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C H A P T E R          95 

                                        PRACTICAL ASPECTS OF HEMATOLOGIC STEM CELL 

                                                                   HARVESTING AND MOBILIZATION


                                                                     Scott D. Rowley and Michele L. Donato





            Hematopoietic stem cell (HSC) products for autologous or allogeneic   UCB from public banks has the advantage of being immediately
            transplantation are available from bone marrow, peripheral blood, or   available, reducing the time to transplantation. Targeting collection
            umbilical cord blood (UCB) sources. Bone marrow was the original   of UCB products from ethnic populations not well represented in
            source of cells for transplantation because of the ease and reliability   donor registries will facilitate treatment of ethnic minority patients.
            of  collecting  adequate  numbers  of  cells  for  transplantation,  and  it   The relative immunologic naïveté of the cord blood donor allows use
            remains  the  standard  with  which  other  sources  of  HSCs  are   of HLA-mismatched products without an undue increase in GVHD
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            compared.                                             risk.  The much smaller quantity of HSCs in the cord blood product
              Peripheral blood stem cell (PBSC) products have virtually replaced   results in slower hematologic recovery and a higher risk for primary
            bone marrow as the HSC component for autologous transplantation   engraftment  failure,  which  may  be  partially  offset  by  infusion  of
            and  are  frequently  used  for  allogeneic  transplantation.  Virtually   multiple products, and the older adult patient, in particular, may also
            all  patients  undergoing  autologous  HSC  transplantation  will  have   be at greater risk for posttransplant infections because of the relative
            PBSCs  as  the  source  of  HSCs,  based  on  the  advantages  of  ease   immature immune system of the donor.
            of  scheduling  of  collections,  greater  quantities  of  HSCs  resulting
            in  faster  hematologic  recovery  and  shorter  and  less  costly  hospital
                1–6
            stays,   and  potentially  lower  risks  for  tumor  cell  contamination   SELECTION AND EVALUATION OF  
            of  the  graft.  The  rapid  engraftment  kinetics  of  PBSCs  compared   THE STEM CELL DONOR
            with  bone  marrow  is  widely  recognized.  Median  times  to  achieve
            an  absolute  neutrophil  count  greater  than  500/µL  and  platelet   Selection of the Stem Cell Donor
            transfusion  independence  after  PBSC  transplantation  typically  are
            approximately 11 to 14 days. The allogeneic donor has a wide range   The primary selection criterion for the patient undergoing autologous
            of options, including marrow, PBSC, or UCB products from human   HSC  collection  and  transplantation  is  the  diagnosis  of  an  illness
            leukocyte antigen (HLA)-compatible or partially compatible related   amenable to treatment with a dose-intense regimen requiring HSC
            or  unrelated  donors.  The  availability  of  HLA-matched  related  or   support.  Extensive  prior  treatments,  especially  with  marrow-toxic
            unrelated donors is the primary consideration in the selection of a   chemotherapy regimens or with radiotherapy, may prohibit collection
            donor, but donor health or donation preferences may restrict what   of adequate quantities of autologous HSCs, which would exclude a
            products  will  be  available  to  the  recipient. The  patient’s  physician   patient from this treatment option. Proper management of patients
            may select a stem cell source based on the expected transplant out-  with  a  disease  amenable  to  dose-intensive  therapy  should  include
            comes. PBSC products, for example, have the greatest quantity of   provisions for HSC collection before extensive marrow-toxic agents
            HSCs and will result in faster hematologic recovery compared with   are administered. In general, however, any serious comorbid illnesses
            marrow  or  UCB  transplants.  Bone  marrow  transplantation  has  a   that would preclude either marrow or PBSC collection would also
            higher risk of graft failure, resulting in a twofold higher probability   disqualify the patient from treatment with dose-intensive regimens
                                                       7
            of second harvest request compared with PBSC donation.  In some   used in preparation for autologous HSC transplantation.
            reports,  PBSC  transplantation  also  results  in  a  survival  advantage.   The selection of the allogeneic HSC donor is more complex. The
            However, PBSC transplantation is associated with a higher risk for   HLA major histocompatibility complex is the primary consideration
            difficult-to-control  chronic  graft-versus-host  disease  (GVHD)  and   in selection of a donor for allogeneic HSC transplantation, since its
            may not be appropriate for use in patients who would not benefit   loci contribute significantly to host-versus-graft (leading to immuno-
            from a robust graft-versus-leukemia effect, such as those treated for   logic rejection of donor HSCs) and to graft-versus-host (leading to
            nonmalignant diseases. The transplant recipient may request a source   GVHD and graft-versus-leukemia) reactions. 17,18  Donor age, gender,
            of  cells,  but  the  donor  has  the  right  to  decide  about  the  method   and parity are secondary considerations in the selection of an alloge-
            of  donation.  Although  GVHD  prophylaxis  with  posttransplant   neic HSC donor. 18,19  Mismatching for killer-cell immunoglobulin-
            methotrexate will slow engraftment, the kinetics of engraftment for   like receptor ligands may reduce the risk for posttransplant relapse of
                                                                       20
            the allogeneic PBSC recipient is similar to that experienced by the   disease.  More than 30% of allogeneic HSC transplants from related
            autologous PBSC recipient. A number of phase III studies involving   or unrelated donors will involve ABO-disparate donors and recipi-
            either autologous or allogeneic HSC transplantation confirmed the   ents, and donor and recipient pairs may also differ for other red blood
            more  rapid  engraftment  kinetics  for  recipients  of  PBSCs, 8–11   and   cell antigens, with no clear evidence of deleterious effect on engraft-
                                                                                       21
            this  effect  is  not  limited  to  HSCs  collected  from  the  peripheral   ment,  survival,  or  GVHD.   Cancer,  autoimmune  disorders,  and
            blood, because cytokine administration to the patient or donor before   genetic diseases such as the hemoglobinopathies can be transmitted
            marrow harvesting will also increase the number of HSCs collected   to the allograft recipient; thus, donor health is an important consid-
            and result in quicker hematologic recovery. 12–14  The disadvantages to   eration in donor selection and determination of donor eligibility.
            use of PBSC components compared with bone marrow or UCB for
            autologous or allogeneic transplantation include the possible need for
            multiple days of collection (especially for autologous transplantation),   Evaluation of Hematopoietic Stem Cell Donor 
            the inability to collect adequate components from all patients and   Suitability and Eligibility
            donors, and a possibly higher risk for chronic GVHD or the occur-
                                                      15
            rence of chronic GVHD that is more difficult to control  (see box   The  immediate  precollection  evaluation  of  a  patient  or  donor  is
            on Choice of Hematologic Stem Cell Product for Transplantation).  intended to address the risks of the collection procedure to the donor

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