Page 1102 - Hematology_ Basic Principles and Practice ( PDFDrive )

972 Part VII Hematologic Malignancies

TABLE Allogeneic Transplantation Guidelines for Adult Acute Myeloid Leukemia Based on Commonly Assessed Cytogenetic and
61.2 Molecular Markers
AML Category Prognostic Impact Allogeneic Transplantation Notes
AML-CR1: Younger Adults
Good-risk disease
APL Favorable No APL is treatable by chemotherapy
CBF-AML without mKIT Favorable No t(8;21) AML with high WBC count at diagnosis
may have worse prognosis
CBF-AML with mKIT Intermediate Possible: MRD, MUD
Uncertain: MMUD, UCB, haplo
Intermediate-Risk Disease
CN-AML with CEBPA Favorable No Benefit likely restricted to DM-CEBPA
CN-AML with mutant NPM1 Favorable Possible: MRD Emerging data suggests allogeneic HSCT benefit
but not FLT-3-ITD for this category, with reduced relapse and
improved DFS in patients >40 years.
CN-AML with FLT-3-ITD Unfavorable a Yes: MRD, MUD Unfavorable risk may be restricted to AML with
Possible : MMUD, UCB, haplo FLT-3-ITD allelic ratio >0.51
b
Other intermediate-risk disease Intermediate or Unfavorable Yes: MRD Likely considerable underlying clinical
a
Likely acceptable : MUD heterogeneity. Molecular risk profiling may
Possible : MMUD, UCB, haplo further delineate risk in this category.
b
Poor-Risk Disease
Monosomal karyotype absent Unfavorable Yes: MRD, MUD
Likely acceptable : MMUD, UCB,
b
haplo
Monosomal karyotype present Very unfavorable Yes: MRD, MUD.
Acceptable : MMUD, UCB, haplo
b
Abnormal 17(p) Very unfavorable Yes: MRD, MUD
Acceptable : MMUD, UCB, haplo
b
AML-CR1: older adults Unfavorable Yes: MRD, MUD
Likely acceptable : MMUD, UCB,
b
haplo
AML-CR1: t-AML, AML/MDS Unfavorable Yes: MRD, MUD Molecular risk profiling may supersede clinical
Acceptable : MMUD, UCB, haplo classification of secondary AML, especially in
b
older patients
AML-CR2 Very unfavorable Yes: MRD, MUD
b
Acceptable : MMUD, UCB, haplo
AML not in remission Very unfavorable Yes: MRD, MUD For selected patients: good performance status,
Uncertain: MMUD, UCB, haplo little comorbidity, lower leukemic burden;
CIBMTR risk score may be useful
a If no sibling donor available.
b If no timely matched donor available.
AML, Acute myeloid leukemia; APL, acute promyelocytic leukemia; CBF, core binding factor; CIBMTR, Center for International Blood and Marrow Transplant Research;
CN, cytogenetically normal; CR1, first complete remission; CR2, second complete remission; haplo, haploidentical; MDS, myelodysplastic syndrome; MMUD, mismatched
unrelated donor; MRD, matched related donor; MUD, matched unrelated donor; t-AML, therapy-related AML; UCB, umbilical cord blood; WBC, white blood cell.

appears to only partly ameliorate the impact of MK-positive karyo- Transplantation Regimen Intensity
type, which remained an adverse prognostic factor after HSCT, and
was associated with a relapse risk of 62% and poor survival of 15% Myeloablative HSCT remains the standard of care for younger adults
at 4 years. 19 with AML. However, treatment-related mortality after MAC remains
Importantly, some if not all of the negative impact of MK and appreciable. Lower-intensity regimens offering less treatment-related
complex karyotype (CK) AML is its association with deletions of toxicity are increasing in popularity. One report retrospectively
chromosome 5 (−5/5q−) and especially with abnormal 17p (site of compared RIC transplantation with chemotherapy in high-risk AML
TP53 gene). In a retrospective analysis of 236 high-risk AML-CR1 on a donor versus no-donor basis. They identified a leukemia-free
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patients of whom nearly half (49%) received reduced-intensity allo- survival benefit in the donor group (54% versus 30%, p = .01).
geneic HSCT, patients with abn(17p) had a 2-year event-free survival Several groups have compared MAC versus RIC transplantation,
(EFS) of 11%, those with −5/5q− but no abn(17p) had a 2-year EFS documenting similar overall and leukemia-free survival, with some
of 29%, and those with high-risk AML (including MK or CK) reporting lower treatment-related mortality offset by increased relapse
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without either abn(17p) or −5/5q− had a 2-year EFS of 49%. risk, especially for patients not in complete remission at time of
Further, in updated analyses, the negative impact of abnl(17p) HSCT. A CIBMTR study compared 3731 MAC, 1041 RIC, and
appears minimally improved after allogeneic HSCT. 21,22 Improving 407 nonmyeloablative (NMA) transplantations, reporting adjusted
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HSCT outcomes in TP53 mutant AML must be a high priority for 5-year OSs of 34%, 33%, and 26%, respectively. The authors
the future. concluded that, although NMA transplantation increased relapse and