Arsenic Trioxide with Ascorbic Acid and High-Dose Melphalan for Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma
| Autor: | Roy B. Jones, Richard E. Champlin, Daniel R. Couriel, Amin M. Alousi, Muzaffar H. Qazilbash, Steven G. Matthes, Rima M. Saliba, Floralyn Mendoza, Marcos de Lima, Sergio Giralt, Chitra Hosing, Marilyn S. Davis, Donna M. Weber, Partow Kebriaei, Michael Wang |
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| Rok vydání: | 2006 |
| Předmět: |
Melphalan
medicine.medical_specialty Neutrophil Engraftment business.industry medicine.medical_treatment Immunology Cell Biology Hematology Hematopoietic stem cell transplantation Ascorbic acid medicine.disease Biochemistry Gastroenterology Surgery chemistry.chemical_compound chemistry Internal medicine Toxicity medicine Arsenic trioxide business Multiple myeloma medicine.drug Preparative Regimen |
| Zdroj: | Blood. 108:3090-3090 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v108.11.3090.3090 |
| Popis: | Backround: Arsenic trioxide (ATO) has been shown to be synergistic with melphalan both in vitro and in vivo. We conducted a phase I/II trial to determine the safety and efficacy of a combination of arsenic trioxide, melphalan and ascorbic acid (AA) as preparative regimen in patients undergoing high-dose therapy (HDT) and autologous hematopoietic progenitor cell transplantation for multiple myeloma (MM). We also assessed the impact ATO levels on melphalan pharmacokinetics (PK), engraftment and toxicity. Methods: Forty-eight patients with secretory myeloma (23 females, 25 males; median age: 54, range: 3570) were treated between 4/04 and 8/05. All patient received melphalan 100 mg/m2 IV on days -4 and -3 and AA 1000 mg/day IV on days -9 to -3. Patients were randomized to 3 arms; no ATO (arm 1), ATO 0.15 mg/kg IV on days -9 to -3 (arm 2) and ATO 0.25 mg/kg IV on days -9 to -3 (arm 3). Twelve patients had disease progression or relapse after a prior autograft. Median CD34 cells dose infused was 4.5 x 106/kg (range 2.3–10.9). Results: Patients in all 3 arms were evenly matched. With a median F/U of 14.0 months (range 6–25) post autograft, no dose-limiting toxicity or non-relapse mortality was seen. Toxicity was limited to grade I or II nausea, vomiting and diarrhea. Median ATO levels on day 0 in arms 1, 2 and 3 were 0.2, 26.3 and 46.2 ng/ml, respectively. Melphalan PK was not altered by ATO pretreatment. Median time to neutrophil engraftment (ANC >500/ dl) was 9 days. There were no engraftment failures or delays in the ATO arms. CR rate for the entire group was 23%, and total response rate (CR + PR) was 75%. 1-year Progression-free survival (PFS) and overall survival (OS) were 75% and 95%, respectively. There was no significant difference in CR, RR, PFS or OS between the 3 arms (p = 0.9, 0.9, 0.4 and 0.6, respectively). A prior autologous transplant (p = 0.02) and abnormal cytogenetics at transplant (p = 0.04) were associated with a significantly shorter remission. Conclusions: ATO + melphalan + ascorbic acid is a safe, effective and well tolerated preparative regimen for patients with multiple myeloma undergoing an autotransplant. A longer follow up is needed to assess the impact of ATO on progression-free and overall survival. |
| Databáze: | OpenAIRE |
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