Advertisement

Chronic Myelomonocytic Leukemia (CMML)

  • Lisa Pleyer
  • Daniel Neureiter
  • Victoria Faber
  • Richard Greil

Abstract

The term chronic “myelomonocytic” leukemia (CMML) indicates that all cells of the myeloid lineage are involved (myelo-), but emphasizes the prominence of monocytoid features (“-mono-”). The hallmarks of CMML are peripheral monocytosis >1, 000/μl, with <20% bone marrow blasts and the presence of bone marrowdysplasia.CMML shares clinical and biological features with both myelodysplastic syndromes (MDS) and chronic myeloproliferative diseases (CMPDs), and may take on predominantly myelodysplastic (MD-CMML) or myelprolifearative (MP-CMML) characteristics (e.g., Ref. [1]). There is a dynamic evolution through increasing monocyte counts in approximately one-third of patients (see Fig. 7.1). MDSRA patients may develop peripheral monocytosis during the course of their disease and ultimately progress to CMML [2]. Approximately one-fifth of patients with MDS present with a monocyte count of above 10% in the peripheral blood without fulfilling the FAB/WHO criteria for the diagnosis of CMML. A high incidence of disease progression to CMML has been reported for this subgroup [3] (see Fig. 7.1).
Fig. 7.1

Static and dynamic classification of CMML (adapted from Ref. [4]). Approximately 20% of patients with MDS present with a monocyte count >10%, but do not fulfill the WHO criteria for the diagnosis of CMML. 1/3 of these patients progresses to MD-CMML and 1/3 of these may go on to progress to MP-CMML. RA Refractory anemia; RARS refractory anemia with ringed sideroblasts; CMML chronic myelomonocytic leukemia; PB peripheral blood

Keywords

Myelodysplastic Syndrome JAK2 V617F International Prognostic Score System Reduce Intensity Conditioning Bone Marrow Blast 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [1]
    Michaux JL, Martiat P (1993) Chronic myelomonocytic leukaemia (CMML) — a myelodysplastic or myeloproliferative syndrome? Leuk Lymphoma 9: 35–41PubMedCrossRefGoogle Scholar
  2. [2]
    Breccia M, Cannella L, Frustaci A, Stefanizzi C, D’Elia GM, Alimena G (2008) Chronic myelomonocytic leukemia with antecedent refractory anemia with excess blasts: further evidence for the arbitrary nature of current classification systems. Leuk Lymphoma 49: 1292–1296PubMedCrossRefGoogle Scholar
  3. [3]
    Rigolin GM, Cuneo A, Roberti MG, Bardi A, Castoldi G (1997) Myelodysplastic syndromes with monocytic component: hematologic and cytogenetic characterization. Haematologica 82: 25–30PubMedGoogle Scholar
  4. [4]
    Bowen DT (2005) Chronic myelomonocytic leukemia: lost in classification? Hematol Oncol 23: 26–33PubMedCrossRefGoogle Scholar
  5. [5]
    Bennett JM, Catovsky D, Daniel MT et al. (1976) Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol 33: 451–458PubMedCrossRefGoogle Scholar
  6. [6]
    Voglova J, Chrobak L, Neuwirtova R, Malaskova V, Straka L (2001) Myelodysplastic and myeloproliferative type of chronic myelomonocytic leukemia — distinct subgroups or two stages of the same disease? Leuk Res 25: 493–499PubMedCrossRefGoogle Scholar
  7. [7]
    Germing U, Gattermann N, Minning H, Heyll A, Aul C (1998) Problems in the classification of CMML — dysplastic versus proliferative type. Leuk Res 22: 871–878PubMedCrossRefGoogle Scholar
  8. [8]
    Greenberg P, Cox C, LeBeau MM et al. (1997) International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89: 2079–2088PubMedGoogle Scholar
  9. [9]
    Onida F, Beran M (2004) Chronic myelomonocytic leukemia: myeloproliferative variant. Curr Hematol Rep 3: 218–226PubMedGoogle Scholar
  10. [10]
    Bennett JM (2000) World Health Organization classification of the acute leukemias and myelodysplastic syndrome. Int J Hematol 72: 131–133PubMedGoogle Scholar
