OUTCOMES IN PATIENTS WITH B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA RECEIVING INOTUZUMAB OZOGAMICIN AND PROCEEDING TO HEMATOPOIETIC STEM CELL TRANSPLANTATION
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Inotuzumab ozogamicin (InO), a CD22-directed antibody-drug conjugate indicated for relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL), is associated with hepatotoxicity and hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), particularly after post-hematopoietic stem cell transplantation (HSCT). In this sttudy, we evaluate HSCT outcomes in patients (pts) who received InO before HSCT. This observational, post-authorization safety study included pts (>=18y) in the US with B-cell precursor ALL and R/R ALL who received InO and proceeded to first allogeneic HSCT. Post-HSCT outcomes included overall survival (OS), non-relapse mortality (NRM), relapse, and adverse events (AEs). Multivariate analysis examined prognostic factors for NRM and VOD. This final analysis is based om 5-y data. 261 pts (median age 39y, 58% male) were evaluated: 36% in first complete remission (CR1), 46% in CR2, 11% in CR>=3, 4% in first relapse, 1% in >= third relapse, and 2% with primary induction failure. Prior to HSCT, 32%, 47%, 14%, 5% and <1%received 1,2,3,4, and 5 InO cycles respectively: 120 pts received InO monotherapy and 112 received InO with systemic therapy (data unavailable for 29 pts). CR/CRi and MRD negativity was achieved in 80% and 64% of pts respectively after InO> Median time from last InO dose to HSCT was 2.5 mo. Post-HSCT 18-mo OS was 54% and 50% and 18-mo NRM was 22% and 25% for pts with ALL and R/R ALL respectively; most common causes of NRM were VOD (26%, 24%) and graft-versus-host disease (GVHD: 22%, 19%). AEs<=100d post-HSCT occuring in >=30% of pts with ALL and R/R ALL respectively were bacterial infection (51%, 56%), viral infection (44%, 44%) and acute GVHD (grades II-IV; 43%, 41%). 35 pts with ALL developed VOD: 15 cases were mild, 20 were severe and 22 died <= 18 mo post-HSCT; 8/35 pts received prophylactic defibrotide (22/244 of all pts). Transplant sources for the 15 mild and 20 severe cases of VOD, respectively, were peripheral blood stem cells (n+10,12), bone marrow (n+4,8) and umbilical cord blood (n = 1,0). VOD incidence <=100d post-HSCT was, respectively: 20%, 17%, 10% and 16% in pts with cumulative InO doses of <1,8, 1.8-2.7, 2.8-3.2, and >= 3.3 mg/m2; and 15%, 2%, 17% and 14% in pts with time from las InO dose to HSCT of 1, 1.1-1.6, 1.7-4, and >=3 mo. 204 pts with ALL were included in multivariate analyses; Karnofsky score <90 or unknown (vs 90-100) and dual alkylators (compared by MAC/no dual alkylators and RIC/non-MAC) were significant negative prognostic factors for NRM at 18 mo. Dual alkylators were the only significant negative prognostic factor for VOD at 100d (compared by MAC/no dual alkylators and RIC/non-MAC). In this real-world population of adults withh ALL who received InO before HSCT, including heavily pretreated pts, 18-mo OS was 54% and 18-mo NRM was 22%. Common AEs post-HSCT were bacterial infection, viral infection, and acute GVHD. VOD incidence was consistent with previous reports and dual alkylators should be avoided, when possible, in this subset of pts. Pts receiving these regimens should be considered for clinical trials testing novel prophylactic treatments for post-HSCT endothelal dysfunction syndromes, such as VOD.
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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) | 0.001 | 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) | 0.000 | 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 it