Outcomes of Adult Philadelphia Positive Acute Lymphoblastic Leukemia Patients Treated with Pediatric Multi-Agent Chemotherapy and Imatinib and the Impact of Residual Disease Monitoring on Survival
Bibliographic record
Abstract
Abstract The prognosis of Philadelphia positive acute lymphoblastic leukemia (Ph+ ALL) has improved markedly after the introduction of BCR ABL1 targeted tyrosine kinase inhibitors (TKI). With the addition of upfront TKI, ~90 % of patient will achieve complete remission (CR). Allogenic stem cell transplant (alloSCT) remains the cornerstone of post remission therapy based on large trials that predate the introduction of TKIs. This approach has since been challenged in more recent studies in which similar outcomes were observed with lifetime TKI therapy. Several reports have suggested a correlation between achieving a molecular negativity with chemotherapy + TKI and long term outcome, in patients who did not receive alloSCT, suggesting that a monitoring strategy might spare some patients with excellent response to chemotherapy and TKI the toxicity of (alloSCT), and with comparable outcome. We previously reported good overall survival and event free survival in patients treated with a TKI-modified version of the Dana Farber Cancer Institute (DFCI) pediatric ALL protocol. In this retrospective analysis we compared the long term outcome of Ph+ ALL patients who were transplanted and those who were not, mainly due to the unavailability of a donor. In addition, we reviewed the effect of residual disease monitoring (RDM) at post induction, 3, 6, 9 and 12 months, and correlated the achievement of complete and major molecular responses with survival. In the present study, 167 patients diagnosed with Ph+ ALL in our center were evaluated from year 2001-2015. One hundred and thirty three (133) received DFCI chemotherapy + imatinib. One hundred and nineteen (119; 89%) patients achieved CR following the induction phase. Fifty nine (59; 44.3 %) subsequently received an allogenic stem cell transplant from a sibling or matched unrelated donor, leaving 74 patients who were not transplanted and were evaluated for RDM. While there was no significant difference between the overall survival (OS) for the transplanted and not transplanted cohorts (median survival 3.3 years vs 5.3 years, and 5 year- OS 40% vs 50 %, respectively; p value = 0.40), there was an improved relapse free survival (RFS) in the transplanted group (5- year RFS, 55% vs 75%, respectively; p value= 0.033). Achieving CMR with un-detectable transcripts post-induction, and at 3 and 6 months, showed superior OS compared to those not achieving CMR (p values of 0.029, 0.0086 and 0.028, respectively), whereas superior RFS was associated with molecular negativity at 3, 6 and 9 months ( p values of 0.0076,0.0023 and 0.03, respectively). Molecular negativity at 12 months had no impact on survival. In conclusion, our data confirm that while the RFS of patients with Ph+ ALL who did not undergo alloSCT as post remission therapy was inferior to that of those who did, OS was similar in the two groups. Monitoring of residual disease at early time points during therapy, and especially at 3 and 6 months, appears to identify patients with a lower chance of relapse who can likely be spared the toxicity of alloSCT, and receive chemotherapy + TKI, followed by ongoing TKI maintenance. Further RDM studies are needed to better stratify such patients and to facilitate alloSCT decision making. Figure Figure. Disclosures Gupta: Incyte Corporation: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Schimmer:Novartis: Honoraria. Schuh:Amgen: Membership on an entity's Board of Directors or advisory committees.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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".