Current therapeutic strategies for acute myeloid leukaemia
Jonathan E. Kolitz
Leukemia Service, Monter Cancer Center, North Shore University Hospital, New York University School of Medicine, Lake Success, NY, USA
Search for more papers by this authorJonathan E. Kolitz
Leukemia Service, Monter Cancer Center, North Shore University Hospital, New York University School of Medicine, Lake Success, NY, USA
Search for more papers by this authorSummary
Improvements in survival in adult acute myeloid leukaemia (AML) have yet to be gleaned from either refinements in the understanding of the pathophysiology of the disease or from the expanding pool of targeted therapies. Outcomes have remained particularly dismal in older patients. Ongoing and planned trials will assess the effects of drugs targeting biological pathways whose clinical importance may vary as a function of the unique genotype and phenotype of each case of AML. The success of these ventures will ultimately require well-designed clinical trials in subsets of patients with risk being dependent not only on age and cytogenetics, but on additional, increasingly quantifiable biological variables. Inhibitors of fms-like tyrosine kinase-3, farnesyl transferase, apoptotic and angiogenic pathways are being studied alone and in combination with chemotherapy. Biological therapies, including monoclonal antibodies, peptide vaccines and interleukin-2, are undergoing evaluation. The role of autologous as well as allogeneic myeloablative and reduced-intensity transplantation continues to be defined. Several potentially useful new cytotoxic agents are being introduced. Critically important to advancing the field in light of such an increasing number of choices is a reassessment of traditional phase II trial designs so that more efficient evaluation of new therapies may take place, even as well-designed phase III trials continue to be performed.
References
- Adams, J. (2004) The proteasome: a suitable antineoplastic target. Nature Reviews Cancer, 4, 349–360.
- Amadori, S., Suciu, S., Willemze, R., Mandelli, F., Selleslag, D., Stauder, R., Ho, A., Denzlinger, C., Leone, G., Fillet, G., Muus, P., Beeldens, F., Anak, O. & De Witte, T. (2004) Up-front window trial of gemtuzumab ozogamicin (GO) in previously untreated elderly patients with AML: an EORTC Leukemia Group Study. Blood, 104, 877a.
- Amadori, S., Suciu, S., Jehn, U., Stasi, R., Thomas, X., Marie, J.-P., Muus, P., Lefrere, F., Berneman, Z., Fillet, G., Denzlinger, C., Willemze, R., Leoni, P., Leone, G., Casini, M., Ricciuti, F., Vignetti, M., Beeldens, F., Mandelli, F., De Witte, T. & for the E.G.L.G. (2005) Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study. Blood, 106, 27–34.
- AML Collaborative Group (1998) A systematic collaborative overview of randomized trials comparing idarubicin with daunorubicin (or other anthracyclines) as induction therapy for acute myeloid leukaemia. British Journal of Haematology, 103, 100–109.
- Appelbaum, F.R., Gundacker, H., Head, D.R., Slovak, M.L., Willman, C.L., Godwin, J.E., Anderson, J.E. & Petersdorf, S.H. (2006) Age and acute myeloid leukemia. Blood, 107, 3481–3485.
- Attar, E.C., De Angelo, D.J., Sirulnik, A., Wadleigh, M., Ballen, K.K., Miller, K.B., Galinsky, I., Neuberg, D., Trehu, E., Schenkein, D., Stone, R.M. & Amrein, P.C. (2005) Addition of bortezomib (Velcade) to AML induction chemotherapy is well tolerated and results in a high complete remission rate. Blood, 106, 2782a.
- Bachman, K.E., Park, B.H., Rhee, I., Rajagopalan, H., Herman, J.G., Baylin, S.B., Kinzler, K.W. & Vogelstein, B. (2003) Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene. Cancer Cell, 3, 89–95.
- Baer, M.R., George, S.L., Dodge, R.K., O'Loughlin, K.L., Minderman, H., Caligiuri, M.A., Anastasi, J., Powell, B.L., Kolitz, J.E., Schiffer, C.A., Bloomfield, C.D. & Larson, R.A. (2002) Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720. Blood, 100, 1224–1232.
- Baer, M.R., Cuviello, N.W., Shoemaker, J.S., Barrier, Jr, R., Caligiuri, M.A., Kolitz, J.E., Powell, B.L., Larson, R.A. & Bloomfield, C.D. (2005) Treatment failure is strongly predicted by P-glycoprotein (Pgp) function but not by multidrug resistance protein (MRP-1), breast cancer resistance protein (BCRP) or lung resistance protein (LRP) in acute myeloid leukemia (AML) patients 60 years and older receiving intensive chemotherapy (CALGB 9720/9760). Blood, 106, 661a.
- Baldus, C.D., Tanner, S.M., Ruppert, A.S., Whitman, S.P., Archer, K.J., Marcucci, G., Caligiuri, M.A., Carroll, A.J., Vardiman, J.W., Powell, B.L., Allen, S.L., Moore, J.O., Larson, R.A., Kolitz, J.E., De La Chapelle, A. & Bloomfield, C.D. (2003) BAALC expression predicts clinical outcome of de novo acute myeloid leukemia patients with normal cytogenetics: a Cancer and Leukemia Group B Study. Blood, 102, 1613–1618.
- Becker, P.S. (2004) Growth factor priming in therapy of acute myelogenous leukemia. Current Hematology Reports, 3, 413–418.
- Bench, A.J., Erber, W.N. & Scott, M.A. (2005) Molecular genetic analysis of haematological malignancies: I. Acute leukaemias and myeloproliferative disorders. Clinical and Laboratory Haematology, 27, 148–171.
-
Berman, E.,
Wiernik, P.,
Vogler, R.,
Velez-Garcia, E.,
Bartolucci, A. &
Whaley, F.S. (1997) Long-term follow-up of three randomized trials comparing idarubicin and daunorubicin as induction therapies for patients with untreated acute myeloid leukemia.
Cancer, 80, 2181–2185.
10.1002/(SICI)1097-0142(19971201)80:11+<2181::AID-CNCR3>3.0.CO;2-L CAS PubMed Web of Science® Google Scholar
- Bienz, M., Ludwig, M., Mueller, B.U., Oppliger Leibundgut, E., Ratschiller, D., Solenthaler, M., Fey, M.F. & Pabst, T. (2005a) Risk assessment in patients with acute myeloid leukemia and a normal karyotype. Clinical Cancer Research, 11, 1416–1424.
- Bienz, M., Ludwig, M., Leibundgut, E.O., Mueller, B.U., Ratschiller, D., Solenthaler, M., Fey, M.F. & Pabst, T. (2005b) Risk assessment in patients with acute myeloid leukemia and a normal karyotype. Clinical Cancer Research, 11, 1416–1424.
- Bishop, J.F., Lowenthal, R.M., Joshua, D., Matthews, J.P., Todd, D., Cobcroft, R., Whiteside, M.G., Kronenberg, H., Ma, D. & Dodds, A. (1990) Etoposide in acute nonlymphocytic leukemia. Australian Leukemia Study Group. Blood, 75, 27–32.
- Bishop, J.F., Matthews, J.P., Young, G.A., Bradstock, K. & Lowenthal, R.M. (1998) Intensified induction chemotherapy with high dose cytarabine and etoposide for acute myeloid leukemia: a review and updated results of the Australian Leukemia Study Group. Leukemia and Lymphoma, 28, 315–327.
- Bloomfield, C.D., Lawrence, D., Byrd, J.C., Carroll, A., Pettenati, M.J., Tantravahi, R., Patil, S.R., Davey, F.R., Berg, D.T., Schiffer, C.A., Arthur, D.C. & Mayer, R.J. (1998) Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype. Cancer Research, 58, 4173–4179.
- Blum, W., Bruner-Klisovic, R., Liu, S., Byrd, J.C., Liu, Z., Chan, K.K., Kefauver, C., Huynh, L., Grever, M.R. & Marcucci, G. (2005) Phase I study of low dose decitabine in patients with acute myeloid leukemia (AML): pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity. Blood, 106, 1861a.
