title: Dose-intensified bendamustine followed by autologous peripheral blood stem cell support in relapsed and refractory multiple myeloma with impaired bone marrow function.
abstract: Therapeutic options in heavily pretreated relapsed/refractory multiple myeloma patients are often very limited because of impaired bone marrow function. Bendamustine is effective in multiple myeloma and has a favourable toxicity profile. We hypothesized that dose-intensified bendamustine (180 mg/m2, day 1 and 2) followed by autologous blood stem cell support (ASCS) would improve bone marrow function with low post-transplant toxicity in patients with severely impaired haematopoiesis. We analyzed 28 consecutive myeloma patients, with a median of three prior lines of therapy (range 2-7), who had relapsed from the last treatment with very limited bone marrow function and were therefore ineligible for conventional chemotherapy, novel agents or trial enrolment. Dose-intensified bendamustine with ASCS improved haematopoiesis as reflected by increased platelet counts (median 40/nl vs 94/nl, p = 0.0004) and white blood cell counts (3.0/nl vs 4.8/nl, p = 0.02) at day +100. The median time until engraftment of platelets (>50/nl) was 11 days (0-24 days) and of white cell counts (>1.0/nl) 0 days (0-24 days). At least, a minimal response was achieved in 36% of patients. The disease stabilization rate was 50% while the median progression-free survival rate was limited to 2.14 months. Most importantly, patients were once again eligible for alternative treatments including enrolment into clinical trials. We conclude that dose-intensified bendamustine followed by ASCS is safe and feasible for multiple myeloma patients with very limited bone marrow reserve. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Max-Eder-Group 'Experimental Therapies for Hematologic Malignancies', Department of Medicine V, Heidelberg University Hospital and German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Breitkreutz
authors.affiliation: Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Becker
authors.affiliation: Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.affiliation: Department of Medicine V, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Florentina
authors.initials: F
authors.lastname: Kosely
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Heining
authors.affiliation: Department of Medicine V, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Hillengass
authors.affiliation: Department of Medicine V, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Egerer
authors.affiliation: Department of Medicine V, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg, Germany.|Department of Medicine V, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.affiliation: Max-Eder-Group 'Experimental Therapies for Hematologic Malignancies', Department of Medicine V, Heidelberg University Hospital and German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Medicine V, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Raab
mesh_terms: D000328:Adult; D000368:Aged; D064592:Autografts; D000069461:Bendamustine Hydrochloride / Q000008:administration & dosage*; D001853:Bone Marrow / Q000503:physiopathology*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation; D015996:Survival Rate; D019172:Transplantation Conditioning
chemical_list: D000069461:Bendamustine Hydrochloride
keywords: autologous blood stem cells; bendamustine; bone marrow function; multiple myeloma