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M.H. Sidiqi et al.
Discussion
Increased plasma cell proliferation rate has been recog- nized as a predictor of a more aggressive clinical course in patients with myeloma and amyloidosis.3-6,11 The early studies of plasma cell proliferation rate were carried out with BrDU incorporation and microscopic review of plas- ma cells on the slide. However, flow cytometric evaluation of proliferation index is much more robust, precise and reproducible.11 In addition, since flow cytometry immunophenotying is already the standard of care for the diagnosis of plasma cell neoplasms, incorporation of prolif- eration measurement by DAPI staining is an easy addition to currently run assays, and therefore readily available for any clinical laboratory to perform. Since all patients with light chain amyloidosis require a bone marrow for assess- ment, ample material should be available for direct meas- urement of the proliferative index at time of diagnosis.
The proliferative index is an independent predictor of survival and adds importantly to what is currently avail- able based on the pre-transplantation variable of Mayo Stage as well as the post hoc variables of depth of response and conditioning dose of chemotherapy. We note that patients with an elevated PCPI had more cardiac involve- ment and a higher pre-transplant light chain level. Despite this, elevated PCPI remained an independent predictor of survival in a multivariate model that included the power- ful prognostic factor of Mayo Stage, a variable that incor- porates both cardiac biomarkers and light chain level in staging patients with AL amyloidosis. Pre-transplantation chemotherapy was associated with an improved overall
those with a low PCPI. Therefore the plasma cell prolifer- ative index may be used as a potential guide to identify patients that may benefit most from pre-transplantation chemotherapy, suggesting that patients with an Elevated labeling index should be strongly considered for induction chemotherapy prior to transplantation. In addition, an Elevated PCPI predicts earlier progression, suggesting that consolidation chemotherapy or maintenance post trans- plant should be considered for this patient population. Given that hematologic response is a strong predictor of survival, achieving deeper responses in this cohort may help improve outcomes.
Our data also reveal higher 100-day mortality in patients with an Elevated PCPI. Patients with an Elevated PCPI were more likely to have cardiac involvement and a higher Mayo Stage; both have been associated with a worse prognosis.10,12 In addition, patients with an Elevated PCPI were more likely to receive chemotherapy, with potential toxicity, prior to transplantation.
Our study is limited by its retrospective nature and potentially by a change in the method of testing for the plasma cell proliferation index during the study time peri- od. We have tried to account for the difference in assay sensitivity by establishing unique cut offs for elevated PCPI for the two methods. In addition, our study includes patients over a time period of almost 14 years and selec- tion criteria for stem cell transplant eligibility in AL amy- loidosis have significantly changed over this time. Despite these limitations, the significance of the labeling index on survival independent of previously known factors is an important addition to the prognosis of patients with this serious disorder.
response rate in patients with an elevated
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