Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY.

Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia.
Blood. 1988 Aug;72(2):567-72.
Description: This was the first report in the English literature describing the effectiveness of all-trans-retinoic acid for the treatment of acute promyelocytic leukemia.
PubMed citation 3165295

Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A, Shepherd L, Willman C, Bloomfield CD, Rowe JM, and Wiernik PH.

All-trans-retinoic acid in acute promyelocytic leukemia.
N Engl J Med. 1997 Oct 9; 337(15): 1021-1028.
Description: This study demonstrated that the addition of All-trans-retinoic acid (ATRA) to either induction or maintenance therapy improves disease-free and overall survival in acute promyelocytic leukemia.
PubMed citation number: 9321529

Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E, Fey M, Rayon C, Huguet F, Sotto JJ, Gardin C, Makhoul PC, Travade P, Solary E, Fegueux N, Bordessoule D, Miguel JS, Link H, Desablens B, Stamatoullas A, Deconinck E, Maloisel F, Castaigne S, Preudhomme C, and Degos L.

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. The European APL Group.
Blood. 1999 Aug 15;94(4):1192-200.
Description: This study also demonstrated that the use of chemotherapy with ATRA during induction therapy and the subsequent use of low-dose chemotherapy with intermittent ATRA for maintenance improves relapse-free survival.
PubMed citation number: 10438706

Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QY, Zhu J, Tang W, Sun GL, Yang KQ, Chen Y, Zhou L, Fang ZW, Wang YT, Ma J, Zhang P, Zhang TD, Chen SJ, Chen Z, and Wang ZY.

Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients.
Blood. 1997 May 1; 89(9): 3354-3360.
Description: This was the first study published in the English literature demonstrating the remarkable activity of arsenic trioxide in patients with relapsed acute promyelocytic leukemia (9 out of 10 patients achieving complete remission).
PubMed citation number: 9129042

Soignet SL, Maslak P, Wang ZG, Jhanwar S, Calleja E, Dardashti LJ, Corso D, DeBlasio A, Gabrilove J, Scheinberg DA, Pandolfi PP, and Warrell RP Jr.

Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide.
N Engl J Med. 1998 Nov 5; 339(19): 1341-1348.
Description: This was the first US study demonstrating the effectiveness of arsenic trioxide for treatment of patients with relapsed acute promyelocytic leukemia (11 of 12 patients achieved complete remissions) and showed that responses were associated with incomplete cytodifferentiation of leukemic blasts and induction of apoptosis.
PubMed citation number: 9801394

Kakizuka A, Miller WH Jr, Umesono K, Warrell RP Jr, Frankel SR, Murty VV, Dmitrovsky E, and Evans RM.

Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML.
Cell. 1991 Aug 23; 66(4): 663-674.
Description: This study identified PML-RARa as the product of the t(15;17) translocation in acute promyelocytic leukemia and suggested that non-liganded PML-RARa functions as a novel dominant- negative oncogene that arrests myelocytic differentiation.
PubMed citation number: 1652368

Diverio D, Rossi V, Avvisati G, De Santis S, Pistilli A, Pane F, Saglio G, Martinelli G, Petti MC, Santoro A, Pelicci PG, Mandelli F, Biondi A, and Lo Coco F.

Early detection of relapse by prospective revrse transcriptase-polymerase chain reaction analysis of the PML/RARalpha fusion gene in patients with acute promyelocytic leukemia enrolled in the GIMEMA-AIEOP multicenter “AIDA” trial. GIMEMA-AIEOP Multicenter “AIDA” Trial.
Blood. 1998 Aug 1; 92(3): 784-789.
Description: This was the first prospective study demonstrating the predictive value of reverse transcriptase polymerase chain reaction for PML-RARa as a means of detecting minimal residual disease and predicting eventual relapse in acute promyelocytic leukemia.
PubMed citation number: 9680345

Rai KR, Holland JF, Glidewell OJ, Weinberg V, Brunner K, Obrecht JP, Preisler HD, Nawabi IW, Prager D, Carey RW, Cooper MR, Haurani F, Hutchison JL, Silver RT, Falkson G, Wiernik P, Hoagland HC, Bloomfield CD, James GW, Gottlieb A, Ramanan SV, Blom J, Nissen NI, Bank A, Ellison RR, Kung F, Henry P, McIntyre OR, Kaan SK.

