Long-term outcome after marrow transplantation from HLA-identical sibling donors for acquired aplastic anaemia using cyclophosphamide and in-vivo anti-CD52 monoclonal antibodies
Bibliographic record
Abstract
Despite excellent survival of marrow transplantation (BMT) in acquired severe aplastic anemia (SAA) using sibling donors, graft-versus-host disease (GVHD) continues to remain a major problem resulting in long-term complications and impaired quality of life. Between Aug 1989 and Aug 2004, 35 patients at our centre with acquired SAA underwent BMT from HLA-identical sibling donors using cyclophosphamide (CY) 50 mg/kg × 4 (days −5 to −2) and anti-CD52 MoAb 0.75–1 mg/kg BW as conditioning. Prior to 1999, rat derived anti-CD52 MoAb (Campath-1G) was used. We switched to humanised version of anti-CD52 MoAb (Alemtuzumab) when it became available in 1999. Median age at BMT was 17 yrs (range 4–46). Prior to BMT, 58% were heavily transfused (>50 transfusions) and 42% had previously failed ATG. Unmanipulated bone marrow was used as source of stem cells in all except one. GVHD prophylaxis was with cyclosporine (CSA) alone in 21 (60%) patients; 14 received anti-CD52 MoAb in addition to CSA. Eight patients had graft failure (primary, 4; secondary, 4) with a cumulative incidence of 23%. Graft failure was non-significantly higher in those receiving CSA and anti-CD52 MoAb as GVHD prophylaxis. No cases of graft failure are seen in 10 patients treated after 1999. The cumulative incidence of acute grade II-IV GVHD and chronic GVHD was 13% and 4%, respectively. None developed extensive chronic GVHD. Of the 19 recipients positive for cytomegalovirus (CMV), reactivation was seen in 5 (26%) with in 100 days. No cases of late CMV reactivation were observed. Six patients died of complications related to BMT at a median of 248 days (range 47–414). With a median follow-up of 59 months, the 5-year survival was 83% (95% C.I. 68–96). There was a non-significant trend towards improved survival in patients transplanted after 1995 (94% vs. 74%). Of the 29 survivors, serial chimerism studies were available on 20 and showed: 100% donor cells, 15; stable mixed chimerism with >85% donor cells, 3; and autologous recovery, 2. All survivors are transfusion-independent and have performance status of 100% except one who developed avascular necrosis. We conclude that the conditioning regimen containing CY and anti-CD52 MoAb is well tolerated and efficacious for acquired SAA using HLA-matched sibling donors. Based on the encouraging results of our study, further investigations are in progress evaluating the role of Alemtuzumab in the transplant protocols for AA using CSA alone as GVHD prophylaxis.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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".