute lymphoblastic leukemia. Blood 1995;86:2091-7.
66. Nachman J, Sather HN, Cherlow JM, et al. Response of children with high-risk acute lymphoblastic leukemia treated with and without cranial irradiation: a report from the Children's Cancer Group. J Clin Oncol 1998; 16:920-30.
67. Pui C-H, Mahmoud HH, Rivera GK, et al. Early intensification of intrathecal chemotherapy virtually eliminates central nervous system relapse in children with acute lymphoblastic leukemia. Blood 1998;92:411-5.
68. Ottmann OG, Hoelzer D, Gracien E, et al. Concomitant granulocyte colony-stimulating factor and induction chemoradiotherapy in adult acute lymphoblastic leukemia: a randomized phase III trial. Blood 1995;86:444-50.
69. Pui C-H, Boyett JM, Hughes WT, et al. Human granulocyte colony-stimulating factor after induction chemotherapy in children with acute lymphoblastic leukemia. N Engl J Med 1997;336:1781-7.
70. Geissler K, Koller E, Hubmann E, et al. Granulocyte colony-stimulating factor as an adjunct to induction chemotherapy for adult acute lymphoblastic leukemia - a randomized phase-III study. Blood 1997;90:590-6.
71. Balis FM, Lester CM, Chrousos GP, Heideman RL, Poplack DG. Differences in cerebrospinal fluid penetration of corticosteroids: possible relationship to the prevention of meningeal leukemia. J Clin Oncol 1987;5:202-7.
72. Otten J, Suciu S, Lutz P, et al. The importance of L-asparaginase (A'ase) in the treatment of acute lymphoblastic leukemia (ALL) in children: results of the EORTC 58881 randomized phase III trial showing greater efficiency of Escherichia coli (E. coli) as compared to Erwinia (Erw) A'ase. Blood 1996;88:Suppl 1:669a. abstract.
73. Cuttner J, Mick R, Budman DR, et al. Phase III trial of brief intensive treatment of adult acute lymphoblastic leukemia comparing daunorubicin and mitoxantrone: a CALGB study. Leukemia 1991;5:425-31.
74. Fière D, Lepage E, Sebban C, et al. Adult acute lymphoblastic leukemia: a multicentric randomized trial testing bone marrow transplantation as postremission therapy. J Clin Oncol 1993;11:1990-2001.
75. Synold TW, Relling MV, Boyctt JM, et al. Blast cell methotrexate-polyglutamate accumulation in vivo differs by lineage, ploidy, and methotrexate dose in acute lymphoblastic leukemia. J Clin Invest 1994;94:1996-2001.
76. Galpin AJ, Schuetz JD, Masson E, et al. Differences in folylpolyglutamate synthetase and dihydrofolate reductase expression in human B-lineage versus T-lineage leukemic lymphoblasts: mechanisms for lineage differences in methotrexate polyglutamylation and cytotoxicity. Mol Pharmacol 1997;52:155-63.
77. Cassileth PA, Andersen JW, Bennett JM, et al. Adult acute lymphocytic leukemia: the Eastern Cooperative Oncology Group experience. Leukemia 1992;6:Suppl 2:178-81.
78. Whitehead VM, Vuchich MJ, Lauer SJ, et al. Accumulation of high levels of methotrexate polyglutamates in lymphoblasts from children with hyperdiploid (>50 chromosomes) B-lineage acute lymphoblastic leukemia: a Pediatric Oncology Group study. Blood 1992;80:1316-23.
79. Lennard L, Lilleyman JS, Van Loon J, Weinshilboum RM. Genetic variation in response to 6-mercaptopurine for childhood acute lymphoblastic leukaemia. Lancet 1990;336:225-9.
80. Chessells JM, Harrison G, Lilleyman JS, Bailey CC, Richards SM. Continuing (maintenance) therapy in lymphoblastic leukaemia: lessons from MRC UKALL X. Br J Haematol 1997;98:945-51.
81. Evans WE, Horner M, Chu YQ, Kalwinsky D, Roberts WM. Altered mercaptopurine metabolism, toxic effects, and dosage requirement in a thiopurine methyltransferase-deficient child with acute lymphocytic leukemia. J Pediatr 1991;119:985-9.
82. Yates CR, Krynetski EY, Loennechen T, et al. Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Ann Intern Med 1997;126:608-14.
83. Schmiegelow K, Glomstein A, Kristinsson J, Salmi T, Schrøder H, Björk O. Impact of morning versus evening schedule for oral methotrexate and 6-mercaptopurine on relapse risk for children with acute lymphoblastic leukemia. J Pediatr Hematol Oncol 1997;19:102-9.
