Clinical Outcome of Unrelated Cord Blood Engraftment for Children with Juvenile Myelomonocytic Leukemia

Objective: To evaluate the clinical efficacy and safety of unrelated cord blood engraftment in the treatment of Juvenile Myelomonocytic Leukemia.

Method: Seventy-three JMML children received cord blood transplantation since 2018. 47 children with cord blood engrafment were analyzed retrospectively. The median at diagnosis age was 35 months (12 to 99). Of them, 8 patients with NF-1 mutation, 24 with PTPN11 mutation, 2 with Nras somatic mutation, 4 with Kras somatic mutation, 8 with multiple mutation.

The transplantation regimen was divided into two groups: Complementary transplantation group (CT-group) i.e. 55 patients underwent unrelated cord blood(UCB) following haploidentical stem cells transplantation(see blood 2016 128:1235 and blood 2019 134: 4181).UCB-cells engrafted finally in 31 patients,(others with haplo-engrafted).Conditioning regimen composed of Cyclophosphamide (Cy), Busulfan (Bu), Thiotepa (TT) and Fludarabine (Flu).

Haploid PBSC (MNC >15×10⁸/kg) was infused on day 0. GVHD prophylaxis consisted of PTCy on day+3 to +4,and FK506 and Mycophenolate Mofetil (MMF). Unrelated cord blood was infused on day+6.

The next group was haploid DLI Bridging unrelated cord blood transplantation group (LCB-group) . Conditioning regimen composed of Cla+Ara-C for 4 days, and the haploid donor DLI was infused on day-11 (the number of infusion donor Lymphocyte was 4-8 ×10⁸/kg) ,Cy, FLU, BU and TT started on day-8~-3. Unrelated cord blood was infused on day 0.GVHD prophylaxis consisted of FK506 and Mycophenolate Mofetil (MMF).

Unrelated cord blood matching requires ≥7/10 HLA locus , and Kir assay was carried out at the same time. Cord blood with Haplotype Cen-Bx was preferred.

Results: The median follow-up time was 32 months(2 to 52ms).47 patients were engrafted with cord blood in the two groups totally. In the CT group,Haplo-cells and UCB-cells engrafted finally in 24 and 31 patients, respectively.In the LCB group, only 1 of 17 cases developed primary graft failure,who achieved disease-free survival after the second haploid transplantation. Of the 47 patients with cord blood engraftment in the two groups, the median number of infusion TNC and CD34+ from cord blood were 8.1(3.3~17)×10⁷/kg and 0.25(0.08~4.0)×10⁶/kg, respectively. The median times to neutrophil more than 0.5×10⁹/L and platelet more than 20×10⁹/L were 38 (19-67) days and 36(12-67) days post-HSCT, respectively. The Overall survival (OS) and leukemia free survival (LFS) were 97.9% and 95.8%, respectively. There were no significant difference in the OS and LFS between CT group and LCB group (p=0.18 and p=0.50, respectively). The cumulative incidences of grades Ⅱ-Ⅳ° aGVHD was 29.8% (14pts).There were 4 patients with grade III° and Ⅳ° aGVHD ，all of whom were effectively improved. Chronic GVHD occurred in 13 patients who mainly had mild skin involvement. Only one of them had mild BO. The transplantation-related mortality was 2.1% (1 case died of severe pre-engraftment syndrome in LCB group). The transient reactivation of virus was mainly caused by HHV-6. One case developed HHV-6 virus encephalitis.And no VOD occurred.

Summary: UnrelatedCord blood engraftment has significant clinical efficacy in the treatment of JMML,and it is relatively safe and reliable.UnrelatedCord blood could be used as a priority donor for such children.

No relevant conflicts of interest to declare.