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Labeling index in light chain amyloidosis
Figure 1. Overall survival and progression-free survival. PCPI: plasma cell proliferation index; ASCT: autologous stem cell transplant; PFS: progression-free survival; OS: overall survival.
Table 2. Hematologic response.
CR VGPR PR NR
Low PCPI n (%)
150 (44) 101 (29) 48 (14) 44 (13)
Elevated PCPI n (%) P 0.86
63 (40) 0.44 49 (31)
25 (16)
21 (13)
NA 5 7
CR: complete response;VGPR: very good partial response; PR: partial response; NR: no response; NA: not available; PCPI: plasma cell proliferation index.
cell proliferative index (PCPI) performed on bone marrow samples at diagnosis. The PCPI is expressed as a percentage of plasma cells in S phase. Patients with insufficient plasma cells identified for an accurate assessment of the PCPI were excluded.
Prior to May of 2012, the plasma cell proliferative index was measured using the bromodeoxyuridine (BrdU) method described previously.4 From May 2012 onwards, the BrdU method was replaced by the DNA content measurement using a flow cytometry technique and a summary of this method is available in the Online Supplementary Appendix.
We initially analyzed all patients with a PCPI performed using the BrdU method (n=390). The median PCPI was 0% with at least two-thirds (69%) of patients having a PCPI of 0%. Amongst the patients with a PCPI performed using the flow cytometric method (n=123), the median PCPI was 0.3% with approximately two-thirds (65%) of patients having a PCPI of 0.5% or under. To account for differences in the sensitivity of the methods, we established “Low” PCPI as 0% by the BrdU method and 0.5% or under by the flow cytometry method. “Elevated” PCPI was defined as over 0% by the BrdU method and over 0.5% by the flow cytometric method. This established two cohorts of patients: those with a Low PCPI (n=348) and those with an Elevated PCPI (n=165). Patients’, disease and treatment characteristics as well as outcomes were assessed between the two groups.
Organ involvement and hematologic response were assessed according to consensus criteria.7,8 Risk stratification was according to the Mayo 2012 and 2004 staging systems.9,10 Patients were selected for ASCT using available criteria at the time of transplant. Patients were mobilized, conditioned and transplanted according to previously published institutional pro- tocols. Response was measured at approximately 100 days post ASCT according to up-dated consensus criteria. Overall response rate (ORR) was defined as a partial response (PR) or greater.
Statistical analysis was performed on JMP software (SAS, Cary, NC, USA). Patients’ and disease related factors were compared using the χ2 test for categorical variables and the Wilcoxon signed rank test for continuous variables. Survival analysis was per- formed using the Kaplan-Meier method. Overall survival (OS) was calculated from day 0 of bone marrow transplant to death from any cause. All-cause mortality at 100 days was defined as death from any cause within 100 days post ASCT. The Cox proportional hazards model was used to assess for predictors of OS. The vari- ables included in the univariate analysis were age, sex, number of organs involved, bone marrow plasma cells, Mayo Stage, condi- tioning dose, pre-transplantation chemotherapy, and PCPI. Variables reaching a P<0.1 were included in the multivariate analysis.
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