84. Sackmann-Muriel F, Felice MS, Zubizarreta P, Chantada G, Barbieri MAF, Rossi J. Improved outcome in higher-risk acute lymphoblastic leukemia with a hybrid (Berlin-Frankfurt-Münster/St. Jude's) therapy. Int J Pediatr Hematol Oncol 1996;3:439-49.
85. Appelbaum FR. Allogeneic hematopoietic stem cell transplantation for acute leukemia. Semin Oncol 1997;24:114-23.
86. Barrett AJ, Horowitz MM, Pollock BH, et al. Bone marrow transplants from HLA-identical siblings as compared with chemotherapy for children with acute lymphoblastic leukemia in a second remission. N Engl J Med 1994;331:1253-8.
87. Uderzo C, Valsecchi MG, Bacigalupo A, et al. Treatment of childhood acute lymphoblastic leukemia in second remission with allogeneic bone marrow transplantation and chemotherapy: ten-year experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association. J Clin Oncol 1995;13:352-8.
88. Sebban C, Lepage E, Vernant J-P, et al. Allogeneic bone marrow transplantation in adult acute lymphoblastic leukemia in first complete remission: a comparative study. J Clin Oncol 1994;12:2580-7.
89. Sierra J, Radich J, Hansen JA, et al. Marrow transplants from unrelated donors for treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 1997;90:1410-4.
90. Hongeng S, Krance RA, Bowman LC, et al. Outcomes of transplantation with matched-sibling and unrelated-donor bone marrow in children with leukaemia. Lancet 1997;350:767-71.
91. Gluckman E, Rocha V, Boyer-Chammard A, et al. Outcome of cordblood transplantation from related and unrelated donors. N Engl J Med 1997;337:373-81.
92. Winick NJ, Bowman WP, Kamen BA, et al. Unexpected acute neurologic toxicity in the treatment of children with acute lymphoblastic leukemia. J Natl Cancer Inst 1992;84:252-6.
93. Mahoney DH Jr, Shuster JJ, Nitschke R, et al. Acute neurotoxicity in children with B-precursor acute lymphoid leukemia: an association with intermediate-dose intravenous methotrexate and intrathecal triple therapy - a Pediatric Oncology Group study. J Clin Oncol 1998;16:1712-22.
94. Waber DP, Tarbell NJ, Fairclough D, et al. Cognitive sequelae of treatment in childhood acute lymphoblastic leukemia: cranial radiation requires an accomplice. J Clin Oncol 1995;13:2490-6.
95. Pui C-H, Ribeiro RC, Hancock ML, et al. Acute myeloid leukemia in children treated with epipodophyllotoxins for acute lymphoblastic leukemia. N Engl J Med 1991;325:1682-7.
96. Pui C-H, Relling MV, Rivera GK, et al. Epipodophyllotoxin-related acute myeloid leukemia: a study of 35 cases. Leukemia 1995;9:1990-6.
97. Lipshultz SE, Lipsitz SR, Mone SM, et al. Female sex and higher drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. N Engl J Med 1995;332:1738-43.
98. Hawkins MM, Draper GJ, Winter DJ. Cancer in the offspring of survivors of childhood leukaemia and non-Hodgkin lymphomas. Br J Cancer 1995;71:1335-9.
99. Kenney LB, Nicholson HS, Brasseux C, et al. Birth defects in offspring of adult survivors of childhood acute lymphoblastic leukemia: a Childrens Cancer Group/National Institutes of Health report. Cancer 1996;78:169-76.
100. Sankila R, Olsen JH, Anderson H, et al. Risk of cancer among offspring of childhood-cancer survivors. N Engl J Med 1998;338:1339-44.
101. Kurtzberg J, Keating M, Moore JO, et al. 2-Amino-9-B-D-arabinosyl-6-methoxy-9H-guanine (GW 506U; compound 506U) is highly active in patients with T-cell malignancies: results of a phase I trial in pediatric and adult patients with refractory hematological malignancies. Blood 1996;88: Suppl 1:669a. abstract.
102. Hart I, Colaco C. Fusion induces tumour rejection. Nature 1997; 388:626-7.
103. Braun SE, Chen K, Battiwalla M, Cornetta K. Gene therapy strategies for leukemia. Mol Med Today 1997;3:39-46.
104. Gottesfeld JM, Neely L, Trauger JW, Baird EE, Dervan PB. Regulation of gene expression by small molecules. Nature 1997;387:202-5.
105. Perez-Atayde AR, Sallan SE, Tedrow U, Connors S, Allred E, Folkman J. Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia. Am J Pathol 1997;150:815-21.