Faculty Collaboration Database

Long-term follow up of tandem autologous-allogeneic hematopoietic cell transplantation for multiple myeloma. Haematologica 2019 Feb;104(2):380-391

Date

09/29/2018

Pubmed ID

30262560

Pubmed Central ID

PMC6355483

DOI

10.3324/haematol.2018.200253

Scopus ID

2-s2.0-85061057881 (requires institutional sign-in at Scopus site)   26 Citations

Abstract

We previously reported initial results in 102 multiple myeloma (MM) patients treated with sequential high-dose melphalan and autologous hematopoietic cell transplantation followed by 200 cGy total body irradiation with or without fludarabine 90 mg/m² and allogeneic hematopoietic cell transplantation. Here we present long-term clinical outcomes among the 102 initial patients and among 142 additional patients, with a median follow up of 8.3 (range 1.0-18.1) years. Donors included human leukocyte antigen identical siblings (n=179) and HLA-matched unrelated donors (n=65). A total of 209 patients (86%) received tandem autologous-allogeneic upfront, while thirty-five patients (14%) had failed a previous autologous hematopoietic cell transplantation before the planned autologous-allogeneic transplantation. Thirty-one patients received maintenance treatment at a median of 86 days (range, 61-150) after allogeneic transplantation. Five-year rates of overall survival (OS) and progression-free survival (PFS) were 54% and 31%, respectively. Ten-year OS and PFS were 41% and 19%, respectively. Overall non-relapse mortality was 2% at 100 days and 14% at five years. Patients with induction-refractory disease and those with high-risk biological features experienced shorter OS and PFS. A total of 152 patients experienced disease relapse and 117 of those received salvage treatment. Eighty-three of the 117 patients achieved a clinical response, and for those, the median duration of survival after relapse was 7.8 years. Moreover, a subset of patients who became negative for minimal residual disease (MRD) by flow cytometry experienced a significantly lower relapse rate as compared with MRD-positive patients (P=0.03). Our study showed that the graft-versus-myeloma effect after non-myeloablative allografting allowed long-term disease control in standard and high-risk patient subsets. Ultra-high-risk patients did not appear to benefit from tandem autologous/allogeneic hematopoietic cell transplantation because of early disease relapse. Incorporation of newer anti-MM agents into the initial induction treatments before tandem hematopoietic cell transplantation and during maintenance might improve outcomes of ultra-high-risk patients. Clinical trials included in this study are registered at: clinicaltrials.gov identifiers: 00075478, 00005799, 01251575, 00078858, 00105001, 00027820, 00089011, 00003196, 00006251, 00793572, 00054353, 00014235, 00003954.

Author List

Maffini E, Storer BE, Sandmaier BM, Bruno B, Sahebi F, Shizuru JA, Chauncey TR, Hari P, Lange T, Pulsipher MA, McSweeney PA, Holmberg L, Becker PS, Green DJ, Mielcarek M, Maloney DG, Storb R

Author

Parameswaran Hari MD Adjunct Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Biomarkers
Chromosome Aberrations
Combined Modality Therapy
Female
Hematopoietic Stem Cell Transplantation
Histocompatibility Testing
Humans
Male
Middle Aged
Multiple Myeloma
Neoplasm Staging
Prognosis
Survival Analysis
Transplantation Chimera
Transplantation Conditioning
Transplantation, Autologous
Transplantation, Homologous
Treatment Outcome