Treatment of acute myelocytic leukemia: a study by cancer and leukemia group B.
Blood. 1981 Dec;58(6):1203-12.
Description: This was the prospective, randomized trial that demonstrated the superiority of the "7 and 3" regimen of cytarabine and daunorubicin as induction therapy for AML, a regimen that remains standard of care 25 years later.
PubMed citation number: 6946847

Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, Omura GA, Moore JO, McIntyre OR, and Frei E 3rd.

Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B.
N Engl J Med. 1994 Oct 6; 331(14): 896-903.
Description: This study demonstrated a dose response to cytarabine with patients under 60 achieving longer disease-free survival with high-dose cytarabine (44% DFS at four years) compared with low (24%) and intermediate (29%) doses. Disease-free survival was uniformly poor for patients over 60 (16% or less).
PubMed citation number: 8078551

Burnett AK, Goldstone AH, Stevens RM, Hann IM, Rees JK, Gray RG, and Wheatley K.

Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukemia in first remission: results of MRC AML 10 trial. UK Medical Research Council Adult and Children’s Leukaemia Working Parties.
Lancet. 1999 Mar 7; 351(9104): 700-708.
Description: This study showed that the addition of autologous bone marrow transplantation to induction and consolidation chemotherapy improved disease-free survival but failed to show an improvement in overall survival due to transplant-related mortality.
PubMed citation number: 9504514

Cassileth PA, Harrington DP, Appelbaum FR, Lazarus HM, Rowe JM, Paietta E, Willman C, Hurd DD, Bennett JM, Blume KG, Head DR, and Wiernik PH.

Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med. 1998 Dec 3; 339(23): 1649-1656.
Description: This study failed to show an advantage of autologous or allogeneic bone marrow transplantation compared with chemotherapy (high-dose cytarabine consolidation) for patients with acute myeloid leukemia in first complete remission after induction therapy (and in fact suggested an overall survival advantage for patients treated with chemotherapy).
PubMed citation number: 9834301

Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, Leoni F, Damasio E, Visani G, Papa G, et al.

Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto (GIMEMA) leukemia cooperative groups.
N Engl J Med. 1995 Jan 26; 332(4): 217-223.
Description: This study demonstrated an improved disease-free survival for acute myeloid leukemia patients in first complete remission treated with autologous and allogeneic bone marrow transplantation compared with consolidation chemotherapy but no difference in overall survival between the three treatment strategies.
PubMed citation number: 7808487

Bloomfield CD, Lawrence D, Byrd JC, Carroll A, Pettenati MJ, Tantravahi R, Patil SR, Davey FR, Berg DT, Schiffer CA, Arthur DC, and Mayer RJ.

Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype.
Cancer Res. 1998 Sep 15; 58(18): 4173-4179.
Description: This study showed that response to and leukemia-free survival after high-dose cytarabine (HIDAC) consolidation chemotherapy varies significantly between cytogenetic subtypes, with core binding factor (CBF) acute myeloid leukemias (t(8;21), t(16;16), del(16), and inv(16)) demonstrating the best response to HIDAC therapy.
PubMed citation number: 9751631

Keating MJ, Smith TL, Kantarjian H, Cork A, Walters R, Trujillo JM, McCredie KB, Gehan EA, and Freireich EJ

.

Cytogenetic pattern in acute myelogenous leukemia: a major reproducible determinant of outcome.
Leukemia. 1988 Jul; 2(7): 403-412.
Description: This was the first study to show that cytogenetic profile is an independent predictor of response to treatment and duration of remission.
PubMed citation number: 3164797

Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, Rees J, Hann I, Stevens R, Burnett A, and Goldstone A.

The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children’s Leukaemia Working Parties.
Blood. 1998 Oct 1; 92(7): 2322-2333.
Description: This is the largest of numerous studies published demonstrating that cytogenetic profile is a powerful, independent prognostic factor for response to induction therapy, relapse risk, and overall survival in acute myeloid leukemia.
PubMed citation number: 9746770

Leith CP, Kopecky KJ, Godwin J, McConnell T, Slovak ML, Chen IM, Head DR, Appelbaum FR, and Willman CL.

