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Hematopoietic stem cell transplantation for patients with AML in first complete remission

Jan J. Cornelissen and Didier Blaise

Article Figures & Data

Figures

  • Figure 1

    Kaplan-Meier estimates of overall survival of AML intermediate-risk patients in CR1, age 40 to 60 years, by type of postremission therapy (updated results from Cornelissen et al53). HSCT recipients showed significantly better OS than patients receiving chemotherapeutic postremission therapy (P = .001). AlloMAB, myeloablative alloHSCT; AlloRIC, reduced intensity conditioning alloHSCT; Auto, autologous HSCT; CT, chemotherapy; ELN, European Leukemia Net. F, female; LR, logistic regression.

Tables

  • Table 1

    Recommendation for alloHSCT in AML CR1 based on integrated risk profiles

    AML risk group‡AML risk assessment criteria at diagnosisMRD after cycle 2Risk of relapse following consolidation approachPrognostic scores for NRM that indicate alloHSCT as preferred consolidation
    Chemotherapy or autoHSCT (%)AlloHSCT (%)EBMT score52HCT-CI score53NRM risk (%)
    Good–t(8;21) or AML1-ETO, WBC <20Positive or negative35-4015-20NA (≤1)NA (<1)10-15
    –inv16/t(16;16) or CBFB-MYH11
    –CEBPA-biallelic mutant-positive
    –FLT3-ITD-negative/NMP1-positive
    Intermediate–CN –X –Y, WBC <100, CReNegative50-5520-25≤2≤2<20-25
    –t(8;21) or AML1-ETO plus WBC >20
    or mutant KIT
    Poor–CN –X –Y, WBC <100, CRePositive70-8030-40≤3-4≤3-4<30
    –t(8;21) or AML1-ETO, WBC >20Positive
    and/or mutant KIT
    –CN –X –Y, WBC <100, no CReNegative
    –CN –X –Y, WBC >100Negative
    –CA, but non-CBF, MK-negative, no abn3q26
    Very poor–CN –X –Y, WBC >100Positive>9040-50≤5≤5<40
    –CA, but non-CBF, MK-negative, no abn3q26, EVI1-negativePositive
    –MK-positivePositive or negative
    –abn3q26
    –Non-CBF, EVI1-positive
    –Non-CBF with mutant p53, or –mutant RUNX1, or mutant ASXL1 –or biallelic FLT3-ITD with –FLT3-ITD:FLT3 WT ratio of >0.6
    • Adapted from the European Leukemia Net recommendation by adding new molecular markers and MRD.5 The proposed patient-specific use of alloHSCT in AML CR1 integrates the individual risks for relapse and NRM and aims for a disease-free survival benefit of at least 10% for the individual patient compared with consolidation by a non-alloHSCT approach. The categorization of AML is based on cytogenetic, molecular, and clinical parameters (including white blood cell count [WBC]); subcategories are now designated good, intermediate, poor, and very poor, as currently used by the HOVON-SAKK Cooperative Consortium.

    • CA, cytogentic abnormalities; CBF, core binding factor; CN, cytogenetically normal; CRe, early complete remission; HCT-CI, hematopoietic cell transplantation comorbidity index; ITD, internal tandem duplication; MK, monosomal karyotype; NA, not applicable; –X –Y, deleted X or Y chromosome.

  • Table 2

    Recent studies of alloHSCT using haploidentical donors in AML

    First author, year of study, study group, type of studyAML patients characteristicsOutcome, by donor typeStudy conclusions
    Age at diagnosis (y) (range)AML in CR1 (%)Median follow-up, moConditioningStem cell sourceGVHD preventionDonor type and No.NRMRelapseLFS
    Ciceri, 2008, retrospective, multicentric9636 (16-66)1447Myeloablative, 100%PBSCEx vivo T-cell depletion, 100%; ATG, 89%Haploidentical, 860.360.160.48The choice between haploidentical and UCB transplantation may be based on center expertise, policy, costs of the procedures, and the availability of clinical trials.
    Ruggeri, 2015 EBMT, retrospective, multicentric9545 (18-72)3424Myeloablative, 61%BM; PBSCPT-HDCy, 32%UCB, 5580.300.320.38Cumulative incidence of relapse was not different between the 2 groups; adjusted LFS and OS were comparable.
    Haploidentical, 3600.270.410.32
    Wang, 2015, prospective, multicentric10128 (15-57)10032Myeloablative, 100%BM + PBSCATG, 100%MSD, 2190.080.150.78This comparison suggests that outcome after haploidentical HSCT (with ATG) is comparable to matched sibling alloHSCT.
    Haploidentical, 2310.130.150.74
    Ciurea, 2015, IBMTR, retrospective, multicentric9757 (21-70)4730-39Myeloablative, 54%BMPT-HDCy, 100%MAC MUD, 1245;0.200.390.42These data suggest that OS after haploidentical HSCT with PT-HDCy is comparable to MUD alloHSCT.
    Haploidentical, 1040.140.440.41
    RIC MUD, 7370.230.420.37
    Haploidentical, 880.090.580.35
    • BM, bone marrow; LFS, leukemia-free survival; MSD, matched sibling donor; MUD, matched unrelated donor; UCB, unrelated cord blood.