  11. [11]
    Bennett JM (2002) Chronic myelomonocytic leukemia. Curr Treat Options Oncol 3: 221–223PubMedCrossRefGoogle Scholar
  12. [12]
    Germing U, Gattermann N, Strupp C, Aivado M, Aul C (2000) Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: a retrospective analysis of 1600 patients. Leuk Res 24: 983–992PubMedCrossRefGoogle Scholar
  13. [13]
    Nosslinger T, Reisner R, Gruner H et al. (2001) Dysplastic versus proliferative CMML — a retrospective analysis of 91 patients from a single institution. Leuk Res 25: 741–747PubMedCrossRefGoogle Scholar
  14. [14]
    Chen B, Zhao WL, Jin J et al. (2005) Clinical and cytogenetic features of 508 Chinese patients with myelodysplastic syndrome and comparison with those in Western countries. Leukemia 19: 767–775PubMedCrossRefGoogle Scholar
  15. [15]
    Lee JH, Lee JH, Shin YR et al. (2003) Application of different prognostic scoring systems and comparison of the FAB and WHO classifications in Korean patients with myelodysplastic syndrome. Leukemia 17: 305–313PubMedCrossRefGoogle Scholar
  16. [16]
    Kouides PA, Bennett JM (1995) Transformation of chronic myelomonocytic leukemia to acute lymphoblastic leukemia: case report and review of the literature of lymphoblastic transformation of myelodysplastic syndrome. Am J Hematol 49: 157–162PubMedCrossRefGoogle Scholar
  17. [17]
    Everson MP, Brown CB, Lilly MB (1989) Interleukin-6 and granulocyte-macrophage colony-stimulating factor are candidate growth factors for chronic myelomonocytic leukemia cells. Blood 74: 1472–1476PubMedGoogle Scholar
  18. [18]
    Ramshaw HS, Bardy PG, Lee MA, Lopez AF (2002) Chronic myelomonocytic leukemia requires granulocyte-macrophage colony-stimulating factor for growth in vitro and in vivo. Exp Hematol 30: 1124–1131PubMedCrossRefGoogle Scholar
  19. [19]
    Emanuel PD, Bates LJ, Castleberry RP, Gualtieri RJ, Zuckerman KS (1991) Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors. Blood 77: 925–929PubMedGoogle Scholar
  20. [20]
    Oscier DG, Worsley A, Darlow S, Figes A, Williams JD, Hamblin TJ (1989) Correlation of bone marrow colony growth in the myelodysplastic syndromes with the FAB classification and the Bournemouth score. Leuk Res 13: 833–839PubMedCrossRefGoogle Scholar
  21. [21]
    Geissler K, Ohler L, Fodinger M et al. (1996) Interleukin 10 inhibits growth and granulocyte/macrophage colony-stimulating factor production in chronic myelomonocytic leukemia cells. J Exp Med 184: 1377–1384PubMedCrossRefGoogle Scholar
  22. [22]
    Steensma DP, Dewald GW, Lasho TL et al. (2005) The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both “atypical” myeloproliferative disorders and myelodysplastic syndromes. Blood 106: 1207–1209PubMedCrossRefGoogle Scholar
  23. [23]
    Pich A, Riera L, Sismondi F et al. (2009) JAK2V617F activating mutation is associated with the myeloproliferative type of chronic myelomonocytic leukaemia. J Clin Pathol 62: 798–801PubMedCrossRefGoogle Scholar
  24. [24]
    Gelsi-Boyer V, Trouplin V, Adelaide J et al. (2008) Genome profiling of chronic myelomonocytic leukemia: frequent alterations of RAS and RUNX1 genes. BMC Cancer 8: 299PubMedCrossRefGoogle Scholar
  25. [25]
    Padua RA, Carter G, Hughes D et al. (1988) RAS mutations in myelodysplasia detected by amplification, oligonucleotide hybridization, and transformation. Leukemia 2: 503–510PubMedGoogle Scholar
  26. [26]
    Collins SJ, Howard M, Andrews DF, Agura E, Radich J (1989) Rare occurrence of N-ras point mutations in Philadelphia chromosome positive chronic myeloid leukemia. Blood 73: 1028–1032PubMedGoogle Scholar
  27. [27]
    Tsurumi S, Nakamura Y, Maki K et al. (2002) N-ras and p53 gene mutations in Japanese patients with myeloproliferative disorders. Am J Hematol 71: 131–133PubMedCrossRefGoogle Scholar
