Philadelphia-Negative Clonal Hematopoiesis Following Imatinib Therapy in Patients with Chronic Myeloid Leukemia (CML).
Bibliographic record
Abstract
Abstract There is an increasing number of reports of Philadelphia-negative (Ph-) clonal hematopoiesis developing in patients (pts) with CML treated with imatinib. The significance of these abnormalities remains unclear. To examine the incidence, natural history and risk factors for the development of Ph- clones, we undertook a retrospective review of 142 consecutive pts with CML treated with imatinib and followed at VGH or BCCA between June 1999 and July 2004. Four pts were excluded due to incomplete records. Out of 138 pts, there were 76 (55%) males. The median age at diagnosis was 48.6 yrs (range 19.3–82.8). At the time of initiation of imatinib, 93 (67%) pts were in stable phase, 33 (24%) in accelerated phase and 12 (9%) in blast phase. 126 pts had received prior therapy with hydroxyurea (81%), interferon (53%), hematopoietic stem cell transplantation (17%), cytarabine (11%), or other therapy (17%). The median number of prior therapies was 2 (range 0–4). The median time from diagnosis to treatment with imatinib was 12.7 mos (range 0–240.1) and the median duration of imatinib therapy was 15.2 mos (range 0.6–45.1). Best responses to imatinib were complete hematologic response (96%), major cytogenetic response (53%) and complete cytogenetic response (43%). The event-free survival (EFS) at 3 yrs from the start of imatinib was 59% (95%CI 47–70%). Of the 138 pts, 7 (5%) pts developed Ph- clonal abnormalities: −7 and +8 (2 pts), +8 (2 pts), −7 (1 pt), −X and −22 (1 pt) and t(12;16) (1 pt). One pt had −7 and 1 pt had +8 in both Ph- and Ph+ cells. For the pts who developed Ph- clonal abnormalities, the median time from diagnosis to the start of imatinib was 28.4 mos (range 0.7–143.9). Six of these 7 pts had received prior therapy. The median time from the start of imatinib therapy to the development of the Ph- clone was 11.9 mos (range 2.7–23.5). All but two of the Ph- clones were transient and none was associated with myelodysplasia. Two of the 7 pts had progressed on imatinib. There was no difference in EFS or overall survival between pts with or without Ph- clones. In univariate analysis comparing characteristics of pts with and without Ph- clones, no predictive factors could be identified. In conclusion, the development of Ph- clonal hematopoiesis in pts with CML treated with imatinib occurred in ~5% of this series and did not appear to confer a worse prognosis. The majority of the Ph- clones included −7 and/or +8 and were transient without associated myelodysplasia. Finally, the observation of −7 (to our knowledge the first such case reported) or +8 in both Ph- and Ph+ cells in the same patient could be explained by the existence of a Ph- monoclonal state prior to the BCR/ABL mutation.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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".