Page 1800 - Hematology_ Basic Principles and Practice ( PDFDrive )

1604 Part X Transplantation

HCT-CI and R-DRI are increasingly used in clinical decision making
to determine patient eligibility and optimal conditioning intensity DISEASE-SPECIFIC INDICATIONS FOR ALLOGENEIC
pre-HCT. TRANSPLANTATION
Acute Myeloid Leukemia
CLINICAL RESEARCH IN ALLOGENEIC
TRANSPLANTATION There is general agreement that most patients under the age of about
60 years who fail conventional therapy and who have good perfor-
The number of HCTs performed in the US is increasing at a rate of mance status are best treated with allogeneic transplantation if an
approximately 5% per year. Only a minority of patients have their appropriate related or unrelated donor is available. HCT is not rec-
transplants performed on clinical trials. Challenges unique to the field ommended for those with favorable risk cytogenetics in first complete
of HCT such as small numbers treated at individual centers, the wide remission (CR1).
variety of indications and multiple competing risks in the peritrans- The National Comprehensive Cancer Network (NCCN) guide-
plant period, make it difficult to perform single center studies. To lines, widely used to guide cancer therapy in the US, distinguishes
overcome these challenges, in the US, a national multicenter trans- between patients ≤60 versus those >60 years. Among younger
plant study network (BMT-CTN) has been established. The patients, the panel recommended a postremission strategy based on
BMT-CTN has thus far launched 36 multicenter trials and accrued factors such as the expected relapse rates with high dose cytarabine
more than 7000 patients. therapy alone, salvage treatment options at relapse and patient-specific
While clinical trials focus on short- and intermediate-term comorbidities that predict for TRM. The guidelines uniformly
outcomes, there is also a need for long-term follow up of trans- endorsed allogeneic HCT, from related or unrelated donors including
plant recipients. Outcomes registries, such as those maintained by cord blood HCT, in first CR for patients with unfavorable cytogenetic
the CIBMTR and EBMT, are important in facilitating additional or molecular abnormalities, therapy-related AML or prior myelodys-
clinical research. The CIBMTR maintains a large database of clinical plasia. Among those older than 60 years, the recommendation was
information on the outcome of HCTs performed in 500 transplant to consider HCT as an early option in those achieving a CR and as
centers in nearly 50 countries. The database includes information treatment for induction failure only in patients with low volume
on more than 370,000 transplant recipients. Data quality and residual disease. For relapsed AML, HCT was recommended irrespec-
consecutive registration are ensured through extensive computer tive of age but only after a second CR was achieved or in the context
checks and on-site audits. Data collection is through a web-based of a clinical trial. For patients with acute promyelocytic leukemia, the
data entry program. Some important questions, such as results of recommendation was to reserve allogeneic HCT for relapsed patients
HCT in specific patient groups and rare diseases, analysis of prog- with persistent disease despite salvage therapy.
nostic factors, evaluation of new transplant regimens, comparison The ASBMT evidence-based policy for allogeneic HCT in AML
of HCT with nontransplant therapy, defining intercenter variability recommends HCT in the relapse setting (after achievement of CR2)
in practice and outcome are difficult to address in randomized trials and in patients with poor-risk cytogenetics in first remission. The
and can be studied using registry data. Analysis of outcomes after ASBMT guidelines did not routinely recommend: allogeneic HCT
transplantation needs an understanding of statistic methodologies for patients with intermediate risk cytogenetics; or the routine use of
such as multistate modeling. Such models involve competing risks myeloablative conditioning for patients over age 55 years. The
problems such as the study of relapse versus death in remission or the European Leukemia-Net guidelines are mostly in line with the
complex interrelationship between engraftment, transplant complica- ASBMT evidence-based policy, but provide greater detail about
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tions (such as infection or GVHD), and primary events such as death allogeneic HCT in cytogenetically normal (CN) AML. These
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or relapse. Outcomes registries also provide a platform to analyze the guidelines recommend considering HCT for patients with CN-AML
availability, access, disparities, and economics of HCT. A biospeci- and unfavorable molecular markers, that is, those who lack the favor-
men repository maintained by the NMDP and associated with the able genotypes of mutated nucleophosmin 1 (NPM1) without
CIBMTR database allows the linkage of clinical and immunologic FMS-related tyrosine kinase 3-internal tandems duplication (FLT3-
data for analysis and has led to important insights into transplant ITD) or mutated CCAAT/enhancer binding protein alpha (CEBPA).
immunobiology. In addition, allogeneic HCT was endorsed for FLT3-ITD + AML.
A systematic review of various national guidelines found the
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LONG-TERM SURVIVAL AFTER ALLOGENEIC following :
TRANSPLANTATION a. Consistent recommendations that patients with relapsed or refrac-
tory disease or high-risk cytogenetics be considered for HCT
Most deaths related to HCT occur within the first 2 years. However, early;
an analysis of 2 year survivors found that, compared with age and b. Consistent recommendations that patients with good prognosis
nationality matched death rates among the general population, sub- cytogenetics receive HCT only after failure of nontransplant
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sequent survival was still inferior for HCT recipients. Overall, 85% therapy;
of 2-year survivors were still alive at 10 years post-HCT. Late relapse c. Inconsistent recommendations for patients with intermediate risk
was the major cause of late deaths and was associated with advanced disease or without a family donor regarding transplantation in first
disease at HCT. Older age and GVHD were the other major predic- remission;
tors of late mortality. d. Lack of consensus regarding the efficacy of reduced-intensity
The number of long-term HCT survivors is growing. Most conditioning;
5-year survivors are well, off all immune suppression and leading e. Most national guidelines recommend a risk-based approach to
normal lives. However, transplant recipients remain at risk for late guide selection of chemotherapy versus transplant approaches
complications including late infections, cataracts, abnormalities of using factors such as patient age, comorbid conditions, disease
growth and development, thyroid disorders, chronic lung disease and phenotype at diagnosis and the number of cycles of therapy before
avascular necrosis. There is also an increased incidence of leukemias, remission.
myelodysplasia, and solid tumors in transplant recipients compared
with the general population. Lifelong surveillance is necessary,
as is increased awareness of late complications among the many Acute Lymphoblastic Leukemia
nontransplant physicians who will care for these patients. Recom-
mended long-term follow up of HCT recipients is summarized in Allogeneic HCT in first remission from related or unrelated donors
Box 104.4. is generally accepted as the most effective available therapy for