- De Botton, S., Fawaz, A., Chevret, S., Dombret, H., Thomas, X., Sanz, M., Guerci, A., San Miguel, J., De La Serna, J., Stoppa, A.M., Reman, O., Stamatoulas, A., Fey, M., Cahn, J.Y., Sotto, J.J., Bourhis, J.H., Parry, A., Chomienne, C., Degos, L. & Fenaux, P. (2005) Autologous and allogeneic stem-cell transplantation as salvage treatment of acute promyelocytic leukemia initially treated with all-trans-retinoic acid: a retrospective analysis of the European Acute Promyelocytic Leukemia Group. Journal of Clinical Oncology, 23, 120–126.
- Bowen, D.T., Frew, M.E., Hills, R., Gale, R.E., Wheatley, K., Groves, M.J., Langabeer, S.E., Kottaridis, P.D., Moorman, A.V., Burnett, A.K. & Linch, D.C. (2005) RAS mutation in acute myeloid leukemia is associated with distinct cytogenetic subgroups but does not influence outcome in patients younger than 60 years. Blood, 106, 2113–2119.
- Brookes, S.T., Whitely, E., Egger, M., Smith, G.D., Mulheran, P.A. & Peters, T.J. (2004) Subgroup analyses in randomized trials: risks of subgroup-specific analyses; power and sample size for the interaction test. Journal of Clinical Epidemiology, 57, 229–236.
- Brune, M., Castaigne, S., Catalano, J., Gehlsen, K., Ho, A.D., Hofmann, W.-K., Hogge, D.E., Nilsson, B., Or, R., Romero, A.I., Rowe, J.M., Simonsson, B., Spearing, R., Stadtmauer, E.A., Szer, J., Wallhult, E. & Hellstrand, K. (2006) Improved leukemia-free survival after post-consolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase III trial. Blood, 2005–2010–4073.
- Bullinger, L., Dohner, K., Bair, E., Frohling, S., Schlenk, R.F., Tibshirani, R., Dohner, H. & Pollack, J.R. (2004) Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia. New England Journal of Medicine, 350, 1605–1616.
- Burnett, A.K., Goldstone, A.H., Stevens, R.M., Hann, I.M., Rees, J.K., Gray, R.G. & Wheatley, K. (1998) Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: results of MRC AML 10 trial. UK Medical Research Council Adult and Children's Leukaemia Working Parties. Lancet, 351, 700–708.
- Burnett, A., Hills, R.K., Goldstone, AH, Prentice, A., Milligan, D., Pallis, M., Russell, N., Truran, L.N. & Wheatley, K. (2003) Attempts to modulate chemoresistance in older patients with AML using PSC-833 – results of the LRF AML14 Trial. Blood, 102, Abstract 226.
- Burnett, A.K., Milligan, D., Prentice, A.G., Goldstone, A.H., McMullin, M.F. & Wheatley, K. (2004) Low dose Ara-C versus hydroxyurea with or without retinoid in older patients not considered fit for intensive chemotherapy: the UK NCRI AML14 Trial. Blood, 104, 872a.
- Burnett, A.K., Milligan, D.W., Prentice, A.G., Goldstone, A.H., McMullin, M.F., Hills, R.K. & Wheatley, K. (2005) Modification or dose or treatment duration has no impact on outcome of AML in older patients: preliminary results of the UK NCRI AML14 Trial. Blood, 106, 543a.
- Byrd, J.C., Dodge, R.K., Carroll, A., Baer, M.R., Edwards, C., Stamberg, J., Qumsiyeh, M., Moore, J.O., Mayer, R.J., Davey, F., Schiffer, C.A. & Bloomfield, C.D. (1999) Patients with t(8;21)(q22;q22) and acute myeloid leukemia have superior failure-free and overall survival when repetitive cycles of high-dose cytarabine are administered. Journal of Clinical Oncology, 17, 3767–3775.
- Byrd, J.C., Mrozek, K., Dodge, R.K., Carroll, A.J., Edwards, C.G., Arthur, D.C., Pettenati, M.J., Patil, S.R., Rao, K.W., Watson, M.S., Koduru, P.R.K., Moore, J.O., Stone, R.M., Mayer, R.J., Feldman, E.J., Davey, F.R., Schiffer, C.A., Larson, R.A. & Bloomfield, C.D. (2002) Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood, 100, 4325–4336.
- Byrd, J.C., Ruppert, A.S., Mrozek, K., Carroll, A.J., Edwards, C.G., Arthur, D.C., Pettenati, M.J., Stamberg, J., Koduru, P.R.K., Moore, J.O., Mayer, R.J., Davey, F.R., Larson, R.A. & Bloomfield, C.D. (2004) Repetitive cycles of high-dose cytarabine benefit patients with acute myeloid leukemia and inv(16)(p13q22) or t(16;16)(p13;q22): results from CALGB 8461. Journal of Clinical Oncology, 22, 1087–1094.
- Byrd, J.C., Marcucci, G., Parthun, M.R., Xiao, J.J., Klisovic, R.B., Moran, M., Lin, T.S., Liu, S., Sklenar, A.R., Davis, M.E., Lucas, D.M., Fischer, B., Shank, R., Tejaswi, S.L., Binkley, P., Wright, J., Chan, K.K. & Grever, M.R. (2005) A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia. Blood, 105, 959–967.
- Carter, B.Z., Mak, D.H., Schober, W.D., McQueen, T., Harris, D., Estrov, Z., Evans, R.L. & Andreeff, M. (2006) Triptolide induces caspase-dependent cell death mediated via the mitochondrial pathway in leukemic cells. DOI 10.1182/blood-2005-09-3898. Blood, 108, 630–637.
- Cheson, B.D., Bennett, J.M., Kopecky, K.J., Buchner, T., Willman, C.L., Estey, E.H., Schiffer, C.A., Doehner, H., Tallman, M.S., Lister, T.A., Lo-Coco, F., Willemze, R., Biondi, A., Hiddemann, W., Larson, R.A., Lowenberg, B., Sanz, M.A., Head, D.R., Ohno, R. & Bloomfield, C.D. (2003) Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and Reporting Standards for Therapeutic Trials in acute myeloid leukemia. Journal of Clinical Oncology, 21, 4642–4649.
- Cortes, J., Thomas, D., Koller, C., Giles, F., Estey, E., Faderl, S., Garcia-Manero, G., McConkey, D., Patel, G., Guerciolini, R., Wright, J. & Kantarjian, H. (2004) Phase I study of bortezomib in refractory or relapsed acute leukemias. Clinical Cancer Research, 10, 3371–3376.
- Cortes, J., Garcia-Manero, G., O'Brien, S., Verstovsek, S., Estrov, Z., Giles, F., Ravandi, F., Wright, J. & Kantarjian, H. (2005) Farnesyl transferase inhibitor (Tipifarnib, Zarnestra; Z) in combination with standard chemotherapy with idarubicin (Ida) and cytarabine (ara-C) for patients (pts) with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). Blood, 106, 2796a.
- Derolf, A.R., Landgren, O., Dickman, P., Kristinsson, S.Y. & Bjorkholm, M. (2005) Prognosis in acute myeloid leukemia: a population-based study on 5809 patients diagnosed in Sweden 1973–2001. Blood, 106, 1845a.
- Dey, B.R., McAfee, S., Colby, C., Sackstein, R., Saidman, S., Tarbell, N., Sachs, D.H., Sykes, M. & Spitzer, T.R. (2003) Impact of prophylactic donor leukocyte infusions on mixed chimerism, graft-versus-host disease, and antitumor response in patients with advanced hematologic malignancies treated with nonmyeloablative conditioning and allogeneic bone marrow transplantation. Biology of Blood and Marrow Transplantation, 9, 320–329.
