Page 1106 - Hematology_ Basic Principles and Practice ( PDFDrive )

976 Part VII Hematologic Malignancies

Contemporary Results of Transplantation for authors did not compare outcomes to a cohort of patients treated
with supportive care alone.
Myelodysplastic Syndrome
Clinical Results in Reduced-Intensity
Recent analyses of the CIBMTR have suggested improving outcomes
for MDS transplantation. An analysis of 701 adult subjects that Conditioning Transplantation
received a transplant between 2002 and 2006 demonstrated nearly
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50% OS when a matched sibling donor was used. While these Previously HSCT was available to only a minority of patients with
results were not statistically different when compared with 8/8 HLA- MDS, because 75% of patients are older than 60 years at diagnosis
matched unrelated donors, the 3-year OS in this group was 38%. and are not candidates for MAC regimens. Because older patients
Using a less well matched unrelated donor, however, was associated have a poorer prognosis than their younger counterparts, there is
with poorer long term survival. a great impetus to develop strategies for older individuals. Within
It is becoming increasingly evident that allogeneic transplantation the RIC literature, there is great variability in the reported condi-
offers a survival advantage over conventional therapies in MDS. One tioning intensity; however, the commonality of these regimens is
prospective trial that assigned subjects in a donor vs. no donor analysis that they can be safely offered to patients previously deemed too
demonstrated a survival advantage in the donor arm over those old or to have too much comorbidity for high-dose therapy. It
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without a donor. Importantly, in this analysis, there did not appear appears that late relapses after MAC HSCT are not common, but
to be a decrement in early survival in the donor arm, suggesting that high-intensity regimens are associated with higher treatment-related
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early transplant-related mortality after transplantation is comparable mortality. This further justified the shift towards reduced intensity
to mortality associated with nontransplant therapies in a high-risk conditioning.
subject cohort. To confirm these findings, two additional large pro- The City of Hope group reported on their outcomes using a RIC
spective biologic assignment trials have been initiated in Europe and regimen of fludarabine and melphalan in 43 patients with MDS or
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North America. AML. OS was 53% at 2 years, with a 16% relapse rate. Treating
over 90 patients with AML (n = 74) or AML (n = 22) using a targeted
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busulfan and fludarabine regimen, de Lima et al reported 1-year
Clinical Results in Myeloablative Transplantation treatment-related mortality of only 3%, without a compromise in
antitumor activity. Using the more commonly applied RIC regimen
There are few reports of transplantation uniquely for patients with of fludarabine with busulfan, albeit with different intensities (and
the myelodysplastic disorders, because most reports include both including some patients with AML), other groups have demonstrated
patients with AML and those with MDS. Those few analyses that do similar outcomes, with treatment-related mortality of 13–27%,
exist unfortunately often present biased results, because there is inher- relapse rates of 23–32%, disease-free survival of 38–68%, and OS of
ent patient selection in the reported studies. The bias in these analyses, 39–79%. 82–85
although recognized by physicians and patients alike, is often over-
looked, because patients who choose early HSCT often identify with
those included in the analysis to justify their decision. Comparative Results: Myeloablative and Reduced-
One of the largest reports of MAC HSCT for MDS is from the Intensity Regimens in Myelodysplastic Syndrome
Seattle group. Using a targeted busulfan strategy in patients undergo-
ing related or unrelated donor HSCT, results were stratified by pre- Several analyses have compared RIC with conventional MAC trans-
transplant International Prognostic Scoring System (IPSS; see plantation, and the majority of them suggest similar outcomes. The
Chapter 60) risk score. 75,76 Patients were prospectively enrolled in the premise behind all of these comparisons is that RIC should be associ-
targeted busulfan treatment program; however, the decision to ated with a reduction in early treatment-related mortality, whereas
undergo transplantation was based upon physician and patient MAC approaches should be associated with a reduction in disease
preference. Results in this study were correlated with IPSS stage, relapse. The net effect of these two opposing risks is no difference in
suggesting that outcomes were improved with HSCT at an earlier outcomes. For example, at the Dana-Farber Cancer Institute, the
disease stage. This would be expected because patients with earlier- outcomes of 136 patients with advanced MDS or acute myelogenous
stage disease have received less treatment (thus less comorbidity) and leukemia who underwent transplantation were compared when strati-
1
may also have more indolent disease biology. Among the patients in fied by conditioning regimen intensity. OS at 2 years was the same
the lowest IPSS score group there were no relapses, whereas the following RIC as for MAC transplantation (28% versus 34%,
relapse rate was 42% for patients in the highest IPSS category. As a p = .89); however, the causes of treatment failure were significantly
consequence, 3-year survival was 80% in the lowest IPSS risk group different, with more relapse in the RIC group (61% versus 38%,
but was under 30% for patients in the high IPSS category. Mutation p = .02), but higher treatment-related mortality in the MAC group
analysis will need to be incorporated into prognostic systems as we (32% versus 15% at 100 days) as anticipated. Overall treatment-
go forward. related mortality, however, was no different (p = .28). In this report,
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Similarly, de Witte et al examined outcomes of HSCT for patients were treated according to patient and physician preference,
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patients with earlier-stage MDS (refractory anemia or refractory whereas in a similar single-center analysis reported by Martino et al,
+
anemia and ringed sideroblasts). This analysis studied 374 patients patients were prospectively assigned to RIC or CD34 selected MAC
who underwent HSCT from either matched, sibling, or unrelated transplantation based on patient age. In this analysis, nonrelapse
donors. Both standard MAC and RIC regimens were used. IPSS score mortality and OS were no different between groups.
could be calculated in fewer than half of the patients, and HSCTs Similar to single-center studies, large retrospective database studies
were performed over a decade-long period, such that inherent differ- comparing RIC and high-intensity HSCT have been performed. A
ences in transplantation technology resulted in improved overall CIBMTR review of the outcomes of 550 patients 50 years of age or
survival over time. Although factors such as conditioning intensity, older who underwent matched sibling donor HSCT showed no
stem cell source, and donor status did not affect outcome, recipient difference in MAC and RIC outcomes. In an even larger CIBMTR
age and duration of identified MDS diagnosis were important predic- analysis that included both patients with MDS and those with AML,
tors of overall survival. Earlier transplantation was associated with an patients were stratified into MAC, RIC, and truly NMA subgroups.
absolute increase in overall survival of 10% at 4 years (57% versus Although results for MDS alone are not available, overall outcomes
47%, p = .02) and was associated with improved relapse-free survival indicated less-favorable long-term results for NMA regimens when
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in multivariable analysis. Despite the finding of improved outcome compared with higher-intensity regimens. In an analysis by the
with earlier HSCT, this should not be interpreted as a recommenda- European Group for Blood and Marrow Transplantation (EBMT) of
tion for early HSCT in individuals with low-risk MDS, because the over 800 patients with MDS, the 3-year relapse rate was significantly