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a References 157 5. Jacobs AD, Gale RP (1984) Recent advances in the biology and treatment of acute lymphoblastic leukemia in adults. N Engl J Med 311:1219–1231 6. Baccarani M, Corbelli G, Amadori S, Drenthe-Schronk A, Willemze R, Meloni G, Cardozo PL, Haanen C, Mandelli F, Tura S (1982) Adolescent and adult acute lymphoblastic leukemia: Prognostic features and outcome of therapy: A study of 293 patients. Blood 60:677–684 7. Hoelzer D, Thiel E, Löffler H, Bodenstein H, Plaumann L, Büchner T, Urbanitz D, Koch P, Heimpel H, Engelhardt R, et al. (1984) Intensified therapy in acute lymphoblastic and acute undifferentiated leukemia in adults. Blood 64:38–47 8. Lister TA, Whitehouse JMA, Beard MEJ, Brearley RL, Wrigley PF, Oliver RT, Freeman JE, Woodruff RK, Malpas JS, Paxton AM, Crowther D (1978) Combination chemotherapy for acute lymphoblastic leukaemia in adults. Br Med J 1:199–203 9. Schauer P, Arlin ZA, Mertelsmann R, Cirrincione C, Friedman A, Gee TS, Dowling M, Kempin S, Straus DJ, Koziner B, et al. (1983) Treatment of acute lymphoblastic leukemia in adults: Results of the L- 10 and L-10M protocols. J Clin Oncol 462–470 10. Fiere D, Marty M, Solal-Celigny P, Harousseau JL, Gorin NC, Desablens B, Brière J, David B, Bordessoule D, Hayat M, et al. (1989) Induction massive et consolidation précoce des leucémies aigus lymphoïdes de l’adulte. Etude pilote de faisabilité et évolution lointaine. Presse Méd (Paris) 18:221–223 11. Fiere D, Extra JM, David B, Witz F, Vernand JP, Gastaut JA, Dauriac C, Pris J, Marty M (1987) Treatment of 218 adult acute lymphoblastic leukemias. Semin Oncol 14:64–66 12. Vernant JP, Marit G, Maraninchi D, Guyotat D, Kuentz M, Cordonnier C, Reiffers J (1988) Allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia in first complete remission. J Clin Oncol 6:227–231 13. Gaynor J, Chapman D, Little C, McKenzie S, Miller W, Andreeff M, Arlin Z, Berman E, Kempin S, Gee T, et al. (1988) A cause specific hazard rate analysis of prognostic factors among 199 adults with acute lymphoblastic leukemia. The Memorial Hospital experience since 1969. J Clin Oncol 6:1014–1030 14. Fiere D, Broustet A, Leblond V, Maraninchi D, Castaigne S, Flesch M, Varet B, Vernant JP, Milpied N, Troussard X, et al. (1990) Comparison of chemotherapy and autologous and allogeneic transplantation as postinduction regimen in adult acute lymphoblastic leukemia: A preliminary multicentric study. Hamatol Bluttransfus 33:409–412 15. Fiere D, Lepage E, Sebban C, Boucheix C, Gisselbrecht C, Vernant JP, Varet B, Broustet A, Cahn JY, Rigal-Huguet F, et al. for the French Group on Therapy for Adult Acute Lymphoblastic Leukemia (1993) Adult acute lymphoblastic leukemia: A multicentric randomized trial testing bone marrow transplantation as postremission therapy. J Clin Oncol 11:1990–2001 16. Hoelzer D, Thiel E, Löffler H, Büchner T, Ganser A, Heil G, Koch P, Freund M, Diedrich H, Rühl H, et al. (1988) Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood 71:123–131 17. Linker CA, Levitt LJ, O‘Donnell M, Forman SJ, Ries CA (1991) Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: A follow-up report. Blood 78:2814–2822 18. Thiebaut A, Vernant JP, Degos L, Rigal Huguet F, Reiffers J, Sebban C, Lepage E, Thomas X, Fiere D (2000) Adult acute lymphocytic leukemia study testing chemotherapy and