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Review

Molecular therapeutics of myelodysplasia and myelodysplasia-related leukaemias

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Pages 151-163 | Published online: 25 Feb 2005

Bibliography

  • MUNDLE SD, VENUGOPAL P, CARTLIDGE JD et al: Indica-tion of an involvement of interleukin-16 converting enzyme-like protease in intramedullary apoptotic cell death in the bone marrow of patients with myelodys-plastic syndromes. Blood (1996) 88:2640–2647.
  • RAJAPASKA R, GINZTON N, ROTT LS, GRENBERG PL: Al-tered oncoprotein expression and apoptosis in myelo-dysplastic syndrome marrow cells. Blood (1996) 88:4275–4287.
  • RAZA A, ALVI S, BROADY-ROBINSON L, SHOWEL M et al.: Cell cycle kinetic studies in 68 patients with myelodys-plastic syndromes following intravenous iodo-and/or bromodeoxyuridine. Exp. Hematol. (1997) 25:530–535.
  • KITAGAWA M, YAMAGUCHI S, TAKAHASHI M et al.: Lo-calization of Fas and Fas ligand in bone marrow cells demonstrating myelodysplasia. Leukemia (1998) 12:486–492.
  • QUESNEL B, GUILLERM G, VEREECQUE R et al. Methyla-tion of the p15 INK4b gene in myelodysplastic syndromes is frequent and acquired during disease progression. Blood (1998) 91:2985–2990.
  • •It is interesting that in MDS the pl5INK4B methylation corre-lates with disease progression and with extent of bone mar-roow blast involvement.
  • UCHIDA T, KINOSHITA T, NAGAI H et al.: Hypermethyla-tion of the pl5INK4B gene in myelodysplastic syn-dromes. Blood (1997) 90 (4) :1403–1409.
  • COUNTS JL, GOODMAN JI: Alterations in DNA methyla-tion may play a variety of roles in carcinogenesis. Cell (1995) 83:13–15.
  • MELKI JR, WARNECKE P, VINCENT PC, CLARK SJ: In-creased DNA methyltransferase expression in leukae-mia. Leukemia (1998) 12(3):311–316.
  • HANNON GJ, BEACH D: p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nature (1994) 371:257–261.
  • JUTTERMAN R, LI E, JAENISCH R: Toxicity of 5-aza-2'-deoxycytidine to mammalian cells is mediated primar-ily by covalent trapping of DNA methyltransferase rather than DNA demethylation. Proc. Natl. Acad. Sci. USA (1994) 91:11797–11801.
  • NAGATA S, GOLSTEIN P: The Fas death factor. Science(1995) 267:1449–1456.
  • •An excellent review of the Fas signalling pathway in apoptosis.
  • RAZA A, MUNDLE S, SHETTY V et al.: Novel insights into the biology of myelodysplastic syndromes: excessive apoptosis and the role of cytokines. Int. J. Hematol. (1996) 63:265–278.
  • ENARI M, JUG H, NAGATA S: Involvement of an ICE-like protease in Fas-mediated apoptosis. Nature (1995) 375:78–81.
  • LOS M, VAN DE CRAEN M, PENNING LC et al.: Require-ment of an ICE/CED3 protease for Fas/APO-1-mediated apoptosis. Nature (1995) 375:81–83.
  • ENARI M, TALANIAN RV, WONG WW et al.: Sequential ac-tiavtion of ICE-like and CPP32-like proteases during Fas-mediated apoptosis. Nature (1996) 380:723–726.
  • NAGAFUJI K, SHIBUYA T, HARADA M et al.: Functional expression of Fas antigen (CD95) on hematopoeitic progenitor cells. Blood (1995) 86:883–889.
  • RAZA A, VENUGOPAL P, GEZER S et al.: Pilot study of pentoxifylline and ciprofloxacin with or without dex-amethasone produces encouraging results in myelo-dysplastic syndromes. In: Acute Leukemias VII: Experimental Approaches and Novel Therapies. Hiddeman et al. (Eds.), Springer-Verlag, Berlin, Heidelberg (1998) 42–51.
  • •A provocative clinical trial of antitumour necrosis factor-based therapy aimed at overcoming apoptosis.
