Langerhans Cell Histiocytosis with Hematological Dysfunction, Refractory to Standard Therapy Could Be Cured by an Association of 2-CdA and Ara-C: Concordant Results from the Observational Survey of Treated Patients and from a Nation Wide Registry.
Notice bibliographique
Résumé
Abstract In Children’s Langerhans cell histiocytosis, hematological dysfunction refractory to standard regimen, is the major cause of death until recently. In 2005, (Eur J Cancer, Bernard F et al, 2005) we have reported the results of a pilot study of 2-CdA and Ara-C in this extremely rare subset of patients. Among 10 patients enrolled between 1996 and 2004 (group 1), seven were cured, but three died, two of toxicity, and one after subsequent bone marrow transplantation. We report here A) the results of the 9 additional patients treated in France between mid 2004 and july 2007 (group 2) and B) the results of the national registry which had collected at the national level all cases of LCH in france since 1983. A) The group 2 comprised 9 patients who have all received at least two courses of Ara-C (1000 mg/m2/d) and 2-CdA (9 mg/m2/d) administered for 5 days. Maintenance therapy usually involved 6 courses of 2-CdA (5mg/m2 for 3 days every 3 weeks). Group 2 was comparable to group 1 for median diagnosis age (group 1: 0.78 years vs group 2: 0.73 years), as well as the number of organs involved. The delay between LCH diagnosis and 2-CdA Ara-C onset was shorter in the group 2 (group 1: 0.98 years- group 2: 0.35 years). The initial regimen to treat LCH was the same in the two groups (Vinblastine + steroid +- Methotrexate = LCH III protocol). Group 1 had received several second line therapies before 2-CdA Ara-C, while group 2 had received only the 2-Cda Ara-C as a second line therapy. Grade IV WHO haematological toxicities were observed in all patients, but no toxic death was observed in the group 2. One patient in group 2 underwent a 2-CdA overdose (injection at 10-fold the dose) but no major side effect was observed and latter the protocol was completed. After 2 courses, a decrease in disease activity was observed in all patients, but none had achieved a complete remission status after 2 courses. One patient had received a subsequent HSCT with an attenuated conditioning regimen with a very short hematological recovery at day 15, while the other patients had received only standard chemotherapy regimen as maintenance. Complete remission was achieved in the 8 assessable patients (including the patient who had received HSCT) and one patient had still an active disease but only 2 months after 2-Cda Arac onset. B) In the national French LCH register, 103 cases with hematological dysfunction, among 827 patients (<18 years), were registered from 1983 to 2007. In the same period, 45 deaths were observed, 34 (75%) with haematological dysfunction. In the latter group, the death rate dramatically decreased since the recommendation of 2-Cda Arac as salvage therapy for patients haematological dysfunction refractory to standard chemotherapy in France (1996) as 28 deaths were observed in the 54 patients diagnosed before 1996 (51%) and 6 among 49 patients since 1996 (12%) (p<0.001). In conclusion, 2-CdA and Ara-C combined chemotherapy has major activity to treat refractory LCH with haematological dysfunction, despite a high toxicity. This promising results warrant confirmation in the phase II open labelled study LCHS2005, officially open in France, and in Canada and in few centers in USA.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| 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) | 0,000 | 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 tête enseignante, pas un consensus.
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