Molecular monitoring of cerebrospinal fluid can predict clinical relapse in acute lymphoblastic leukemia with eosinophilia.
In a patient with precursor B-cell acute lymphoblastic leukemia (ALL) associated with eosinophilia that completely responded to induction chemotherapy, we assayed serial remission cerebrospinal fluid and bone marrow specimens for minimal residual disease using a quantitative polymerase chain reaction assay to assess for clone-specific immunoglobulin heavy-chain gene cluster (IGH) gene rearrangement. Cerebrospinal fluid eosinophilia and minimal residual disease were detected on day 406, preceding the morphologic diagnosis of central nervous system relapse on day 578. By day 841, the bone marrow had 35% blasts. Despite aggressive therapy, including unrelated umbilical cord blood transplantation, the patient developed testicular and bone marrow relapses and died of disease. We conclude that increasing levels of minimal residual disease in cerebrospinal fluid can predict recurrence of ALL prior to clinical and morphologic relapse. Furthermore, we demonstrate a novel translocation in this tumor, the t(5;9)(q31;p24), that possibly led to fusion of the interleukin-3 (IL3) (5q31) and JAK2 (9p24) genes and may explain the concomitant appearance of eosinophilia and ALL.
Nuñez
Cesar A
CA
Department of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Zipf
Theodore F
TF
Roberts
W Mark
WM
Medeiros
L Jeffrey
LJ
Hayes
Kimberly
K
Bueso-Ramos
Carlos E
CE
D002555:Cerebrospinal Fluid / Q000276:immunology*; D002648:Child; D004802:Eosinophilia / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000235:genetics; D017809:Fatal Outcome; D020869:Gene Expression Profiling / Q000379:methods*; D005803:Genes, Immunoglobulin / Q000235:genetics; D006801:Humans; D015448:Leukemia, B-Cell / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000235:genetics; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics; D018365:Neoplasm, Residual / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000235:genetics; D011237:Predictive Value of Tests