Haploidentical‐ versus identical‐sibling transplant for high‐risk pediatric AML: A multi‐center study

Abstract

Background Human leukocyte antigen‐identical sibling donor (ISD)‐hematopoietic stem cell transplantation (SCT) is a potentially curative treatment for high‐risk pediatric acute myeloid leukemia (AML). A haploidentical donor (HID) is readily available to almost all children. Previous studies have demonstrated that patients with HID‐SCT had similar outcomes compared to ISD‐SCT for pediatric and adult AML. However, the role of HID‐SCT in high‐risk pediatric AML is unclear. Methods To compare the overall survival of high‐risk AML children who underwent either HID‐SCT or ISD‐SCT, we analyzed 179 cases of high‐risk AML patients under 18 years of age treated with either ISD‐SCT (n = 23) or HID‐SCT (n = 156). Granulocyte colony‐stimulating factor plus anti‐thymocyte globulin‐based regimens were used for HID‐SCT. We also analyzed the subgroup data of AML patients at first complete remission (CR1) before SCT with known cytogenetic risk. Results The numbers of adverse cytogenetic risk recipients were 8 (34.8%) and 13 (18.8%) in the ISD‐SCT group and the HID‐SCT group, and the number of patients with disease status beyond CR1 were 6 (26.1%) and 14 (20.3%) in the two groups. The cumulative rates of grades II‐IV acute graft‐versus‐host disease (GVHD) were 13.0% in the ISD‐SCT group and 34.8% in the HID‐SCT group (P = 0.062), with a three‐year cumulative rates of chronic GVHD at 14.1% and 34.9%, respectively (P = 0.091). The relapse rate in the ISD‐SCT group was significantly higher than that in the HID‐SCT group (39.1% vs. 16.4%, P = 0.027); with non‐relapse mortality at 0.0% and 10.6% (P = 0.113), respectively. The three‐year overall survival rates were 73.0% for the ISD‐SCT group and 74.6% for the HID‐SCT group (P = 0.689). In subgroup analysis, the three‐year relapse rate in the ISD‐SCT group was higher than that in the HID‐SCT group (50.0% vs. 9.2%, P = 0.001) and the three‐year DFS in the ISD‐SCT group (50.0%) was lower than that in the HID‐SCT group (81.2%) (P = 0.021). Conclusions Unmanipulated HID‐SCT achieved DFS and OS outcomes comparable to those of ISD‐SCT for high‐risk pediatric AML patients with potentially higher rate but manageable GVHD.

Allogeneic hematopoietic stem cell transplant in pediatric acute myeloid leukemia: Lessons learnt from a tertiary care center in India

“…The incidence of both acute and chronic GVHD (7% and 9%, respectively) in our cohort of patients was lower than contemporary trials (12%‐14%) 29,30 . This may be due to the longer duration of administration of cyclosporine in our patients (9‐12 months) as against the more accepted duration of 6 months; this has been shown to reduce GVHD 31,32 .…”

“…28 The incidence of both acute and chronic GVHD (7% and 9%, respectively) in our cohort of patients was lower than contemporary trials (12%-14%). 29,30 This may be due to the longer duration of administration of cyclosporine in our patients (9-12 months) as against the more accepted duration of 6 months; this has been shown to reduce GVHD. 31,32 Though we speculate that a longer duration of cyclosporine administration may have possibly increased the risk of AML relapse, there is evidence to the contrary that a longer duration of cyclosporine significantly reduces the incidence of chronic GVHD, without affecting the risk of relapse.…”

Immunomodulatory Effects of Bendamustine in Hematopoietic Cell Transplantation

“…This is especially challenging for minority patients [ 59 , 60 , 61 ]. As such, more and more institutions have begun implementing haploidentical (haplo) HCT [ 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ]. This both increases donor availability and decreases delays involved in finding and collecting stem cells from an unrelated donor.…”

Allogeneic Hematopoietic Stem Cell Transplantation Mobilized With Pegylated Granulocyte Colony-Stimulating Factor Ameliorates Severe Acute Graft-Versus-Host Disease Through Enrichment of Monocytic Myeloid-Derived Suppressor Cells in the Graft: A Real World Experience

“…GVHD remains one of the major causes of morbidity and mortality in allograft recipients. Recent progress (33)(34)(35) in mismatched HSCT has changed the algorithm of donor selection in many transplantation centers. Consequently, haploidentical (haplo)-HSCT has also been increasingly used at our center.…”