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1201 Related Vs Unrelated Donors After Auto-Allo Tandem Stem Cell Transplantation for Newly Diagnosed Patients with Multiple Myeloma

Oral and Poster Abstracts
Poster Session: Clinical Results - Alternative Donor Transplantation Poster I
Saturday, December 5, 2009, 5:30 PM-7:30 PM
Hall E (Ernest N. Morial Convention Center)
Poster Board I-223

Nicolaus Kröger, MD1*, Tatjana Zabelina2*, Marion Heinzelmann3*, Georgia Schilling4*, Christine Wolschke5*, Heinrich Lellek6*, Thomas Stübig7*, Maite Lestin7*, Haefaa Alchalby8*, Francis Ayuk9*, Djordje Atanackovic, M.D.10*, Ulrike Bacher4*, Boris Fehse7* and Axel R. Zander2

1University Medical Center Hamburg, Hamburg, Germany
2Stem Cell Transplantation, University Medical Center Hamburg, Hamburg, Germany
3Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
4University Hospital, Hamburg, Germany
5Department of Stem Cell Transplantation, University Medical Center, Hamburg, Germany
6Institute for Transfusion Medicine, University Medical Center Hamburg Eppendorf, Hamburg, Germany
7Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany
8Stem cell Transplantation, University Hospital Hamburg, Hamburg, Germany
9Department of Stem Cell Transplantation, University Medical Center Hamburg, Hamburg, Germany
10Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Introduction: Autologous stem cell transplantation followed by a dose-reduced conditioning and allogeneic stem cell transplantation from HLA-identical siblings has become a treatment option for patients with multiple myeloma. However, only a minority of the patients with multiple myeloma has an HLA-identical sibling and the experience using unrelated donor in this setting is limited. Patients and Methods: From 1997 to 2007, 73 patients (male:45; female:28) with multiple myeloma stage II/III and a median age of 49 years (r, 29-64) were included in a prospective trial to determine the efficacy of a tandem auto-allogeneic stem cell transplantation SCT) from HLA-identical sibling (n=24) or unrelated donors (n=45). Unrelated donor were either fully HLA matched (n=29) or had one mismatch (n=16).Deletion 13q14 could be analyses in 64 pts was found to be positive in 66% of the pts. Del13q14 was more present in patient with unrelated (n=42) than with related (n=22) donors. Stem cell source was PBSC (n=69) or bone marrow (n=4). Induction-chemotherapy consisted of a median of 4 cycles anthracycline-based therapy in 60 pts, or of thalidomide- (n=3) or bortezomib- (n=8) based regimen. 6 pts did not respond to induction therapy and received salvage chemotherapy before autologous SCT. Conditioning prior auto SCT consisted of melphalan 200mg/m². After a median of 110 days (range 39-228) patients received a reduced intensity regimen with melphalan (140 mg/m²)/fludarabine regimen followed by allogeneic SCT from related (n=24) or unrelated (n=45) donors. GvHD prophylaxis consisted of anti-lymphocyte globulin (ATG-Fresenius®), cyclopsorin A and short course of MTX. Results: No primary or secondary graft failure was observed and leukocyte engraftment was achieved after a median of 15 days (range, 9-27) , respectively. Acute graft-versus-host disease (GvHD) grade II to IV occurred in 38% and chronic GvHD in 22% of the patients. Limited GvHD was seen in 16 % and extensive GvHD was seen in 6 % of the patients. There was no difference regarding incidence of GvHD between HLA-identical sibling and unrelated donors. Overall response rate at day 100 was 94% including 55% complete remission (CR) and did not differ between related and unrelated SCT. Cumulative incidence (CI) of non-relapse mortality at one year was 20% (95% CI:11-29%) and did not differ between MUD and MRD (21 vs 17%, p 0.35).  The cumulative incidence of relapse at 3 and 5 years was 30% (95% CI:19-41%) and 42% (95% CI: 29-55%), respectively with no difference between related and unrelated SCT at 5 years: 36 vs 44%(p= 0.6). The only significant factor for higher relapse incidence at 5 years was the presence of del13q14 (60 vs 20%, p= 0.007). After a median follow up of 40 months (r., 26-100), the estimated 5-year progression-free (PFS) and overall survival (OS) rates were 31% (95%CI: 19-43%) and 54% (95% CI: 42-64%), respectively, with no difference between related and unrelated SCT. Due to the higher relapse incidence only presence of del13q resulted in a significant worse 5- year OS and DFS (45 vs 77%, p=0.02 and 18 vs 57%, p=0.04). Conclusions: Unrelated donors as stem cell source for auto-allogeneic tandem stem cell transplantation for newly diagnosed myeloma patients resulted in similar NRM, relapse-incidence, DFS and OS than HLA-identical sibling transplantation and can therefore be used as alternative stem cell source. Outcome after transplantation is better for patients lacking del 13q14.

Disclosures: No relevant conflicts of interest to declare.

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