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.
Department of Medicine, Branch Hospital, Nagoya University School of Medicine, Japan.
H
H
Kiyoi
S
S
Kojima
K
K
Kato
T
T
Matsuyama
Y
Y
Kodera
R
R
Ohno
T
T
Naoe
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