Department of Pediatrics, West China Second University Hospital, Sichuan University.
Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, Sichuan, China.
Medicine (Baltimore). 2020 Dec 11;99(50):e23606. doi: 10.1097/MD.0000000000023606.
Juvenile myelomonocytic leukemia (JMML) is a rare myeloproliferative neoplasm of early childhood characterized by excessive proliferation of myelomonocytic cells and an aggressive clinical course. Allogenic hematopoietic stem cell transplantation (HSCT) is a firmly established treatment, but patients without fully matched donors have poor prognoses. Disease recurrence is the main cause of treatment failure. Meanwhile, most cases with splenomegaly present with platelet transfusion refractoriness, but splenectomy remains controversial. DNA hypermethylation correlates with poor prognosis in JMML; however, hypomethylating therapy alone does not eradicate leukemic clones. Thus, a suitable treatment with a good success rate remains elusive.
Here, we report our experience with a patient who suffered from recurrent fever, pallor, abdominal distention, leukocytosis, and thrombocytopenia with a silent past history and family history of somatic KRAS mutation. The patient was treated with decitabine as a bridging therapy before haploidentical HSCT. Decitabine was also used prophylactically after transplantation.
We arrived at a JMML diagnosis after observing leukocytosis, less than 20% blast cells in the peripheral blood and bone marrow, increased monocyte counts, negativity for the BCR-ABL fusion gene, positivity for somatic KRAS mutation, and massive splenomegaly.
The patient accepted splenectomy before HSCT, and haploidentical HSCT was applied after treatment with a DNA-hypomethylating agent. The hypomethylating agent was administered for 1 year after HSCT to prevent disease recurrence.
The patient presented with complete remission of the disease and mild graft versus host disease for 26 months after treatment with decitabine and HSCT.
Combining haploidentical HSCT and DNA-hypomethylating agents may improve the prognosis of JMML. Meanwhile, splenectomy could be an effective option in cases with massive splenomegaly and platelet transfusion refractoriness.
幼年型粒单核细胞白血病（JMML）是一种罕见的儿童期骨髓增生性肿瘤，其特征为髓单核细胞过度增殖和侵袭性临床病程。同种异体造血干细胞移植（HSCT）是一种既定的治疗方法，但没有完全匹配供体的患者预后较差。疾病复发是治疗失败的主要原因。同时，大多数伴有脾肿大的病例存在血小板输注抵抗，但脾切除术仍存在争议。JMML 中 DNA 高甲基化与不良预后相关；然而，单独使用去甲基化治疗并不能消除白血病克隆。因此，一种成功率高的合适治疗方法仍然难以捉摸。
在这里，我们报告了一例患有复发性发热、苍白、腹胀、白细胞增多和血小板减少的患者的经验，该患者过去有沉默的病史和体细胞 KRAS 突变的家族史。在半相合 HSCT 之前，该患者接受地西他滨作为桥接治疗。移植后也预防性使用地西他滨。
我们观察到白细胞增多、外周血和骨髓中少于 20%的原始细胞、单核细胞计数增加、BCR-ABL 融合基因阴性、体细胞 KRAS 突变阳性和巨大脾肿大，诊断为 JMML。
该患者在 HSCT 前接受了脾切除术，在接受 DNA 去甲基化剂治疗后进行了半相合 HSCT。HSCT 后用去甲基化剂治疗 1 年，以预防疾病复发。
该患者在接受地西他滨和 HSCT 治疗后 26 个月疾病完全缓解，出现轻度移植物抗宿主病。
联合半相合 HSCT 和 DNA 去甲基化剂可能改善 JMML 的预后。同时，对于伴有巨大脾肿大和血小板输注抵抗的病例，脾切除术可能是一种有效选择。
