title: Phase II Study of Propylene Glycol-Free Melphalan Combined with Carmustine, Etoposide, and Cytarabine for Myeloablative Conditioning in Lymphoma Patients Undergoing Autologous Stem Cell Transplantation.
abstract: The lyophilized formulation of melphalan has several limitations based on its marginal solubility, limited stability after reconstitution, and the requirement to reconstitute it in propylene glycol (PG). PG-free melphalan (Evomela; Spectrum Pharmaceuticals, Irvine CA) overcomes these limitations by using the solubilizing agent Captisol (Ligand Pharmaceuticals, Inc., LaJolla CA) to improve the stability of the reconstituted melphalan and avoid the potential toxicities of PG. This phase II study investigated the safety and efficacy of high-dose PG-free melphalan when included in the carmustine, etoposide, and cytarabine (BEAM) regimen for adult patients with non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL). Carmustine, etoposide, and cytarabine were given at standard doses on day -6 through day -3. PG-free melphalan, 140 mg/m2, was infused over 30 minutes on day -2. The primary endpoint was toxicity. Fifty patients (33 NHL/17 HL) completed BEAM with PG-free melphalan and stem cell infusion. The most common grades 3 to 4 nonhematologic toxicities were neutropenic fever (68%), infections (36%), and electrolyte abnormalities. Forty-one patients (82%) had oral mucositis, which was mostly grades 1 to 2 (6% grade 3). Moderate or severe gastrointestinal toxicities were uncommon. There were no treatment-related deaths. Forty-nine patients (98%) had neutrophil and platelet engraftment at a median of 10 and 19 days, respectively. At response assessment at 60 to 100 days after autologous stem cell transplantation, 42 patients (82%) were in complete remission, 2 in partial remission, and 6 had progressive disease. Progression-free survival at 1 year was 70%. These results demonstrate that PG-free melphalan can be used in place of the standard, lyophilized formulation of melphalan in the BEAM regimen for lymphoma patients undergoing autologous stem cell transplantation. It has a safety profile that compares favorably with standard lyophilized melphalan, and the engraftment rate and response rates were consistent with expectations.
authors: Department of Medicine, Section of Bone Marrow Transplant and Leukemia, Washington University School of Medicine, St. Louis, Missouri. Electronic address: acashen@wustl.edu.
authors: Amanda F
authors: AF
authors: Cashen
authors: Department of Medicine, Section of Bone Marrow Transplant and Leukemia, Washington University School of Medicine, St. Louis, Missouri.
authors: Theresa
authors: T
authors: Fletcher
authors: Department of Medicine, Section of Bone Marrow Transplant and Leukemia, Washington University School of Medicine, St. Louis, Missouri.
authors: Connie
authors: C
authors: Ceriotti
authors: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors: Feng
authors: F
authors: Gao
authors: Department of Medicine, Section of Bone Marrow Transplant and Leukemia, Washington University School of Medicine, St. Louis, Missouri.
authors: Armin
authors: A
authors: Ghobadi
authors: Department of Medicine, Section of Bone Marrow Transplant and Leukemia, Washington University School of Medicine, St. Louis, Missouri.
authors: Ravi
authors: R
authors: Vij
authors: Department of Medicine, Section of Bone Marrow Transplant and Leukemia, Washington University School of Medicine, St. Louis, Missouri.
authors: Keith
authors: K
authors: Stockerl-Goldstein
authors: Department of Medicine, Section of Bone Marrow Transplant and Leukemia, Washington University School of Medicine, St. Louis, Missouri.
authors: John
authors: J
authors: DiPersio
authors: Department of Medicine, Section of Bone Marrow Transplant and Leukemia, Washington University School of Medicine, St. Louis, Missouri.
authors: Camille
authors: C
authors: Abboud
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002330:Carmustine / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D008223:Lymphoma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000633:toxicity; D019653:Myeloablative Agonists / Q000008:administration & dosage*; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019653:Myeloablative Agonists; D003561:Cytarabine; D005047:Etoposide; D008558:Melphalan; D002330:Carmustine
keywords: Autologous stem cell transplant; Hodgkin lymphoma; Melphalan; Non-Hodgkin lymphoma; Propylene glycol