  28. [28]
    Janssen JW, Steenvoorden AC, Lyons J et al. (1987) RAS gene mutations in acute and chronic myelocytic leukemias, chronic myeloproliferative disorders, and myelodysplastic syndromes. Proc Natl Acad Sci USA 84: 9228–9232PubMedCrossRefGoogle Scholar
  29. [29]
    Tyner JW, Erickson H, Deininger MW et al. (2009) High-throughput sequencing screen reveals novel, transforming RAS mutations in myeloid leukemia patients. Blood 113: 1749–1755PubMedCrossRefGoogle Scholar
  30. [30]
    MacKenzie KL, Dolnikov A, Millington M, Shounan Y, Symonds G (1999) Mutant N-ras induces myeloproliferative disorders and apoptosis in bone marrow repopulated mice. Blood 93: 2043–2056PubMedGoogle Scholar
  31. [31]
    Le DT, Kong N, Zhu Y et al. (2004) Somatic inactivation of Nf1 in hematopoietic cells results in a progressive myeloproliferative disorder. Blood 103: 4243–4250PubMedCrossRefGoogle Scholar
  32. [32]
    Yasuda T, Shirakata M, Iwama A et al. (2004) Role of Dok-1 and Dok-2 in myeloid homeostasis and suppression of leukemia. J Exp Med 200: 1681–1687PubMedCrossRefGoogle Scholar
  33. [33]
    Shih LY, Huang CF, Wang PN et al. (2004) Acquisition of FLT3 or N-ras mutations is frequently associated with progression of myelodysplastic syndrome to acute myeloid leukemia. Leukemia 18: 466–475PubMedCrossRefGoogle Scholar
  34. [34]
    Kuo MC, Liang DC, Huang CF et al. (2009) RUNX1 mutations are frequent in chronic myelomonocytic leukemia and mutations at the C-terminal region might predict acute myeloid leukemia transformation. Leukemia 23: 1426–1431PubMedCrossRefGoogle Scholar
  35. [35]
    Zinkel SS, Ong CC, Ferguson DO et al. (2003) Proapoptotic BID is required for myeloid homeostasis and tumor suppression. Genes Dev 17: 229–239PubMedCrossRefGoogle Scholar
  36. [36]
    Tartaglia M, Niemeyer CM, Fragale A et al. (2003) Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nat Genet 34: 148–150PubMedCrossRefGoogle Scholar
  37. [37]
    Flotho C, Valcamonica S, Mach-Pascual S et al. (1999) RAS mutations and clonality analysis in children with juvenile myelomonocytic leukemia (JMML). Leukemia 13: 32–37PubMedCrossRefGoogle Scholar
  38. [38]
    Side LE, Emanuel PD, Taylor B et al. (1998) Mutations of the NF1 gene in children with juvenile myelomonocytic leukemia without clinical evidence of neurofibromatosis, type 1. Blood 92: 267–272PubMedGoogle Scholar
  39. [39]
    Miles DK, Freedman MH, Stephens K et al. (1996) Patterns of hematopoietic lineage involvement in children with neurofibromatosis type 1 and malignant myeloid disorders. Blood 88: 4314–4320PubMedGoogle Scholar
  40. [40]
    Loh ML, Martinelli S, Cordeddu V et al. (2005) Acquired PTPN11 mutations occur rarely in adult patients with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leuk Res 29: 459–462PubMedCrossRefGoogle Scholar
  41. [41]
    Levine RL (2009) Mechanisms of mutations in myeloproliferative neoplasms. Best Pract Res Clin Haematol 22: 489–494PubMedCrossRefGoogle Scholar
  42. [42]
    Abdel-Wahab O, Mullally A, Hedvat C et al. (2009) Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood 114: 144–147PubMedCrossRefGoogle Scholar
  43. [43]
    Jankowska AM, Szpurka H, Tiu RV et al. (2009) Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. Blood 113: 6403–6410PubMedCrossRefGoogle Scholar
  44. [44]
    Kosmider O, Gelsi-Boyer V, Cheok M et al. (2009) TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs). Blood 114: 3285–3291PubMedCrossRefGoogle Scholar
  45. [45]
    Kosmider O, Gelsi-Boyer V, Ciudad M et al. (2009) TET2 gene mutation is a frequent and adverse event in chronic myelomonocytic leukemia. Haematologica 94: 1676–1681PubMedCrossRefGoogle Scholar
