Abstract
Introduction
Haploidentical stem cells are becoming an alternative stem cell source for patients lacking an HLA-identical sibling or 10/10 HLA-matched donor. While an increasing number of studies for patients with acute leukemia, malignant lymphoma, and MDS are reported there are only very few results of haploidentical stem cell transplants in myeloma patients.
Method and patients
In EBMT registry 50 MMpatients with a median age of 55 y (r: 37 - 73) with relapse after autograft who received a mismatched related stem cell graft after myeloablative (n = 12, 25%) or reduced intensity conditioning (n = 37, 75%) between 2004 and 2014 were reported. The median time to relapse after single (n = 28, 56%) or tandem (n = 18, 36%) autologous stem cell transplantation was 6.2 months (r: 0.1 - 30.5) and the median time between last autograft and allograft was 17.4 months (r: 2 = 74 months).
At time of allograft 4 (8%) of the patients were in CR, 21 (42%) in PR, 9 (18%) had stable disease or minor response, and 15 (30%) had progressive disease. The majority (84%) received peripheral blood stem cells as graft source and GvHD prophylaxis with ex- or in-vivo T-cell depletion (CD34 selection or ATG) (Cyclophosphamide post transplant) was performed in 37% of the patients while 63% did not receive any in-vivo or ex-vivo T-cell depletion.
Results
After a median follow-up of 52 months (95% CI: 12-112) the cumulative incidence of non-relapse mortality at 1 year was 20% (95% CI: 9 - 31%) and the cumulative incidence of relapse at 3 years was 56% (95% CI: 42 - 70%) resulting in an estimated 3-year PFS and OS of 15% (95% CI: 5 - 26%) 31% (95% CI: 7 - 45%), respectively. Significant factor for improved OS in a univariate analysis was only the use of BM (3 y OS: 71% (95% CI: 38 -100%) vs. 24% (95% CI: 11 - 38%), p = 0.02) and for relapse a higher but not significant incidence for ex-vivo T-cell depletion was observed (p = 0.07). The use of cyclophosphamide post transplantation as GvHD prophylaxis did not influence NRM, relapse incidence, PFS, OS, or chronic GvHD.
Conclusion
Haploidentical stem cell transplantation after relapse to an autograft is feasible for MMpatients. Major treatment failure is the high incidence of relapse. Post-transplant cyclophosphamide had no major impact on outcome in this limited number of patients.
Dreger: medac: Other: Travel grants; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Riemser: Consultancy, Research Funding; Jansen: Consultancy; Jansen: Consultancy; medac: Other; medac: Other: Travel grants; medac: Other: Travel grants; medac: Other; Gilead: Consultancy, Speakers Bureau; medac: Other; medac: Other; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Jansen: Consultancy; Jansen: Consultancy; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; Gilead: Consultancy, Speakers Bureau; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Riemser: Consultancy, Research Funding; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Riemser: Consultancy, Research Funding; Jansen: Consultancy; Riemser: Consultancy, Research Funding; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Jansen: Consultancy; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; medac: Other: Travel grants; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; medac: Other: Travel grants; medac: Other: Travel grants; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau. Corradini: Amgen: Honoraria; Novartis: Honoraria; Roche: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Gilead: Honoraria. Zuckerman: BioSight Ltd.: Consultancy. Ciceri: GSK: Other: B-thalassemia gene therapy was developed by Fondazione Telethon and Ospedale San Raffaele and has been inlicenced by GSK that provides funding for the clinical trial, Research Funding. Petersen: Sanofi: Membership on an entity's Board of Directors or advisory committees. Schönland: Sanofi: Research Funding; prothena: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Speakers Bureau. Garderet: Amgen: Honoraria; Takeda: Honoraria.
Author notes
Asterisk with author names denotes non-ASH members.
