A Canadian Blood and Marrow Transplant Group (CBMTG) Randomised Trial Comparing G-CSF Mobilized Peripheral Blood Versus G-CSF Stimulated Bone Marrow In Recipients Of Sibling Allografts For Hematologic Malignancies
Bibliographic record
Abstract
Abstract G-CSF mobilized peripheral blood (G-PB) allografts lead to faster hematologic recovery than marrow grafts, but with more chronic GvHD(cGvHD). We hypothesized that G-CSF stimulated marrow (G-BM) may result in faster hematological recovery with less cGvHD. Methods We conducted a Phase III randomised multicenter trial of matched sibling G-PB vs G-BM allografts in adults with hematologic malignancies. The primary endpoint was time to treatment failure defined as the first occurrence of extensive cGvHD, relapse or death from any cause. Thirteen centers in Canada, Saudi Arabia, U.S., Australia and New Zealand enrolled patients. Adaptive stratification (minimization) balanced treatment groups by center, disease, disease risk and conditioning. Donors received G-CSF 5 mg/kg/d sc for 4 or 5 days and underwent apheresis on Day 5 and, if necessary, on Day 6 or marrow harvest on Day 5. Eligible recipients between 16 and 65 years received myeloablative conditioning and cyclosporine/methotrexate as GvHD prophylaxis. The study began before widespread adoption of the NIH GvHD consensus guidelines so cGvHD was characterized as limited or extensive. Immunophenotyping and functional assays performed on donor cells were correlated with incidence of cGvHD. Results Between 2007 and 2012, 230 sibling donor-recipients were randomized to receive either a G-PB or G-BM allograft; 3 randomized to G-PB and 4 to G-BM were inevaluable (4 relapsed before transplant, 1 donor withdrew before collection, 1 recipient withdrew consent and 1 was ineligible (non-myeloablative conditioning)). Indication for allograft was AML (109; 49%), ALL (57; 25%); MDS/MPD(31; 14%), CML(13; 6%), lymphoproliferative disorder(NHL/MCL/CLL)(12; 5%) and biphenotypic leukemia(1). 77(70%)(G-PB) and 71(63%)(G-BM) recipients had low-risk disease (AML or ALL in CR1, RA, RARS, CML in 1st CP). Donor and recipient ages, sex and CMV immune status were balanced between groups. Donors tolerated mobilization well although one donor (G-PB) died of a cardiac event while receiving G-CSF. Median nucleated cells per kg were 7.59x108 (2.73-18.64) and 5.92x108 (0.94-13.23) in the G-PB and G-BM arms respectively (P<0.0001). Median CD34 cells per kg were 5.50x106 (2.03-23.94) and 3.22x106 (0.29-8.71) respectively (P<0.0001). 94% of G-PB donors underwent 1 apheresis. Median volume of harvested G-BM was 1127mL (350-1731mL). With a median follow-up of 36 months (range 9.6-48), using Cox proportional hazards multivariable modelling adjusted for the 4 minimization factors, time to treatment failure did not differ significantly between arms (HR 0.91; 95% CI 0.68-1.22; P= 0.52). There was a significantly delayed time to onset of overall cGvHD in the G-BM arm (HR=0.66; 95% CI 0.46-0.95; P=0.03) but time to onset of extensive cGvHD did not differ significantly between arms (HR=0.76; 95% CI 0.52-1.10; P=0.15). Other results are shown below: Evaluation of donor immune populations showed that IFNg+ CD4 T cells and CD56bright NK cells were protective against cGvHD in G-PB and G-BM recipients. In contrast, specific B cell populations consistent with memory or exhausted B cells were associated with cGvHD in G-PB recipients (CD19+CD27+, p=0.05, CD19+ CD21lo, p=0.009) but not in G-BM. Conclusions In this large prospective randomized trial, the primary endpoint of time to treatment failure did not differ between G-PB and G-BM. OS and RFS were also not significantly different between arms. Neutrophil and platelet recovery were slower by a median of 3 days with G-BM. However, time to overall cGvHD was significantly delayed in G-BM recipients with non-significant trends of less acute and less extensive cGvHD with G-BM. cGvHD correlated with different cell populations in G-PB and G-BM suggesting that donor source can influence the mechanism of cGvHD. Further analyses are underway to determine the clinical impact of these differences. 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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".