- Dillman, R.O., Davis, R.B., Green, M.R., Weiss, R.B., Gottlieb, A.J., Caplan, S., Kopel, S., Preisler, H., McIntyre, O.R. & Schiffer, C. (1991) A comparative study of two different doses of cytarabine for acute myeloid leukemia: a phase III trial of Cancer and Leukemia Group B. Blood, 78, 2520–2526.
- Dombret, H., Chastang, C., Fenaux, P., Reiffers, J., Bordessoule, D., Bouabdallah, R., Mandelli, F., Ferrant, A., Auzanneau, G., Tilly, H., Yver, A. & Degos, L. for the AML Cooperative Study Group (1995) A controlled study of recombinant human granulocyte colony-stimulating factor in elderly patients after treatment for acute myelogenous leukemia. AML Cooperative Study Group. New England Journal of Medicine, 332, 1678–1683.
- Ermann, J., Hoffmann, P., Edinger, M., Dutt, S., Blankenberg, F.G., Higgins, J.P., Negrin, R.S., Fathman, C.G. & Strober, S. (2005) Only the CD62L + subpopulation of CD4 + CD25 + regulatory T cells protects from lethal acute GVHD. Blood, 105, 2220–2226.
- Estey, E.H., Thall, P.F., Cortes, J.E., Giles, F.J., O'Brien, S., Pierce, S.A., Wang, X., Kantarjian, H.M. & Beran, M. (2001) Comparison of idarubicin + ara-C-, fludarabine + ara-C-, and topotecan + ara-C-based regimens in treatment of newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts in transformation, or refractory anemia with excess blasts. Blood, 98, 3575–3583.
- Estey, E.H., Garcia-Manero, G., Giles, F.J., Cortes, J., O'Brien, S. & Kantarjian, H.M. (2005) Clinical relevance of CRp in untreated AML. Blood, 106, 541a.
- Estey, E., Garcia-Manero, G., Ferrajoli, A., Faderl, S., Verstovsek, S., Jones, D. & Kantarjian, H. (2006) Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood, 107, 3469–3473.
- Faderl, S., Verstovsek, S., Cortes, J., Ravandi, F., Beran, M., Garcia-Manero, G., Ferrajoli, A., Estrov, Z., O'Brien, S., Coller, C., Giles, F.J., Wierda, W., Kwari, M. & Kantarjian H.M. (2006) Clofarabine and cytarabine combination as induction therapy for acute myeloid leukemia (AML) in patients >50 years. Blood, 108, 45–51.
- Farag, S.S., George, S.L., Lee, E.J., Baer, M., Dodge, R.K., Becknell, B., Fehniger, T., Silverman, L.R., Crawford, J., Bloomfield, C.D., Larson, R.A., Schiffer, C.A. & Caligiuri, M.A. (2002) Postremission therapy with low-dose interleukin 2 with or without intermediate pulse dose interleukin 2 therapy is well tolerated in elderly patients with acute myeloid leukemia: Cancer and Leukemia Group B Study 9420. Clinical Cancer Research, 8, 2812–2819.
- Farag, S.S., Ruppert, A.S., Mrozek, K., Mayer, R.J., Stone, R.M., Carroll, A.J., Powell, B.L., Moore, J.O., Pettenati, M.J., Koduru, P.R.K., Stamberg, J., Baer, M.R., Block, A.W., Vardiman, J.W., Kolitz, J.E., Schiffer, C.A., Larson, R.A. & Bloomfield, C.D. (2005) Outcome of induction and postremission therapy in younger adults with acute myeloid leukemia with normal karyotype: a Cancer and Leukemia Group B Study. Journal of Clinical Oncology, 23, 482–493.
- Feldman, E.J., Brandwein, J., Stone, R., Kalaycio, M., Moore, J., O'Connor, J., Wedel, N., Roboz, G.J., Miller, C., Chopra, R., Jurcic, J.C., Brown, R., Ehmann, W.C., Schulman, P., Frankel, S.R., De Angelo, D. & Scheinberg, D. (2005) Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia. Journal of Clinical Oncology, 23, 4110–4116.
- Fenaux, P., Chastang, C., Chevret, S., Sanz, M., Dombret, H., Archimbaud, E., Fey, M., Rayon, C., Huguet, F., Sotto, J.-J., Gardin, C., Makhoul, P.C., Travade, P., Solary, E., Fegueux, N., Bordessoule, D., Miguel, J.S., Link, H., Desablens, B., Stamatoullas, A., Deconinck, E., Maloisel, F., Castaigne, S., Preudhomme, C. & Degos, L. (1999) A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. Blood, 94, 1192–1200.
- Fiedler, W., Mesters, R., Tinnefeld, H., Loges, S., Staib, P., Duhrsen, U., Flasshove, M., Ottmann, O.G., Jung, W., Cavalli, F., Kuse, R., Thomalla, J., Serve, H., O'Farrell, A.M., Jacobs, M., Brega, N.M., Scigalla, P., Hossfeld, D.K. & Berdel, W.E. (2003) A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia. Blood, 102, 2763–2767.
- Fiedler, W., Serve, H., Dohner, H., Schwittay, M., Ottmann, O.G., O'Farrell, A.-M., Bello, C.L., Allred, R., Manning, W.C., Cherrington, J.M., Louie, S.G., Hong, W., Brega, N.M., Massimini, G., Scigalla, P., Berdel, W.E. & Hossfeld, D.K. (2004) A phase I study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease. Blood, 105, 986–993.
- Foa, R. (1996) Interleukin 2 in the management of acute leukaemia. British Journal of Haematology, 92, 1–8.
- Frankel, A.E., Powell, B.L., Hall, P.D., Case, L.D. & Kreitman, R.J. (2002) Phase I trial of a novel diphtheria toxin/granulocyte macrophage colony-stimulating factor fusion protein (DT388GMCSF) for refractory or relapsed acute myeloid leukemia. Clinical Cancer Research, 8, 1004–1013.
- Frohling, S., Schlenk, R.F., Stolze, I., Bihlmayr, J., Benner, A., Kreitmeier, S., Tobis, K., Dohner, H. & Dohner, K. (2004) CEBPA mutations in younger adults with acute myeloid leukemia and normal cytogenetics: prognostic relevance and analysis of cooperating mutations. Journal of Clinical Oncology, 22, 624–633.
- Gabrilove, J.L., McConnell, M.-J., Berkofsky-Fessler, W., Sirulnik, A.L., Sharma, S., Silverman, L.R., Isola, L., Mandeli, J. & Licht, J. (2005) A phase I-II pilot study of divalproex sodium alone and in combination with all-trans-retinoic acid (ATRA) in relapsed or refractory acute myeloid leukemia. Blood, 106, 2799a..
- Gale, R.E., Hills, R., Pizzey, A.R., Kottaridis, P.D., Swirsky, D., Gilkes, A.F., Nugent, E., Mills, K.I., Wheatley, K., Solomon, E., Burnett, A.K., Linch, D.C., Grimwade, D. & for the NCRI Adult Leukaemia Working Party (2005) Relationship between FLT3 mutation status, biologic characteristics, and response to targeted therapy in acute promyelocytic leukemia. Blood, 106, 3768–3776.
- Garcia-Manero, G., Yang, H., Sanchez-Gonzalez, B., Verstovsek, S., Ferrajoli, A., Keating, M., Andreeff, M., O'Brien, S., Cortes, J., Wierda, W., Faderl, S., Koller, C., Davis, J., Morris, G., Issa, J.-P., Frankel, S.R., Richon, V., Fine, B. & Kantarjian, H. (2005) Final results of a phase I study of the histone deacetylase inhibitor vorinostat (Suberoyanilide Hydroxamic Acid, SAHA), in patients with leukemia and myelodysplastic syndrome. Blood, 106, 2801a.
- Gerrard, G., Payne, E., Baker, R.J., Jones, D.T., Potter, M., Prentice, H.G., Ethell, M., McCullough, H., Burgess, M., Mehta, A.B. & Ganeshaguru, K. (2004) Clinical effects and P-glycoprotein inhibition in patients with acute myeloid leukemia treated with zosuquidar trihydrochloride, daunorubicin and cytarabine. Haematologica, 89, 782–790.
