Treatment of Adult Acute Lymphoblastic Leukemia (ALL) with a Modified DFCI Pediatric Regimen - The Princess Margaret Experience.
Bibliographic record
Abstract
Abstract Between June 2000 and December 2004, 68 adult patients with newly diagnosed ALL were treated at Princess Margaret Hospital in Toronto, Canada using a modified Dana Farber Cancer Institute pediatric ALL protocol (DFCI 91-01). This protocol includes a remission induction phase, a CNS prophylaxis phase with intrathecal chemotherapy and 12 Gy cranial irradiation, a 30-week intensification phase, and a 72-week maintenance phase. Since 2002, bcr-abl+ patients received concurrent therapy with imatinib mesylate. Before 2002, all patients in CR1 were referred for allogeneic stem cell transplant (alloSCT) if a suitable matched sibling donor was identified (n=11); after 2002, only high-risk patients were referred for alloSCT (n=14). In addition bcr-abl+ and t(4:11) patients were considered for matched unrelated donor alloSCT. Median age was 34.5 years (range, 17–61 years). Sixteen (23.5%) patients were bcr-abl+ and 13 (19.1%) pre-B with WBC > 30. Ten of 16 (62.5%) of the bcr-abl+ patients received concurrent imatinib mesylate; 11 of 16 (69%) of these subsequently underwent alloSCT. The complete remission (CR) rate was 85.4% (58/68), with a 5.9% induction death rate. CNS prophylaxis was administered to 54 patients and was well tolerated. Fifty-seven patients proceeded to therapy in the intensification phase, which consisted of vincristine (VCR) 2 mg × 10 doses, L-asparaginase (l-asp) 12,500 IU/m2 weekly × 30 doses, doxorubicin 30 mg/m2 × 7 doses, 6-mercaptopurine, dexamethasone and methotrexate. Thirty-four patients completed this phase, while 18 patients had an abbreviated course of intensification before proceeding to alloSCT. Major side effects during the intensification phase included grade 3–4 neutropenia (63%), peripheral neuropathy (40%), thrombosis (17.5%) and central venous catheter infection (18.2%). Intensification was administered on an outpatient basis with 12/57 (21%) requiring hospitalization for any reason. Maintenance therapy was given to 32 patients and was well tolerated. At a median follow-up of 2.7 years (range, 0.05–5.8 years), both median overall survival (OS) and relapse free survival (RFS) were 4.9 years. Among non-transplanted patients (n=44), Kaplan-Meier 3-year OS and RFS were 65.5% and 77.3%, respectively with most deaths occurring in induction or from progressive leukemia in primary non-responders. For the entire group, younger age (< 25 years) was associated with improved OS and RFS (p= 0.03) whereas bcr-abl positivity was not. Due to neuropathy, vinblastine (VBL) was substituted for VCR in 13/33 (39.4%) patients during intensification without affecting RFS and OS (p=0.22). Of the 34 patients who completed intensification without relapse, those who received >80% of the targeted l-asp dose had a significantly longer OS (p=0.02) and RFS (p=0.04). These results demonstrate the feasibility of administering the pediatric DFCI protocol to adults up to the age of 61 years with acceptable toxicity. As with the DFCI pediatric experience (Blood2001; 97(5): 1211-8), the ability to deliver >80% of the targeted l-asparaginase dose during the intensification phase appears to produce improved efficacy. Longer follow-up will be needed to further characterize the anti-leukemic efficacy of this regimen in adults.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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 teacher head, 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".