Hematopoietic Stem Cell Transplantation (SCT) for Hematologic Malignancy from Matched Related Donors (MRD) with a Myeloablative Once Daily IV Busulfan (Bu)/Fludarabine (Flu) Based Regimen (FLUBUP) with Thymoglobulin: Outcomes in 200 Patients with over One Year Follow-Up.
Bibliographic record
Abstract
Abstract Earlier reports indicated that a myelablative protocol based on once daily IV Bu with Flu plus rabbit antithymocyte globulin appeared effective and relatively well tolerated. Since 1999 this has been our standard regimen for all pts with hematologic malignancy, including those who might otherwise be candidates for non-myeloablative regimens. Two hundred MRD SCT patients (pts) were treated between 05/99 and 07/05. Chemotherapy comprised fludarabine 50mg/m2 on days -6 to -2 and IV busulfan (Busulfex, PDL Pharma) 3.2 mg/kg daily days -5 to -2 inclusive. Forty-six acute leukemia pts had additional TBI 200cGy x 2 on day (D) -1 or 0. Prophylaxis for GVHD was cyclosporine A, methotrexate with folinic acid and Thymoglobulin (Genzyme) 4.5 mg/kg in divided doses over 3 consecutive days pretransplant finishing D0. Cell source was mobilized blood cells (BCT) in 172 and marrow (BMT) in 28. Median age was 46 (range 18–65) and follow-up of survivors was 13–87 months (median 42). As engraftment and GVHD did not differ significantly data for BMT and BCT were combined. Two pts had graft failure (1 with autologous recovery) and two died before D28. The remaining 196 evaluable pts engrafted granulocytes at median of 16 days (range 2–42). Platelets engrafted in 194 pts at a median of 18 days (0–101), 2 died before engraftment on days 29 & 72. Incidence of acute GVHD grade II-IV, acute GVHD grade III-IV and chronic GVHD was 14±2%, 3±1% and 54±4% respectively. Five pts died before D100 of GVHD (1), candidiasis (1), influenza B (1), veno-occlusive disease (1) and myocardial infarction (1), after D100 15 deaths were related to GVHD (11), pneumonia/ARDS (2), graft failure (1) and pulmonary embolus (1). One case of PTLD resolved with rituxan, there was no serious neurological toxicity. For low-risk (acute leukemia CR1/CR2, CML CP1) pts 3 year TRM was 4±3% for those ≤45 years old (n = 54) and 6±4% for those >45 (n = 31). Corresponding figures for all others (high risk) were 6±4% (n = 40) and 27±7% (18±5% at one year, n = 75) (p = 0.04). [table 1] We conclude that FLUBUP appears to be well-tolerated with little mortality attributable to the regimen itself. In partular, concerns about excessive immune suppression (partularly causing PTLD) and neurotoxicity have not been substantiated. Chronic GVHD is the major cause of non-relapse death. Control of early morbidity and mortality from GVHD may allow intensification of the regimen, for example by adding TBI. There is also evidence that the safety can be improved by monitoring Bu levels. The effect of age on TRM is only apparent in high-risk pts, the challenge is to reduce mortality from chronic GVHD in these individuals without sacrificing graft-vs.-malignancy. 3 year outcomes (%) for groups with >10 pts Disease/stage n survival TRM * p = 0.07 AML CR1/2 (no TBI) 32 66±8 9±5 AML CR1/2 (TBI)* 16 94±6 0 AML advanced (no TBI) 18 22±10 17±9 MDS 15 79±11 24±12 ALL CR1/2 15 73±11 8±7 CML CP1 22 100% 0 CLL/Richter’s (as primary indication) 14 68±13 16±10 Multiple Myeloma 13 54±14 8±7 NHL (low grade/mantle) 21 75±10 17±9 All pts 200 66±3 12±3
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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 | 0.000 | 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".