autologous and allogeneic transplantation. A follow-up report of the French protocol LALA 87. Hematol Oncol Clin North Am 14:1353–1365 19. Horowitz MM, Messerer D, Hoelzer D, Gale RP, Neiss A, Atkinson K, Barrett AJ, Büchner T, Freund M, Heil G, et al. (1991) Chemotherapy compared with bone marrow transplantation for adults with acute lymphoblastic leukemia in first remission. Ann Intern Med 115:13–18 20. Oh H, Gale RP, Zhang MJ, Passweg JR, Ino T, Murakami H, Ohno R, Rowlings PA, Sobocinski KA, Tanimoto M, et al. (1998) Chemotherapy vs. HLA-identical sibling bone marrow transplants for adults with acute lymphoblastic leukemia in first remission. Bone Marrow Transplant 22:253–257 21. Gale RP, Park RE, Dubois RW, Herzig GP, Hocking WG, Horowitz MM, Keating A, Kempin S, Linker CA, Schiffer CA, et al. (1998) Delphi-panel analysis of appropriateness of high-dose therapy and bone marrow transplants in adults with acute lymphoblastic leukemia in first remission. Leuk Res 22:973–981 22. Thomas X, Danala C, Bach QK, Dufour P, Christian B, Corront B, Bosly A, Bastion Y, Gratecos N, Leblay R, et al. (1995) Sequential induction chemotherapy with vincristine, daunorubicin, cyclophosphamide and prednisone in adult acute lymphoblastic leukemia. Ann Hematol 70:65–69 23. Hoelzer D (1994) Treatment of acute lymphoblastic leukemia. Semin Hematol 31:1–15 24. Thomas X, Boiron JM, Huguet F, Dombret H, Bradstock K, Vey N, Kovacsovics T, Delannoy A, Fegueux N, Fenaux P, et al. (2004) Outcome of treatment in adults with acute lymphoblastic leukemia: Analysis of the LALA-94 trial. J Clin Oncol 22:4075–4086 25. Dombret H, Gabert J, Boiron JM, Rigal-Huguet F, Blaise D, Thomas X, Delannoy A, Buzyn A, Bilhou-Nabera C, Cayuela JM, et al. for the Groupe d‘Etude et de Traitement de la Leucémie Aiguë Lymphoblastique de l’Adulte (GET-LALA Group) (2002) Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia7Results of the prospective multicenter LALA-94 trial. Blood 100:2357–2366 26. Weiss M, Maslak P, Felman E, Berman E, Bertino J, Gee T, Megherian L, Seiter K, Scheinberg D, Golde D (1996) Cytarabine with high dose mitoxantrone induces rapid complete remission in adult acute lymphoblastic leukemia without the use of vincristine or prednisone. J Clin Oncol 14:2480–2485 27. Thomas X, Boiron JM, Huguet F, Reman O, Sutton L, Turlure P, Garban F, Gardin C, Espinouse D, Boulat O, et al. for the Groupe d‘Etude et de Traitement de la Leucémie Aiguë Lymphoblastique de l’Adulte (GET-LALA Group) (2004) Efficacy of granulocyte and granulocyte-macrophage colony-stimulating factors in the induction treatment of adult acute lymphoblastic leukemia: A multicenter randomized study. Hematol J 5:384–394 28. Rohatiner AZ, Bassan R, Battista R, Barnett MJ, Gregory W, Lim J, Amess J, Oza A, Barbui T, Horton M (1990) High dose cytosine arabinoside in the initial treatment of adults with acute lymphoblastic leukaemia. Br J Cancer 62:454–458 29. Cassileth PA, Andersen JW, Bennett JM, Hoagland HC, Mazza JJ, O‘Connell MC, Paietta E, Wiernik P (1992) Adult acute lymphocytic leukemia: The Eastern Cooperative Oncology Group experience. Leukemia 6(Suppl 2):178–181 30. Hoelzer D, Thiel E, Ludwig WD, Löffler H, Büchner T, Freund M, Heil G, Hiddemann W, Maschemeyer G, Volkers B (1992) The German