  • RAZA A, QAWI H, ANDRIC T et al: A novel cytoprotective + anticytokine strategy to improve the ineffective hematopoiesis in myelodysplastic syndromes (MDS): use of amifostine + pentoxifylline/ciprofloxacin/dex-amethasone (PCD). Proc. Am. Soc. Clin. Oncol. (1998) 17:4a.
  • ITO T, MAY WS: Drug development train gathering steam. Nature Med. (1996) 2:403–404.
  • EGAN SE, GIDDINGS BW, BROOKS MW, BUDAY L, SIZE-LAND AM, WEINBERG RA: Association of Sos Ras ex-change protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation. Nature (1993) 363:45–51.
  • LI N, BATZER A, DALY R et al.: Guanine nucleotide-releasing factor hSosl binds to Grb2 and links tyrosine kinases to Ras signalling. Nature (1993) 363:85–88.
  • SASAOKA T, LANGLOIS WJ, LEITNER JW, DRAZNIN B, OLEFSKY JM: The signalling pathway coupling epider-mal growth factor receptors to activation of p211.". J. Biol. Chem. (1994) 51:32621–23625.
  • KINOSHITA T, YOKOTA T, ARAI K, MIYAJIMA A: Suppres-sion of apopotic death in hematopoietic cells by sig-nalling through the IL-3/GM-CSF receptors. EMBO J. (1995) 14:266–275.
  • KINOSHITA T, YOKOTA T, ARAI K, MIYAJIMA A: Regula-tion of Bc1-2 expression by oncogenic Ras protein in hematopoietic cells. Oncogene (1995) 10:2207–2212.
  • PEEPER DS, UPTON TM, LADHA MH et al.: Ras signalling linked to cell cycle machinery by the retinoblastoma protein. Nature (1997) 386:177–181.
  • BARTRAM CR: Molecular genetic aspects of myelodys-plastic syndromes. Semin. Hematol. (1996) 33:139–149.
  • PAQUETTE RL, LANDAW EM, PIERRE RV et al.: N-ras mu-tations are associated with poor prognosis and in-creased risk of leukemia in myelodysplastic syndrome. Blood (1993) 82:590–599.
  • TAYLOR JA, SANDLER DP, BLOOMFIELD CD et al.: Ras on-cogene activation and occupational exposures in acute myeloid leukemia. J. Natl. Cancer. Inst. (1992) 84:1626–1632.
  • HIRSCH-GINSBERG C, LEMAISTRE AC, KANTARJIAN H et al.: RAS mutations are rare events in Philadelphia chromosome-negative/bcr gene rearrangement-negative chronic myelogenous leukemia, but are prevalent in chronic myelomonocytic leukemia. Blood (1990) 86:1214–1219.
  • PADUA RA, GUINN BA, AL-SABAH A et al.: RAS, FMS and p53 mutations and poor clinical outcome in myelodys-plasias: a 10 year follow-up. Leukemia (1998) 12(6):887–892.
  • BOS JL, VERLAAN-DE VRIES M, VAN DER EB AJ et al.: Muta-tions in N-ras predominate in acute myeloid leukemia. Blood (1987) 69:1237–1241.
  • NEUBAUER A, DODGE RK, GEORGE SL et al.: Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia. Blood (1994) 83:1603–1611.
  • THORN J, MOLLOY P, ILAND H: SSCP detection of N-raspromoter mutations in AML patients. Exp. Hematol (1995) 23:1098–1103.
  • BOLLAG G, CLAPP DW, SHIH S et al. Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells. Nature Genet. (1996) 12:144–148.
  • SHANNON KM, O'CONNELL P, MARTIN GA et al: Loss of the normal NF1 allele from the bone marrow of chil-dren with Type I neurofibromatosis and malignant myeloid disorders. NewEng]] Med. (1994) 330:597–601.
  • LUNA-FINEMAN S, SHANNON KM, LANGE BJ: Childhood monosomy 7: epidemiology, biology and mechanistic implications. Blood (1995) 85:1985–1999.
  • KARP JE, SMITH MA: The molecular pathogenesis of treatment-induced (secondary) leukemias: founda-tions for treatment and prevention. Semin. Oncol. (1997) 24:103–113.
