Safety and Efficacy of Hematopoietic Stem Cell Remobilization with Plerixafor (Mozobil®) + G-CSF In Pediatric Patients with Malignant Disorders
Notice bibliographique
Résumé
Abstract Abstract 2245 Background: High dose chemo/radiotherapy followed by autologous hematopoietic stem cell (HSC) transplantation (HSCT) is indicated in several pediatric malignant disorders such as neuroblastoma and relapsed Hodgkin's disease. Ideally, 2–5 × 106 CD34+ cells/kg should be infused during autologous peripheral blood (PB) HSCT to support timely and durable engraftment and improve transplant outcomes. In patients who have received repetitive cycles of intensive chemotherapy, this target is not always achieved with standard mobilization regimens. Plerixafor, a novel CXCR4 antagonist, when combined with granulocyte colony-stimulating factor (G-CSF), can safely and predictably mobilize adequate numbers of CD34+ HSC to support transplantation in adult patients with myeloma and lymphoma. We report on the safety and efficacy of PB HSC mobilization with plerixafor + G-CSF in pediatric patients with cancer. Methods: This is a retrospective analysis of all children with various malignant disorders who were enrolled in the US plerixafor compassionate use program (CUP; NCT00291811). Patients who had previously failed HSC mobilization (defined as the inability to collect ≥2 x106 CD34+ cells/kg or achieve an adequate PB CD34+ cell count, typically ≥10 CD34+ cells/μl) with growth factor +/− chemotherapy were treated with plerixafor + G-CSF. The goal was to collect ≥2 × 106 CD34+ cells/kg for autologous HSCT. G-CSF (10μg/kg SC) was administered daily for 5 days. Plerixafor (0.24 mg/kg SC) was given in the evening on Day 4, ~11 hours prior to apheresis. Plerixafor, G-CSF and apheresis were repeated daily until ≥2 × 106 CD34+ cells/kg had been collected. Results: A total of 16 patients with non Hodgkin's lymphoma (3), Hodgkin's disease (1), CNS tumors (4), Ewing's sarcoma (4), neuroblastoma (2), osteogenic sarcoma (1) and desmoplastic small cell tumor (1) underwent the procedure. The median age was 14 years and 7 (44%) patients were male. In previous mobilization attempts, 5 patients failed to collect the minimum transplantable cell dose with a median yield of 0.44 x106 (range: 0.17–2.2 × 106) CD34+ cells/kg. Apheresis was never attempted in11 patients due to low PB CD34+ cell levels; median cells/μl was 1.0 (range, 0.01–12) in 9 patients with available data. Initial mobilization regimens included growth factor alone in 6 patients and growth factor + chemotherapy in 9 patients (data unavailable for 1 patient). When re-challenged for mobilization with plerixafor + G-CSF, 14 (88%) patients successfully collected ≥2 × 106 CD34+ cells/kg; this included all 4 (100%) patients with lymphoma and 10 (83%) patients with solid tumors. The median time to collect the target cell dose was 1.5 days (range 1–5 days). The median CD34+ cell yield from all patients was 3.5 × 106 cells/kg (range 0.96 – 9.80 × 106); patients with lymphoma and solid tumors collected a median of 7.2 (range 3.2 – 7.9) × 106 and 3.3 (range 0.96 –9.8) × 106 CD34+ cells/kg, respectively. Eleven (69%) patients proceeded to transplant including all 4 (100%) patients with lymphoma and 7 (58%) patients with solid tumors. One patient with neuroblastoma received a tandem transplant. The median infused cell dose was 4.18 × 106 CD34+ cells/kg (range 1.7 – 7.6 × 106). The median time to neutrophil and platelet engraftment was 14 and 33 days, respectively. Plerixafor-related adverse events were mostly mild, and observed in 5 (31%) patients. They included administration site reactions (4), vomiting (2), nausea (1) and oral paraesthesia (1). No patient experienced a serious adverse event. Conclusions: Treatment with plerixafor + G-CSF safely and effectively mobilized HSC in the majority of pediatric patients with malignant disorders after failure of standard mobilization with growth factor ± chemotherapy. Successful stem cell mobilization allowed consideration of autologous HSCT when indicated. Mobilization with plerixafor was safe and resulted in prompt engraftment. Many of these patients could not have proceeded to transplant without this intervention. Disclosures: Off Label Use: Plerixafor (Mozobil®), a hematopoietic stem cell mobilizer, is approved by the US FDA in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma. McCarty: Genzyme, Amgen: Honoraria, Research Funding. Angell: Genzyme Corporation: Employment, Equity Ownership. Huebner: Genzyme Corporation: Employment, Equity Ownership.
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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 | 0,001 | 0,002 |
| 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 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 ».