Significant reduction of the hybrid BCR/ABL transcripts after induction and consolidation therapy is a powerful predictor of treatment response in adult philadelphia-positive acute lymphoblastic leukemia

• Published in: Leukemia Vol. 19; no. 4; pp. 628 - 635
• Main Authors: PANE, F, CIMINO, G, MECUCCI, C, MARTINELLI, G, SAGLIO, G, ROTOLI, B, MANDELLI, F, SALVATORE, F, FOA, R, IZZO, B, CAMERA, A, VITALE, A, QUINTARELLI, C, PICARDI, M, SPECCHIA, G, MANCINI, M, CUNEO, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.04.2005; Nature Publishing Group
• Subjects: Abl gene; Abl protein; Acute lymphoblastic leukemia; Adolescent; Adult; Antibiotics, Antineoplastic - therapeutic use; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic Agents, Phytogenic - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asparaginase - therapeutic use; BCR gene; BCR protein; Biological and medical sciences; Chromosome aberrations; Consolidation; Cytarabine - therapeutic use; Daunorubicin; Daunorubicin - therapeutic use; Female; Follow-Up Studies; Fusion protein; Fusion Proteins, bcr-abl - genetics; Hematologic and hematopoietic diseases; Hematology; Humans; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphatic leukemia; Male; Medical genetics; Medical prognosis; Medical sciences; Middle Aged; Minimal residual disease; Neoplasm, Residual - drug therapy; Neoplasm, Residual - genetics; Neoplasm, Residual - mortality; Patients; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality; Predictive Value of Tests; Prognosis; Reduction; Remission; Remission (Medicine); Reverse Transcriptase Polymerase Chain Reaction; Therapy; Vincristine - therapeutic use; Chromosomal aberration; Prognosis; real-time PCR; Abnormal chromosome C9; Messenger RNA; Lymphoproliferative syndrome; Abnormal chromosome G22; Adult; Acute lymphocytic leukemia; Hybrid gene; Ph-ALL; Chromosome translocation; Human; Hematology; Enzyme; Transferases; Acute; Acute leukemia; Minimal residual disease; Malignant hemopathy; Real time; Consolidation treatment; Induction treatment; Philadelphia chromosome; Polymerase chain reaction; Protein kinase; Bcr-abl protein; Abnormal chromosome; Molecular biology; Predictive factor
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2403683

Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) has a dismal prognosis. We prospectively evaluated minimal residual disease (MRD) by measuring BCR/ ABL levels with a quantitative real-time PCR procedure after induction and after consolidation in 45 adults with Ph+ ALL who obtained complete hematological remission after a high-dose daunorubicin induction schedule. At diagnosis, the mean BCR-ABL/GUS ratio was 1.55 +/- 1.78. A total of 42 patients evaluable for outcome analysis were operationally divided into two MRD groups: good molecular responders (GMRs; n = 28) with > 2 log reduction of residual disease after induction and > 3 log reduction after consolidation therapy, and poor molecular responders (PMRs; n = 14) who, despite complete hematological remission, had a higher MRD at both time points. In GMR, the actuarial probability of relapse-free, disease-free and overall survival at two years was 38, 27 and 48%, respectively, as compared to 0, 0 and 0% in PMR (P = 0.0035, 0.0076 and 0.0026, respectively). Salvage therapy induced a second sustained complete hematological remission in three GMR patients, but in no PMR patient. Our data indicate that, as already shown in children, adult Ph+ ALL patients have a heterogeneous sensitivity to treatment, and that early quantification of residual disease is a prognostic parameter in this disease.