Infusion of large number of circulating myeloma cells
does not influence survival of patients undergoing
autologous stem cell transplantation
H. Knollman; A. Suvannasankha, MD; M. Yu
Y ,
u PhD; R. Britton; S. Srivastava,
Srivastava MD; R. P.
P Nelson Jr.,
Jr MD; J. E.
Schwartz, MD, FRCP; M. Robertson, MD; K. Cornetta, MD; S. Farag, MBBS, PhD; R. Abonour,
Abonour MD.
ABSTRACT
METHODS
RESULTS
Introduction: Multiple myeloma (MM), a monoclonal disorder of plasma cells,
An Excel spreadsheet was created which contained the names of the 349 patients that
There is no relationship in univariate or multivariate analyses
constitutes 10% of all hematologic malignancies.
Autologous stem-cell
underwent ASCT at the medical center at Indiana University in Indianapolis between January 1999
between the number of plasma cells in the bone marrow and
transplantation (ASCT) has become a mainstay of treatment for MM, being offered
and April 2008. For each patient, the date of ASCT was recorded, as well as the date of death or last
B2m at diagnosis, as well as the presence or absence of
to patients with a good performance status in an attempt to put patients in remission
date known alive. The latter were used to calculate overall survival using univariate and multivariate
myeloma stem cells, on overall survival.
and to minimize disease-related morbidity. We attempt here to define the role of
analyses with the Cox proportional hazards model.
infusing mobilized myeloma cells on the survival of patients undergoing ASCT.
Laboratory Data
P-value
The doses of CD34+ cells as well as CD45-/CD38+ were measured by flow cytometry and
Methods: After obtaining an Institutional Review Board approval, we conducted a
recorded into the spreadsheet. Additionally, there was a variety of data collected for each patient at
% bone marrow plasma cells
0.47
retrospective analysis on MM patients undergoing ASCT at our center. Data of
three time points throughout the patient's disease course: at diagnosis, at time of transplant, and
Beta 2 microglobulin at diagnosis
0.61
disease status graft characteristics and outcome were collected
As part of the
three months pos
p t-transplant. This recorded laboratory data included percent of mye
y loma cells in the
disease status, graft characteristics, and outcome were collected. As part of the
bone marrow, B2 microglobulin, IgG, IgA, kappa and lambda light chain, monoclonal protein in the
CD45 (zero vs. present)
0.22
flow panel used to assess the mobilized ASC, monoclonal myeloma cells were
identified by gating on a population of cells that express high levels of CD38 but do
*derived from multivariate Cox Model Analysis.
serum and urine, albumin, creatinine, calcium, and hemoglobin. It was also noted whether the
not stain or weakly with CD45 (CD38+/CD45-). OS was calculated from the date
patient had bony disease at the time of diagnosis, and if cytogenetics were normal or abnormal.
of ASCT to the time of death or last contact. Survival analysis was performed using
P-values considering dose of CD45
the method of Kaplan and Meier (KP). Univariate and multivariate analysis was
performed using the Cox proportional hazards model.
Laboratory Data
P-value
RESULTS
% bone marrow plasma cells
0.30
Results: 349 patients underwent ASCT between January 1999 and April 2008 at
Indiana University Medical Center in Indianapolis. Complete data on autograft
Beta 2 microglobulin at diagnosis
0.83
Patient Charcteristics
charact
char
eri
act
s
eri ti
t c
i s were available
l
on 303 pati
pat e
i nt
e s
nt .
The mobilization regime
i
n was
CD45 (i
(continuous)
07
0. 4
74
Cyclophosphamide and GCSF for the majority of the patients and GCSF for the
Median Age (Range)
58 (25 ­ 78)
*derived from multivariate Cox Model Analysis.
more recent transplants. Melphalan at 200 mg/m2 was give 18 hours prior ASC
Male:Female
201:148
infusion. In 199 patients there were no CD38+/CD45- cells detected. Among the
Myeloma Type (at diagnosis)
104 patients with evidence of CD38+/CD45- cells the range was 0.1-10.2 x10^6
CONCLUSIONS
cells/kg and there was no difference in survival in this patient group compared to
IgG
211
the group without evidence of contaminating myeloma cells (p= 0.54). Continuous
IgA
70
Based on univariate and multivariate analysis from the data collected from
variable analysis also did not reveal any relationship between the dose of
349 patients who underwent ASCT at Indiana University Medical Center between
Non-secretory
12
CD38+/CD45- cells and survival (p=0.84). There may be a survival advantage
1999 and 2008, neither the presence or absence of myeloma stem cells in the
after 40 moths for those receiving CD38+/CD45- cells, however the scientific
Light Chain
53
autograft, nor the dose of these cells, influences overall survival. Therefore, CD45
rationale isnot well undt
derstood. Neither B2
B
il
microgl b
o uli
linnor the
b
num ers of
Plasma
Plasma Cell
Cell Le
Leukemia
kemia
3
and CD38 flow cytometric analysis of mobilized stem cells in the autograft may not
plasma cells in the bone marrow were relevant in multivariate analysis (p= 0.42 and
be necessary. The analysis does suggest a survival advantage for the ASCT patient
0.13, respectively).
population receiving CD45-/CD38+ cells in the autograft, the significance of which
is unknown.
Conclusion: The presence of myeloma cells in the autograft does not appear to
Effect of presence or absence of infused myeloma
influence overall survival and the inclusion of CD45 and CD38 flow cytometric
Also from analysis of this ASCT data, it appears that neither the level of beta-
analysis of mobilized stem cells may not be necessary.
cells in ASCT on patients' overall survival
2-microglobulin nor the percent of bone marrow plasma cells at diagnosis are
statistically significant for patient survival. Therefore, it is not possible at this time
to use either of these levels at diagnosis as a prognostic indicator.
INTRODUCTION
FUTURE AIMS
Multiple myeloma (MM) is a monoclonal plasma cell disorder that has
Analyze/collect data to study time to progression rather than overall survival.
traditionally been thought to be incurable, although remission can be achieved with
ASCT and various chemotherapies and steroids. Patients with a good performance
Further characterization of the apparent survival benefit in the 40-90 month
status are usually offered high-dose therapy (HDT) followed by ASCT.
post-transplant period of receiving infused myeloma stem cells in ASCT.
HDT/ASCT is associated with complete response (CR) rates of up to 40%.
Although a significant proportion of patients have a durable response after
In the era
er
of modern agen
age ts
t , one
on
coul
co d
ul
study
t
the level of mobilization of
HDT/ASCT, others relapse relatively quickly and do not appear to benefit from the
myeloma stem cells. Since novel agents have become available for salvage
procedure, which may impact the overall survival (OS) of these patients. We are
therapy after relapse, an interesting study would be to compare time to relapse
interested to analyze the ASCT that occurred at our medical center, Indiana
and overall survival of patients with ASCT occurring five to ten years ago with
University, during a ten year span of time to evaluate the effect, if any, that infused
the more recent transplants.
myeloma cells and other laboratory data from time of diagnosis have on patient
survival.
Continue data collection for patients at three time points ­ at diagnosis, at
transplant, and 3-6 month follow up ­ to evaluate for other possible prognostic
indicators.

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