  46. [46]
    Sole F, Espinet B, Sanz GF et al. (2000) Incidence, characterization and prognostic significance of chromosomal abnormalities in 640 patients with primary myelodysplastic syndromes. Grupo Cooperativo Espanol de Citogenetica Hematologica. Br J Haematol 108: 346–356PubMedCrossRefGoogle Scholar
  47. [47]
    Apperley JF, Gardembas M, Melo JV et al. (2002) Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med 347: 481–487PubMedCrossRefGoogle Scholar
  48. [48]
    Magnusson MK, Meade KE, Nakamura R, Barrett J, Dunbar CE (2002) Activity of STI571 in chronic myelomonocytic leukemia with a platelet-derived growth factor beta receptor fusion oncogene. Blood 100: 1088–1091PubMedCrossRefGoogle Scholar
  49. [49]
    David M, Cross NC, Burgstaller S et al. (2007) Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders. Blood 109: 61–64PubMedCrossRefGoogle Scholar
  50. [50]
    Suh B, Park TS, Kim JS et al. (2009) Chronic myelomonocytic leukemia with der (9) t (1;9) (q11;q34) as a sole abnormality. Ann Clin Lab Sci 39: 307–312PubMedGoogle Scholar
  51. [51]
    Pedersen-Bjergaard J, Pedersen M, Roulston D, Philip P (1995) Different genetic pathways in leukemogenesis for patients presenting with therapy-related myelodysplasia and therapy-related acute myeloid leukemia. Blood 86: 3542–3552PubMedGoogle Scholar
  52. [52]
    Michels SD, McKenna RW, Arthur DC, Brunning RD (1985) Therapy-related acute myeloid leukemia and myelodysplastic syndrome: a clinical and morphologic study of 65 cases. Blood 65: 1364–1372PubMedGoogle Scholar
  53. [53]
    Mauritzson N, Albin M, Rylander L et al. (2002) Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976–1993 and on 5098 unselected cases reported in the literature 1974–2001. Leukemia 16: 2366–2378PubMedCrossRefGoogle Scholar
  54. [54]
    del Canizo MC, Sanz G, San Miguel JF et al. (1989) Chronic myelomonocytic leukemia — clinicobiological characteristics: a multivariate analysis in a series of 70 cases. Eur J Haematol 42: 466–473PubMedGoogle Scholar
  55. [55]
    Chen B, Ma Y, Xu X et al. (2009) Analyses on clinical characteristic and prognoses of 41 patients with chronic myelomonocytic leukemia in China. Leuk Res [Epub ahead of print]Google Scholar
  56. [56]
    Mani S, Duffy TP (1994) Pericardial tamponade in chronic myelomonocytic leukemia. Chest 106: 967–970PubMedCrossRefGoogle Scholar
  57. [57]
    Strupp C, Germing U, Trommer I, Gattermann N, Aul C (2000) Pericardial effusion in chronic myelomonocytic leukemia (CMML): a case report and review of the literature. Leuk Res 24: 1059–1062PubMedCrossRefGoogle Scholar
  58. [58]
    Elliott MA (2006) Chronic neutrophilic leukemia and chronic myelomonocytic leukemia: WHO defined. Best Pract Res Clin Haematol 19: 571–593PubMedCrossRefGoogle Scholar
  59. [59]
    Fenaux P, Beuscart R, Lai JL, Jouet JP, Bauters F (1988) Prognostic factors in adult chronic myelomonocytic leukemia: an analysis of 107 cases. J Clin Oncol 6: 1417–1424PubMedGoogle Scholar
  60. [60]
    Chen YC, Chou JM, Letendre L, Li CY (2005) Clinical importance of bone marrow monocytic nodules in patients with myelodysplasia: retrospective analysis of 21 cases. Am J Hematol 79: 329–331PubMedCrossRefGoogle Scholar
  61. [61]
    Onida F, Kantarjian HM, Smith TL et al. (2002) Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients. Blood 99: 840–849PubMedCrossRefGoogle Scholar
  62. [62]
    Germing U, Kundgen A, Gattermann N (2004) Risk assessment in chronic myelomonocytic leukemia (CMML). Leuk Lymphoma 45: 1311–1318PubMedCrossRefGoogle Scholar
  63. [63]
    Beran M, Wen S, Shen Y et al. (2007) Prognostic factors and risk assessment in chronic myelomonocytic leukemia: validation study of the M.D. Anderson Prognostic Scoring System. Leuk Lymphoma 48: 1150–1160PubMedCrossRefGoogle Scholar