158 Chapter 11 · Conventional Therapy in Adult Acute Lymphoblastic Leukemia: Review of the LALA Program multicentre trials for treatment of acute lymphoblastic leukemia in adults. Leukemia 6(Suppl 2):175–177 31. Zhang MJ, Hoelzer D, Horowitz MM, Gale RP, Messerer D, Klein JP, Löffler H, Sobocinski KA, Thiel E, Weisdorf DJ (1995) Long-term follow-up of adults with acute lymphoblastic leukemia in first remission treated with chemotherapy or bone marrow transplantation. Ann Intern Med 123:428–431 32. Sebban C, Lepage E, Vernant JP, Gluckman E, Attal M, Reiffers J, Sutton L, Racadot E, Michallet M, Maraninchi D, et al. for the French Group of Therapy of Adult Acute Lymphoblastic Leukemia (1994) Allogeneic bone marrow transplantation in adult acute lymphoblastic leukemia in first complete remission: A comparative study. J Clin Oncol 12:2580–2587 33. Charrin C, Thomas X, Ffrench M, Le QH, Andrieux J, Mozziconacci MJ, La JL, Bilhou-Nabera C, Michaux L, Bernheim A, et al. (2004) A report of the LALA-94 and LALA-SA groups on hypodiploidy with 30 to 39 chromosomes and near-triploidy: 2 possible expressions of a sole entity conferring poor prognosis in adult acute lymphoblastic leukemia (ALL). Blood 104:2444–2451 34. Kiehl MG, Kraut L, Schwerdtfeger R, Hertenstein B, Remberger M, Kroeger N, Stelljes M, Bornhaeuser M, Martin H, Scheid C, et al. (2004) Outcome of allogeneic hematopoietic stem-cell transplantation in adult patients with acute lymphoblastic leukemia: No difference in related compared with unrelated transplant in first complete remission. J Clin Oncol 22:2816–2825 35. Rowe JM, Richards S, Burnett AK, Wiernik PH, Harrison G, Lazarus HM, Franklin IM, Prentice GH, Durrant JI, Tallman MS, et al. (2001) Favorable results of allogeneic bone marrow transplantation (BMT) for adults with Philadelphia (Ph)-chromosome-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR): Results from the International ALL trial (MRC UKALL XII/ECOG E2993). Blood 98:481a 36. Dhedin N, Thomas X, Huguet F, Lhéritier V, Boiron JM, Micléa JM, Vey N, Kuentz M, Charrin C, Boucheix C, et al. for the LALA Group (2002) No superiority of autologous stem cell transplantation over chemotherapy alone in adult Ph-negative ALL in first complete remission: A long follow-up report combining results of LALA 85, 87 and 94 trials. Blood 100(Suppl 1):217a 37. Kantarjian HM, Walters RS, Keating MJ, Smith TL, O‘Brien S, Estey EH, Huh YO, Spinolo J, Dicke K, Barlogie B, et al. (1990) Results of the vincristine, doxorubicin, and dexamethasone regimen in adults with standard and high-risk acute lymphocytic leukemia. J Clin Oncol 8:994–1004 38. Boucheix C, David B, Sebban C, Racadot E, Bene MC, Bernard A, Campos L, Jouault H, Sigaux F, Lepage E, et al. for the French Group on Therapy for Adult Acute Lymphoblastic Leukemia (1994) Immunophenotype of adult acute lymphoblastic leukemia, clinical parameters and outcome: An analysis of a prospective trial including 562 tested patients (LALA-87). Blood 84:1603–1612 39. Sebban C, Browman GP, Lepage E, Fiere D (1995) Prognostic value of early response to chemotherapy assessed by the day 15 bone marrow aspiration in adult acute lymphoblastic leukemia: A prospective analysis of 437 cases and its application for designing induction chemotherapy trials. Leuk Res 19:861–868 40. Asnafi V, Buzyn A, Thomas X, Huguet F, Vey N, Boiron JM, Reman O, Cayuela JM, Lhéritier V, Vernant JP, et al. (2005) Impact of TCR status and genotype on outcome in