Comparison of Allogeneic Stem Cell Transplantation from Familial-Mismatched/Haploidentical Donors and from Unrelated Donors in Adults with High-Risk Acute Myelogenous Leukemia

Abstract

To weigh the pros and cons of familial-mismatched/haploidentical transplantation (FMT) in patients with high-risk acute myelogenous leukemia, we assessed outcomes of 23 patients who underwent FMT, using reduced-intensity conditioning with total body irradiation 800 cGy/busulfan/fludarabine/antithymocyte globulin without ex vivo T cell depletion, compared to 33 patients who underwent well-matched unrelated donor transplantation (WM-UDT) and 13 who underwent partially matched unrelated donor transplantation (PM-UDT) during the same period. The FMT patients had not only a similar pattern of engraftment and immune reconstitution as the WM-UDT and PM-UDT patients but also comparable incidences and severity of acute and chronic graft-versus-host disease. The FMT patients did not experience any form of engraftment failure. However, the cumulative incidence of cytomegalovirus DNAemia was significantly higher in the FMT group compared with the other groups (P = .036). After a median follow-up of 28 months, overall survival, disease-free survival, relapse, and nonrelapse mortality were 83%, 74%, 20%, and 7%, respectively, for WM-UDT; 51%, 51%, 31%, and 18% for PM-UDT; and 66%, 64%, 26%, and 10% for FMT. This demonstrates a trend for favorable survival outcomes of WM-UDT over FMT and of FMT over PM-UDT. However, we found no significant statistical differences in survival according to donor type. These data need to be interpreted cautiously because of limited power calculations due to the small number of each donor group. This pilot study suggests the feasibility of FMT using our novel regimen with careful evaluation of CMV DNAemia compared with WM-UDT and PM-UDT. Further trials with larger numbers of patients, comparing FMT directly with transplantation with other donor types, are needed.

Long-term clinical outcomes of hematopoietic cell transplantation for intermediate-to-poor-risk acute myeloid leukemia during first remission according to available donor types

“…These data suggest that frontline FMMT can be a feasible choice when MSD is unavailable prior to an URD search. In several previous studies, FMMT was compared retrospectively to chemotherapy alone, as well as WM-URD and PM-URD transplantation [19, 32–34], all of which indicated that frontline FMMT might be a good alternative choice for intermediate- to poor-risk AML. However, the limitations of a retrospective design, short follow-up duration, and different treatment modalities using post-HCT cyclophosphamide made this conclusion uncertain.…”

“…For FMMT, we applied a novel conditioning regimen consisting of intermediate-dose TBI (800 cGy), fludarabine, busulfan, and low-dose ATG, along with a CD34+ stem-cell dose of at least 5.0 × 10 6 cells/kg, which, as reported previously, showed a prompt and sustained engraftment with no graft failure [19, 35, 36]. This regimen was used in 80 patients comprising all risk karyotypes and showed a low NRM (12.2%) rate and good OS when patients were in CR1 before HCT [35].…”

“…Anti-thymocyte globulin (ATG) at a dose of 2.5 mg/kg (1.25 mg/kg on D-3 and D-2) was administered for patients receiving stem cells from PM-URD. For FMMT, we administered fludarabine (150 mg/m 2 ) and busulfan (6.4 mg/kg) with 800 cGy of TBI and ATG at a dose of 5 mg/kg (1.25 mg/kg on D-4 to D-1), all of which were described previously [19, 35]. We initially recommended BM for the stem cell source, and many of the MSD agreed, but many URD preferred PB.…”

“…When searching for HCT donors, if a MSD is not available, a WM-URD is another standard choice since the survival outcomes are comparable due to the development of immunosuppressive agents [17, 18]. When neither standard HCT donors are available, alternative donor types, such as a partially-matched unrelated donor (PM-URD) or a familial mismatched/haploidentical transplantation (FMMT), are now being considered [19]. …”

“…We have previously analyzed the clinical outcomes of FMMT compared to WM-URD and PM-URD in a pilot study with a small number of patients and a short follow-up duration [19]. In the current study, we analyzed the long-term HCT outcomes of several donor types, including AUTO-HCT, MSD, WM-URD, PM-URD and FMMT, in intermediate- to poor-risk AML patients in CR1.…”