  • PEDERSEN-BJERGAARD J, PEDERSEN M, ROULSTON D, PHILIP P: Different genetic pathways in leukemogene-sis for patients presenting with therapy-related myelo-dysplasia and therapy-related acute myeloid leukemia. Blood (1995) 86:3542–3552.
  • FISCHER K, FROHLING S, SCHERER SW et al.: Molecular cytogenetic delineation of deletions and transloca-tions involving chromosome band 7q22 in myeloid leukemias. Blood (1997) 89:2036–2041.
  • JOHNSON EJ, SCHERER SW, OSBORNE L et al.: Molecular definition of a narrow interval at 7q22.1 associated with myelodysplasia. Blood (1996) 87:3579–3586.
  • LE BEAU MM, ESPINOSA III R, DAVIS EM et al: Cytoge-netic and molecular delineation of a region of chromo-some 7 commonly deleted in malignant myeloid diseases. Blood (1996) 88:1930–1935.
  • BARRINGTON RE, SUBLER MA, RANDS E et al.: A farnesyl-transferase inhibitor induces tumor regression in transgenic mice harboring mutliple oncogenic muta-tions by mediating alterations in both cell cycle con-trol and apoptosis. Mol. Cell Biol. (1998) 18:85–92.
  • JAMES GL, GOLDSTEIN JL, BROWN MS et al.: Benzodi-azepine peptidomimetics: potent inhibitors of ras far-nesylation in animal cells. Science (1993) 260:1937–1942.
  • KOHL NE, OMER CA, CONNER MW et al.: Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice. Nature Med. (1995) 1:792–797.
  • GELB MH: Protein prenylation, et cetera: signal trans-duction in two dimensions. Science (1997) 27:1750–1751.
  • KHOSVARI-FAR R, COX AD, KATO K, DER CJ: Protein prenylation: key to ras function and cancer interven-tion. Cell Growth Diff (1992) 3:461–469.
  • HAAG JD, LINDSTROM MJ, GOULD MN: Limonene-induced regression of mammary carcinomas. Cancer Res. (1992) 52:4021–4026.
  • UCHIDA N, COMBS J, CHEN S et al.: Primitive human he-matopoietic cells displaying differential efflux of the rhodamine 123 dye have distinct biological activities. Blood (1996) 88:1297–1305.
  • LEITH CP, CHEN I-M, KOPECKY KJ et al.: Correlation of multidrug resistance (MDR1) protein expression with functional dye/drug efflux in acute myeloid leukemia by multiparameter flow cytometry: identification of discordant MDR-/efflux+ and MDR1+/efflux-cases. Blood (1995) 86:2329–2342.
  • HAASE D, FEURING-BUSKE M, KONEMANN S et al: Evi-dence for malignant transformation in acute myeloid leukemia at the level of early hematopoietic stem cells by cytogenetic analysis of CD34+ subpopulations. Blood (1995) 86:2906–2912.
  • MEHROTRA B, GEORGE TI, KAVANAU K et al.: Cytoge-netically aberrant cells in the stem cell compartment (CD34+1in-) in acute myeloid leukemia. Blood (1995) 86:1139–1147.
  • LEITH CP, KOPECKY KJ, GODWIN J et al.: Acute myeloid leukemia in the elderly: assessment of multidrug resis-tance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to stan-dard chemotherapy. A Southwest Oncology Group study. Blood (1997) 89:3323–3329.
  • ••Among elderly patients with acute myeloid leukaemia(AML), those with secondary AML (defined on the basis of antecedent MDS or previous exposure to leukaemogenic chemotherapy) exhibit a poor response to chemotherapy.
  • NAKAYAMA M, WADA M, HARADA T et al.: Hypomethy-lation status of CpG sites at the promoter region and overexpression of the human MDR1 gene in acute myeloid leukaemia. Blood (1998) 92:4296–4307.
  • KORNBLAU SM, ESTEY E, MADDEN T et al.: Phase I study of mitoxantrone plus etoposide with multidrug block-ade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia. J. Clin. Oncol. (1997) 15:1796–1802.