adult T-cell acute lymphoblastic leukemia: A LALA-94 study. Blood 105:3072–3078 41. Huguet F, Pigneux A, Delabesse E, Thomas X, Beldjord K, Escoffre- Barbe M, Harousseau JL, Reman O, Garban F, Buzyn A, et al. for the Group for Reseach on Adult Acute Lymphoblastic Leukemia (GRAALL) (2005) Blood 106(Suppl 1):(abstr 874) 42. Ellison RR, Mick R, Cuttner J, Schiffer CA, Silver RT, Henderson ES, Woliver T, Royston I, Davey FR, Glicksman AS, et al. (1991) The effect of postinduction intensification treatment with cytarabine and daunorubicin in adult acute lymphoblastic leukemia: A prospective randomized clinical trial by Cancer and Leukemia Group B. J Clin Oncol 9:2002–2015 43. Taylor PRA, Reid MM, Bown N, Hamilton PJ, Proctor SJ (1992) Acute lymphoblastic leukemia in patients aged 60 years and over: A population-based study of incidence and outcome. Blood 80:1813–1817 44. Kantarjian HM, O‘Brien S, Smith T, Estey EH, Beran M, Preti A, Pierce S, Keating MJ (1994) Acute lymphocytic leukaemia in the elderly: Characteristics and outcome with the vincristine-adriamycin-dexamethasone (VAD) regimen. Br J Haematol 88:94–100 45. Delannoy A, Ferrant A, Bosly A, Chatelain C, Doyen C, Martiat P, Michaux JL, Sokal G (1990) Acute lymphoblastic leukemia in the elderly. Eur J Haematol 45:90–93 46. Delannoy A, Sebban C, Cony-Makhoul P, Cazin B, Cordonnier C, Bouabdallah R, Cahn JY, Dreyfus F, Sadoun A, Vernant JP, et al. (1997) Age-adapted induction treatment of acute lymphoblastic leukemia in the elderly and assessment of maintenance with interferon combined with chemotherapy. A multicentric prospective study in forty patients. Leukemia 11:1429–1434 47. Einheim S, Ost A, Grimfors G, Grander D, Bjorkholm M (1990) Prolonged remission induced by interferon in a patient with refractory T-cell ALL. Lancet i:794–795 48. Ochs J, Brecher ML, Mahoney D, Vega R, Pollock BH, Buchanan GR, Whitehead VM, Ravindranath Y, Freedman AI (1991) Recombinant interferon alfa given before and in combination with standard chemotherapy in children with acute lymphoblastic leukemia in first marrow relapse: A Pediatric Oncology group pilot study. J Clin Oncol 9:777–782 49. Meyers JD, Flournoy N, Sanders JE, McGuffin RW, Newton BA, Fisher LD, Lum LG, Appelbaum FR, Doney K, Sullivan KM, et al. (1987) Prophylactic use of human leukocyte interferon after allogeneic marrow transplantation. Ann Intern Med 107:809–816 50. Diaz MO, Rubin CM, Harden A, Ziemin S, Larson RA, Le Beau MM, Rowley JD (1990) Deletions of interferon genes in acute lymphoblastic leukemia. New Engl J Med 322:77–82 51. Delannoy A, Cazin B, Thomas X, Bouabdallah R, Boiron JM, Huguet F, Straetmans N, Zerazhi H, Vernant JP, Dombret H, et al. (2002) Treatment of acute lymphocytic leukemia in the elderly: An evaluation of vindesine during induction and of interferon alpha given as a single agent after comlete remission. Leuk Lymphoma 43:75–81 52. Thomas X, Olteanu N, Charrin C, Lhéritier V, Magaud JP, Fiere D (2001) Acute lymphoblastic leukemia in the elderly: The Edouard Herriot Hospital experience. Am J Hematol 67:73–83 53. Ottmann OG, Druker BT, Sawyers CL, Goldman JM, Reiffers J, Silver RT, Tura S, Fischer T, Deininger MW, Schiffer CA, et al. (2002) A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias. Blood 100:1965–1971
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E.H. Estey · S.H. Faderl · H. M.
