80
5.3 Mobilization and Collection of Peripheral Blood Stem Cells
It is general consensus that circulating peripheral CD34+ blood stem cells PBSC are
collected and used for ASCT in patients with MM. According to the IMWG the
mobilization of peripheral stem cells in myeloma patients should be performed in
an early stage of the disease, preferably within the first four cycles of induction
therapy with novel antimyeloma agents [ 43 , 44 ]. The importance of collection of
appropriate amount of hematopoietic stem cells to perform a second ASCT during
the early course of the disease cannot be understated [ 48 ]. In general, increasing
age, more than 12 months of antimyeloma treatment prior to stem cell collection,
less than 200 × 10(9)/l platelets prior to mobilization, and mobilization with growth
factors only were correlated with negative CD34+ yield [ 53 ].
GCSF alone or cyclophosphamide (C) plus granulocytecolony stimulating factor
(GCSF) are the most widely used stem cell mobilization regimen for patients with
MM [ 54 , 55 ]. In a randomized phase II trial 34 patients were treated with C + GSCF
(cyclophosphamide 2 g/m^2 ) (arm A) and 35 with GCSF alone (arm B). In arm A 94%
reached the goal of stem cell collection of at least 3 × 10(6)/kg, in arm B it was only
77% (p = 0.084). The median number of apheresis needed was significantly lower in
arm A than in arm B (1 vs. 2, p = 0.035), and two patients required plerixafor in arm
A and five in arm B [ 54 ]. In the Total Therapy trials it is shown that DTPACE (dexa
methasone, thalidomide, cisplatin, adriamycin, cyclophosphamide and etoposide),
VDTPACE (plus bortezomib) and MVDTPACE (plus melphalan) are considered
excellent mobilizing regimen for collection of CD34+ cells [ 53 , 56 , 57 ].
In 2008 the U.S. food and drug administration (FDA) approved the application
of plerixafor in combination with GCSF for mobilization of hematopoietic stem
cells to the peripheral blood for collection and subsequent autologous transplanta
tion in MM. Plerixafor antagonizes the binding of the chemokine stromal cell
derived factor1 (SDF1) to its related receptor CXCR4 which leads to a rapid and
reversible mobilization and release of hematopoietic stem cells into the peripheral
blood [ 58 ]. Afifi et al. have demonstrated that the addition of plerixafor to C + GCSF
was associated with higher success of SC collection, less toxicities and less finan
cial burden compared to C + GCSF alone, mainly due to lesser rate of hospitaliza
tion, decreased rate of salvage mobilization, and decreased GCSF usage [ 54 ].
5.4 Total Therapy in MM
The Total Therapy (TT) concept was introduced at our institution by Bart Barlogie
30 years ago to overcome refractoriness and relapsing course of MM. The main goal
was to give all available antimyeloma agents upfront in order to achieve synergistic
impact and address clonal heterogeneity and drugresistance in myeloma cells in
order to prevent later relapse. The backbone of each TT trial is the application of
two successive ASCTs in the framework of induction, consolidation and
S. Thanendrarajan and T.K. Garg