Transplantation In First Complete Remission

ALL has a relatively poor prognosis in adults with long-term survival in only 30-40% of newly diagnosed individuals.5 Traditional risk factors defining "high-risk" disease include advanced age, very elevated WBC at presentation, immunophenotype (Pro-B cell ALL), the presence of adverse cytogenetic changes (i.e., t(9:22) and t(4:11)), and a delay in the time to achieve a first remission.5 Newer prognostic factors include the presence of minimal residual disease detected by sensitive molecular techniques and gene-expression profile hierarchical clustering and expression analysis.4 As outcome in high-risk disease is significantly worse than for standard risk disease (most notably for adverse cytogenetic changes), many analyses on cohorts of high-risk patients transplanted in first remission have been performed.

Single center data on transplantation for ALL are extremely heterogeneous. One report of an experience treating 39 adults with high-risk features in first remission, with a uniform conditioning regimen of total body irradiation and etoposide, yielded a relapse rate of only 15%, with an event-free survival of 64% at 10 years.6 However, a review of 99 patients from six trials, all with Ph+ ALL transplanted in first remission using fully matched, sibling or unrelated donors demonstrated disease-free survival of 0-86%.7 Numerous other single-arm studies have reported similarly heterogeneous outcomes.8

True randomized evidence supporting the role of allo-geneic transplantation for ALL in first complete remission is lacking. An attempt to address this question has been addressed with studies of biologic assignment, where patients with histocompatible donors are assigned to allogeneic transplantation, while those patients without suitable donors are randomized to autologous transplantation or conventional chemotherapy. Table 36.1 summarizes the results from the published comparative trials. The GOELAM used a biologic assignment strategy and assigned allogeneic transplantation or consolidative chemotherapy followed by autol-ogous transplantation to 156 patients younger than 50 years, all with high-risk ALL. Transplant-related mortality was only 15% and at 6 years, disease-free survival was greater in the allogeneic transplant arm (75 vs 46%, p = 0.0027; Figure 36.1).10 The LALA group used a similar strategy and assigned allogeneic transplant to Ph+ patients with a sibling donor and compared outcomes

Table 36.1 Trials of biologic randomization in ALL, since 1990

Trial, (year of

Entry criteria and

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