  • SOLARY E, WITZ B, CAILLOT D et al.: Combination ofquinine as a potential reversing agent with mitoxan-trone and cytarabine for the treatment of acute leuke-mias: a randomized multicenter study. Blood (1996) 88:1198–1205.
  • HOEFSLOOT LH, VAN AMELSVOORT MP, BROEDERS CAM et al.: Erythropoietin-induced activation of STAT5 is impaired in the myelodysplastic syndromes. Blood (1997) 89:1690–1700.
  • BRADA S, DE WOLF J, HENDRIKS D et al.: The supportive effects of erythropoietin and mast cell growth factor on CD34/CD36-sorted bone marrow cells of myelo-dysplasia patients. Blood (1996) 88:505–510.
  • OGATA K, AN E, KAMIJUBO K et al.: Cell cycle modula-tion by hematopoietic growth factors in myelodys-plastic syndromes: analysis by three-color flow cytometry. (1997) 25:8–18.
  • VADHAN-RAJ S, KEATING M, LEMAISTRE A et al.: Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodys-plastic syndromes. New Engl. J. Med. (1987) 317:1545–1552.
  • HERRMANN F, LINDEMANN A, KLEIN H et al: Effect of re-combinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndrome with excess blasts. Leukemia (1989) 3:335–338.
  • GANSER A, VOLKERS B, GREHER J et al.: Recombinanthuman granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes-a Phase I/II trial. Blood (1989) 73:31–37.
  • WILLEMZE R, VAN DER LELY N, ZWIERZINA H et al.: A ran-domized phase-I/II multicenter study of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy for patients with myelodys-plastic syndromes and a relatively low risk of acute leukemia. EORTC Leukemia Cooperative Group. Ann. Hematol. (1992) 64:173–180.
  • ••It is interesting that cytogenetic abnormalities in MDS arealso predictive of the response to GM-CSF. In this study, 14 of 16 patients with normal karyotypes responded to GM-CSF, compared with 14 of 27 with abnormal karyotypes.
  • KOBAJASHI J, OKABE T, OZAWA K et al.: Treatment ofMyelodysplastic Syndromes with recombinant human granulocyte colony-stimulating factor: a preliminary report. Am. J. Med. (1989) 86:178–1182.
  • NEGRIN RS, HAEUBER DH, NAGLER A et al.: Treatment ofmyelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor: a Phase I-II trial. Ann. Intern. Med. (1989) 110:976–984.
  • NEGRIN RS, HAEUBER DH, NAGLER A et al.: Maintenancetreatment of patients with myelodysplastic syn-dromes using recombinant human granulocyte colony-stimulating factor. Blood (1990) 76:36–43.
  • GREENBERG P, TAYLOR K, LARSON R et al.: Phase III ran-domized multicenter trial of G-CSF vs observation for myelodysplastic syndromes (MDS). Blood (1993) 82 (Suppl. 1) :196a [Abstract].
  • •The final report of this study, when completed, would be a very welcome addition to the literature.
  • SCHUSTER MW, THOMPSON JA, LARSON R et al.: Ran-domized trial of subcutaneous GM-CSF versus observa-tion in patients with myelodysplastic syndrome or aplastic anemia. Proc. Am. Soc. Clin. Oncol (1990) A703.
  • HELLSTROM-LINDBERG E: Efficacy of erythropoietin in the myelodysplastic syndromes. An analysis of 205 pa-tients in 17 studies. Br. J. Haematol. (1995) 89:67–71.
  • ••A summary of the findings from many small but well-conducted trials.
  • HELLSTROM-LINDBERG E, AHLGREN T, BEGUIN Y et al.: Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin: results from a randomized Phase II study and long-term follow-up of 71 patients. Blood (1998) 92:68–75.
  • •GM-CSF plus EPO successfully ameliorated anaemia in a sig-nificant proportion of patients, even over several months.
  • NEGRIN RS, STEIN R, DOHERTY K et al.: Maintenance treatment of the anemia of myelodysplastic syn-dromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evi-dence for in vivo synergy. Blood (1996) 87:4076–4081.
  • •Further evidence of the beneficial effects of G-CSF plus EPO in a subgroup of patients.
  • KOEFFLER HP, HEITJAN D, MERTELSMANN R et al.: Ran-domized study of 13-cis retinoic acid v placebo in the myelodysplastic disorders. Blood (1988) 71:703–708.
