Atypical Chronic Myeloid Leukemia in Two Pediatric Patients.
Atypical chronic myeloid leukemia, BCR-ABL1-negative, (aCML) is a rare myeloid neoplasm. Recent adult data suggest the leukemic cells in a subset of patients are dependent on JAK/STAT signaling and harbor CSF3R-activating mutations. We hypothesized that, similar to adult patients, the presence of CSF3R-activating mutations would be clinically relevant in pediatric myeloid neoplasms as patients would be sensitive to the JAK inhibitor, ruxolitinib. We report two cases of morphologically similar pediatric aCML, BCR-ABL1-negative based on WHO 2008 criteria. One patient had CSF3R-activating mutation (T618I) and demonstrated a robust response to ruxolitinib, which was used to bridge to a successful stem cell transplant. The other patient did not have a CSF3R-activating mutation and succumbed to refractory disease <6 months from diagnosis. This report documents CSF3R-T618I in pediatric aCML and demonstrates the efficacy of ruxolitinib in a pediatric malignancy. As the third documented case successfully treating aCML with ruxolitinib, this case highlights the importance of prompt CSF3R sequencing analysis for myeloproliferative and myelodysplastic/myeloproliferative neoplasms.
Department of Pediatrics, Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Jason L
JL
Freedman
Department of Pediatrics, Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Ami V
AV
Desai
Department of Pediatrics, Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
L Charles
LC
Bailey
Department of Pediatrics, Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Richard
R
Aplenc
HematoLogics, Inc., Seattle, Washington.
Bettina
B
Burnworth
HematoLogics, Inc., Seattle, Washington.
Barbara K
BK
Zehentner
Department of Pediatrics, Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
David T
DT
Teachey
Department of Pathology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Gerald
G
Wertheim
D000293:Adolescent; D002648:Child; D005260:Female; D006801:Humans; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000188:drug therapy* / Q000235:genetics*; D009154:Mutation; D009570:Nitriles; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines; D016184:Receptors, Colony-Stimulating Factor / Q000235:genetics*
C517047:CSF3R protein, human; D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; D016184:Receptors, Colony-Stimulating Factor; C540383:ruxolitinib
BCR-ABL1 negative; atypical CML; leukemia; myeloid; pediatrics