今日の臨床サポート

急性前骨髄球性白血病

著者: 麻生範雄 埼玉医科大学国際医療センター造血器腫瘍科

監修: 木崎昌弘 埼玉医科大学総合医療センター

著者校正/監修レビュー済:2018/02/28
患者向け説明資料

概要・推奨   

疾患のポイント:
  1. 急性前骨髄球性白血病(APL)は急性骨髄性白血病(AML)の1病型で、AMLの約10%を占める。FAB分類のM3およびM3v(v;variant)に当たり、M3は細胞質の豊富な顆粒やアウエル小体を多数有するFaggot細胞が特徴的である。一方、M3vは顆粒やアウエル小体を欠き、形態診断が難しい。
  1. 過剰線溶を伴う(DIC)を来しやすく、出血症状での発症や脳出血、肺出血による早期死亡が多い。
  1. t(15;17)陽性APLの初発症状と血液・凝固異常:
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  1. APLの診断は、末梢血液および骨髄の塗抹標本により特徴的な細胞形態をしたAPL細胞を同定することである。ただし、5~10%にみられるM3vの形態診断は困難なことが多く、当初、他のAMLと診断されることが少なくない。そのようなケースでは、PML-RARA融合遺伝子(APLの約98%に認める)または他のRARAとの融合遺伝子(APLの約2%に認める)をFISH法あるいはRT-PCR法で認めればAPLと診断される。
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  1. 寛解後は、化学療法による3コースの地固め療法を行い、骨髄細胞のPML-RARA遺伝子を指標とする分子遺伝学的寛解への導入を目指す()。またATRAによる維持療法も広く行われている。 化学療法は、アントラサイクリン系単独ないしはシタラビンとの併用が多い。
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  1. 急性前骨髄球性白血病(APL)は特異的な染色体異常t(15;17)を示し、その結果PML-RARA融合遺伝子を認める。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
麻生範雄 : 報酬額(エスアールエル株式会社),奨学(奨励)寄付など(中外製薬株式会社)[2021年]
監修:木崎昌弘 : 講演料(ブリストル・マイヤーズスクイブ,ヤンセンファーマ,ノバルティスファーマ,セルジーン,MSD,小野薬品,武田薬品,大日本住友製薬),研究費・助成金など(武田薬品),奨学(奨励)寄付など(協和キリン,中外製薬,武田薬品,小野薬品,第一三共)[2021年]

病態・疫学・診察

疾患情報  
  1. 急性前骨髄球性白血病(APL)は 急性骨髄性白血病 (AML)の1病型で、AMLの約10%を占める[1]
  1. FAB分類のM3およびM3v(v;variant)に当たり、M3は細胞質の豊富な顆粒やアウエル小体を多数有するFaggot細胞が特徴的である。一方、M3vは顆粒やアウエル小体を欠き、形態診断が難しい。
  1. APL (M3)例の骨髄塗抹標本のメイギムザ染色:<図表>
  1. APL (M3v)例の骨髄塗抹標本のメイギムザ染色:<図表>
  1. 過剰線溶を伴う 播種性血管内凝固 (DIC)を来しやすく、出血症状での発症や脳出血、肺出血による早期死亡が多い[2]。 エビデンス 
  1. t(15;17)陽性APLの初発症状と血液・凝固異常:<図表>
  1. 染色体転座t(15;17)由来のPML-RARA遺伝子を大半の症例に認め、PML-RARα蛋白を標的とする全トランス型レチノイン酸(ATRA)および亜ヒ酸(ATO)による分子標的治療が有効である[1][3]
  1. APL細胞の染色体転座:<図表>
  1. ATRAと化学療法による寛解導入療法および化学療法による地固め療法が標準治療である[4]。 エビデンス  エビデンス 
  1. 初発APLの診断と治療のアルゴリズム:アルゴリズム
問診・診察のポイント  
  1. 出血症状での発症が多いので全身の皮下出血や口腔内出血などに注意する。抜歯後の止血困難や女性では、 過多月経 も多い。また、消化管出血、肺出血、脳出血などの臓器出血の有無にも注意して問診、診察を行う。