  64. [64]
    Worsley A, Oscier DG, Stevens J et al. (1988) Prognostic features of chronic myelomonocytic leukaemia: a modified Bournemouth score gives the best prediction of survival. Br J Haematol 68: 17–21PubMedCrossRefGoogle Scholar
  65. [65]
    Aul C, Gattermann N, Heyll A, Germing U, Derigs G, Schneider W (1992) Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system. Leukemia 6: 52–59PubMedGoogle Scholar
  66. [66]
    Germing U, Strupp C, Aivado M, Gattermann N (2002) New prognostic parameters for chronic myelomonocytic leukemia. Blood 100: 731–732PubMedCrossRefGoogle Scholar
  67. [67]
    Sanz GF, Sanz MA, Vallespi T et al. (1989) Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients. Blood 74: 395–408PubMedGoogle Scholar
  68. [68]
    Breccia M, Latagliata R, Mengarelli A, Biondo F, Mandelli F, Alimena G (2004) Prognostic factors in myelodysplastic and myeloproliferative types of chronic myelomonocytic leukemia: a retrospective analysis of 83 patients from a single institution. Haematologica 89: 866–868PubMedGoogle Scholar
  69. [69]
    Wattel E, Guerci A, Hecquet B et al. (1996) A randomized trial of hydroxyurea versus VP16 in adult chronic myelomonocytic leukemia. Groupe Francais des Myelodysplasies and European CMML Group. Blood 88: 2480–2487PubMedGoogle Scholar
  70. [70]
    Doll DC, Kasper LM, Taetle R, List AF (1998) Treatment with low-dose oral etoposide in patients with myelodysplastic syndromes. Leuk Res 22: 7–12PubMedCrossRefGoogle Scholar
  71. [71]
    Miller KB, Kim K, Morrison FS et al. (1992) The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: a phase-III intergroup study. Ann Hematol 65: 162–168PubMedCrossRefGoogle Scholar
  72. [72]
    Beran M, Estey E, O’Brien SM et al. (1998) Results of topotecan single-agent therapy in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leuk Lymphoma 31: 521–531PubMedGoogle Scholar
  73. [73]
    Kantarjian H, Beran M, Cortes J et al. (2006) Long-term follow-up results of the combination of topotecan and cytarabine and other intensive chemotherapy regimens in myelodysplastic syndrome. Cancer 106: 1099–1109PubMedCrossRefGoogle Scholar
  74. [74]
    Beran M, Kantarjian HM (2000) Topotecan (hycamptin) and topotecan-containing regimens in the treatment of hematologic malignancies. Ann NY Acad Sci 922: 247–259PubMedGoogle Scholar
  75. [75]
    Beran M, Estey E, O’Brien S et al. (1999) Topotecan and cytarabine is an active combination regimen in myelodysplastic syndromes and chronic myelomonocytic leukemia. J Clin Oncol 17: 2819–2830PubMedGoogle Scholar
  76. [76]
    Beran M (2000) Intensive chemotherapy for patients with high-risk myelodysplastic syndrome. Int J Hematol 72: 139–150PubMedGoogle Scholar
  77. [77]
    Klein CE, Kastrissios H, Miller AA et al. (2006) Pharmacokinetics, pharmacodynamics and adherence to oral topotecan in myelodysplastic syndromes: a Cancer and Leukemia Group B study. Cancer Chemother Pharmacol 57: 199–206PubMedCrossRefGoogle Scholar
  78. [78]
    Quintas-Cardama A, Kantarjian H, O’Brien S et al. (2006) Activity of 9-nitro-camptothecin, an oral topoisomerase I inhibitor, in myelodysplastic syndrome and chronic myelomonocytic leukemia. Cancer 107: 1525–1529PubMedCrossRefGoogle Scholar
  79. [79]
    Raza A, Lisak L, Billmeier J et al. (2006) Phase II study of topotecan and thalidomide in patients with high-risk myelodysplastic syndromes. Leuk Lymphoma 47: 433–440PubMedCrossRefGoogle Scholar
  80. [80]
    Grinblatt DL, Yu D, Hars V et al. (2009) Treatment of myelodysplastic syndrome with 2 schedules and doses of oral topotecan: a randomized phase 2 trial by the Cancer and Leukemia Group B (CALGB 19803). Cancer 115: 84–93PubMedCrossRefGoogle Scholar
