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.
Notice bibliographique
Résumé
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
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».