Page 1221 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 67 Chronic Myeloid Leukemia 1067

years (80%), relapse (13%), or EFS (68% for CY/TBI and 71% for increased with delay; rather there is a modest effect of delay on relapse
BU/CY). Updated results showed OS of 78% at 10 years with BU/ rate and nonrelapse mortality. A CIBMTR report suggested that
CY versus 64% with CY/TBI. The absorption and metabolism of exposure to low-dose BU led to a worse outcome with subsequent
BU varies considerably from patient to patient, and BU assays were transplantation. Reports have suggested that exposure to IFN might
incorporated into transplant trials. Patients with a steady-state BU worsen the outcome of unrelated donor transplant, but data on the
concentration less than the median value (<917 ng/mL) of the cohort effect of IFN on matched sibling transplantation were less clear. In
had a significantly higher risk for disease recurrence and worse OS a recent German report, the 5-year survival rate from transplant was
than those with levels greater than 917 ng/mL. A subsequent report 46% for the 50 patients who received IFN within the last 90 days
of 131 consecutive CML CP patients who received transplants from before transplant and 71% for the 36 patients who did not. These
HLA-identical relatives showed a 3-year survival of 86%, a relapse observations suggest that IFN should be avoided, if possible, in the
rate of only 8%, and a nonrelapse mortality rate of 14%. Surprisingly, months immediately preceding allogeneic HCT.
there were no significant differences in outcome related to patient age The form of GVHD prophylaxis used in treatment regimens also
up to 65 years of age. influences the outcome of transplantation for CML, especially in
Only approximately one-third of patients have HLA-matched CP. Although successful in reducing the incidence of GVHD, T-cell
family members to serve as donors. Although early results with depletion in CML was associated with high rates of graft failure
matched unrelated donor transplantation in CML showed results and relapse, leading to poorer disease-free and OS. These findings
somewhat poorer than those seen with matched siblings, advances in illustrated the critical role of the graft-versus-leukemia (GVL) effect
donor selection, graft-versus-host disease (GVHD) prophylaxis, and in eradicating CML following allogeneic transplantation. Because
supportive care have resulted in continued improvements in outcome. of these observations, T-cell depletion was largely abandoned as a
Thus, in many institutions results following unrelated transplants method to control GVHD in CML transplants. However, there
are almost equivalent to those seen with matched siblings (with a has been renewed interest in the possibility of preventing GVHD
caveat that unrelated donor transplants have a lower age patient without loss of a GVL effect by combining T-cell depletion with an
exclusion), and registry data of multiple centers report 65% survival intensified conditioning regimen and delayed reinfusion of viable
at 5 years among younger patients transplanted within a year of donor lymphocytes.
diagnosis. Several studies have investigated the effect of prior imatinib and
Marrow was used as the stem cell source in all initial transplant transplant outcomes. Early reports warned of an increase in regimen-
studies. Two large randomized trials involving a variety of hematologic related toxicity and mortality, especially from hepatic causes. Larger
malignancies have shown that use of filgrastim (G-CSF)-mobilized studies have failed to show a deleterious effect of pretransplant ima-
peripheral blood hematopoietic cells leads to more rapid myeloid and tinib (Fig. 67.9). A study of only CML patients showed no difference
platelet recovery when compared with marrow, with no significant in regimen-related mortality, survival, or relapse between 140 patients
difference in acute or chronic GVHD and an OS advantage. Although who received imatinib versus 200 historical controls. Curiously, in a
there was a trend toward improved survival in CML patients with the few studies, the incidence of chronic GVHD has been significantly
use of peripheral blood, it should be noted that these studies were lower in patients receiving imatinib before transplant. However, an
not prospectively designed to address the role of peripheral blood analysis from the CIBMTR of CML patients undergoing allogeneic
versus marrow for individual disease states. Furthermore, the results transplantation showed that the cumulative incidence rates of acute and
of a randomized study of CP CML showed no statistically significant chronic GVHD and treatment-related mortality were not affected by
differences in outcome between the marrow and peripheral blood pre-HCT IM exposure. On multivariate analysis conventional prog-
groups, although relapse rates were lower in the peripheral blood nostic indicators remained the strongest determinants of transplant
26
group and chronic GVHD occurrence was higher compared with outcomes. The biology underlying this effect is unknown. Alloge-
patients transplanted with marrow. neic transplantation appears to be an effective treatment for T315I-
Several studies have shown that an increased interval from diag- mutated leukemias, providing acceptable survival rates with long-term
nosis to transplant is associated with a worse transplant outcome control of the malignancy without detectable residual disease in
for patients treated in CP. No single cause of failure is markedly some cases. 27

1.0

0.8
Probability of survival 0.6 No imatinib (CP, n = 183)

Imatinib (CP, n = 72)
0.4
No imatinib (AP or CP2, n = 38)
No imatinib (BC, n = 10)
Imatinib (BC, n = 13)
0.2 Imatinib (AP or CP2, n = 60)
Censor
0
0 1 2 3 4 5 6
Posttransplant (years)
Fig. 67.9 EFFECT OF PRIOR TREATMENT WITH IMATINIB ON OVERALL SURVIVAL AFTER
TRANSPLANTATION. AP, Accelerated phase; BC, blast crisis; CP, chronic phase; CP2, a return to chronic
phase after treatment for accelerated phase or blast crisis disease. (Data from Oehler VG, Gooley T, Snyder DS,
et al: The effects of imatinib mesylate treatment before allogeneic transplantation for chronic myeloid leukemia. Blood
109:1782, 2007.)