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文献 

著者: R Ohno, N Asou, K Ohnishi
雑誌名: Leukemia. 2003 Aug;17(8):1454-63. doi: 10.1038/sj.leu.2403031.
Abstract/Text Acute promyelocytic leukemia (APL) has become a curable disease by all-trans retinoic acid (ATRA)-based induction therapy followed by two or three courses of consolidation chemotherapy. Currently around 90% of newly diagnosed patients with APL achieve complete remission (CR) and over 70% of patients are curable. To further increase the CR and cure rates, detection and diagnosis of this disease at its early stage is very important, hopefully before the appearance of APL-associated coagulopathy. In induction therapy, concomitant chemotherapy is indispensable, except for patients with low initial leukocyte counts. Prophylactic use of intrathecal methotrexate and cytarabine should be done, particularly for patients with hyperleukocytosis. If patients relapse hematologically or even molecularly, arsenic trioxide will be the treatment of choice under careful electrocardiogram monitoring. Am80, liposomal ATRA, gemtuzumab ozogamicin or ATRA in combination with cytotoxic drugs may be used at this stage or later. Allogeneic SCT will be the treatment of choice after patients of age <50 years have relapsed, provided that they have HLA-identical family donors or DNA-identical unrelated donors.

PMID 12886231  Leukemia. 2003 Aug;17(8):1454-63. doi: 10.1038/sj.leu.2・・・
著者: Masamitsu Yanada, Tadashi Matsushita, Norio Asou, Yuji Kishimoto, Motohiro Tsuzuki, Yasuhiro Maeda, Kentaro Horikawa, Masaya Okada, Shigeki Ohtake, Fumiharu Yagasaki, Tadashi Matsumoto, Yukihiko Kimura, Katsuji Shinagawa, Masako Iwanaga, Yasushi Miyazaki, Ryuzo Ohno, Tomoki Naoe
雑誌名: Eur J Haematol. 2007 Mar;78(3):213-9. doi: 10.1111/j.1600-0609.2006.00803.x. Epub 2007 Jan 16.
Abstract/Text BACKGROUND: Even after the introduction of all-trans retinoic acid (ATRA), early hemorrhagic death remains a major cause of remission induction failure for acute promyelocytic leukemia (APL).
METHODS: To investigate severe hemorrhagic complications during remission induction therapy with respect to incidence, risk factors, and influence on outcome. Results were analyzed for 279 patients enrolled in the APL97 study conducted by the Japan Adult Leukemia Study Group (JALSG).
RESULTS: Severe hemorrhage occurred in 18 patients (6.5%). Although most of them were receiving frequent transfusions, the targeted levels of platelet counts (30 x 10(9)/L) and plasma fibrinogen (1.5 g/L) for this study were reached at the day of bleeding in only 71% and 40%, respectively. Nine of them succumbed to an early death, while the remaining nine patients eventually achieved complete remission (CR). The 5-yr event-free survival rate was 68.1% for those who did not suffer severe hemorrhage, and 31.1% for those who did (P < 0.0001). For patients who achieved CR, on the other hand, there was no difference in disease-free survival between patients with and without severe hemorrhage (P = 0.6043). Risk factor analysis identified three pretreatment variables associated with severe hemorrhage: initial fibrinogen level, white blood cell count, and performance status. Additionally, patients with severe hemorrhage were more easily prone to develop retinoic acid syndrome or pneumonia than patients without hemorrhage.
CONCLUSIONS: These results indicate that fatal hemorrhage represents a major obstacle in curing APL, and that patients with such high-risk features may benefit from more aggressive supportive care.