- Giles, F.J., Garcia-Manero, G., Cortes, J.E., Baker, S.D., Miller, C.B., O'Brien, S.M., Thomas, D.A., Andreeff, M., Bivins, C., Jolivet, J. & Kantarjian, H.M. (2002) Phase II study of troxacitabine, a novel dioxolane nucleoside analog, in patients with refractory leukemia. Journal of Clinical Oncology, 20, 656–664.
- Giles, F.J., Kantarjian, H.M., Cortes, J.E., Garcia-Manero, G., Verstovsek, S., Faderl, S., Thomas, D.A., Ferrajoli, A., O'Brien, S., Wathen, J.K., Xiao, L.C., Berry, D.A. & Estey, E.H. (2003) Adaptive randomized study of idarubicin and cytarabine versus troxacitabine and cytarabine versus troxacitabine and idarubicin in untreated patients 50 years or older with adverse karyotype acute myeloid leukemia. Journal of Clinical Oncology, 21, 1722–1727.
- Giles, F., Verstovsek, S., Thomas, D., Gerson, S., Cortes, J., Faderl, S., Ferrajoli, A., Ravandi, F., Kornblau, S., Garcia-Manero, G., Jabbour, E., O'Brien, S., Karsten, V., Cahill, A., Yee, K., Albitar, M., Sznol, M. & Kantarjian, H. (2005) Phase I study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, combined with cytarabine in patients with refractory leukemia. Clinical Cancer Research, 11, 7817–7824.
- Giles, F.J., Bellamy, W.T., Estrov, Z., O'Brien, S.M., Verstovsek, S., Ravandi, F., Beran, M., Bycott, P., Pithavala, Y., Steinfeldt, H., Reich, S.D., List, A.F. & Yee, K.W. (2006) The anti-angiogenesis agent, AG-013736, has minimal activity in elderly patients with poor prognosis acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Leukemia Research, 30, 801–811.
- Gilliland, D.G. & Griffin, J.D. (2002) The roles of FLT3 in hematopoiesis and leukemia. Blood, 100, 1532–1542.
- Gleixner, K.V., Mayerhofer, M., Aichberger, K.J., Derdak, S., Sonneck, K., Bohm, A., Gruze, A., Samorapoompichit, P., Manley, P.W., Fabbro, D., Pickl, W.F., Sillaber, C. & Valent, P. (2006) PKC412 inhibits in vitro growth of neoplastic human mast cells expressing the D816V-mutated variant of KIT: comparison with AMN107, imatinib, and cladribine (2CdA) and evaluation of cooperative drug effects. Blood, 107, 752–759.
- Goldstone, A.H., Burnett, A.K., Wheatley, K., Smith, A.G., Hutchinson, R.M. & Clark, R.E. (2001) Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older patients: the results of the United Kingdom Medical Research Council AML11 trial. Blood, 98, 1302–1311.
- Griswold, I.J., Shen, L.J., La Rosee, P., Demehri, S., Heinrich, M.C., Braziel, R.M., McGreevey, L., Haley, A.D., Giese, N., Druker, B.J. & Deininger, M.W.N. (2004) Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis. Blood, 104, 2912–2918.
- Growney, J.D., Clark, J.J., Adelsperger, J., Stone, R., Fabbro, D., Griffin, J.D. & Gilliland, D.G. (2005) Activation mutations of human c-KIT resistant to imatinib mesylate are sensitive to the tyrosine kinase inhibitor PKC412. Blood, 106, 721–724.
- Guzman, M.L., Neering, S.J., Upchurch, D., Grimes, B., Howard, D.S., Rizzieri, D.A., Luger, S.M. & Jordan, C.T. (2001) Nuclear factor-kappaB is constitutively activated in primitive human acute myelogenous leukemia cells. Blood, 98, 2301–2307.
- Harousseau, J., Reiffers, J., Lowenberg, B, Thomas, X., Huguet, F., Fenaux, P., Stone, R.M., Lancet, J., Arani, R., Rackoff, W. & Thib, A. (2003) Zarnestra (R115777) in patients with relapsed and refractory acute myelogenous leukemia (AML): results of a multicenter phase 2 study. Blood, 102, 176a.
- Hatfield, K.J., Olsnes, A.M., Gjertsen, B.T. & Bruserud, O. (2005) Antiangiogenic therapy in acute myelogenous leukemia: targeting of vascular endothelial growth factor and interleukin 8 as possible antileukemic strategies. Current Cancer Drug Targets, 5, 229–248.
- Hegenbart, U., Niederwieser, D., Sandmaier, B.M., Maris, M.B., Shizuru, J.A., Greinix, H., Cordonnier, C., Rio, B., Gratwohl, A., Lange, T., Al-Ali, H., Storer, B., Maloney, D., McSweeney, P., Chauncey, T., Agura, E., Bruno, B., Maziarz, R.T., Petersen, F. & Storb, R. (2006) Treatment for acute myelogenous leukemia by low-dose, total-body, irradiation-based conditioning and hematopoietic cell transplantation from related and unrelated donors. Journal of Clinical Oncology, 24, 444–453.
- Heidel, F., Solem, F.K., Breitenbuecher, F., Lipka, D.B., Kasper, S., Thiede, M.H., Brandts, C., Serve, H., Roesel, J., Giles, F., Feldman, E., Ehninger, G., Schiller, G.J., Nimer, S., Stone, R.M., Wang, Y., Kindler, T., Cohen, P.S., Huber, C. & Fischer, T. (2006) Clinical resistance to the kinase inhibitor PKC412 in acute myeloid leukemia by mutation of Asn-676 in the FLT3 tyrosine kinase domain. Blood, 107, 293–300.
- Heuser, M., Wingen, L.U., Steinemann, D., Cario, G., Von Neuhoff, N., Tauscher, M., Bullinger, L., Krauter, J., Heil, G., Dohner, H., Schlegelberger, B. & Ganser, A. (2005) Gene-expression profiles and their association with drug resistance in adult acute myeloid leukemia. Haematologica, 90, 1484–1492.
- Van Den Heuvel-Eibrink, M.M., Van Der Holt, B., Te Boekhorst, P.A., Pieters, R., Schoester, M., Lowenberg, B. & Sonneveld, P. (1997) MDR 1 expression is an independent prognostic factor for response and survival in de novo acute myeloid leukaemia. British Journal of Haematology, 99, 76–83.
- Van Der Holt, B., Lowenberg, B., Burnett, A.K., Knauf, W.U., Shepherd, J., Piccaluga, P.P., Ossenkoppele, G.J., Verhoef, G.E., Ferrant, A., Crump, M., Selleslag, D., Theobald, M., Fey, M.F., Vellenga, E., Dugan, M. & Sonneveld, P. (2005) The value of the MDR1 reversal agent PSC-833 in addition to daunorubicin and cytarabine in the treatment of elderly patients with previously untreated acute myeloid leukemia (AML), in relation to MDR1 status at diagnosis. Blood, 106, 2646–2654.
- Illmer, T., Thiede, C., Fredersdorf, A., Stadler, S., Neubauer, A., Ehninger, G. & Schaich, M. (2005) Activation of the RAS pathway is predictive for a chemosensitive phenotype of acute myelogenous leukemia blasts. Clinical Cancer Research, 11, 3217–3224.
- Juliusson, G., Billstrom, R., Gruber, A., Hellstrom-Lindberg, E., Hoglund, M., Karlsson, K., Stockelberg, D., Wahlin, A., Astrom, M., Arnesson, C., Brunell-Abrahamsson, U., Carstensen, J., Fredriksson, E., Holmberg, E., Nordenskjold, K. & Wiklund, F. (2006) Attitude towards remission induction for elderly patients with acute myeloid leukemia influences survival. Leukemia, 20, 42–47.
