Comparison of autologous and allogeneic hematopoietic cell transplantation strategies in patients with primary plasma cell leukemia, with dynamic prediction modeling
Sarah Lawless,
Simona Iacobelli,
Nina Simone Knelange,
Patrice Chevallier,
Didier Blaise,
Noel Milpied,
Roberto Foà,
Jan J. Cornelissen,
Bruno Lioure,
Ruben Benjamin,
Xavier Poiré,
Monique C. Minnema,
Matthew Collin,
Stig Lenhoff,
John A. Snowden,
Stella Santarone,
Keith M. O. Wilson,
Fernanda Trigo,
Peter Dreger,
Lara H. Böhmer,
Hein Putter,
Laurent Garderet,
Nicolaus Kröger,
Ibrahim Yaukoub-Agha,
Stefan Schönland,
Curly Morris
Affiliations
Sarah Lawless
Belfast City Hospital, Belfast
Simona Iacobelli
Tor Vergata University, Rome
Nina Simone Knelange
EBMT Data Office Leiden, Leiden
Patrice Chevallier
CHU Nantes, Nantes
Didier Blaise
ICRCM, INSERM, CNRS, AMU and Institut Paoli Calmettes, Marseille
Noel Milpied
CHU Bordeaux, Pessac
Roberto Foà
Univ.`La Sapienza`, Rome
Jan J. Cornelissen
Erasmus MC Cancer Institute, Rotterdam
Bruno Lioure
Nouvel Hopital Civil, Strasbourg
Ruben Benjamin
Kings College Hospital, London
Xavier Poiré
Cliniques Universitaires St. Luc, Brussels
Monique C. Minnema
University Medical Center, Utrecht, Utrecht
Matthew Collin
Freeman Hospital, Newcastle
Stig Lenhoff
Skanes University Hospital, Lund
John A. Snowden
Sheffield Teaching Hospitals Foundation Trust, Sheffield
Stella Santarone
Ospedale Civile, Pescara
Keith M. O. Wilson
University Hospital of Wales, Cardiff Wales
Fernanda Trigo
Hospital Sao Joao, Porto
Peter Dreger
University of Heidelberg, Heidelberg
Lara H. Böhmer
Haga Teaching Hospital The Hague
Hein Putter
Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden
Laurent Garderet
Hospital Saint Antoine, Paris
Nicolaus Kröger
University Hospital Eppendorf, Hamburg
Ibrahim Yaukoub-Agha
CHU de Lille, Univ Lille, INSERM U1286, Infinite, 59000 Lille, Lille
Primary plasma cell leukemia (pPCL) is a rare and challenging malignancy. There are limited data regarding optimum transplant approaches. We therefore undertook a retrospective analysis from 1998-2014 of 751 patients with pPCL undergoing one of four transplant strategies; single autologous transplant (single auto), single allogeneic transplant (allo-first) or a combined tandem approach with an allogeneic transplant following an autologous transplant (auto-allo) or a tandem autologous transplant (auto-auto). To avoid time bias, multiple analytic approaches were employed including Cox models with time-dependent covariates and dynamic prediction by landmarking. Initial comparisons were made between patients undergoing allo-first (n=70) versus auto-first (n=681), regardless of a subsequent second transplant. The allo-first group had a lower relapse rate (45.9%, 95% confidence interval [95% CI]: 33.2-58.6 vs. 68.4%, 64.4-72.4) but higher non-relapse mortality (27%, 95% CI: 15.9-38.1 vs. 7.3%, 5.2-9.4) at 36 months. Patients who underwent allo-first had a remarkably higher risk in the first 100 days for both overall survival and progression-free survival. Patients undergoing auto-allo (n=122) had no increased risk in the short term and a significant benefit in progression-free survival after 100 days compared to those undergoing single auto (hazard ratio [HR]=0.69, 95% CI: 0.52- 0.92; P=0.012). Auto-auto (n=117) was an effective option for patients achieving complete remission prior to their first transplant, whereas in patients who did not achieve complete remission prior to transplantation our modeling predicted that auto-allo was superior. This is the largest retrospective study reporting on transplantation in pPCL to date. We confirm a significant mortality risk within the first 100 days for allo-first and suggest that tandem transplant strategies are superior. Disease status at time of transplant influences outcome. This knowledge may help to guide clinical decisions on transplant strategy.