Late Development of Cytogenetic Abnormalities in Ph Negative Cells of Chronic Myeloid Leukemia Patients Treated with Imatinib.
Bibliographic record
Abstract
Abstract Abstract 1108 Poster Board I-130 Clonal cytogenetics abnormalities in Ph negative metaphases (CCA/Ph-) are observed in a variable fraction of Chronic Myeloid Leukemia (CML) patients (pts) after they obtain a Complete Cytogenetic Remission (CCyR). It is not known whether such abnormalities develop soon after CCyR or if they can appear as a late event. Cytogenetic analysis remains the only methodology able to detect such abnormalities and its use in pts in CCyR after several years of imatinib therapy is being questioned. The Imatinib Long Term Effect (ILTE) study enrolled 948 CML pts in 24 centers around the world (Europe, North/South America, Africa, Middle East and Asia); in order to be eligible, pts had to achieve a CCyR within 2 years after starting imatinib. These pts are being followed for long term side effects such as loss of CCyR, toxicities including second cancers, and survival. Within the ILTE cohort, 384 eligible pts received imatinib for > 5 years and remained in CCyR at 5 years. In 309 cases, at least one standard routine cytogenetic analysis after 5 years of treatment was available. The median duration of imatinib treatment is 6.5 years in this group of pts. A cytogenetic abnormality in the Ph negative metaphases was detected in 18 cases (5.8%; 99% Confidence Interval: 0-10.1%); the number of available cytogenetics analyses positive for CCA/Ph- varied from 1 to 12 per patient. The percentages of pts positive for CCA/Ph- in the the different participating centers ranged between 0 and 28.6%. Of the 18 cases positive for CCA/Ph-, 10 were diagnosed within the first 5 years of treatment, and 8 cases afterwards. Three pts (17%) developed abnormalities during the first 2 years of treatment, 5 (28%) during the third or fourth year, 4 (22%) during the fifth or sixth year, and 6 (33%) during year 7, 8 or 9. Abnormalities were: deletion of Y chromosome (7 cases), trisomy 8, del 7q (2 cases each), monosomy 7, trisomy 6, del 9q, Y duplication, del 13, del 18. With a median follow up of 4.5 years after first detection, none of the patients have developed acute leukemia or myelodysplasia. In addition none of these 18 pts lost his/her CCyR status. CCA/Ph-are detectable in a low but consistent proportion of CML pts in CCyR; their occurrence is not limited to the first 5 years of treatment. Our study supports the notion that patients with CCA/Ph- have a favorable prognosis, despite the similarity of the abnormalities to those observed in acute leukemia and myelodysplasia, suggesting CCA/Ph- to be quite slow in their evolution. These data suggest that the search for CCA/Ph- should not be limited to the first years of imatinib treatment. Disclosures No relevant conflicts of interest to declare.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".