Molecular assessment of pretransplant chemotherapy in the treatment of juvenile myelomonocytic leukemia

Pediatr Blood Cancer. 2019 Nov;66(11):e27948. doi: 10.1002/pbc.27948. Epub 2019 Jul 26.


Background: 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.

Procedure: 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.

Results: 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.

Conclusions: 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.

Keywords: JMML; chemotherapy; molecular response; outcome; stem cell transplantation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • DNA, Neoplasm / blood
  • Drug Evaluation
  • Drug Monitoring
  • Female
  • Follow-Up Studies
  • Genes, Neoplasm*
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / therapy
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Infant
  • Leukemia, Myelomonocytic, Juvenile / blood
  • Leukemia, Myelomonocytic, Juvenile / drug therapy*
  • Leukemia, Myelomonocytic, Juvenile / genetics
  • Leukemia, Myelomonocytic, Juvenile / therapy
  • Male
  • Neoadjuvant Therapy*
  • Neoplasm Proteins / genetics
  • Progression-Free Survival
  • Recurrence
  • Retrospective Studies
  • Sequence Analysis, DNA*
  • Splenectomy
  • Transplantation Conditioning
  • Tumor Burden / drug effects*


  • Antimetabolites, Antineoplastic
  • DNA, Neoplasm
  • Neoplasm Proteins