Impact of Modifying Conditioning and Immunosuppressive Strategies in Allogeneic Hematopoietic Stem Cell Transplantation in Children with Acute Lymphoblastic Leukemia
Bibliographic record
Abstract
Background:Hematopoietic stem cell transplants (HSCT) is indicated for some very high-risk childhood acute lymphoblastic leukemia (ALL) patients in complete remission 1 (CR1) and for patients in >CR2. Relapse remains the most frequent complication after transplant. In 2012, in order to decrease the relapse rate, we modified our conditioning and GVHD prophylaxis regimen. Total body irradiation doses were increased, etoposide removed and fludarabine introduced. Anti-thymocyte globulin (ATG) was removed of GVHD prophylaxis regimen and mycophenolate mofetil was added for unrelated marrow grafts. The aim of this study was to compare outcome between previous (PS) and new strategies (NS) prior and after 2012. Methods: This retrospective study included all 47 patients aged 0 to 18 years old who underwent a first HSCT for ALL at Sainte-Justine University Health Center from 2007 to 2017. Our primary endpoint was 2-year event-free survival (EFS) between PS (n=22) and NS (n=25) groups. Secondary endpoints included overall survival (OS), relapse, GVHD, immunological recovery and infection rates. Results: Demographic parameters and leukemia characteristics were not significantly different between groups. In the PS group, median age was 6.1 years [2.7;13.5] and 41% of patients were female. In the NS group, median age was 7.1 years [2.4;11.4] and 44% of patients were female. B-cell and T-cell lineage leukemias were present in respectively 82% and 18% of PS and 76% and 24% in NS. Fourteen percent of patients were transplanted in CR1 in the PS versus 40 % in the NS group. EFS at 2 and 5 years were respectively 46% and 36% with the PS compared to 60% and 53% with the NS (p=0.170). OS at 5 years was significantly higher with the NS (46% vs 75%, p=0.05). Morphologic relapse rates at 5 years of PS and NS were 55% and 30% (p=0.14). Acute GVHD rate at 6 months was superior with the NS (41% vs 80%, p=0.002). Chronic GVHD rate at 5 years was similar between groups. At least one proven infection at 100 days was documented in 96% compared to 88% of patients with the PS and NS respectively (p=0.08). Neutrophil recovery at 60 days and platelets recovery at 180 days were not significantly different. T-cell Immune recovery at 6 months was superior in the NS. Median (min;max) CD3 counts in PS and NS were respectively 339 (132;1152) versus 946 (284;1944) (p=0.009), CD4 counts were 221 (65;612) versus 594 (238;920) (p=0.046) and CD8 counts were 55 (34;414) versus 320 (210;1104) (p<0.001). Conclusion: Compared to the PS, the NS of conditioning regimen and GVHD prophylaxis shows a significant improvement in OS and a tendency towards decreased relapse and increased EFS. However, we found a significant increase in acute GVHD with this regimen, which is explained by the removal of ATG from the regimen. These results highlight the necessity to adjust our strategy with HSCT ALL with the aim of maintaining graft versus leukemia effect without increasing GVHD. Emerging immunotherapy (such as antibody-based and chimeric antigen receptor T cell therapies) might shift the management of refractory and relapsed ALL and our current approach to HSCT. Disclosures Bittencourt: Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy, Other: Travel, accommodations expenses.
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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 | 0.002 |
| 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".