Analysis of Risk Factors Influencing Outcomes After Unrelated Cord Blood Transplantation In Children with Juvenile Myelomonocytic Leukemia. An Eurocord, EBMT, EWOG-MDS, CIBMTR Study
Bibliographic record
Abstract
Abstract Abstract 533 Juvenile myelomonocytic leukemia (JMML) is a rare and lethal myeloproliferative disease of young childhood. Currently, allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment option. DFS at 5 years after HLA identical and unrelated HSCT was 55% (n=48) and 49% (n=52) in a largest series of patients published so far and mainly transplanted with bone marrow cells. Unrelated Cord Blood Transplantation (UCBT) is considered an alternative option for patients who lack an HLA-matched donor. We retrospectively analyzed 110 children, given a first single unmanipulated UCBT, from 1995 to 2010, and reported to Eurocord-EBMT and CIBMTR. Median age was 1 year (range 0.08–6.4) at diagnosis and 2 years (0.5-7.5) at transplantation, respectively. Median time interval between diagnosis and UCBT was 6 months (1-58); before transplantation, 88 patients were treated with low- or high-dose chemotherapy and splenectomy was performed in 24 children. Among 100 patients with available cytogenetic data, monosomy of chromosome 7 was the most frequent abnormality (24%). All but 8 patients received a myeloablative conditioning, Busulfan-Cyclophosphamide-Melphalan (BuCyMel) was used in 48 patients, total body irradiation (TBI) and Cyclophosphamide in 19 patients and combination of Busulfan-Cyclophosphamide with other drugs in 21 patients. Cyclosporin+steroid was the most common graft-versus-host disease (GvHD) prophylaxis (80%) and ATG was added in 86% of patients. Nineteen percent of units were HLA-identical (antigen level for HLA-A and B, allelic for DRB1), while 43% and 38% had 1 or 2–3 mismatches, respectively. Median TNC infused was 7.1×10e7/kg (1.7-27.6). Median follow-up was 44 months (3-169). At 60 days, cumulative incidence (CI) of neutrophil (PMN) recovery was 80±4%, with a median time to PMN recovery of 25 days. Grades II-IV acute GvHD developed in 45 patients, 100 days-CI of grade II-IV aGvHD was 40±5%. Among 90 patients at risk, 17 developed chronic GvHD and 4 years-CI was 16±4%. At 4 years CI of relapse was 37±5% (n=38); age older than 1 year at diagnosis was the only independent factor associated with increased risk of relapse (HR 2.3, p=0.038). Of note, among 58 patients with available data for level of fetal hemoglobin (HbF), a higher level of HbF (>35%) seemed to be associated with increased relapse incidence (57% versus 31% for remainders; p=0.05). At 4 years, DFS was 43±5%, in multivariate analysis independent factors associated with better DFS were: age younger than 1 year at diagnosis (53% vs 30%, HR 2.4, p=0.001), graft with 0 or 1 HLA mismatched cord blood unit (48% vs 34%, HR=2.1, p=0.006) and cytogenetic without monosomy 7 (48% vs 26%; HR=1.95, p=0.027). At 4 years, CI of transplant related mortality (TRM) was 20±4%; in multivariate analysis, cytogenetic with monosomy 7 (HR=2.7, p=0.036) and transplantation performed before 2003 (HR=3.7, p=0.015) were factors associated with increased TRM. In fact, CI of TRM was 14% after 2003 compared to 30% before 2003. Estimated overall survival (OS) at 4 years was 51±5%, and in multivariate analysis factors associated with decreased OS were: age older than 1 year at diagnosis (42% vs 60%; HR=2.03, p=0.032), and cytogenetic with monosomy 7, (30% vs 57%; HR=2.6, p=0.004). Fifty-one patients died after transplant, 53% for relapse and 47% for transplant related causes. In conclusion, UCBT may cure approximately 50% of patients with JMML who lack a matched related donor. Presence of monosomy 7 is associated with decreased DFS and increased TRM, independent of other factors. Other patient- (age at diagnosis) and transplantation-related factors (HLA and year of transplantation) were also associated with outcomes. Disease recurrence remains the major cause of treatment failure, and strategies to reduce the risk of relapse are warranted. Disclosures: Wagner: CORD:USE: Membership on an entity's Board of Directors or advisory committees; VidaCord: Membership on an entity's Board of Directors or advisory committees.
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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 | 0.001 |
| Bibliometrics | 0.001 | 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".