PMID 17241371  Eur J Haematol. 2007 Mar;78(3):213-9. doi: 10.1111/j.16・・・
著者: D Grimwade, A Biondi, M J Mozziconacci, A Hagemeijer, R Berger, M Neat, K Howe, N Dastugue, J Jansen, I Radford-Weiss, F Lo Coco, M Lessard, J M Hernandez, E Delabesse, D Head, V Liso, D Sainty, G Flandrin, E Solomon, F Birg, M Lafage-Pochitaloff
雑誌名: Blood. 2000 Aug 15;96(4):1297-308.
Abstract/Text Acute promyelocytic leukemia (APL) is typified by the t(15;17), generating the PML-RAR alpha fusion and predicting a beneficial response to retinoids. However, a sizeable minority of APL cases lack the classic t(15;17), prompting the establishment of the European Working Party to further characterize this group. Such cases were referred to a workshop held in Monza, Italy and subjected to morphologic, cytogenetic, and molecular review, yielding 60 evaluable patients. In the majority (42 of 60), molecular analyses revealed underlying PML/RAR alpha rearrangements due to insertions (28 of 42) or more complex mechanisms, including 3-way and simple variant translocations (14 of 42). Metaphase fluorescence in situ hybridization (FISH) demonstrated that insertions most commonly led to formation of the PML-RAR alpha fusion gene on 15q. In 11 of 60 workshop patients, PLZF/RAR alpha rearrangements were identified, including 2 patients lacking the t(11;17)(q23;q21). In one case with a normal karyotype, FISH analysis revealed insertion of RAR alpha into 11q23, and PLZF-RAR alpha was the sole fusion gene formed. Two patients were found to have t(5;17), one with a diffuse nuclear NPM staining pattern and with NPM-RAR alpha and RAR alpha-NPM transcripts detected. In the other with an unbalanced der(5)t(5;17)(q13;q21) and a nucleolar NPM localization pattern, an NPM/RAR alpha rearrangement was excluded, and FISH revealed deletion of one RAR alpha allele. In the remaining 5 workshop patients, no evidence was found for a rearrangement of RAR alpha, indicating that in rare instances, alternative mechanisms could mediate the differentiation block that typifies this disease. This study highlights the importance of combining morphologic, cytogenetic, and molecular analyses for optimal management of APL patients and better understanding of the pathogenesis of the disease. (Blood. 2000;96:1297-1308)

PMID 10942371  Blood. 2000 Aug 15;96(4):1297-308.
著者: Miguel A Sanz, David Grimwade, Martin S Tallman, Bob Lowenberg, Pierre Fenaux, Elihu H Estey, Tomoki Naoe, Eva Lengfelder, Thomas Büchner, Hartmut Döhner, Alan K Burnett, Francesco Lo-Coco
雑誌名: Blood. 2009 Feb 26;113(9):1875-91. doi: 10.1182/blood-2008-04-150250. Epub 2008 Sep 23.
Abstract/Text The introduction of all-trans retinoic acid (ATRA) and, more recently, arsenic trioxide (ATO) into the therapy of acute promyelocytic leukemia (APL) has revolutionized the management and outcome of this disease. Several treatment strategies using these agents, usually in combination with chemotherapy, but also without or with minimal use of cytotoxic agents, have provided excellent therapeutic results. Cure of APL patients, however, is also dependent on peculiar aspects related to the management and supportive measures that are crucial to counteract life-threatening complications associated with the disease biology and molecularly targeted treatment. The European LeukemiaNet recently appointed an international panel of experts to develop evidence- and expert opinion-based guidelines on the diagnosis and management of APL. Together with providing current indications on genetic diagnosis, modern risk-adapted front-line therapy and salvage treatment, the review contains specific recommendations for the identification and management of most important complications such as the bleeding disorder, APL differentiation syndrome, QT prolongation and other ATRA- and ATO-related toxicities, as well as for molecular assessment of response to treatment. Finally, the approach to special situations is also discussed, including management of APL in children, elderly patients, and pregnant women.