- Jurcic, J.G., Larson, S.M., Sgouros, G., McDevitt, M.R., Finn, R.D., Divgi, C.R., Ballangrud, A.M., Hamacher, K.A., Ma, D., Humm, J.L., Brechbiel, M.W., Molinet, R. & Scheinberg, D.A. (2002) Targeted alpha particle immunotherapy for myeloid leukemia. Blood, 100, 1233–1239.
- Kantarjian, H., Gandhi, V., Cortes, J., Verstovsek, S., Du, M., Garcia-Manero, G., Giles, F., Faderl, S., O'Brien, S., Jeha, S., Davis, J., Shaked, Z., Craig, A., Keating, M., Plunkett, W. & Freireich, E.J. (2003) Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia. Blood, 102, 2379–2386.
- Kantarjian, H., Issa, J.P., Rosenfeld, C.S., Bennett, J.M., Albitar, M., DiPersio, J., Klimek, V., Slack, J., De Castro, C., Ravandi, F., Helmer, III, R., Shen, L., Nimer, S.D., Leavitt, R., Raza, A. & Saba, H. (2006) Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer, 106, 1794–1803.
- Karp, J.E., Gojo, I., Pili, R., Gocke, C.D., Greer, J., Guo, C., Qian, D., Morris, L., Tidwell, M., Chen, H. & Zwiebel, J. (2004) Targeting vascular endothelial growth factor for relapsed and refractory adult acute myelogenous leukemias: therapy with sequential 1-beta-d-arabinofuranosylcytosine, mitoxantrone, and bevacizumab. Clinical Cancer Research, 10, 3577–3585.
- Karp, J.E., Gojo, I., Greer, J., Smith, B.D., Klein, M., Lancet, J.E., Gore, S.D., Morris, L., Thibault, A., Rybak, M.E. & Wright, J.J. (2005) Tipifarnib (Zarnestra, R115777) as maintenance therapy for adults in complete remission (CR) following induction and consolidation therapies for poor-risk acute myelogenous leukemia (AML): a phase II trial. Blood, 106, 2783a.
- Kell, W.J., Burnett, A.K., Chopra, R., Yin, J.A.L., Clark, R.E., Rohatiner, A., Culligan, D., Hunter, A., Prentice, A.G. & Milligan, D.W. (2003) A feasibility study of simultaneous administration of gemtuzumab ozogamicin with intensive chemotherapy in induction and consolidation in younger patients with acute myeloid leukemia. Blood, 102, 4277–4283.
- Kern, W., Schoch, C., Haferlach, T. & Schnittger, S. (2005) Monitoring of minimal residual disease in acute myeloid leukemia. Critical Reviews in Oncology/Hematology, 56, 283–309.
- Kindler, T., Breitenbuecher, F., Marx, A., Beck, J., Hess, G., Weinkauf, B., Duyster, J., Peschel, C., Kirkpatrick, C.J., Theobald, M., Gschaidmeier, H., Huber, C. & Fischer, T. (2004) Efficacy and safety of imatinib in adult patients with c-kit-positive acute myeloid leukemia. Blood, 103, 3644–3654.
- Knudson, A.G. (2000) Chasing the cancer demon. Annual Review of Genetics, 34, 1–19.
- Kolitz, J., George, S., Dodge, R., Hurd, D., Powell, B., Allen, S., Velez-Garcia, E., Moore, J., Shea, T., Hoke, E., Caligiuri, M., Vardiman, J., Bloomfield, C. & Larson, R. (2004) Dose escalation studies of cytarabine, daunorubicin, and etoposide with and without multidrug resistance modulation with PSC-833 in untreated adults with acute myeloid leukemia younger than 60 years: final induction results of Cancer and Leukemia Group B Study 9621. Journal of Clinical Oncology, 22, 4290–4301.
- Kolitz, J.E., George, S.L., Marcucci, G., Vij, R., Powell, B.L., Allen, S.L., De Angelo, D.J., Shea, T., Stock, W., Hars, V., Hoke, E., Vardiman, J.W., Bloomfield, C.D. & Larson, R.A. (2005) A randomized comparison of induction therapy for untreated acute myeloid leukemia (AML) in patients <60 years using P-glycoprotein (Pgp) modulation with valspodar (PSC833): preliminary results of Cancer and Leukemia Group B Study 19808. Blood, 106, 122a.
- Kuendgen, A., Schmid, M., Schlenk, R., Knipp, S., Hildebrandt, B., Steidl, C., Germing, U., Haas, R., Dohner, H. & Gattermann, N. (2006) The histone deacetylase (HDAC) inhibitor valproic acid as monotherapy or in combination with all-trans retinoic acid in patients with acute myeloid leukemia. Cancer, 106, 112–119.
- Lai, R., Estey, E., Shen, Y., Despa, S., Kantarjian, H., Beran, M., Maushouri, T., Quackenbuch, R.C., Keating, M. & Albitar, M. (2002) Clinical significance of plasma endostatin in acute myeloid leukemia/myelodysplastic syndrome. Cancer, 94, 14–17.
- Lancet, J.E., Gotlib, J., Gojo, I., Feldman, E.J., Morris, L., Thibault, A., Liesveld, J.L., Greer, J., Dugan, K., Raponi, M., Wright, J.J., Greenberg, P.L. & Karp, J.E. (2004) Tipifarnib (ZARNESTRATM) in previously untreated poor-risk AML of the elderly: updated results of a multicenter phase 2 trial. Blood, 104, 87a.
- Lapillonne, H., Renneville, A., Auvrignon, A., Flamant, C., Blaise, A., Perot, C., Lai, J.-L., Ballerini, P., Mazingue, F., Fasola, S., Dehee, A., Bellman, F., Adam, M., Labopin, M., Douay, L., Leverger, G., Preudhomme, C. & Landman-Parker, J. (2006) High WT1 expression after induction therapy predicts high risk of relapse and death in pediatric acute myeloid leukemia. Journal of Clinical Oncology, 24, 1507–1515.
- Larson, R.A., Sievers, E.L., Stadtmauer, E.A., Lowenberg, B., Estey, E.H., Dombret, H., Theobald, M., Voliotis, D., Bennett, J.M., Richie, M., Leopold, L.H., Berger, M.S., Sherman, M.L., Loken, M.R., Van Dongen, J.J., Bernstein, I.D. & Appelbaum, F.R. (2005) Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer, 104, 1442–1452.
- Leith, C.P., Kopecky, K.J., Godwin, J., McConnell, T., Slovak, M.L., Chen, I.M., Head, D.R., Appelbaum, F.R. & Willman, C.L. (1997) Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study. Blood, 89, 3323–3329.
- Levi, I., Grotto, I., Yerushalmi, R., Ben-Bassat, I. & Shpilberg, O. (2004) Meta-analysis of autologous bone marrow transplantation versus chemotherapy in adult patients with acute myeloid leukemia in first remission. Leukemia Research, 28, 605–612.
- Levis, M., Pham, R., Smith, B.D. & Small, D. (2004) In vitro studies of a FLT3 inhibitor combined with chemotherapy: sequence of administration is important to achieve synergistic cytotoxic effects. Blood, 104, 1145–1150.
- Levis, M., Smith, B.D., Beran, M., Baer, M.R., Erba, H.P., Cripe, L., Coutre, S., Advani, A., Perl, A., Devetten, M., Stuart, R., Tallman, M.S., Brown, P., Tremmel, L. & Small, D. (2005) A randomized, open-label study of lestaurtinib (CEP-701), an oral FLT3 inhibitor, administered in sequence with chemotherapy in patients with relapsed AML harboring FLT3 activating mutations: clinical response correlates with successful FLT3 inhibition. Blood, 106, 403a.
- Linker, C.A. (2003) Autologous stem cell transplantation for acute myeloid leukemia. Bone Marrow Transplantation, 31, 731–738.
