Minimal residual disease in acute lymphoblastic leukemia detected by immune selection and gene rearrangement analysis.
We have developed an assay for the detection of malignant residual cells in the bone marrow from patients with B- or T-lineage acute lymphoblastic leukemia (ALL) in clinical remission. This assay involves an immune selection step followed by immunoglobulin or T-cell receptor gene rearrangement analysis and allows the detection of one contaminating tumor cell out of 1,000 normal bone marrow cells. We have examined the bone marrow of 11 patients with adult ALL in remission over a 24-month period. Five patients relapsed in the bone marrow and one in the CNS. The assay allowed the detection of minimal residual disease in four of five patients that subsequently relapsed in the bone marrow, 1.5 to 9 months before the relapse became morphologically and clinically manifest. Residual disease was not found in the bone marrow from patients in continuous remission and from the single patient who relapsed in the CNS. We conclude that the ability of the assay described here to detect minimal residual disease with high specificity can provide information for further understanding of the biology of ALL and hopefully for the clinical management of patients with this disease.
Bregni
M
M
C. Gandini Bone Marrow Transplantation Unit, Division of Medical Oncology, Istituto Nazionale Tumori, Milano, Italy.
Siena
S
S
Neri
A
A
Bassan
R
R
Barbui
T
T
Delia
D
D
Bonadonna
G
G
Dalla Favera
R
R
Gianni
A M
AM
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000032:analysis / Q000276:immunology / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D015321:Gene Rearrangement; D006801:Humans; D008875:Middle Aged; D015166:Monitoring, Immunologic; D009364:Neoplasm Recurrence, Local / Q000032:analysis / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D013997:Time Factors
D004273:DNA, Neoplasm