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Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab

Yasmin Abaza, Hagop Kantarjian, Guillermo Garcia-Manero, Elihu Estey, Gautam Borthakur, Elias Jabbour, Stefan Faderl, Susan O’Brien, William Wierda, Sherry Pierce, Mark Brandt, Deborah McCue, Rajyalakshmi Luthra, Keyur Patel, Steven Kornblau, Tapan Kadia, Naval Daver, Courtney DiNardo, Nitin Jain, Srdan Verstovsek, Alessandra Ferrajoli, Michael Andreeff, Marina Konopleva, Zeev Estrov, Maria Foudray, David McCue, Jorge Cortes and Farhad Ravandi

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Tables

  • Table 1.

    Patient characteristics at diagnosis

    Characteristics (N = 187)Number (%)Median (range)
    Age, y50 (14-84)
     ≥6052 (28)
    Sex
     Male97 (52)
     Female90 (48)
    Risk category
     High-risk54 (29)
     Low-risk133 (71)
    Leukocyte count (×109/L)2.2 (0.3-187.9)
    Platelet count (×109/L)36 (3-261)
    Cytogenetics
     t(15;17)122 (65)
     t(15;17) + other cytogenetic abnormalities45 (24)
     Diploid (RT-PCR +)10 (5)
     Not done/insufficient metaphases (RT-PCR+)9 (5)
     Hyperdiploid (RT-PCR +)1 (0.5)
    FAB morphology
     M3163 (87)
     M3v22 (12)
     Unknown2 (1)
    PML-RARA isoforms
     Short78 (42)
     Long105 (56)
     Both4 (2)
    • FAB, French-American-British.

  • Table 2.

    Characteristics of relapsed acute promyelocytic leukemia patients

    Patient no.Risk categoryAge (y)SexCytogeneticsFLT3 statusTime to first relapse (mo)Type of first relapse
    1High52FDiploidND9.2Molecular*
    2Low42M46XY t(15;17) [20]ND79.5Hematological/molecular
    3High38M46XY t(15;17) [19]ND9Hematological/molecular
    4High79M46XY t(15;17), der (17) i (17) (q10) [18]; 46 XY [2]Neg12.4Molecular*
    5High18M46XY t(15;17) [19]ND9.4Molecular*
    6Low19FDiploidNeg9.5Hematological
    7High35M46XY t(15;17) [16]; 46 idem, del 7 [1]; 46 XY [3]Neg7.9Hematological
    • BM, bone marrow; CNS, central nervous system; F, female; M, Male; MRD-SCT, matched-related donor stem cell transplantation; mo, months; No., number; ND, not done; Neg, negative.

    • * Molecular relapses: Patient No.1 experienced a molecular relapse after 9.2 mo received salvage ATRA/ATO/GO achieved molecular remission, but then had a hematological relapse (BM+CNS) with time to hematological relapse of 18.8 mo (9.6 mo after molecular relapse). Patient No. 4 experienced a molecular relapse after 12.4 mo received salvage GO without achieving molecular remission and had a hematological relapse (CNS alone) with time to hematological relapse of 16.4 mo (4 mo after molecular relapse). Patient No. 5 experienced a molecular relapse after 9.4 mo received salvage ATRA/ATO/GO/IDA achieved molecular remission which was followed by MRD-SCT.

  • Table 3.

    Causes of death unrelated to acute promyelocytic leukemia:

    Patient (N = 17)Age (y)CR duration (mo)Cause of deathResponse at time of deathComments
    16969.9Stage IV GISTCR
    2778Prostate cancerCR
    37560Prostate cancerCR
    46096.2H&N cancerCR
    5474.9Prostate cancerCR
    66477.5MelanomaCR
    77473.4Pancreatic cancerCR
    87016.5MelanomaCR
    96958.4ESRD on HDCRRenal biopsy showed glomerulosclerosis. Pt had DM.
    107515.7ESRD on HDCRReceived 1 cycle. Therapy discontinued because of fluid overload and worsening creatinine. Pt had other comorbidities including CHF, DM, and HTN.
    11389Pneumococcal meningitisCRPt was 644 D post-SCT and was off immunosuppression. Pt had hepatic insufficiency.
    12640.9Sepsis/pneumoniaCRs/p 2 cycles, sepsis unrelated to study drugs. Pt had DM and HTN.
    13219.3Infection and pulmonary embolismCRPatient was treated with ATRA/ATO/GO on protocol for 2.5 mo and achieved CR but taken off protocol because of ATRA intolerance; ATO/GO off protocol: for 2 mo; IDA off protocol: C3 D59
    14697CHF and cardiac arrestCRC3 D31 on protocol. Pt had history of CAD s/p bypass surgery, HTN, and hyperlipidemia.
    158125.2UnknownCRLost to follow-up
    1681106.8UnknownCRLost to follow-up
    174339.2UnknownCRLost to follow-up
    • C, cycle; CHF, congestive heart failure; D, day; DM, diabetes mellitus; ESRD, end-stage renal disease; GIST, gastrointestinal stromal tumor; HD, hemodialysis: H&N, head and neck; HTN, hypertension; mo, month; Pt, patient; s/p, status post.