Alemtuzumab Used with Fludarabine and Cyclophosphamide (FCC) for Stem Cell Transplantation in Acquired Aplastic Anemia Is Associated with a Low Risk of Graft Versus Host Disease and Viral Infections and with Sustained Engraftment.
Bibliographic record
Abstract
Abstract Abstract 1084 Poster Board I-106 Graft rejection and chronic GVHD remain major obstacles to successful outcome after stem cell transplantation (SCT) for aplastic anemia (AA). Using cyclophosphamide (CY) 200mg/kg with ATG, rejection occurs in 5-10% and chronic GVHD in 30-40% of patients transplanted from HLA matched sibling donors (MSD). For unrelated donor (UD) SCT using Fludarabine with CY and ATG, rejection occurs in 18% (30% for patients > 14 years of age) and chronic GVHD in 27%. We have pioneered the use of Alemtuzumab with CY in AA SCT and shown a reduction in GVHD although graft rejection was high at 24%. More recently, Fludarabine has been added to the conditioning to reduce graft rejection. In this retrospective, multi-center study, we report outcomes after SCT for acquired AA in 37 patients using Alemtuzumab, Fludarabine and CY (FCC) conditioning regimen. Alemtuzumab dose was 0.2mg/kg x5 days (n=20), 60mgx1 (n=12), 25mgx4 (n=4) and 40mgx1+30mgx2 (n=1). All patients received Fludarabine 30mg/m2x4 and CY 300mg/m2 x4 (FCC). Patients were transplanted from 1999 to 2009. Median follow up of survivors was 641days (range 72-3547). Disease severity was ‘very severe’ in10, ‘severe’ in 20 and ‘non-severe’ in 7 patients. SCT was performed using MSD in 15 patients (40%) and UD in 22 (60%), of whom all but one were matched for 8/8 or 10/10 alleles. Median age was 35 years (range 8-55). Stem cell source was bone marrow (BM) in 21 (57%), peripheral blood stem cells (PBSC) in 7 (19%), BM+PBSC in 5 (13%) and G-mobilised BM in 4 (11%). Time from diagnosis to SCT was < 12 months in 57% of patients and > 12 months in 41%. 8/15 (53%) of sibling transplants and 18/22 (82%) of UD transplants received immunosuppressive therapy prior to SCT. There were 5 cases of graft failure, early rejection in 2 UD SCT and late graft rejection in 3 (one UD and two MSD). Of the 5 patients with graft rejection, BM was used as the stem cell source in 3, G-mobilised BM in one and PBSC in one. Cumulative incidence of graft failure at 1 year was 15% ± 4% (14% for MSD and 15% for UD SCT). For patients transplanted > 12 months from diagnosis, graft failure was 25% compared with 10% for patients transplanted within 12 months (p= 0.191). Acute GVHD occurred in 13.5% patients, grade I-II in all cases. Chronic GVHD occurred in only one patient (2.7%, extensive). Data for CMV and adenovirus infections was available in 21 patients, and in 20 patients for EBV. CMV reactivation occurred in 2/21 (9.5%) patients, with one case of CMV disease. EBV infection occurred in 2/20 patients (10%): one responded to Rituximab and one patient died from progressive EBV PTLD. There were no cases of adenovirus infection. Overall survival (OS) at 3 years was 89% (93% for MSD and 85% for UD SCT, p= 0.658). For all patients, OS was 95% when time from diagnosis to SCT was < 12 months and 80% for > 12 months (p= 0.273). For patients > 40 years of age, there was no significant difference in OS compared with patients < 40 years old (93% vs 82%). There were 3 deaths, one from chronic GVHD and CMV at day + 427, one from graft failure at day +134 and one due to EBV PTLD at day +180. We conclude that the use of Alemtuzumab with Fludarabine and CY (FCC) for MSD and UD SCT for acquired AA is associated with excellent survival, a low incidence of acute and chronic GVHD and a low incidence of viral infections. Disclosures Marsh: Genzyme: Consultancy, Honoraria. Off Label Use: Alemtuzumab used for conditioning for stem cell transplantation for aplastic anemia. Gupta:Genzyme: Honoraria, Research Funding.
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 | 0.000 |
| 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".