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E. H. Estey Department of Leukemia
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VI Table of Contents 14 Philadelphi
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VIII Contributors S. H. Faderl Depa
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X Contributors D. Wartenberg Depart
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Therapy of AML Elihu Estey Contents
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a 1.2 · Standard Therapy 3 Table 1
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a 1.2 · Standard Therapy 5 Table 1
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a 1.2 · Standard Therapy 7 tween G
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a 1.2 · Standard Therapy 9 Fig. 1.
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a 1.2 · Standard Therapy 11 of tre
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a 1.2 · Standard Therapy 13 Table
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a 1.2 · Standard Therapy 15 permit
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a References 17 19. Care RS, Valk P
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a References 19 6-thioguanine in th
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Acute Myeloid Leukemia: Epidemiolog
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a 3.1 · Epidemiology 49 3.1.4 Gend
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a 3.2 · Etiology 51 part of the in
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a 3.2 · Etiology 53 for the develo
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a References 55 38. Crane MM, Stom
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Relapsed and Refractory Acute Myelo
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a 4.2 · Prognostic Factors in Pati
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a 4.3 · Treatment of Relapsed and
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a 4.4 · Hematopoietic Stem Cell Tr
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a 4.6 · Gemtuzumab Ozogamicin 65 T
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a 4.7 · Relapsed and Refractory Ac
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a 4.7 · Relapsed and Refractory Ac
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a References 71 The ability of immu
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a References 73 39. Vogler WR, McCa
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a References 75 95. Sievers EL, Lar
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Part II - Acute Lymphoblastic Leuke
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78 Chapter 5 · Acute Lymphoblastic
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Molecular Biology and Genetics Meir
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a 6.3 · Structural Aberrations 97
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a 6.3 · Structural Aberrations 99
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a 6.5 · Molecular Aberrations 101
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a References 103 clear that homozyg
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Page 93 and 94: Diagnosis of Acute Lymphoblastic Le
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Page 111 and 112: a 7.3 · Diagnosis 115 The vast maj
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Page 115 and 116: General Approach to the Therapy of
Page 117 and 118: a 9.3 · New Agents 133 dose methot
Page 119 and 120: a References 135 4. Gökbuget N, Ho
Page 121 and 122: 138 Chapter 10 · Recent Clinical T
Page 129 and 130: 146 Chapter 11 · Conventional Ther
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Page 143 and 144: ALL Therapy: Review of the MD Ander
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Page 159 and 160: Philadelphia Chromosome-Positive Ac
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Page 171 and 172: a References 189 acute lymphoblasti
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210 Chapter 16 · Treatment of Lymp
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216 Chapter 17 · The Role of Allog
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230 Chapter 18 · The Role of Autol
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238 Chapter 19 · Novel Therapies i
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248 Chapter 20 · Minimal Residual
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264 Chapter 21 · Central Nervous S
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276 Chapter 22 · Relapsed Acute Ly
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278 Chapter 22 · Relapsed Acute Ly
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Emergencies in Acute Lymphoblastic
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a 23.5 · Hyperleukocytosis 283 LA
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a 23.9 · Neurological Complication
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a References 287 29. Hingorani AD,
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Subject Index A aberrant methylatio
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a Subject Index 291 CREB, see enhan
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a Subject Index 293 MUD, see matche
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