Detection of minimal residual disease in patients with childhood common acute lymphoblastic leukemia after autologous bone marrow transplantation with ex vivo purging and systemic IL-2 infusion: unsuccessful prediction of subsequent relapse.
We sequentially analyzed minimal residual disease (MRD) in 7 children with common acute lymphoblastic leukemia (cALL) after autologous bone marrow transplantation (ABMT) with ex vivo purging followed by systemic interleukin-2 infusion. After ABMT, 3 of the 7 patients remained in complete remission (CR) for more than 1 year, and 4 subsequently relapsed. MRD was estimated by polymerase chain reaction amplification to detect the leukemia clone-specific immunoglobulin heavy chain third complementarity determining region (IgH CDR-III). The IgH CDR-III sequences from the relapsed patients were identical with those determined at each respective initial diagnosis. In 2 patients, the levels of MRD were 10(-2) and 10(-5) in the harvested bone marrow (BM) cells, and even after purging the levels were 10(-4) and 10(-5) cells, respectively. One of the 2 patients relapsed 3 months after ABMT, while the other remained in CR for 33 months after ABMT. Among the 4 patients who subsequently relapsed after ABMT, MRD was not detected in the BM samples even 1 month before relapse. Our results suggest that PCR-negativity does not necessarily indicate a lower risk of subsequent relapse. Detection of MRD tends to favor the assessment of the therapeutic effects rather than prediction of relapse.
Kiyoi
H
H
Department of Medicine, Branch Hospital, Nagoya University School of Medicine, Japan.
Kojima
S
S
Kato
K
K
Matsuyama
T
T
Kodera
Y
Y
Ohno
R
R
Naoe
T
T
D001483:Base Sequence; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000032:analysis*; D007135:Immunoglobulin Variable Region / Q000032:analysis; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000627:therapeutic use*; D008297:Male; D008969:Molecular Sequence Data; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D011237:Predictive Value of Tests; D012008:Recurrence; D014182:Transplantation, Autologous
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007376:Interleukin-2