Outcome of Stem Cell Transplantation for Pediatric Acute Lymphoblastic Leukemia: Comparison of Matched Related Donor Verses Matched Unrelated Donor. Important Role of Graft Versus Host Disease in Preventing Relapse.
Bibliographic record
Abstract
Abstract Seventy percent of children with acute lymphoblastic leukemia (ALL) who benefit from stem cell transplantation (SCT) lack a human leukocyte antigen (HLA) matched related donor (MRD). For these children SCT from a matched unrelated donor (MUD) represents an alternative therapeutic option. Our objective was, to review the outcome of children (0–18years) with ALL whom received a fully matched marrow allografts at our institution between July 1998 - December 2003. All children were conditioned with cyclophosphamide (50mg/kg infused over 1 hour daily for 4 days) followed by fractionated total body irradiation (TBI; 1200cGy, 6 fractions over 3 days). Cyclosporine A and a short course of methotrexate were used for graft versus host disease (GVHD) prophylaxis. Results: We performed 23 fully MRD and 23 fully MUD SCT during the study period. Median age at time of SCT was 10.2 y (range 2.2–17.5) and 8.2 y (range 1–16.5) for the MRD and MUD groups, respectively. Remission status at time of SCT; For the MRD group, complete remission (CR) 1, 2 and 3 were 5, 15 and 3 patients, respectively. For the MUD group, CR 1, 2 and 3 were 6, 14 and 3 patients, respectively. All patients engrafted for neutrophils (defined as absolute neutrophil count (ANC) of > 0.5 x 109/l for 2 consecutive days) with a median time of 18 days (range 12–28) and 16 days (range 10–25) for the MRD and MUD groups, respectively. In both groups, low grade acute(a) GVHD (I-II) occurred in 50% of the cases. However, high grade aGVHD (III-IV) occurred in 7/23 patients in the MUD group compared to only 1 patient with grade III aGVHD in the MRD group. Three years event free survival (EFS) for the whole group was 47 ± 8% with overall survival (OS), 50 ± 8%. EFS (3y) according to remission status was; 64 ± 15% for CR1, 51 ± 10% for CR2 and 33 ± 19% for CR3, P = 0.06. Twelve out of thirteen deaths in the MRD group were caused by leukemia relapse versus 3 out of 8 deaths in the MUD group. Transplant related mortality (TRM) was 5/8 deaths in the MUD group versus 1/13 deaths in the MRD group. Three years EFS and overall survival (OS) were, 37 ± 11%, 39 ± 11% for the MRD group and 63 ± 10%, 64 ± 10% (P = 0.16) for the MUD group. For the whole group, EFS according to aGVHD was, 29 ± 15% for no aGVHD, 51 ± 11% for low grade aGVHD and 60 ± 15% for high grade. Conclusion: Acute graft versus host disease is associated with less relapse post SCT for pediatric ALL, presumably through a graft-versus-leukemia effect. Our data suggests that outcomes can be improved further through exploring means of inducing aGVHD while reducing the toxicity of SCT. In MRD SCT where the likelihood of aGVHD is less and therefore relapse rate is higher, and in order to maximize survival in the non aGVHD group, attempts for aGVHD induction by early manipulation of the immunosuppressive medications or a low dose pre-emptive donor lymphocyte infusion in the first 60 days post engraftment, need to be explored in future studies.
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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 | 0.000 |
| 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".