  • GORDON MS, NEMUNAITIS J, HOFFMAN R et al.: A Phase I trial of recombinant human interleukin-6 in patients with myelodysplastic syndromes and thrombocy-topenia. Blood (1995) 85:3066–3076.
  • GANSER A, OTTMANN OG, SEIPELT G et al.: Effect of long-term treatment with recombinant human interleukin-3 in patients with myelodysplastic syn-dromes. Leukemia (1993) 7:696–701.
  • GERHATZ HH, ZWIERZINA HH, WALTHER J et al.: Interleukin-3 plus low-dose cytosine arabinoside for advanced myelodysplasia: a pilot study. Cancer Invest. (1996) 14:299–306.
  • ECONOMOPOULOS T, PAPAGEOGIOU E, STATHAKIS N et al.: Treatment of myelodysplastic syndromes with hu-man granulocyte-macrophage colony-stimulating fac-tor (GM-CSF) or GM-CSF combined with low-dose cytosine arabinoside. Eur. J. Haematol (1992) 49:138–142.
  • GERHARTZ J, MARCUS R, DELMER A et al.: A randomized Phase II study of low-dose cytosine arabinoside plus GM-CSF in MDS with a high risk of developing leuke-mia. Leukemia (1994) 8:16–24.
  • HOFFKEN K, OVERKAMP F, STIRBU J et al.: Recombinant human granulocyte-macrophage colony-stimulating factor and low-dose cytosine-arabinoside in the treat-ment of patients with myelodysplastic syndromes. A Phase II study. Onkologie (1990) 13:33–37.
  • ASOU H, KOIKE M, ELSTNER E et al.: 19-nor Vitamin-D analogs: a new class of potent inhibitors of prolifera-tion and inducers of differentiation of human myeloid leukemia cell lines. Blood (1998) 92:2441–2449.
  • MUNKER R, KOBAYASHI T, ELSTNER E et al.: A new series of vitamin D analogs is highly active for clonal inhibi-tion, differentiation, and induction of WAF1 in mye-loid leukemia. Blood (1996) 88:2201–2209.
  • HENGST L, DULIC V, SLINGERLAND JM, LEES E, REED SI: A cell cycle-regulated inhibitor of cyclin-dependent ki-nases. Proc. Natl. Acad. ScI USA (1994) 91:5291–5295.
  • POLYAK K, LEE MH, ERDJUMENT-BROMAGE H et al.: Cloning of p271(1P1, a cyclin-dependent kinase inhibi-tor and a potential mediator of extracellular antimito-genic signals. Cell (1994) 78:59–66.
  • RUSSO AA, JEFFREY PD, PATTEN AK, MASSAGUE J, PAV-LETICH NP: Crystal structure of the p271(1P1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 compex. Nature (1996) 382:325–331.
  • TOYOSHIMA H, HUNTER T: p27, a novel inhibitor of G1 cyclin-cdk protein kinase activity, is related to p21. Cell (1994) 78:67–74.
  • HOGLUND M, JOHANSSON B, PEDERSEN-BJERGAARD J, MAYNEN P, MITELMAN F: Molecular characterization of 12p abnormalities in hematologic malignancies: dele-tion of K1P1, rearrangement of TEL, and amplification of CCND2. Blood (1996) 87:324–330.
  • KOBAYASHI H, MONTGOMERY KT, BOHLANDER SK et al: Fluorescence in situ hybridization mapping of translocations and deletions involving the short arm human chromosome 12 in malignant hematologic dis-ease. Blood (1994) 84:3473–3482.
  • SATO Y, SUTO Y, PIETENPOL J et al.: TEL and K1P1 de-fine the smallest region of deletions on 12p13 in hema-topoietic malignancies. Blood (1995) 86:1525–1533.
  • BLAZSEK I, FARABOS C, QUITTET P et al.: Bone marrow stromal defects and la, 25-dihydroxyvitamin D3 defi-ciency underlying human myeloid leukemias. Cancer Detect. Prevent. (1996) 20:31–42.
