Page 1107 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 61 Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome in Adults 977

Age 50-60 Age >60
1.0 1.0
0.8 0.8

Probability 0.4 Probability 0.4
Myeloablative 0.6 0.6

0.2 0.2

0 0
0 10 20 30 40 50 0 10 20 30 40 50
Time since transplant (months) Time since transplant (months)

Alive after relapse Alive after relapse
Dead after relapse Dead after relapse
Nonrelapse death Nonrelapse death

1.0 1.0

0.8 0.8

Probability 0.4 Probability 0.4
RIC 0.6 0.6

0.2 0.2

0 0
0 10 20 30 40 50 0 10 20 30 40 50
Time since transplant (months) Time since transplant (months)
Alive after relapse Alive after relapse
Dead after relapse Dead after relapse
Nonrelapse death Nonrelapse death
Fig. 61.3 COMPETING RISK CUMULATIVE INCIDENCES FOR RELAPSE AND NONRELAPSE
MORTALITY AMONG INDIVIDUALS ABOVE AGE 50 YEARS. RIC, Reduced-intensity conditioning.
(Data from Lim Z, Brand R, Martino R, et al: Allogeneic hematopoietic stem-cell transplantation for patients 50 years or
older with myelodysplastic syndromes or secondary acute myeloid leukemia, J Clin Oncol 28:405, 2010.)

higher after RIC (HR, 1.64; p = .001), but with less treatment-related A second prospective randomized trial was recently reported by
mortality (HR, 0.61; p = .015), leading to similar 3-year OS (45% the EBMT. The RIC-MAC trial randomized 129 subjects up to age
versus 41%, p = .8). When limited to individuals above 50 years of 65 (60 with an unrelated donor) to either an ablative or reduced-
age, no difference in outcome stratified by conditioning intensity intensity busulfan regimen. There were no statistical differences in
87
(32% versus 30%, p = .73) was noted. Competing risk cumulative nonrelapse mortality, relapse or disease-free survival, but in multivari-
incidences for relapse and nonrelapse mortality are shown in able regression modeling, there was a survival advantage for subjects
Fig. 61.3. who received reduced-intensity conditioning. 88
It is important to consider that none of these retrospective studies
adjusted for comorbidity, and it is almost certain that if reanalyzed,
the RIC cohorts would contain a higher proportion of patients with Using Prognostic Models to Define the Role and
more comorbid conditions. Because only a minority of studies sug- Timing of Transplantation
gested that regimen intensity is important for long-term outcomes,
some patients, including those without significant comorbidity, have
now opted for earlier RIC transplantation, because treatment-related Clinical, Laboratory, and Cytogenetic
morbidity and mortality after this procedure is lower than after tra- Prognostic Factors
ditional MAC transplantation. In order to compare outcomes pro-
spectively among patients eligible to undergo both MAC and RIC Comparative registry analyses have documented the benefit of HSCT
89
transplantation, the Bone Marrow Transplant Clinical Trials Network over conventional supportive and disease-modifying agents in MDS ;
initiated a randomized, controlled trial in patients 18 to 65 years of however, this should not be interpreted as an indication for HSCT
age. This trial was closed prior to completion of accrual because of in all patients. Despite the curative potential of HSCT, transplanta-
better outcomes in the myeloablative cohort; however, the results for tion carries substantial risk for early morbidity and mortality, and
patients with MDS have not been released at the time of this careful consideration must be made regarding the appropriateness of
publication. each potential recipient and the timing at which transplantation is