Clinical separation of cGvHD and GvL and better GvHD-free/relapse-free survival (GRFS) after unrelated cord blood transplantation for AML

Abstract

Few studies have presented a comparison of myeloablative cord blood transplantation (CBT) and HLA-identical sibling hematopoietic cell transplantation (HCT) for AML in a disease-specific analysis, and the evaluation of GvHD-free and relapse-free survival (GRFS) in AML patients after unrelated CBT has not been reported. A total of 162 consecutive AML patients receiving intensified myeloablative unrelated CBT (n = 107) or allogeneic PBSC transplantation (allo-PBSCT) or bone marrow transplantation (BMT) from an HLA-identical sibling donor (n = 55) were investigated. Neutrophil or platelet engraftment was slower in the CBT cohort compared with that in the allo-PBSCT/BMT cohort. The incidence of grade II-IV or grade III-IV acute GvHD (aGvHD) and transplant-related mortality (TRM) were not significantly different in the two cohorts. Compared with the allo-PBSCT/BMT cohort, the CBT cohort had a significantly lower rate of chronic GvHD (cGvHD) (13.7% vs 28.3%; P = 0.047) or extensive cGvHD (9.9% vs 24.1%; hazard ratio (HR) = 2.06, P = 0.039). The incidence of relapse at 5 years in the CBT cohort was significantly lower than that in the allo-PBSCT/BMT cohort (15.3% vs 36.1%; HR = 4.62, P = 0.009). The probabilities of overall survival and leukemia-free survival were similar between the two cohorts. The adjusted 5-year probability of GRFS was higher after CBT than that after allo-PBSCT/BMT (55.4% vs 39.2%; HR = 1.63, P = 0.042). The present study suggests that, for AML patients, intensified myeloablative unrelated CBT is associated with less cGvHD and a lower risk of relapse. In addition, these patients do not experience excessive TRM or severe aGvHD that translates into better GRFS compared with those patients who undergo HLA-identical sibling allo-PBSCT/BMT; this observation may reflect the clinical separation between cGvHD and GvL within our CBT protocol. INTRODUCTIONAllogeneic hematopoietic cell transplantation (allo-HCT) is a promising curative approach for treating high-risk or relapsed/ refractory AML. Unrelated cord blood transplantation (CBT) is increasingly being employed as an alternative transplant strategy for AML patients who lack a related or unrelated donor with an identical HLA type. Cord blood (CB) has some potential advantages, including the absence of donor risk, rapid accessibility and less rigorous requirement for HLA compatibility. Recently, reduced-intensity conditioning followed by CBT has been conducted for high-risk AML patients to decrease the early transplant-related mortality (TRM), 1,2 but the incidence of relapse was high (nearly 50%), and the long-term survival was very poor. New strategies should be further investigated to improve the antileukemic effect after CBT. We have reported that myeloablative CBT can result in improved survival and decreased relapse rates in adult or pediatric recipients with hematologic malignancies 3,4 compared with transplants from HLA-matched sibling donors (MSD); however, few studies have presented a comparative analysis of myeloablative CBT and allo-HCT fro...

Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study

“…Despite the possible GVL effect, cGVHD was reported to have an adverse effect on NRM41 and was the main cause of poor quality of life after transplantation 42. However, low probability of cGVHD has always been one of the advantages of CB,43 and many studies reported that the relapse rate in CBT was similar to or lower than in other kinds of HCT,44, 45, 46 which reflected the clinical separation of cGVHD and the GVL effect in CB. Furthermore, our previous study showed that long‐term survivors with CBT had less cGVHD and higher quality of life compared to HCT in HLA‐identical sibling's donors 47.…”

Graft‐Versus‐Tumor Effect in Major Histocompatibility Complex–Mismatched Mouse Liver Transplantation

“…Both HLA‐mismatched HSCT and DLI have a stronger antitumor effect than HLA‐matched HSCT, but they may also bring a greater risk of GVHD, one of the fatal complications after HSCT . Therefore, efforts have been made over the last 2 decades to explore the difference between the mechanism of GVT and GVHD and to design strategies to separate GVT from GVHD . One important difference is that the threshold number of T cells triggering GVT is relatively lower.…”

“…(31)(32)(33)(34) Therefore, efforts have been made over the last 2 decades to explore the difference between the mechanism of GVT and GVHD and to design strategies to separate GVT from GVHD. (35,36) One important difference is that the threshold number of T cells triggering GVT is relatively lower. This assumption is supported by clinical experience that low-dose DLI is generally sufficient to reduce the risk of relapse of the tumor without GVHD.…”

Reduced-Toxicity Myeloablative Conditioning Consisting of Fludarabine/Busulfan/Low-Dose Total Body Irradiation/Granulocyte Colony-Stimulating Factor–Combined Cytarabine in Single Cord Blood Transplantation for Elderly Patients with Nonremission Myeloid Malignancies

“…Those data clearly indicate that in patients with a similar bulk of disease at transplant, CBT would reduce relapse incidence and be preferable to other hematopoietic cell sources. More recently, an encouraging report from China showed that the relapse incidence was significantly lower after CBT than for BMT/PBSCT from matched sibling donors for AML [50], suggesting again that the GVL effects after CBT might be stronger than those after matched related BMT/PBSCT. Our study showed the relapse incidence at 2 years after CBT was 26% even in patients with nonremission myeloid malignancies, which was better than previous reports of allogeneic BMT/PBSCT for nonremission patients [41,51].…”