Good correlation between RT-PCR analysis and relapse in Philadelphia (Ph1)-positive acute lymphoblastic leukemia (ALL)

• Published in: Leukemia Vol. 11; no. 2; pp. 294 - 298
• Main Authors: PREUDHOMME, C, HENIC, N, COSSON, A, FENAUX, P, CAZIN, B, LAÏ, J. L, BERTHEAS, M. F, VANRUMBEKE, M, LEMOINE, F, JOUET, J. P, DECONNINCK, E, NELKEN, B
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.02.1997; Nature Publishing Group
• Subjects: Abl protein; Acute lymphoblastic leukemia; Adult; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; BCR protein; Biological and medical sciences; Bone marrow; Bone Marrow - pathology; Bone Marrow Transplantation; Chemotherapy; Child; Cytogenetics; DNA, Neoplasm - genetics; Follow-Up Studies; Fusion protein; Fusion Proteins, bcr-abl - genetics; Hematology; Humans; Investigative techniques, diagnostic techniques (general aspects); Leukemia; Lymphatic leukemia; Medical sciences; Neoplasm Proteins - genetics; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polymerase Chain Reaction; Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Predictive Value of Tests; Prognosis; Prospective Studies; Recurrence; Remission; RNA, Messenger - analysis; RNA, Messenger - blood; RNA, Neoplasm - analysis; RNA, Neoplasm - blood; Sensitivity analysis; Sensitivity and Specificity; Treatment Failure; Chromosomal aberration; Human; Relapse; RNA-directed DNA polymerase; Enzyme; Transferases; Acute; Minimal residual disease; Malignant hemopathy; Philadelphia chromosome; Polymerase chain reaction; Nucleotidyltransferases; Lymphoproliferative syndrome; C-Onc gene; Cytogenetics; Abnormal chromosome; Diagnosis; Acute lymphocytic leukemia; Molecular biology; Hybrid gene; Protooncogene; Chromosome translocation
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2400567

We sequentially performed cytogenetic analysis and RT-PCR analysis of BCR-ABL transcripts in 17 cases of Ph1-positive ALL who had achieved hematological complete remission (CR) with intensive chemotherapy (CT). Sixteen cases were studied prospectively. All but one of the patients had reached cytogenetic CR, but cytogenetic has low sensitivity in predicting relapse. Twelve patients relapsed, three died in first CR and two were alive in first CR. Two of five, two of four, and five of nine patients who were allografted (in first or second CR), autografted and received consolidation CT, respectively, achieved negative two-round PCR in the bone marrow (BM): three died in CR, three remained in CR with negative two-step PCR in the BM and three relapsed after 22 to 28 months. In all cases, relapse was preceded by switch to PCR positivity in the BM by 4 to 6 months. The remaining nine patients remained PCR-positive in the BM and relapsed after 2 to 16 months. In the four autografted cases, PCR was positive at the time of bone marrow harvest. The two patients who received a purged transplant achieved negative PCR and prolonged CR, whereas the two patients who received an unpurged transplant remained PCR positive and relapsed. In 34% of the samples where analysis was concomitant, sensitivity of PCR proved lower in the blood than in the BM. These findings show that RT-PCR is a useful tool in the monitoring of MRD in Ph1 positive ALL.