- Linker, C.A., Ries, C.A., Damon, L.E., Sayre, P., Navarro, W., Rugo, H.S., Rubin, A., Case, D., Crilley, P., Topolsky, D., Brodsky, I., Zamkoff, K. & Wolfe, J.L. (2000) Autologous stem cell transplantation for acute myeloid leukemia in first remission. Biology of Blood Marrow Transplantation, 6, 50–57.
- List, A.F., Kopecky, K.J., Willman, C.L., Head, D.R., Persons, D.L., Slovak, M.L., Dorr, R., Karanes, C., Hynes, H.E., Doroshow, J.H., Shurafa, M. & Appelbaum, F.R. (2001) Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study. Blood, 98, 3212–3220.
- List, A., Kurtin, S., Roe, D.J., Buresh, A., Mahadevan, D., Fuchs, D., Rimsza, L., Heaton, R., Knight, R. & Zeldis, J.B. (2005) Efficacy of lenalidomide in myelodysplastic syndromes. New England Journal of Medicine, 352, 549–557.
- Liu, S., Shen, T., Huynh, L., Klisovic, M.I., Rush, L.J., Ford, J.L., Yu, J., Becknell, B., Li, Y., Liu, C., Vukosavljevic, T., Whitman, S.P., Chang, K.-S., Byrd, J.C., Perrotti, D., Plass, C. & Marcucci, G. (2005) Interplay of RUNX1/MTG8 and DNA methyltransferase 1 in acute myeloid leukemia. Cancer Research, 65, 1277–1284.
- Loges, S., Heil, G., Bruweleit, M., Schoder, V., Butzal, M., Fischer, U., Gehling, U.M., Schuch, G., Hossfeld, D.K. & Fiedler, W. (2005) Analysis of concerted expression of angiogenic growth factors in acute myeloid leukemia: expression of angiopoietin-2 represents an independent prognostic factor for overall survival. Journal of Clinical Oncology, 23, 1109–1117.
- Lowenberg, B., Van Putten, W., Theobald, M., Gmur, J., Verdonck, L., Sonneveld, P., Fey, M., Schouten, H., De Greef, G., Ferrant, A., Kovacsovics, T., Gratwohl, A., Daenen, S., Huijgens, P. & Boogaerts, M. (2003) Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia. New England Journal of Medicine, 349, 743–752.
- Maggio, S.C., Rosato, R.R., Kramer, L.B., Dai, Y., Rahmani, M., Paik, D.S., Czarnik, A.C., Payne, S.G., Spiegel, S. & Grant, S. (2004) The histone deacetylase inhibitor MS-275 interacts synergistically with fludarabine to induce apoptosis in human leukemia cells. Cancer Research, 64, 2590–2600.
- Mahadevan, D. & List, A.F. (2004) Targeting the multidrug resistance-1 transporter in AML: molecular regulation and therapeutic strategies. Blood, 104, 1940–1951.
- Marcucci, G., Mrozek, K., Ruppert, A.S., Archer, K.J., Pettenati, M.J., Heerema, N.A., Carroll, A.J., Koduru, P.R., Kolitz, J.E., Sterling, L.J., Edwards, C.G., Anastasi, J., Larson, R.A. & Bloomfield, C.D. (2004) Abnormal cytogenetics at date of morphologic complete remission predicts short overall and disease-free survival, and higher relapse rate in adult acute myeloid leukemia: results from Cancer and Leukemia Group B Study 8461. Journal of Clinical Oncology, 22, 2410–2418.
- Marcucci, G., Mrozek, K., Ruppert, A.S., Maharry, K., Kolitz, J.E., Moore, J.O., Mayer, R.J., Pettenati, M.J., Powell, B.L., Edwards, C.G., Sterling, L.J., Vardiman, J.W., Schiffer, C.A., Carroll, A.J., Larson, R.A. & Bloomfield, C.D. (2005a) Prognostic factors and outcome of core binding factor acute myeloid leukemia patients with t(8;21) differ from those of patients with inv(16): a Cancer and Leukemia Group B Study. Journal of Clinical Oncology, 23, 5705–5717.
- Marcucci, G., Mrozek, K. & Bloomfield, C.D. (2005b) Molecular heterogeneity and prognostic biomarkers in adults with acute myeloid leukemia and normal cytogenetics. Current Opinion in Hematology, 12, 68–75.
- Marcucci, G., Stock, W., Dai, G., Klisovic, R.B., Liu, S., Klisovic, M.I., Blum, W., Kefauver, C., Sher, D.A., Green, M., Moran, M., Maharry, K., Novick, S., Bloomfield, C.D., Zwiebel, J.A., Larson, R.A., Grever, M.R., Chan, K.K. & Byrd, J.C. (2005c) Phase I study of oblimersen sodium, an antisense to Bcl-2, in untreated older patients with acute myeloid leukemia: pharmacokinetics, pharmacodynamics, and clinical activity. Journal of Clinical Oncology, 23, 3404–3411.
- Marcucci, G., Baldus, C.D., Ruppert, A.S., Radmacher, M.D., Mrozek, K., Whitman, S.P., Kolitz, J.E., Edwards, C.G., Vardiman, J.W., Powell, B.L., Baer, M.R., Moore, J.O., Perrotti, D., Caligiuri, M.A., Carroll, A.J., Larson, R.A., De La Chapelle, A. & Bloomfield, C.D. (2005d) Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: a Cancer and Leukemia Group B Study. Journal of Clinical Oncology, 23, 9234–9242.
- Maslak, P., Chanel, S., Camacho, L.H., Soignet, S., Pandolfi, P.P., Guernah, I., Warrell, R. & Nimer, S. (2006) Pilot study of combination transcriptional modulation therapy with sodium phenylbutyrate and 5-azacytidine in patients with acute myeloid leukemia or myelodysplastic syndrome. Leukemia, 20, 212–217.
- Mathews, V., George, B., Lakshmi, K.M., Viswabandya, A., Bajel, A., Balasubramanian, P., Shaji, R.V., Srivastava, V.M., Srivastava, A. & Chandy, M. (2006) Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood, 107, 2627–2632.
- Mayer, R.J., Davis, R.B., Schiffer, C.A., Berg, D.T., Powell, B.L., Schulman, P., Omura, G.A., Moore, J.O., McIntyre, O.R. & Frei, III, E. (1994) Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. New England Journal of Medicine, 331, 896–903.
- Milella, M., Precupanu, C.M., Gregorj, C., Ricciardi, M.R., Petrucci, M.T., Kornblau, S.M., Tafuri, A. & Andreeff, M. (2005) Beyond single pathway inhibition: MEK inhibitors as a platform for the development of pharmacological combinations with synergistic anti-leukemic effects. Current Pharmaceutical Design, 11, 2779–2795.
- Milligan, D.W., Wheatley, K., Littlewood, T., Craig, J.I.O. & Burnett, A.K. for the NCRI Haematological Oncology Clinical Studies Group (2006) Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial. Blood, 107, 4614–4622.
- Mohi, M.G., Boulton, C., Gu, T.-L., Sternberg, D.W., Neuberg, D., Griffin, J.D., Gilliland, D.G. & Neel, B.G. (2004) Combination of rapamycin and protein tyrosine kinase (PTK) inhibitors for the treatment of leukemias caused by oncogenic PTKs. Proceedings of the National Academy of Sciences of the United States of America, 101, 3130–3135.
- Molldrem, J.J. (2006) Vaccination for leukemia. Biology of Blood Marrow Transplantation, 12, 13–18.
- Moore, J.O., George, S.L., Dodge, R.K., Amrein, P.C., Powell, B.L., Kolitz, J.E., Baer, M.R., Davey, F.R., Bloomfield, C.D., Larson, R.A. & Schiffer, C.A. (2005) Sequential multiagent chemotherapy is not superior to high-dose cytarabine alone as postremission intensification therapy for acute myeloid leukemia in adults under 60 years of age: Cancer and Leukemia Group B Study 9222. Blood, 105, 3420–3427.
