Salvage of Primary Refractory Acute Leukemia (AL) with High-Dose Etoposide (VP) and Cyclophosphamide (CY) Followed by Early Stem Cell Transplantation (SCT): An Effective Treatment Strategy for AML but Not for All.
Bibliographic record
Abstract
Abstract Primary refractory AL has a poor prognosis although some patients (pts) can be salvaged with allogeneic SCT. Induction of complete remission (CR1) with conventional chemotherapy prior to conditioning and SCT may improve long-term event-free survival (EFS). Between 03/91 and 10/03, 59 adults with primary refractory AL (defined as >15% marrow blast cells on day 30 of induction) were treated with VP 2.4 g/m2 by 34 hr. IV infusion beginning on day 1 followed by CY 2.0 g/m2 IV daily on days 3, 4 and 5 with hyperhydration (3 L/m2/d) as bladder prophylaxis. Six pts received VP 3.0 g/m2 and 1 patient received CY 1.8 g/m2 x 4 days. The study included 39 males and 20 females with a median age of 41 years (range 17–60). Diagnoses were AML (42 pts), ALL (13 pts) and biphenotypic AL (4 pts). Eleven pts (19%) presented with a WBC count > 50 x109/L and MRC karyotype was favourable in 4 pts, intermediate in 34 pts and adverse in 20 pts; metaphase analysis failed in 1 patient. All AML pts had already received high-dose cytosine arabinoside (HIDAC) and either daunorubicin (DNR) (n=33) or mitoxantrone and VP (n=9). ALL pts had previously received DNR, vincristine and prednisone with (n=9) or without (n=4) L-asparaginase. Biphenotypic AL pts had been induced with HIDAC, DNR, vincristine and prednisone. Induction day 30 marrow blast count was > 40% in 35 pts (59%). The most common grade I/II non-hematologic toxicities of VP/CY were oral mucosal (44% of pts), GI (20% of pts) and hepatic (15% of pts); only one patient developed grade III/IV toxicity (pulmonary). Median time to recovery of ANC > 0.5 x109/L and platelets > 20 x109/L was 26 and 22 days, respectively. Three pts (5%) died prior to day 21 of VP/CY and were not evaluable for response (2 pts sepsis, 1 patient pulmonary hemorrhage). Twenty-four pts (43%) were also refractory to VP/CY but 32 pts (57%) entered CR1. Response rates were similar in AML (54%) and ALL/ABL (67%) (p=0.52) and analysis of baseline patient characteristics did not reveal any predictors of response to VP/CY. Twenty-nine of 32 CR1 pts proceeded to SCT (24 allogeneic, 5 autologous); five pts with AL refractory to VP/CY also underwent allogeneic SCT although all subsequently relapsed. Four of the autologous SCT pts relapsed with only one patient remaining alive in CR1. Estimated 5-year EFS for the entire cohort of pts is 23%. The only positive predictor of survival was male sex (p=0.03) and cytogenetic risk group did not influence outcome (p=0.69). In the allogeneic SCT group, 5-year EFS was 45% and was signficantly better for pts with AML (52%) compared to pts with ALL (14%, p=0.04). In conclusion, VP/CY is able to induce CR1 in the majority of pts with primary refractory AL. For pts with AML in CR1 that have a suitable donor, subsequent allogeneic SCT results in a favourable long-term EFS. Although pts with primary refractory ALL have a high CR1 rate with VP/CY, overall outcome for this subgroup remains poor.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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".