Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco, California.
Department of Laboratory Medicine, University of California, San Francisco, California.
Pediatr Blood Cancer. 2019 Nov;66(11):e27948. doi: 10.1002/pbc.27948. Epub 2019 Jul 26.
Despite the intensity of hematopoietic stem cell transplantation (HCT), relapse remains the most common cause of death in juvenile myelomonocytic leukemia (JMML). In contrast to other leukemias where therapy is used to reduce leukemic burden prior to transplant, many patients with JMML proceed directly to HCT with active disease. The objective of this study was to elucidate whether pre-HCT therapy has an effect on the molecular burden of disease and how this affects outcome post-HCT.
Twenty-one patients with JMML who received pre-HCT therapy and were transplanted at UCSF were analyzed in this study. The mutant allele frequency of the driver mutation was assessed before and after pre-HCT therapy, using custom amplicon next-generation sequencing.
Of the 21 patients, seven patients (33%) responded to therapy with a significant reduction in their mutant allele frequency and were classified as molecular responders. Six of these patients received moderate-intensity chemotherapy, one patient received only azacitidine. The 5-year progression-free survival after HCT of molecular responders was 100% versus 61% for nonresponders (P = .12). Survival of molecular nonresponders was not improved by use of high-intensity conditioning, but patients were salvaged if they experienced severe graft versus host disease. There were no baseline clinical characteristics that were associated with response to pre-HCT therapy.
Despite the myelodysplastic nature of JMML, patients treated with pre-HCT therapy can achieve molecular remissions. These patients experienced a trend toward improved outcomes post-HCT. Importantly, molecular testing can be helpful to distinguish between responders and nonresponders and should become an integral part of clinical care.
尽管造血干细胞移植（HCT）的强度很大，但复发仍然是幼年骨髓单核细胞白血病（JMML）患者死亡的最常见原因。与其他在移植前使用治疗方法来降低白血病负担的白血病不同，许多 JMML 患者在疾病活跃期直接进行 HCT。本研究的目的是阐明 HCT 前的治疗是否会影响疾病的分子负担，以及这如何影响 HCT 后的结果。
本研究分析了在 UCSF 接受 HCT 前治疗的 21 例 JMML 患者。使用定制的扩增子下一代测序，在 HCT 前治疗前后评估驱动突变的突变等位基因频率。
在 21 例患者中，有 7 例（33%）对治疗有反应，其突变等位基因频率显著降低，被归类为分子反应者。这 6 例患者接受了中度强度的化疗，1 例患者仅接受了阿扎胞苷治疗。HCT 后，分子反应者的 5 年无进展生存率为 100%，而非反应者为 61%（P=0.12）。虽然使用高强度预处理并不能改善分子非反应者的生存，但如果患者发生严重的移植物抗宿主病，则可以进行挽救治疗。没有与 HCT 前治疗反应相关的基线临床特征。
尽管 JMML 具有骨髓增生异常的性质，但接受 HCT 前治疗的患者可以达到分子缓解。这些患者在 HCT 后有改善结果的趋势。重要的是，分子检测有助于区分反应者和非反应者，应成为临床护理的一个组成部分。