PMID 18812465  Blood. 2009 Feb 26;113(9):1875-91. doi: 10.1182/blood-2・・・
著者: Norio Asou, Yuji Kishimoto, Hitoshi Kiyoi, Masaya Okada, Yasukazu Kawai, Motohiro Tsuzuki, Kentaro Horikawa, Mitsuhiro Matsuda, Katsuji Shinagawa, Tohru Kobayashi, Shigeki Ohtake, Miki Nishimura, Masatomo Takahashi, Fumiharu Yagasaki, Akihiro Takeshita, Yukihiko Kimura, Masako Iwanaga, Tomoki Naoe, Ryuzo Ohno, Japan Adult Leukemia Study Group
雑誌名: Blood. 2007 Jul 1;110(1):59-66. doi: 10.1182/blood-2006-08-043992. Epub 2007 Mar 20.
Abstract/Text To examine the efficacy of intensified maintenance chemotherapy, we conducted a prospective multicenter trial in adult patients with newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Of the 302 registered, 283 patients were assessable and 267 (94%) achieved complete remission. Predicted 6-year overall survival in all assessable patients and disease-free survival in patients who achieved complete remission were 83.9% and 68.5%, respectively. A total of 175 patients negative for PML-RARalpha at the end of consolidation were randomly assigned to receive either intensified maintenance chemotherapy (n = 89) or observation (n = 86). Predicted 6-year disease-free survival was 79.8% for the observation group and 63.1% for the chemotherapy group, showing no statistically significant difference between the 2 groups (P = .20). Predicted 6-year survival of patients assigned to the observation was 98.8%, which was significantly higher than 86.2% in those allocated to the intensified maintenance (P = .014). These results indicate that the intensified maintenance chemotherapy did not improve disease-free survival, but rather conferred a significantly poorer chance of survival in acute promyelocytic leukemia patients who have become negative for the PML-RARalpha fusion transcript after 3 courses of intensive consolidation therapy.

PMID 17374742  Blood. 2007 Jul 1;110(1):59-66. doi: 10.1182/blood-2006・・・
著者: David Grimwade, Jelena V Jovanovic, Robert K Hills, Elizabeth A Nugent, Yashma Patel, Rajinder Flora, Daniela Diverio, Katy Jones, Hannah Aslett, Elaine Batson, Kristian Rennie, Roger Angell, Richard E Clark, Ellen Solomon, Francesco Lo-Coco, Keith Wheatley, Alan K Burnett
雑誌名: J Clin Oncol. 2009 Aug 1;27(22):3650-8. doi: 10.1200/JCO.2008.20.1533. Epub 2009 Jun 8.
Abstract/Text PURPOSE: Molecular diagnostics and early assessment of treatment response that use methodologies capable of detecting submicroscopic disease can distinguish subgroups of patients with leukemia at differing relapse risk. Such information is being incorporated into risk-stratified protocols; however, there are few data concerning prospective use of sequential minimal residual disease (MRD) monitoring to identify more precisely those patients destined to experience relapse, which would allow more tailored therapies.
METHODS: Real-time quantitative polymerase chain reaction (RQ-PCR) assays to detect leukemia-specific transcripts (ie, PML-RARA, RARA-PML) were used to prospectively analyze 6,727 serial blood and marrow samples from 406 patients with newly diagnosed acute promyelocytic leukemia (APL) who were receiving all-trans-retinoic acid and anthracycline-based chemotherapy.
RESULTS: MRD monitoring according to the recommended schedule successfully identified the majority of patients subject to relapse and provided the most powerful predictor of relapse-free survival (RFS) in multivariable analysis (hazard ratio, 17.87; 95% CI, 6.88 to 46.41; P < .0001); MRD monitoring was far superior to presenting WBC (hazard ratio, 1.02; 95% CI, 1.00 to 1.03; P = .02), which is currently widely used to guide therapy. In patients who were predicted to experience relapse on the basis of MRD monitoring, early treatment intervention with arsenic trioxide prevented progression to overt relapse in the majority, and the RFS rate at 1 year from molecular relapse was 73%. By using this strategy, 3-year cumulative incidence of clinical relapse was only 5% in the Medical Research Council AML15 trial.
CONCLUSION: Rigorous sequential RQ-PCR monitoring provides the strongest predictor of RFS in APL and, when coupled with pre-emptive therapy, provides a valid strategy to reduce rates of clinical relapse. This provides a model for development of a more individualized approach to management of other molecularly defined subtypes of acute leukemia.