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. 1997 May 1; 89(9): 3323-3329.
PubMed citation number: This study revealed that elderly patients with AML frequently overexpress the multidrug resistance protein MDR1 and that this is an independent prognostic marker for resistant disease.
PubMed citation number: 9129038

Thiede C, Steudel C, Mohr B, Schaich M, Schakel U, Platzbecker U, Wermke M, Bornhauser M, Ritter M, Neubauer A, Ehninger G, and Illmer T.

Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis.
Blood. 2002 Jun 15; 99(12): 4326-4335.
Description: This is one of several studies demonstrating a high incidence of FLT3 receptor tyrosine kinase-activating mutations in acute myeloid leukemia (internal tandem duplication of the juxtamembrane region in 20.4% of cases or point mutations in the second tyrosine kinase domain in 7.7% of cases), but it also showed that a high ratio of mutant to wild type FLT3 is an independent prognostic marker for disease-free and overall survival.
PubMed citation number: 12036858

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; Dutch-Belgian Hemato-Oncology Cooperative Group; Swiss Group for Clinical Cancer Research.

Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia.
N Engl J Med. 2003 Aug 21; 349(8): 743-52.
Description: This study demonstrated an improved disease-free survival and decreased risk of relapse in patients who received priming therapy with granulocyte-colony stimulating factor (G-CSF), suggesting that G-CSF may sensitize leukemic cells to cell-cycle active chemotherapeutic agents.
PubMed citation number: 12930926

Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, Liesveld JL, Abboud CN, Dewald G, Hayes FA, Tallman MS, Wiernik PH; Eastern Cooperative Oncology.

A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group.
Blood. 2004 Jan 15;103(2):479-85.
Description: This study showed that patient outcomes are similar regardless of the anthracycline (or anthracenedione) used for induction therapy in older AML patients. It also showed that priming with GM-CSF did not improve outcomes and may, in fact, have led to worse complete remission rates due to a delay in initiation of induction therapy.
PubMed citation number: 14512295

Sievers EL, Larson RA, Stadtmauer EA, Estey E, Lowenberg B, Dombret H, Karanes C, Theobald M, Bennett JM, Sherman ML, Berger MS, Eten CB, Loken MR, van Dongen JJ, Bernstein ID, and Appelbaum FR; Mylotarg Study Group.

Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse.
J Clin Oncol. 2001 Jul 1; 19(13): 3244-3254.
Description: This study established the effectiveness of an antibody-targeted chemotherapy agent in patients with relapsed CD33+ acute myeloid leukemia, providing impetus for the use of monoclonal antibodies as a way of targeting leukemic cells.
PubMed citation number: 11432892

Select review articles

Tallman MS, Nabhan C, Feusner JH, Rowe JM.

Acute promyelocytic leukemia: evolving therapeutic strategies.
Blood. 2002 Feb 1; 99(3): 759-67.
PubMed citation number: 11806975

Burnett AK.

Current controversies: which patients with acute myeloid leukaemia should receive a bone marrow transplantation?--an adult treater's view.
Br J Haematol. 2002 Aug; 118(2): 357-64.
PubMed citation number: 12139719

Wheatley K.

Current controversies: which patients with acute myeloid leukaemia should receive a bone marrow transplantation?—a statistician’s view.
Br J Haematol. 2002 Aug; 118(2): 351-356.
PubMed citation number: 12139718

Lowenberg B, Downing JR, Burnett A.

Acute myeloid leukemia.
N Engl J Med. 1999 Sep 30; 341(14): 1051-62.
PubMed citation number: 10502596

Stone RM.

The difficult problem of acute myeloid leukemia in the older adult.
CA Cancer J Clin. 2002 Nov-Dec; 52(6): 363-71.
PubMed citation number: 12469764

Willman CL.

Molecular evaluation of acute myeloid leukemias.
Semin Hematol. 1999 Oct; 36(4): 390-400.
PubMed citation number: 10530720

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