  81. [81]
    Beran M, Kantarjian H, O’Brien S et al. (1996) Topotecan, a topoisomerase I inhibitor, is active in the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 88: 2473–2479PubMedGoogle Scholar
  82. [82]
    Kroger N, Zabelina T, Guardiola P et al. (2002) Allogeneic stem cell transplantation of adult chronic myelomonocytic leukaemia. A report on behalf of the Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol 118: 67–73PubMedCrossRefGoogle Scholar
  83. [83]
    Appelbaum FR, Anderson J (1998) Allogeneic bone marrow transplantation for myelodysplastic syndrome: outcomes analysis according to IPSS score. Leukemia 12 (Suppl 1): S25–S29PubMedGoogle Scholar
  84. [84]
    Tse W, Deeg HJ (2006) Hematopoietic cell transplantation for chronic myeloproliferative disorders. Arch Immunol Ther Exp (Warsz) 54: 375–380CrossRefGoogle Scholar
  85. [85]
    Kerbauy DM, Chyou F, Gooley T et al. (2005) Allogeneic hematopoietic cell transplantation for chronic myelomonocytic leukemia. Biol Blood Marrow Transplant 11: 713–720PubMedCrossRefGoogle Scholar
  86. [86]
    Elliott MA, Tefferi A, Hogan WJ et al. (2006) Allogeneic stem cell transplantation and donor lymphocyte infusions for chronic myelomonocytic leukemia. Bone Marrow Transplant 37: 1003–1008PubMedCrossRefGoogle Scholar
  87. [87]
    Laport GG, Sandmaier BM, Storer BE et al. (2008) Reduced-intensity conditioning followed by allogeneic hematopoietic cell transplantation for adult patients with myelodysplastic syndrome and myeloproliferative disorders. Biol Blood Marrow Transplant 14: 246–255PubMedCrossRefGoogle Scholar
  88. [88]
    Martino R, Iacobelli S, Brand R et al. (2006) Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes. Blood 108: 836–846PubMedCrossRefGoogle Scholar
  89. [89]
    Alyea EP, Kim HT, Ho V et al. (2005) Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age. Blood 105: 1810–1814PubMedCrossRefGoogle Scholar
  90. [90]
    Silverman LR, Demakos EP, Peterson BL et al. (2002) Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 20: 2429–2440PubMedCrossRefGoogle Scholar
  91. [91]
    Wijermans P, Lubbert M, Verhoef G et al. (2000) Low-dose 5-aza-2′-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: a multicenter phase II study in elderly patients. J Clin Oncol 18: 956–962PubMedGoogle Scholar
  92. [92]
    Abdulhaq H, Bushra Haq James M. Rossetti Richard K. Shadduck Entezam Sahovic Dijana Christianson and John Lister (2008) Activity of Azacitidine (AZA) in Chronic Myelomonocytic Leukemeia (CMML). Blood 112: 102Google Scholar
  93. [93]
    Fenaux P, Mufti GJ, Hellstrom-Lindberg E et al. (2009) Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 10 (3): 213–232CrossRefGoogle Scholar
  94. [94]
    Lyons RM, Cosgriff T (2007) Sanjiv Modi Heidi McIntyre Indra Fernando Jay Backstrom and C. L. Beach. Results of the Initial Treatment Phase of a Study of Three Alternative Dosing Schedules of Azacitidine (Vidaza®) in Patients with Myelodysplastic Syndromes (MDS). Blood 110. 2007Google Scholar
  95. [95]
    Lyons RM, Cosgriff TM, Modi SS et al. (2009) Hematologic response to three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes. J Clin Oncol 27: 1850–1856PubMedCrossRefGoogle Scholar
  96. [96]
    Martin MG, Walgren RA, Procknow E et al. (2009) A phase II study of 5-day intravenous azacitidine in patients with myelodysplastic syndromes. Am J Hematol 84: 560–564PubMedCrossRefGoogle Scholar
  97. [97]
    Platzbecker U, Aul C, Ehninger G, Giagounidis A (2009) Reduction of 5-azacitidine induced skin reactions in MDS patients with evening primrose oil. Ann Hematol [Epub ahead of print]Google Scholar
  98. [98]