- O'Connor, O.A., Heaney, M.L., Schwartz, L., Richardson, S., Willim, R., MacGregor-Cortelli, B., Curly, T., Moskowitz, C., Portlock, C., Horwitz, S., Zelenetz, A.D., Frankel, S., Richon, V., Marks, P. & Kelly, W.K. (2006) Clinical experience with intravenous and oral formulations of the novel histone deacetylase inhibitor suberoylanilide hydroxamic acid in patients with advanced hematologic malignancies. Journal of Clinical Oncology, 24, 166–173.
- Oki, Y., Kantarjian, H.M., Zhou, X., Cortes, J., Faderl, S., Verstovsek, S., O'Brien, S., Koller, C., Beran, M., Bekele, B.N., Pierce, S., Thomas, D., Ravandi, F., Wierda, W.G., Giles, F., Ferrajoli, A., Jabbour, E., Keating, M.J., Bueso-Ramos, C.E., Estey, E. & Garcia-Manero, G. (2006) Adult acute megakaryocytic leukemia: an analysis of 37 patients treated at M.D. Anderson Cancer Center. Blood, 107, 880–884.
- Pedersen-Bjergaard, J. & Rowley, J. (1994) The balanced and the unbalanced chromosome aberrations of acute myeloid leukemia may develop in different ways and may contribute differently to malignant transformation. Blood, 83, 2780–2786.
- Preisler, H., Davis, R.B., Kirshner, J., Dupre, E., Richards, Jr, F., Hoagland, H.C., Kopel, S., Levy, R.N., Carey, R. & Schulman, P. (1987) Comparison of three remission induction regimens and two postinduction strategies for the treatment of acute nonlymphocytic leukemia: a Cancer and Leukemia Group B Study. Blood, 69, 1441–1449.
- Qazilbash, M.H., Wieder, E., Rios, R., Lu, S., Kant, S., Giralt, S., Estey, E.H., Thall, P., De Lima, M., Couriel, D., Champlin, R.E., Komanduri, K. & Molldrem, J.J. (2004) Vaccination with the PR1 leukemia-associated antigen can induce complete remission in patients with myeloid leukemia. Blood, 104, 259a.
- Radmacher, M.D., Marcucci, G., Ruppert, A.S., Mrozek, K., Whitman, S.P., Vardiman, J.W., Paschka, P., Vukosavljevic, T., Baldus, C.D., Kolitz, J.E., Caligiuri, M.A., Larson, R.A. & Bloomfield, C.D. (2006) Independent confirmation of a prognostic gene-expression signature in adult acute myeloid leukemia with a normal karyotype: a Cancer and Leukemia Group B Study. Blood (Epub ahead of print).
- Recher, C., Dos Santos, C., Demur, C. & Payrastre, B. (2005) mTOR, a new therapeutic target in acute myeloid leukemia. Cell Cycle, 4, 1540–1549.
- Richardson, D.S. & Newland, A.C. (2000) Current perspectives on the use of growth factors in the therapy of acute myeloid leukaemia; malignancy. Hematology, 5, 189–203.
- Ritter, M., Kim, T.D., Lisske, P., Thiede, C., Schaich, M. & Neubauer, A. (2004) Prognostic significance of N-RAS and K-RAS mutations in 232 patients with acute myeloid leukemia. Haematologica, 89, 1397–1399.
- Roboz, G.J., Dias, S., Lam, G., Lane, W.J., Soignet, S.L., Warrell, Jr, R.P. & Rafii, S. (2000) Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis. Blood, 96, 1525–1530.
- Roboz, G.J., Ritchie, E.K., Allen-Bard, S., Curcio, T.J., Provenzano, J.L., Samuel, M.S., Schuster, M.W., Bloch, A.W. & Feldman, E.J. (2005) Arsenic trioxide (ATO) is safe and effective in combination with low-dose Ara-C (LDAC) for the treatment of IPSS-2 myelodysplastic syndrome (MDS) and poor-prognosis acute myeloid leukemia (AML) in elderly patients. Blood, 106, 2805a..
- Roddie, P.H., Horton, Y. & Turner, M.L. (2002) Primary acute myeloid leukaemia blasts resistant to cytokine-induced differentiation to dendritic-like leukaemia cells can be forced to differentiate by the addition of bryostatin-1. Leukemia, 16, 84–93.
- Rowe, J.M. (2005) Is there a role for postremission therapy in older adults with acute myelogenous leukemia (AML)? Leukemia, 19, 1324–1327.
- Rowe, J.M., Andersen, J.W., Mazza, J.J., Bennett, J.M., Paietta, E., Hayes, F.A., Oette, D., Cassileth, P.A., Stadtmauer, E.A. & Wiernik, P.H. (1995) A randomized placebo-controlled phase III study of granulocyte-macrophage colony-stimulating factor in adult patients (>55 to 70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490). Blood, 86, 457–462.
- Rubinstein, L.V., Korn, E.L., Freidlin, B., Hunsberger, S., Ivy, S.P. & Smith, M.A. (2005) Design issues of randomized phase II trials and a proposal for phase II screening trials. Journal of Clinical Oncology, 23, 7199–7206.
- Sampath, D., Cortes, J., Estrov, Z., Du, M., Shi, Z., Andreeff, M., Gandhi, V. & Plunkett, W. (2006) Pharmacodynamics of cytarabine alone and in combination with 7-hydroxystaurosporine (UCN-01) in AML blasts in vitro and during a clinical trial. Blood, 107, 2517–2524.
- Sanz, M.A., Martin, G., Gonzalez, M., Leon, A., Rayon, C., Rivas, C., Colomer, D., Amutio, E., Capote, F.J., Milone, G.A., De La Serna, J., Roman, J., Barragan, E., Bergua, J., Escoda, L., Parody, R., Negri, S., Calasanz, M.J. & Bolufer, P. (2004) Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood, 103, 1237–1243.
- Sanz, M.A., Tallman, M.S. & Lo-Coco, F. (2005) Tricks of the trade for the appropriate management of newly diagnosed acute promyelocytic leukemia. Blood, 105, 3019–3025.
- Schittenhelm, M.M., Shiraga, S., Schroeder, A., Corbin, A.S., Griffith, D., Lee, F.Y., Bokemeyer, C., Deininger, M.W.N., Druker, B.J. & Heinrich, M.C. (2006) Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies. Cancer Research, 66, 473–481.
- Schlenk, R.F., Germing, U., Hartmann, F., Glasmacher, A., Fischer, J.T., Del Valle, Y., Fuentes, F., Gotze, K., Pralle, H., Nerl, C., Salwender, H., Grimminger, W., Petzer, A., Hensel, M., Benner, A., Zick, L., Dohner, K., Frohling, S. & Dohner, H. (2005) High-dose cytarabine and mitoxantrone in consolidation therapy for acute promyelocytic leukemia. Leukemia, 19, 978–983.
- Schnittger, S., Kohl, T.M., Haferlach, T., Kern, W., Hiddemann, W., Spiekermann, K. & Schoch, C. (2006) KIT-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival. Blood, 107, 1791–1799.
- Scholl, F.A., Dumesic, P.A. & Khavari, P.A. (2005) Effects of active MEK1 expression in vivo. Cancer Letters, 230, 1–5.
- Schuch, G., Oliveira-Ferrer, L., Loges, S., Laack, E., Bokemeyer, C., Hossfeld, D.K., Fiedler, W. & Ergun, S. (2005) Antiangiogenic treatment with endostatin inhibits progression of AML in vivo. Leukemia, 19, 1312–1317.
- Sebti, S.M. & Der, C.J. (2003) Opinion: searching for the elusive targets of farnesyltransferase inhibitors. Nature Reviews Cancer, 3, 945–951.
- Silverman, L.R., Demakos, E.P., Peterson, B.L., Kornblith, A.B., Holland, J.C., Odchimar-Reissig, R., Stone, R.M., Nelson, D., Powell, B.L., DeCastro, C.M., Ellerton, J., Larson, R.A., Schiffer, C.A. & Holland, J.F. (2002) Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the Cancer and Leukemia Group B. Journal of Clinical Oncology, 20, 2429–2440.