PMID 19506161  J Clin Oncol. 2009 Aug 1;27(22):3650-8. doi: 10.1200/JC・・・
著者: Martin S Tallman, Haesook T Kim, Pau Montesinos, Frederick R Appelbaum, Javier de la Serna, John M Bennett, Guillermo Deben, Clara D Bloomfield, Jose Gonzalez, James H Feusner, Marcos Gonzalez, Robert Gallagher, Jose D Gonzalez-San Miguel, Richard A Larson, Gustavo Milone, Elisabeth Paietta, Chelo Rayon, Jacob M Rowe, Concha Rivas, Charles A Schiffer, Edo Vellenga, Lois Shepherd, James L Slack, Peter H Wiernik, Cheryl L Willman, Miguel A Sanz
雑誌名: Blood. 2010 Dec 16;116(25):5650-9. doi: 10.1182/blood-2010-06-288613. Epub 2010 Sep 21.
Abstract/Text Few studies have examined the outcome of large numbers of patients with the microgranular variant (M3V) of acute promyelocytic leukemia (APL) in the all-trans retinoic acid era. Here, the outcome of 155 patients treated with all-trans retinoic acid-based therapy on 3 clinical trials, North American Intergroup protocol I0129 and Programa para el Estudio de la Terapéutica en Hemopatía Maligna protocols LPA96 and LPA99, are reported. The complete remission rate for all 155 patients was 82%, compared with 89% for 748 patients with classical M3 disease. The incidence of the APL differentiation syndrome was 26%, compared with 25% for classical M3 patients, and the early death rate was 13.6% compared with 8.4% for patients with classical M3 morphology. With a median follow-up time among survivors of 7.6 years (range 3.6-14.5), the 5-year overall survival, disease-free survival, and cumulative incidence of relapse for patients with M3V were 70%, 73%, and 24%, respectively. With a median follow-up time among survivors of 7.6 years (range 0.6-14.3), the 5-year overall survival, disease-free survival, and cumulative incidence of relapse among patients with classical M3 morphology were 80% (P = .006 compared with M3V), 81% (P = .07), and 15% (P = .005), respectively. When outcomes were adjusted for the white blood cell count or the relapse risk score, none of these outcomes were significantly different between patients with M3V and classical M3 APL.

PMID 20858857  Blood. 2010 Dec 16;116(25):5650-9. doi: 10.1182/blood-2・・・
著者: Pau Montesinos, Chelo Rayón, Edo Vellenga, Salut Brunet, José González, Marcos González, Aleksandra Holowiecka, Jordi Esteve, Juan Bergua, José D González, Concha Rivas, Mar Tormo, Vicente Rubio, Javier Bueno, Félix Manso, Gustavo Milone, Javier de la Serna, Inmaculada Pérez, Manuel Pérez-Encinas, Isabel Krsnik, Josep M Ribera, Lourdes Escoda, Bob Lowenberg, Miguel A Sanz, PETHEMA, HOVON Groups
雑誌名: Blood. 2011 Feb 10;117(6):1799-805. doi: 10.1182/blood-2010-04-277434. Epub 2010 Dec 8.
Abstract/Text The expression of CD56 antigen in acute promyelocytic leukemia (APL) blasts has been associated with short remission duration and extramedullary relapse. We investigated the clinical significance of CD56 expression in a large series of patients with APL treated with all-trans retinoic acid and anthracycline-based regimens. Between 1996 and 2009, 651 APL patients with available data on CD56 expression were included in 3 subsequent trials (PETHEMA LPA96 and LPA99 and PETHEMA/HOVON LPA2005). Seventy-two patients (11%) were CD56(+) (expression of CD56 in ≥ 20% leukemic promyelocytes). CD56(+) APL was significantly associated with high white blood cell counts; low albumin levels; BCR3 isoform; and the coexpression of CD2, CD34, CD7, HLA-DR, CD15, and CD117 antigens. For CD56(+) APL, the 5-year relapse rate was 22%, compared with a 10% relapse rate for CD56(-) APL (P = .006). In the multivariate analysis, CD56 expression retained the statistical significance together with the relapse-risk score. CD56(+) APL also showed a greater risk of extramedullary relapse (P < .001). In summary, CD56 expression is associated with the coexpression of immaturity-associated and T-cell antigens and is an independent adverse prognostic factor for relapse in patients with APL treated with all-trans-retinoic acid plus idarubicin-derived regimens. This marker may be considered for implementing risk-adapted therapeutic strategies in APL. The LPA2005 trial is registered at http://www.clinicaltrials.gov as NCT00408278.

