Clinical Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Juvenile Myelomonocytic Leukemia: A Report from the Japan Society for Hematopoietic Cell Transplantation

Abstract

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for juvenile myelomonocytic leukemia (JMML), but few large studies of HSCT for JMML exist. Using data from the Japan Society for Hematopoietic Cell Transplantation registry, we analyzed the outcomes of 129 children with JMML who underwent HSCT between 2000 and 2011. The 5-year overall survival (OS) rate and cumulative incidence of relapse were 64% and 34%, respectively. A regimen of busulfan/fludarabine/melphalan was the most commonly used (59 patients) and provided the best outcomes; the 5-year OS rate reached 73%, and the cumulative incidences of relapse and transplantation-related mortality were 26% and 9%, respectively. In contrast, the use of the irradiation-based myeloablative regimen was the most significant risk factor for OS (hazard ratio [HR], 2.92; P = .004) in the multivariate model. In addition, chronic graft-versus-host disease (GVHD) was strongly associated with lower relapse (HR, 0.37; P = .029) and favorable survival (HR, 0.22; P = .006). The current study has shown that a significant proportion of children with JMML can be cured with HSCT, especially those receiving the busulfan/fludarabine/melphalan regimen. Based on the lower relapse and better survival observed in patients with chronic GVHD, additional treatment strategies that focus on enhancing graft-versus-leukemia effects may further improve survival.

Ruxolitinib early administration reduces acute GVHD after alternative donor hematopoietic stem cell transplantation in acute leukemia

“…However, infection remained an important factor leading to nonrelapse mortality of patients, which needed attention. In addition, univariate and multivariate survival analyses were also performed on 55 patients, the results are consistent with previous research reports 19 , 30 – 33 . This further shows that the application of ruxolitinib does not affect the survival of patients.…”

Characteristics of RAS pathway mutations in juvenile myelomonocytic leukaemia: a single‐institution study from Korea

“…The 5-year EFS, OS, and cumulative incidence of relapse (AESE) after HSCT of 51Á1 (12Á5)%, 67Á5 (12Á6)% and 35Á3 (11Á4)% respectively are similar to those reported in previous studies. 13,15,35 We emphasise that most patients in our present cohort received transplants from a haploidentical family donor due to the lack of an HLA-matched donor. However, transplant outcomes were comparable to those of previous studies in which most of the patients received an HLA-matched HSCT.…”

Current Treatment of Juvenile Myelomonocytic Leukemia

“…Busulfan-based myeloablative conditioning regimens are commonly chosen and achieve 55–73% OS with a moderate 10–15% rate of transplant-related mortality but significant probability of leukemia relapse in the order of 25–35% [ 7 , 40 , 101 , 108 , 109 , 110 , 111 , 112 ]. The EWOG-MDS currently recommends a three-alkylator regimen consisting of busulfan (0.8–1.2 mg/kg/dose given 4 doses per day, day 7 to day 4), cyclophosphamide (60 mg/kg/d, day 3 to day 2), and melphalan (125–140 mg/m 2 /d on day 1) [ 40 ].…”

“…Beside the leukemia biology factors discussed above, the way the transplant procedure is handled significantly influences the risk of relapse. It is likely that it is not so much the conditioning regimen but rather the establishment of a graft-versus-leukemia effect that is decisive for the success of allogeneic HSCT in JMML [ 101 , 109 , 110 , 111 ]. For this reason, EWOG-MDS recommends keeping immunosuppressive therapy with cyclosporine A at low levels (trough levels around 80 µg/L) and tapering early (from day +40 in the absence of grade II-IV GVHD).…”