Resolution of CGD Related Colitis after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Chronic Granulomatous Disease—Early Results From the 6903 Study of the Primary Immune Deficiency Treatment Consortium (PIDTC)
Bibliographic record
Abstract
Background: Phagocytes of patients with CGD have a deficient NADPH oxidase and respiratory burst, which limit production of reactive oxygen species. Allogeneic hematopoietic stem cell transplant (HSCT) offers a potential cure with resolution of life-threatening infections. Approximately 50% of CGD patients develop inflammatory bowel disease similar in pathology to Crohn's disease. CGD related colitis is often difficult to treat and increases disease associated morbidity. We sought to determine if CGD related colitis resolved after HSCT in CGD patients. Methods: Subjects were enrolled on PIDTC protocol 6903, a multi-center retrospective and prospective natural history study of patients treated for CGD since 1995. We evaluated survival, transplant strategy, and the incidence of colitis in CGD patients who received HSCT, at baseline and post-HSCT. The 2-year probability of survival among subjects with or without IBD at baseline was estimated by Kaplan-Meier analysis, and the groups were compared using the log-rank test. Results: 153 subjects underwent HSCT for treatment of CGD during 1/1/2005-6/31/2016 and had known baseline colitis. 53 (35%) had a history of colitis prior to HSCT, and, 17 out of 44 evaluable patients (34%) had disease that was not controlled with medications at the time of HSCT. Conditioning regimens included BuCy (27%), BuFlu (27%), Bu + TBI (19%), FluMel (13%), and others (13%). Of these, 32 (21%), 10 (7%), and 6 (4%) subjects received grafts from HLA-matched sibling donors, other HLA-matched related donors, or mismatched related donors, respectively, while 104 (68%) received grafts from unrelated donors. Graft sources included bone marrow (55%), peripheral blood stem cells (28%) or cord blood (17%). Most subjects (71%) received a calcineurin inhibitor for GVHD prophylaxis with or without 1 or more additional agent(s). The 2-year probability of overall survival of those with or without a history of colitis at baseline was 82% (95% CI 68-90%) vs. 87% (95% CI 78-92%); P = .77. Among the 153 subjects with a history of colitis at baseline and evaluated at 2 years post-HSCT, 90% had resolution of colitis, 5% still had colitis symptoms, and 5% had unknown colitis status. Conclusions: Allogeneic HSCT for CGD was associated with anoverall survival of > 80% at 2 years. For at least 90% of CGD patients with a history of colitis at baseline and evaluable at 2 years post-HSCT, resolution of colitis was observed, consistent with curative treatment for colitis related to CGD. Sponsored by: NIAID and ORDR, NCATS, NIH (U54-AI-082973).
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".