title: Allogeneic Hematopoietic Cell Transplantation in Multiple Myeloma: Focus on Longitudinal Assessment of Donor Chimerism, Extramedullary Disease, and High-Risk Cytogenetic Features.
abstract: Although generally not applied as first-line treatment of multiple myeloma, allogeneic hematopoietic cell transplantation (allo-SCT) can still be chosen as ultimate escalation approach in high-risk patients, preferentially within the framework of clinical trials. In this study, we investigated whether decreasing donor chimerism (DC) is predictive for relapse. In addition, we comprehensively determined the impact of several other disease- and treatment-related factors on outcome. One hundred fifty-five multiple myeloma patients whose DC status was followed serially by the short tandem repeat-based techniques at a single lab were included in this retrospective study. Outcome variables were studied in univariate and multivariable analyses. Available were 2.324 DC samples (median, 12 per patient). Loss of full DC was associated with shorter progression-free survival (PFS) (HR, 1.7; 95% CI, 1.1 to 2.6) but did not impact overall survival. Two-thirds of patients with International Myeloma Working Group-defined relapses still displayed a full DC in peripheral blood or bone marrow. Extramedullary manifestations were observed in 33% of patients, accounting for the discrepancy between DC analysis and the actual disease status. In multivariable analysis, the 2 most relevant variables for an unfavorable PFS were progressive disease before allo-SCT (HR, 3.0; 95% CI, 1.5 to 5.9) and allo-SCT at least the second relapse (HR, 2.8; 95% CI, 1.5 to 4.9), whereas for overall survival progressive disease or partial response before allo-SCT had the strongest negative effects (HR, 4.2; 95% CI, 1.9 to 9, and HR, 2.0; 95% CI, 1.0 to 3.8, respectively). Adverse cytogenetics such as del17p, t(4,14) or amp(1q21) were not associated with shorter survival after allo-SCT. Extensive DC sampling beyond robust engraftment does not appear to provide additional information helpful for disease management in most patients and is challenged by a significant incidence of extramedullary disease. In our series, allo-SCT overcame unfavorable cytogenetics.
authors: Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany. Electronic address: LRasche@uams.edu.
authors: Leo
authors: L
authors: Rasche
authors: Department of Internal Medicine I, Carl Gustav Carus University, Dresden, Germany.
authors: Christoph
authors: C
authors: Röllig
authors: DKD Helios Klinik Wiesbaden, Wiesbaden, Germany.
authors: Gernot
authors: G
authors: Stuhler
authors: Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
authors: Sophia
authors: S
authors: Danhof
authors: Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
authors: Stephan
authors: S
authors: Mielke
authors: Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
authors: Goetz Ulrich
authors: GU
authors: Grigoleit
authors: Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
authors: Lea
authors: L
authors: Dissen
authors: Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
authors: Lea
authors: L
authors: Schemmel
authors: Department of Internal Medicine I, Carl Gustav Carus University, Dresden, Germany.
authors: Jan Moritz
authors: JM
authors: Middeke
authors: Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany.
authors: Viktoria
authors: V
authors: Rücker
authors: Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
authors: Martin
authors: M
authors: Schreder
authors: Department of Internal Medicine I, Carl Gustav Carus University, Dresden, Germany.
authors: Johannes
authors: J
authors: Schetelig
authors: Department of Internal Medicine I, Carl Gustav Carus University, Dresden, Germany.
authors: Martin
authors: M
authors: Bornhäuser
authors: Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
authors: Hermann
authors: H
authors: Einsele
authors: Department of Internal Medicine I, Carl Gustav Carus University, Dresden, Germany.
authors: Christian
authors: C
authors: Thiede
authors: Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
authors: Stefan
authors: S
authors: Knop
mesh_terms: D000328:Adult; D046528:Chimerism; D003582:Cytogenetics; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009101:Multiple Myeloma / Q000175:diagnosis / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012008:Recurrence; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D014184:Transplantation, Homologous
keywords: Allogeneic hematopoietic cell transplantation; Chimerism; Donor lymphocyte infusion; Extramedullary disease; High-risk cytogenetics; Multiple myeloma