The Outcome Of Allogeneic Hematopoietic Cell Transplantation In Children With FLT3/ITD-Positive Acute Myelogenous Leukemia
Bibliographic record
Abstract
Abstract FLT3 is a receptor tyrosine kinase expressed on hematopoietic progenitors that regulates hematopoietic development. FLT3 internal tandem duplication (FLT3/ITD) is a somatic mutations whose presence is associated with poor outcome in adults and children with AML. In children with FLT3/ITD who have high allelic ratio (ITD-AR), the progression free survival is estimated to be <20%. Hematopoietic stem-cell transplantation (HSCT) has been a recommended therapeutic option for children who are positive for FLT3. There is limited data on the post transplant outcome for children with FLT3/ITD. We conducted a retrospective study to determine the outcome for all children with FLT3/ITD positive AML who underwent allogeneic HSCT in 4 pediatric centers. Data was collected and analyzed to identify the potential risk factors for overall survival (OS) and event-free survival (EFS). The association with OS and EFS was evaluated by Cox proportional hazard regression with results reported using hazard ratio (95% CI). The survival curve and cumulative incidence were calculated using the Kaplan-Meier method. Between March 2007 and June of 2012, 29 AML patients with FLT3/ITD received HSCT. Median age at HSCT was10.2 years (range 4.5-21.9), 16 were males, and 26 were in first complete remission (CR), 2 with refractory disease and 1 in second CR. Among those with minimal residual disease testing, it was present in 3 (12%) patients in 1stCR. FLT3-ITD allelic ratio at the time of diagnosis was available in 25 patients and among those patient 14 (56%) the ratio was >0.4 (range 0.03-15.99). Eleven patients (38%) received stem-cells from HLA identical siblings while in 18 (62%) an alternative donors stem-cell was utilized (mismatched related donor (n=2), unrelated donor (n=7) or cord blood (n=9)). Eighteen patients (62%) received a total body irradiation (TBI) based preparative regimen while 11 (38%) received a busulfan-based regimen. Graft-versus-host disease (GVHD) prophylaxis consisted of calcineurin inhibitor and mycophenolate for recipients of cord blood HSCT and calcineurin inhibitor plus methotrexate for the rest. Three (10%) patients experienced primary graft failure following cord blood HSCT. All 3 patients received a second graft that resulted in sustained engraftment. The cumulative incidence of neutrophil engraftment at day 42 was 89.6%. Sixteen (55%) patients developed grade 2-4 GVHD and 11 (38%) developed chronic GVHD (6 with severe and 5 mild). None of the patients experienced transplant related mortality. Eleven (38%) patients experienced relapsed disease. The cumulative incidence of relapse at 2 years was 34.7% with 95% CI (20.4%, 54.9%). At 2-years the probability of EFS and OS was 65.3% with 95% CI (45.1%, 79.6%) and 82.2% with 95% CI (58.5%, 91.3%) respectively. Using univariable analysis there was no difference between the EFS of patients who received related donors versus alternative donors, (HR 2.64 (0.79-8.76) p=0.1) and those with residual disease at the time of transplant versus those in complete remission (HR 0.88(0.19-4.09, p=0.8). Patients with higher FLT3/ITD ration at diagnosis had significantly worse EFS (HR 1.42 (1.04-1.93) p=0.03). The use of TBI in the preparative regimen was associated with superior EFS and OS (HR 0.29 (0.08-0.99), p =0.04) and (HR 0.07 (0.01-0.62), p= 0.002) respectively. In conclusion the use of allogeneic HSCT is associated with improved EFS and OS in children with FLT3/ITD positive AML compared to what has been reported in those treated with chemotherapy alone. Disclosures: No relevant conflicts of interest to declare.
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 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 | 0.000 | 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 | 0.001 |
| 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".