Abstract | BACKGROUND: DESIGN AND METHODS:
Minimal residual disease was monitored by polymerase chain reaction using the immunoglobulin heavy-chain gene rearrangement as a molecular marker in 29 relapsed patients who achieved complete remission following reduced intensity conditioning and allogeneic stem cell transplantation. A nested-polymerase chain reaction with patient-specific primers derived from complementarity determining regions (CDR2 and CDR3) was carried out in all the patients. Real-time polymerase chain reaction was performed in patients whose nested reaction gave positive or mixed results. RESULTS: Three patterns of minimal residual disease were observed: negative (31%), mixed (24%), and always positive (45%). The cumulative incidence of relapse according to the minimal residual disease status at 6 and 12 months after transplantation was significantly different between polymerase chain reaction-negative and -positive patients (p=0.031 and p=0.04, respectively). Two-year disease-free survival was 93% and 46% for polymerase chain reaction-negative and -positive patients at 6 months after transplantation, respectively (p=0.012). Similarly, 2-year disease-free survival was 100% and 57% for polymerase chain reaction-negative and -positive patients at 12 months, respectively (p=0.037). No clinical or biological factors were predictive of the achievement of polymerase chain reaction negativity after allogeneic stem cell transplantation. Graft-versus-host disease was more frequent in patients who did not relapse (p=0.04). Quantitative monitoring of minimal residual disease was able to identify polymerase chain reaction-positive patients with a higher risk of relapse. CONCLUSIONS: These findings demonstrate that relapsed patients can achieve molecular remission after reduced intensity conditioning and allogeneic stem cell transplantation and suggest a minimal residual disease-driven intervention that might be useful to prevent overt hematologic relapse.
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Authors | Lucia Farina, Cristiana Carniti, Anna Dodero, Antonio Vendramin, Anna Raganato, Francesco Spina, Francesca Patriarca, Franco Narni, Fabio Benedetti, Attilio Olivieri, Paolo Corradini |
Journal | Haematologica
(Haematologica)
Vol. 94
Issue 5
Pg. 654-62
(May 2009)
ISSN: 1592-8721 [Electronic] Italy |
PMID | 19377072
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Immunoglobulin Heavy Chains
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Topics |
- Adult
- Aged
- Female
- Gene Rearrangement
- Graft vs Host Disease
(diagnosis, genetics)
- Graft vs Leukemia Effect
(genetics)
- Hematopoietic Stem Cell Transplantation
(methods)
- Humans
- Immunoglobulin Heavy Chains
(genetics)
- Leukemia, Lymphocytic, Chronic, B-Cell
(genetics, pathology, surgery)
- Male
- Middle Aged
- Neoplasm Recurrence, Local
- Neoplasm, Residual
(diagnosis, genetics)
- Outcome Assessment, Health Care
(methods)
- Polymerase Chain Reaction
(methods)
- Predictive Value of Tests
- Prognosis
- Reproducibility of Results
- Survival Analysis
- Time Factors
- Transplantation Conditioning
- Transplantation, Homologous
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