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Tandem transplantation for multiple myeloma
determine factors influencing HCT outcomes in univariate and multivariate analyses. Multivariate risk factors analysis included only variables significant at 0.05 level in univariate analysis for any OS, PFS, and relapse incidence. Acute GvHD, chronic GvHD, and post-transplant MM maintenance treatment (administered to 31 patients) were considered as time-dependent co-variates. Since no single variable, other than grade II-IV acute GvHD, had a signifi- cant correlation with NRM by univariate analysis, NRM was not incorporated into multivariate analysis.
Results
Disease response before and after autologous hematopoietic cell transplantation
Disease responses are summarized in Table 2. At the time of autologous HCT, there were no statistical signifi- cant differences among 125 patients who received vin- cristine – doxorubicin – dexamethasone (VAD)-based induction, mainly between 1998 and 2006, and those treated with immunomodulatory/proteasome inhibitor (n=101) triplet regimens (2006-2016) in terms of response rate: 74 (59%) versus 68 (68%) achieved at least a PR, respectively, and only 12 patients were in CR before autol- ogous HCT. Of the 18 who received other induction ther- apies (melphalan plus prednisone, n=6; high-dose dexam- ethasone only, n=11; high-dose dexamethasone plus cyclophosphamide, n=1), 11 achieved PR and 7 PD. After
high-dose melphalan and autologous HCT, 62 patients (26%) were in CR, 47 (19%) VGPR, 93 (38%) PR, and 42 (17%) had PD.
Allogeneic hematopoietic cell transplantation
Sixty-seven percent of the patients had allogeneic HCT within the first 3 months after autologous HCT, 29% between 3 and 6 months and 4% beyond 6 months. Reasons for allogeneic HCT delay included: delayed hemopoietic recovery (59%), abnormal hepatic/renal function (15%), active infection requiring intravenous antibiotics (13%), persisting mucositis (4%), cytomegalovirus reactivation requiring intravenous thera- py (6%), and patient choice (3%). Results after allogeneic HCT are presented with a median follow up of 8.3 (range, 1.0–18.1) years among surviving patients.
Engraftment and GvHD - All 244 patients achieved sus- tained engraftment after allogeneic HCT. Median values of donor chimerism on CD3+ T cells in peripheral blood on days 28, 84, and 180 were 89%, 95%, and 100%, respectively, while median values of donor chimerism of CD33+ myeloid cells were 96%, 100%, and 100%, respec- tively. The cumulative incidence of grade II-IV acute GvHD was 44% with a median onset of 39 days (range, 6- 124), of which 33% was grade II, 7% grade III, and 4% grade IV. Sibling recipients (n=176) experienced less grade II-IV acute GvHD than unrelated (n=65) recipients (38% vs. 64%; P<0.001). Of the 228 patients who survived
A
B
CD
Figure 2. Long-term clinical outcomes after tandem autologous-allogeneic hematopoietic cell transplantation (HCT) for the entire population and stratified for dis- ease-risk groups. Non-relapse mortality (NRM) and relapse incidence (A). Overall survival (OS) and progression-free survival (PFS) for the entire cohort (n=244) (B). OS (C) and PFS (D) for disease-risk stratification groups with standard-risk (n=62), high-risk (n=73), and ultra-high-risk (n=79).
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