PMID 21148082  Blood. 2011 Feb 10;117(6):1799-805. doi: 10.1182/blood-・・・
著者: N Asou, K Adachi, J Tamura, A Kanamaru, S Kageyama, A Hiraoka, E Omoto, H Akiyama, K Tsubaki, K Saito, K Kuriyama, H Oh, K Kitano, S Miyawaki, K Takeyama, O Yamada, K Nishikawa, M Takahashi, S Matsuda, S Ohtake, H Suzushima, N Emi, R Ohno
雑誌名: J Clin Oncol. 1998 Jan;16(1):78-85.
Abstract/Text PURPOSE: We conducted a multicenter study of differentiation therapy with all-trans retinoic acid (ATRA) followed by intensive chemotherapy in patients with newly diagnosed acute promyelocytic leukemia (APL) and analyzed the prognostic factors for predicting complete remission (CR), event-free survival (EFS), and disease-free survival (DFS).
PATIENTS AND METHODS: All patients received ATRA until CR. If patients had an initial leukocyte count greater than 3.0 x 10(9)/L, they received daunorubicin (DNR) and behenoyl cytarabine (BHAC). During therapy, if patients showed blast and promyelocyte counts greater than 1.0 x 10(9)/L, they received additional DNR and BHAC. After achieving CR, patients received three courses of consolidation and six courses of maintenance/intensification chemotherapy.
RESULTS: Of 198 registered, 196 were assessable (age range, 15 to 86 years; median, 46) and 173 (88%) achieved CR. Multivariate analysis showed that no or minor purpura at diagnosis (P = .0046) and age less than 30 years (P = .0076) were favorable factors for achievement of CR. Predicted 4-year overall survival and EFS rates were 74% and 54%, respectively, and the 4-year predicted DFS rate for 173 CR patients was 62%. Multivariate analysis showed that age less than 30 years (P = .0003) and initial leukocyte count less than 10 x 10(9)/L (P = .0296) were prognostic factors for longer EFS, and initial leukocyte count less than 10.0 x 10(9)/L was a sole significant prognostic factor for longer DFS (P = .0001).
CONCLUSION: Our results show that age, hemorrhagic diathesis, and initial leukocyte count are prognostic factors for APL treated with ATRA followed by intensive chemotherapy.

PMID 9440726  J Clin Oncol. 1998 Jan;16(1):78-85.
著者: M A Sanz, F Lo Coco, G Martín, G Avvisati, C Rayón, T Barbui, J Díaz-Mediavilla, G Fioritoni, J D González, V Liso, J Esteve, F Ferrara, P Bolufer, C Bernasconi, M Gonzalez, F Rodeghiero, D Colomer, M C Petti, J M Ribera, F Mandelli
雑誌名: Blood. 2000 Aug 15;96(4):1247-53.
Abstract/Text Preliminary independent reports of the Italian GIMEMA and the Spanish PETHEMA trials for newly diagnosed acute promyelocytic leukemia (APL) indicated a similarly high antileukemic efficacy in terms of complete remission and disease-free survival rates. To better investigate these studies and the prognostic factors influencing relapse risk, this study analyzed the updated results of 217 patients with PML/RAR alpha-positive APL enrolled in GIMEMA (n = 108) and PETHEMA (n = 109). All patients received identical induction (AIDA schedule) and maintenance. For consolidation, GIMEMA patients received 3 courses including idarubicin/cytarabine, mitoxantrone/etoposide, and idarubicin/cytarabine/thioguanine, whereas PETHEMA patients received the same drugs and dose schedule of idarubicin and mitoxantrone with the omission of nonintercalating agents. Depending on whether molecular relapses were classified as censored or uncensored events, the 3-year Kaplan-Meier estimates of relapse-free survival (RFS) for the combined series were 90 +/- 2% and 86 +/- 2%, respectively. Minor differences observed between the 2 patient cohorts were negligible. Multivariate regression analysis of RFS showed that initial leukocyte (WBC) and platelet counts were the only variables with independent prognostic value. The resulting predictive model for RFS demonstrated its capability of segregating patients into low-risk (WBC count 40 x 10(9)/L), intermediate-risk (WBC count 10 x 10(9)/L) groups, with distinctive RFS curves (P <.0001). The conclusions are that omission of nonanthracycline drugs from the AIDA regimen is not associated with reduced antileukemic efficacy and a simple predictive model may be used for risk-adapted therapy in this disease. (Blood. 2000;96:1247-1253)

PMID 10942364  Blood. 2000 Aug 15;96(4):1247-53.

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