  • LIST AF, BRASFIELD F, HEATON R et al.: Stimulation of hematopoiesis by amifostine in patients with myelo-dysplastic syndrome. Blood (1997) 90(9) :3364–3369.
  • ••Interesting initial report of amifostine in MDS showing hae-matological responses in 15/18 patients (83%). Six patients had RAEB or RAEBt; two of them progressed to AML. Treat-ment was well tolerated. These encouraging results warrant a larger trial.
  • GORE SD, WENG LJ, GRIFFIN CA et al.: Impact of pro-longed administration of the putative differentiating agent sodium phenylbutyrate (PB) on hematopoeisis in myelodysplastic syndrome (MDS) and acute mye-loid leukemia (AML). Blood (1998) 92 (Suppl. 1):633a. Ab-stract 2609.
  • ••Although generally well tolerated, infusions of phenylbu-tyrate were, in this study, associated with only modest im-provements in a small number of patients. This drug may find its usefulness in combination with other agents.
  • SAMID D, SHACK S, MYERS CE: Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic pharmacologic concentrations of phenylacetate. j Clin. Invest. (1993) 91:2288–2295.
  • ANDERSON JE, APPELBAUM FR, SCHOCH G et al: Alloge-neic marrow transplantation for myelodysplastic syn-drome with advanced disease morphology: a Phase II study of busulphan, cyclophosphamide, and total-body irradiation and analysis of prognostic factors. J. Clin. Oncol. (1996) 14:220–226.
  • SUTTON L, CHASTANG C, RIBAUD P et al.: Factors influ-encing outcome in de novo myelodysplastic sun-dromes treated by allogeneic bone marrow transplantation: a long term study of 71 patients. Blood (1996) 88:358–365.
  • O'DONNELL MR, LONG GD, PARKER PM et al.: Busul-fan/cyclophosphamide as conditioning regimen for allogeneic bone marrow transplantation for myelo-dysplasia. j Clin. Oncol (1995) 13:2973–2979.
  • NEVILL TJ, FUNG HC, SHEPHERD JD et al.: Cytogenetic abnormalities in primary myelodysplastic syndrome are highly predictive of outcome after allogeneic bone marrow transplantation. Blood (1998) 92 (6) :1910–1917.
  • •Single institution, retrospective study showing correlation of allogeneic BMT outcome with cytogenetics.
  • ANDERSON JE, ANASETTI C, APPELBAUM FR et al: Unre-lated donor marrow transplantation for myelodyspla-sia (MDS) and MDS-related acute myeloid leukaemia. Br. J. Haematol. (1996) 93:59–67.
  • APPLEBAUM FR, ANDERSON J: Allogeneic bone marrow transplantation for myelodysplastic syndrome: out-comes analysis according to IPSS score. Leukemia (1998) 12 (Suppl. 1):S25–S29.
  • ••The International Prognostic Scoring System (IPSS) was ini-tially developed to predict evolution into AML or survival in patients with MDS. The IPSS was also found to be predictive of leukaemia-free survival. It is remarkable that the same score also predicts the outcome of allogeneic BMT for this disease.
  • DELFORGE M, DEMUYNCK H, VANDENBERGHE P et al.: Polyclonal primitive hematopoietic progenitors can be detected in mobilized peripheral blood from pa-tients with high-risk myelodysplastic syndromes. Blood (1995) 86:3660–3667.
  • DEWILL T, VAN BIEZEN A, HERMANS J et al.: Autologous bone marrow transplantation for patients with myelo-dysplastic syndrome (MDS) or acute leukemia follow-ing MDS. Blood (1997) 90:3853–3857.
  • •A registry report, from the European Group for Blood and Marrow Transplantation, of 79 patients, including 55 who were compared to a matched group of patients with de novo AML. Transplant-related mortality was low (10%), result-ing in an encouraging 2-year dfs rate of 28% despite a high relapse rate (>60%). The DFS for matched de novo AML pa-tients was 51%, evidence of the poor prognosis of secondary AML/MDS.
  • DEMUYNCK H, DELFORGE M, VERHOEF GEG et al.: Feasi-bility of peripheral blood progenitor cell harvest and transplantation in patients with poor-risk myelodys-plastic syndromes. Br. J. Haematol (1996) 92:351–359.

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