No Benefit/Detriment of New Donor in Second Hematopoietic Stem Cell Transplantation for Leukemia Relapse
Minimal data are available on outcomes of second allogeneic hematopoietic stem cell transplantation from unrelated donors after first hematopoietic stem cell transplantation in patients with hematologic relapse of acute leukemia. In a study reported in Journal of Clinical Oncology, Maximilian Christopeit, MD, and colleagues in the German Registry for Stem-Cell Transplantation and the Cooperative German Transplant Group evaluated the role of second hematopoietic stem cell transplantation for relapsed acute leukemia after related or unrelated first hematopoietic stem cell transplantation. The investigators analyzed the effect of donor change on stem cell transplantation outcome in both settings. They found that second stem cell transplantation produced 2-year overall survival of 25% among all patients and that donor change had neither a beneficial nor detrimental effect on overall survival.
Study Details
The study involved 179 consecutive patients receiving second hematopoietic stem cell transplantation for acute leukemia relapse after allogeneic first stem cell transplantation in Germany between 1998 and 2009. Median age at second stem cell transplantation was 39 years (range 16–68 years). Patients had acute myeloid leukemia (n = 132), acute lymphoblastic leukemia (n = 46), or unclassified leukemia (n = 1).
Donors at first stem cell transplantation consisted of 75 matched related donors and 104 unrelated donors. At second stem cell transplantation, 133 patients (74%) had unrelated donors. After related first stem cell transplantation, second stem cell transplantation was performed from the same matched related donor in 51% of patients, a different matched related donor in 11%, and an unrelated donor in 39%. After unrelated first stem cell transplantation, 42% received second stem cell transplantation from the same unrelated donor and 58% from a different unrelated donor.
Patient demographic and clinical characteristics were well balanced among patients receiving first hematopoietic stem cell transplantation from a matched related donor vs an unrelated donor. However, patients with unrelated first transplantation received less total-body irradiation (P = .013), more in vivo T-cell depletion (P < .001), and more peripheral blood stem cell grafts (P = .007). At second hematopoietic stem cell transplantation, patients with related first stem cell transplantation had more cyclosporine-based immunosuppression (P = .037) and less in vivo T-cell depletion (P = .02). Overall, 78% of patients received chemotherapy and 21% received donor lymphocyte infusions for initial disease control after relapse. Twenty-six percent of patients received second hematopoietic stem cell transplantation in complete remission.
Outcomes of Second Hematopoietic Stem Cell Transplantation
Independent of donor, 74% of patients achieved complete remission after second hematopoietic stem cell transplantation, with half of these patients experiencing another relapse. Overall survival and leukemia-free survival rates after second hematopoietic stem cell transplantation were 31% and 26% at 1 year and 25% and 21% at 2 years. Two-year overall survival was 39% after related second stem cell transplantation and 19% after unrelated second stem cell transplantation. Long-term survivors were observed even after two unrelated transplantations. Longer remissions after second stem cell transplantation than after first stem cell transplantation were observed in 26% of patients. No significant differences in overall survival or leukemia-free survival were observed between patients with acute lymphoblastic leukemia and those with acute myeloid leukemia.
Overall survival from second hematopoietic stem cell transplantation was greater in patients with related vs unrelated first transplantation (2-year overall survival 37% vs 16%, hazard ratio [HR] = 1.53, P = .016). Independent of donor at first stem cell transplantation, overall survival was longer after related vs unrelated second stem cell transplantation (2-year overall survival 39.5% vs19%, HR = 1.56, P = .03). On univariate analysis, donor change (identical vs alternative donor) improved overall survival slightly from second hematopoietic stem cell transplantation, but the results were not significant (HR = 0.76, P = .114). There was no significant effect of donor change on overall survival on multivariate analysis (HR = 0.984, P = .933).
Outcomes by Related and Unrelated First Hematopoietic Stem Cell Transplantation
Among patients receiving first hematopoietic stem cell transplantation from a matched related donor, 2-year overall survival and leukemia-free survival rates after second stem cell transplantation were 37% and 31%, respectively. Donor change was not associated with better outcome (HR = 0.80, P = .449), although among patients receiving second stem cell transplantation from a different matched related donor (n = 8), estimated 2-year overall survival was 88% (HR = 4.17, P = .048). No difference was found between overall survival after second stem cell transplantation from the same matched related donor and overall survival after second transplantation from a new unrelated donor (2-year overall survival 34% vs 28%, HR = 1.02, P = .891). On multivariate analysis, donor change was not associated with overall survival (HR = 0.81, P = .512)
Among patients receiving first hematopoietic stem cell transplantation from an unrelated donor, 2-year overall survival and leukemia-free survival rates after second hematopoietic stem cell transplantation were 16% and 13%, respectively. On univariate analysis, change of donor at second stem cell transplantation was associated with superior overall survival (estimated 2-year overall survival 11% for identical unrelated donor vs 20% for different unrelated donor, HR = 0.63, P = .037). This advantage was limited to patients without acute graft vs host disease greater than grade 2 and chronic graft-vs-host disease. On multivariate analysis, however, change to another unrelated donor was not significantly associated with overall survival (HR = 1.34, P = .245).
Multivariate analysis for overall survival from second stem cell transplantation confirmed the significant effect of established risk factors, including remission duration after first transplantation (HR = 2.37, P < .001) and stage at second transplantation (HR = 0.53, P = .006).
The investigators concluded: “After relapse from allogeneic [first hematopoietic stem cell transplantation], [second hematopoietic stem cell transplantation] can induce 2-year [overall survival] in approximately 25% of patients. Unrelated [second stem cell transplantation] is feasible after related and unrelated [first stem cell transplantation]. Donor change for [second hematopoietic stem cell transplantation] is a valid option. However, a clear advantage in terms of [overall survival] could not be demonstrated.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