- Silverman, L.R., McKenzie, D.R., Peterson, B.L., Stone, R.M., Powell, B.L., Mayo, C., Backstrom, J.T., Larson, R.A. & The Cancer Leukemia Group B (CALGB) (2005) Response rates in patients with acute myeloid leukemia (AML), treated with azacitidine, using WHO and International Working Group (IWG) criteria for myelodysplastic syndrome (MDS). Blood, 106, 1848a.
- Steudel, C., Wermke, M., Schaich, M., Schakel, U., Illmer, T., Ehninger, G. & Thiede, C. (2003) Comparative analysis of MLL partial tandem duplication and FLT3 internal tandem duplication mutations in 956 adult patients with acute myeloid leukemia. Genes, Chromosomes and Cancer, 37, 237–251.
- Stone, R.M., Fischer, T., Paquette, R., Schiller, G., Schiffer, C.A., Ehninger, G., Cortes, J., Kantarjian, H., DeAngelo, D.A., Yu, R., Zhang, L., Cohen, P.S., Wang, Y., Phillips, P. & Giles, F. (2005) Phase IB study of PKC412, an oral FLT3 kinase inhibitor, in sequential and simultaneous combinations with daunorubicin and cytarabine (DA) induction and high-dose cytarabine consolidation in newly diagnosed patients with AML. Blood, 106, 404a.
- Suciu, S., Mandelli, F., De Witte, T., Zittoun, R., Gallo, E., Labar, B., De Rosa, G., Belhabri, A., Giustolisi, R., Delarue, R., Liso, V., Mirto, S., Leone, G., Bourhis, J.-H., Fioritoni, G., Jehn, U., Amadori, S., Fazi, P., Hagemeijer, A. & Willemze, R. (2003) Allogeneic compared with autologous stem cell transplantation in the treatment of patients younger than 46 years with acute myeloid leukemia (AML) in first complete remission (CR1): an intention-to-treat analysis of the EORTC/GIMEMAAML-10 trial. Blood, 102, 1232–1240.
- Tallman, M.S., Andersen, J.W., Schiffer, C.A., Appelbaum, F.R., Feusner, J.H., Woods, W.G., Ogden, A., Weinstein, H., Shepherd, L., Willman, C., Bloomfield, C.D., Rowe, J.M. & Wiernik, P.H. (2002) All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol. Blood, 100, 4298–4302.
- Tallman, M.S., Perez, W.S., Lazarus, H.M., Gale, R.P., Maziarz, R.T., Rowe, J.M., Marks, D.I., Cahn, J.Y., Bashey, A., Bishop, M.R., Christiansen, N., Frankel, S.R., Garcia, J.J., Ilhan, O., Laughlin, M.J., Liesveld, J., Linker, C., Litzow, M.R., Luger, S., McCarthy, P.L., Milone, G.A., Pavlovsky, S., Phillips, G.L., Russell, J.A., Saez, R.A., Schiller, G., Sierra, J., Weiner, R.S., Zander, A.R., Zhang, M.J., Keating, A., Weisdorf, D.J. & Horowitz, M.M. (2006) Pretransplantation consolidation chemotherapy decreases leukemia relapse after autologous blood and bone marrow transplants for acute myelogenous leukemia in first remission. Biology of Blood Marrow Transplantation, 12, 204–216.
- Thall, P.F. & Estey, E.H. (2005) Some ethical issues in phase II trials in acute leukemia. Clinical Advances in Hematology and Oncology, 3, 943–948.
- Thiede, C., Steudel, C., Mohr, B., Schaich, M., Schakel, U., Platzbecker, U., Wermke, M., Bornhauser, M., Ritter, M., Neubauer, A., Ehninger, G. & Illmer, T. (2002) Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood, 99, 4326–4335.
- Thiede, C., Koch, S., Creutzig, E., Steudel, C., Illmer, T., Schaich, M. & Ehninger, G. (2006) Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML). Blood, 107, 4011–4020.
- Thomas, D.A., Estey, E., Giles, F.J., Faderl, S., Cortes, J., Keating, M., O'Brien, S., Albitar, M. & Kantarjian, H. (2003) Single agent thalidomide in patients with relapsed or refractory acute myeloid leukaemia. British Journal of Haematology, 123, 436–441.
- Valk, P.J.M., Verhaak, R.G.W., Beijen, M.A., Erpelinck, C.A.J., Van Doorn-Khosrovani, S.B.v.W., Boer, J.M., Beverloo, H.B., Moorhouse, M.J., Van Der Spek, P.J., Lowenberg, B. & Delwel, R. (2004) Prognostically useful gene-expression profiles in acute myeloid leukemia. New England Journal of Medicine, 350, 1617–1628.
- Vey, N., Coso, D., Bardou, V.J., Stoppa, A.M., Braud, A.C., Bouabdallah, R., Sainty, D., Mozziconacci, M.J., Lafage, M., Damaj, G., Blaise, D., Gastaut, J.A. & Maraninchi, D. (2004) The benefit of induction chemotherapy in patients age ≥75 years. Cancer, 101, 325–331.
- Wadleigh, M., Richardson, P.G., Zahrieh, D., Lee, S.J., Cutler, C., Ho, V., Alyea, E.P., Antin, J.H., Stone, R.M., Soiffer, R.J. & DeAngelo, D.J. (2003) Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation. Blood, 102, 1578–1582.
- Walter, R.B., Raden, B.W., Hong, T.C., Flowers, D.A., Bernstein, I.D. & Linenberger, M.L. (2003) Multidrug resistance protein attenuates gemtuzumab ozogamicin-induced cytotoxicity in acute myeloid leukemia cells. Blood, 102, 1466–1473.
- Weick, J.K., Kopecky, K.J., Appelbaum, F.R., Head, D.R., Kingsbury, L.L., Balcerzak, S.P., Bickers, J.N., Hynes, H.E., Welborn, J.L., Simon, S.R. & Grever, M. (1996) A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study. Blood, 88, 2841–2851.
- Wheatley, K., Brookes, C.L., Hills, R.K., Goldstone, A.H., Milligan, D.W., Prentice, A.G., Moorman, A.V. & Burnett, A.K. (2005) Prognostic factors in older AML patients receiving intensive and non-intensive therapy: analysis of the UK AML11 and AML14 Trials. Blood, 106, 674a.
- Whitman, S.P., Archer, K.J., Feng, L., Baldus, C., Becknell, B., Carlson, B.D., Carroll, A.J., Mrozek, K., Vardiman, J.W., George, S.L., Kolitz, J.E., Larson, R.A., Bloomfield, C.D. & Caligiuri, M.A. (2001) Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a Cancer and Leukemia Group B Study. Cancer Research, 61, 7233–7239.
- Whitman, S.P., Liu, S., Vukosavljevic, T., Rush, L.J., Yu, L., Liu, C., Klisovic, M.I., Maharry, K., Guimond, M., Strout, M.P., Becknell, B., Dorrance, A., Klisovic, R.B., Plass, C., Bloomfield, C.D., Marcucci, G. & Caligiuri, M.A. (2005) The MLL partial tandem duplication: evidence for recessive gain-of-function in acute myeloid leukemia identifies a novel patient subgroup for molecular targeted therapy. Blood, 106, 345–354.
- Xu, Q., Simpson, S.-E., Scialla, T.J., Bagg, A. & Carroll, M. (2003) Survival of acute myeloid leukemia cells requires PI3 kinase activation. Blood, 102, 972–980.
- Yanada, M., Matsuo, K., Suzuki, T., Kiyoi, H. & Naoe, T. (2005) Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations for acute myeloid leukemia: a meta-analysis. Leukemia, 19, 1345–1349.
- Yee, K.W.L., Cortes, J., Ferrajoli, A., Garcia-Manero, G., Verstovsek, S., Wierda, W., Thomas, D., Faderl, S., King, I. & O'Brien, S.M. (2006) Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome. Leukemia Research, 30, 813–822.