CD34-Selected Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Relapsed, High-Risk Multiple Myeloma

Abstract

We report results of a retrospective analysis of 44 patients with relapsed and high-risk multiple myeloma (MM) undergoing allogeneic CD34-selected hematopoietic stem cell transplantation (HSCT) from HLA-compatible donors. Patients had multiply relapsed disease including relapse at <15 months after autologous transplantation and most patients (28 of 44; 65%) also had high-risk cytogenetics. Before transplantation, patients received busulfan (.8 mg/kg × 10 doses), melphalan (70 mg/m(2) × 2 days), fludarabine (25 mg/m(2) × 5 days), and rabbit antithymocyte globulin (2.5 mg/kg × 2 days). Patients with 10/10 HLA- matched donors were treated prophylactically with low doses of donor lymphocyte infusions (.5 to 1 × 10(6) CD3(+)/kg) starting 4 to 6 months after CD34-selected HSCT. Acute (grade II to IV) graft-versus-host disease (GVHD) and transplantation-related mortality at 12 months were 2% and 18%, respectively. Chronic GVHD was not observed in any patient. Overall and progression-free survival at 2 years were 54% and 31%, respectively. By multivariate analyses, the outcomes of CD34-selected HSCT were influenced by presence of extramedullary disease, disease status before CD34-selected HSCT, and age. This study demonstrates notable safety and efficacy of CD34-selected HSCT in patients with multiply relapsed MM, including those with high-risk cytogenetics.

Keywords: Adoptive immunotherapy; D34-selected hematopoietic stem cell transplantation; Relapsed high-risk multiple myeloma.

Figure 1

Overall and progression-free survival of 44 patients with multiply relapsed multiple myeloma undergoing CD34-selected HSCT.

Figure 2. Overall and progression-free survival based on lines of treatment prior to CD34-selected HSCT

For these analyses, auto-SCT followed by maintenance therapy and tandem auto-SCT plus maintenance therapy were calculated as a single line of treatment as detailed in Table I.

Figure 3. Overall and progression-free survival based on disease status prior to CD34-selected HSCT

Partial remission (PR) vs very good partial remission (VGPR) / complete remission (CR)

Figure 4

Overall and progression-free survival based on presence (n = 13) or absence (n = 31) of extramedullary manifestation prior to CD34-selected HSCT.

Figure 5. Acute GVHD and non-relapse mortality (NRM)

(A) Acute GVHD (grade II–IV) to days +180 post CD34-selected HSCT, (B) NRM post CD34-selected HSCT and (C), NRM based on disease status (PR; n = 21) or (VGPR/CR; n = 23) prior to CD34-selected HSCT.