    Kantarjian H, Issa JP, Rosenfeld CS et al. (2006) Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 106: 1794–1803PubMedCrossRefGoogle Scholar
  99. [99]
    Steensma DP, Baer MR, Slack JL et al. (2009) Multicenter study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial. J Clin Oncol 27: 3842–3848PubMedCrossRefGoogle Scholar
  100. [100]
    Aribi A, Borthakur G, Ravandi F et al. (2007) Activity of decitabine, a hypomethylating agent, in chronic myelomonocytic leukemia. Cancer 109: 713–717PubMedCrossRefGoogle Scholar
  101. [101]
    Iastrebner M, Garay G, Klein G, Flores A, Nucifora E, Alfonso G, Diego M, Basquiera A, Goalons ML, Saracut D, Gonzalez M, Quiroga L, Palmer L, Santini F. Decitabine activity in chronic myelomonocytic leukemia patients. Blood 112: Abstract # 5081Google Scholar
  102. [102]
    Kantarjian H, Oki Y, Garcia-Manero G et al. (2007) Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 109: 52–57PubMedCrossRefGoogle Scholar
  103. [103]
    Wijermans PW, Ruter B, Baer MR, Slack JL, Saba HI, Lubbert M (2008) Efficacy of decitabine in the treatment of patients with chronic myelomonocytic leukemia (CMML). Leuk Res 32: 587–591PubMedCrossRefGoogle Scholar
  104. [104]
    Jabbour E, Garcia-Manero G, Shan J, O’Brien S, Cortes J, Ravandi F, Issa J-PJ, Kantarjian HM (2008) Outcome of Patients (pts) with Myelodysplastic Syndrome (MDS) and Chronic Myelomonocytic Leukemia (CMML) Post Decitabine Failure. Blood 112: Abstract # 1659Google Scholar
  105. [105]
    Gurion R, Vidal L, Gafter-Gvili A et al. (2009) 5-azacitidine prolongs overall survival in patients with myelodysplastic syndrome — systematic review and meta-analysis. Haematologica [Epub ahead of print]Google Scholar
  106. [106]
    Kumar A, List AF, Hozo I, Komrokji R, Djulbegovic B (2009) Decitabine versus 5-azacitidine for the treatment of myelodysplastic syndrome: adjusted indirect meta-analysis. Haematologica [Epub ahead of print]Google Scholar
  107. [107]
    Choi SH, Byun HM, Kwan JM, Issa JP, Yang AS (2007) Hydroxycarbamide in combination with azacitidine or decitabine is antagonistic on DNA methylation inhibition. Br J Haematol 138: 616–623PubMedCrossRefGoogle Scholar
  108. [108]
    Pitini V, Arrigo C, Teti D, Barresi G, Righi M, Alo G (2003) Response to STI571 in chronic myelomonocytic leukemia with platelet derived growth factor beta receptor involvement: a new case report. Haematologica 88: ECR18Google Scholar
  109. [109]
    Kurzrock R, Kantarjian HM, Cortes JE et al. (2003) Farnesyltransferase inhibitor R115777 in myelodysplastic syndrome: clinical and biologic activities in the phase 1 setting. Blood 102: 4527–4534PubMedCrossRefGoogle Scholar
  110. [110]
    Karp JE, Lancet JE, Kaufmann SH et al. (2001) Clinical and biologic activity of the farnesyltransferase inhibitor R115777 in adults with refractory and relapsed acute leukemias: a phase 1 clinical-laboratory correlative trial. Blood 97: 3361–3369PubMedCrossRefGoogle Scholar
  111. [111]
    Feldman EJ (2005) Farnesyltransferase inhibitors in myelodysplastic syndrome. Curr Hematol Rep 4: 186–190PubMedGoogle Scholar
  112. [112]
    Feldman EJ, Cortes J, DeAngelo DJ et al. (2008) On the use of lonafarnib in myelodysplastic syndrome and chronic myelomonocytic leukemia. Leukemia 22: 1707–1711PubMedCrossRefGoogle Scholar
  113. [113]
    Jaffe ES, Harris NL, Stein H, Vardiman JW (2009) WHO calssification of tumors: tumors of haematopoietic and lymphoid tissues.Google Scholar

Copyright information

© Springer-Verlag/Wien 2010

Authors and Affiliations

  • Lisa Pleyer
    • 1
  • Daniel Neureiter
    • 1
  • Victoria Faber
    • 1
  • Richard Greil
    • 1
  1. 1.Universitätsklinik für Innere Medizin IIIParacelsus Medizinische PrivatuniversitätSalzburgAustria

Personalised recommendations