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Hematopoietic cell transplantation (HCT): Sources of hematopoietic stem/progenitor cells

Hematopoietic cell transplantation (HCT): Sources of hematopoietic stem/progenitor cells
Author:
Robert S Negrin, MD
Section Editor:
Nelson J Chao, MD
Deputy Editor:
Alan G Rosmarin, MD
Literature review current through: Jan 2024.
This topic last updated: Jan 19, 2024.

INTRODUCTION — Hematopoietic cell transplantation (HCT) is an important method for treating certain malignant and nonmalignant disorders. HCT offers potential long-term survival for patients with cancers that have a high risk for relapse, relapsed or refractory malignancies that cannot be cured using other approaches, and bone marrow failure states, including for inherited/germline conditions that affect hematopoiesis.

HCT is used to replace malignant (or defective) hematopoietic tissue using a healthy donor's hematopoietic cells. Conditioning therapy (chemotherapy and/or radiation therapy) is given to reduce the burden of disease and to prevent rejection of the donor hematopoietic cells. Hematopoiesis is then restored by infusion of a graft of healthy hematopoietic stem and progenitor cells (HSPCs) from either another individual (allogeneic HCT) or the patient's own cells (autologous HCT).

HSPCs can be obtained from peripheral blood, bone marrow, or umbilical cord blood (UCB), each of which is associated with advantages and disadvantages. Specific graft sources are preferred in certain settings, which should consider the underlying disease (ie, malignant versus nonmalignant), type of transplantation (ie, allogeneic versus autologous), recipient age, and comorbidities. The most important factor in selecting a specific donor for transplantation is immune compatibility between the recipient and donor at HLA loci.

This topic reviews the sources, preferences, and collection of HSPCs for HCT.

Selection of an HCT donor, evaluation of the donor, and the collection of UCB are discussed separately.

●(See "Donor selection for hematopoietic cell transplantation".)

●(See "Selection of an umbilical cord blood graft for hematopoietic cell transplantation".)

●(See "Evaluation of the hematopoietic cell transplantation donor".)

●(See "Collection and storage of umbilical cord blood for hematopoietic cell transplantation".)

HEMATOPOIETIC STEM AND PROGENITOR CELLS — HCT involves treatment with a conditioning regimen (chemotherapy and/or radiation therapy) to reduce the burden of disease, followed by an infusion of a hematopoietic graft to restore blood formation.

Successful engraftment requires infusion of sufficient hematopoietic stem cells and progenitor cells to enable hematopoietic engraftment and provide the rapid proliferation that is needed to restore blood cell formation.

Description — The hematopoietic graft must include adequate quantities of the following cell types:

●Hematopoietic stem cells – Multipotent hematopoietic stem cells (HSCs) have the potential to develop into all blood cell lineages.

HSCs primarily reside in bone marrow, where they comprise <0.1 percent of nucleated cells. They can also be found in small numbers in the peripheral blood of adults and in umbilical cord blood (UCB). HSCs cannot be identified morphologically because they resemble small lymphocytes. As a result, they are primarily identified by immunophenotype or by their functional capacity for self-renewal. Details of the immunophenotype of HSCs are presented below. (See 'Immunophenotype of HSPCs' below.)

HSCs are primarily quiescent. Periodically, a small percentage of HSCs emerge from this quiescent state to enter the cell cycle to proliferate. HSCs can be induced to proliferate and enter the blood stream using filgrastim and other approaches. (See 'Filgrastim' below.)

Further details of HSCs are presented separately. (See "Overview of hematopoietic stem cells".)

●Hematopoietic progenitor cells – Hematopoietic progenitor cells are progeny of HSCs that give rise to an increasingly restricted population of differentiating cells.

Compared with HSCs, progenitor cells have a more restricted capacity to give rise to various blood cell types. There is a hierarchy of development of progenitor cells, in which they begin to commit to either the lymphoid lineages (ie, B cells, T cells, natural killer cells) or to myeloid precursors (ie, erythrocytes, platelets, neutrophils, eosinophils, basophils, monocytes, dendritic cells) (figure 1).

The highly proliferative nature of progenitor cells is needed to meet the ongoing needs for blood cell replacement. It is estimated that 1010 erythrocytes and 108 to 109 leukocytes are produced per hour in the steady state. Because cell numbers are maintained within narrow limits, production of blood cells can be greatly amplified on demand.

HSCs were first defined functionally as populations of cells that could rescue hematopoiesis in lethally irradiated animals. Landmark experiments showed that hematopoiesis could be restored in lethally irradiated mice by shielding the spleen with lead or by infusion of splenocytes from a normal donor [1]. Stem cells could be reisolated from these animals and used to rescue other lethally irradiated animals.

Development of in vitro and in vivo assay systems proved that clonotypic precursor cells were capable of giving rise to both erythroid and myeloid lineages of cells [2,3]. Such experiments enabled recognition of populations of cells that were functionally capable of multilineage repopulation.

Identification and isolation of HSPCs became possible with the development of monoclonal antibodies and advanced cell sorting technologies. Monoclonal antibodies were developed that could recognize proteins on the surface of immature and maturing populations of bone marrow-derived cells. Fluorescence activated cell sorting (FACS) made it possible to isolate populations of cells with properties of HSCs. Using these techniques, intravenous injection of a small population (eg, <100 cells) of highly purified murine HSCs were shown to rescue >95 percent of lethally irradiated animals [4]. Highly purified populations of HSPCs were shown to be capable of rapid and sustained hematopoietic engraftment in clinical trials [5].

Immunophenotype of HSPCs — Human HSCs generally express CD34 and lack antigens associated with mature hematopoietic lineages (lineage [Lin]-negative). (See "Overview of hematopoietic stem cells".)

Clinical trials using highly purified populations of CD34+ cells are capable of rapid and sustained hematopoietic engraftment [5]. Using magnetic bead separation, it is possible to efficiently isolate and purify CD34+ cells that can reconstitute hematopoiesis following HCT conditioning therapy. Further purification of subpopulations of CD34+ cells is possible but is challenging to perform on a clinical scale.

PREFERRED GRAFT SOURCES — HSPCs for HCT can be obtained from peripheral blood, bone marrow, or umbilical cord blood (UCB). Each type of graft source has advantages and disadvantages, and no one source has been proven to be superior to another.

The preferred graft source for an individual transplant recipient is informed by the type of HCT (ie, allogeneic versus autologous), underlying disease (ie, malignant versus nonmalignant), and patient age. The most common graft source for HCT is peripheral blood, but bone marrow grafts are preferred in certain settings. UCB is an option when a histocompatible donor is not identified from related or unrelated donors.

Our approach to the selection of a graft source is similar to that of American Society for Blood and Marrow Transplantation, EBMT (formerly known as the European Society for Blood and Marrow Transplantation), and the United States National Cancer Center Network [6-9].

Allogeneic HCT for malignancies — For allogeneic HCT to treat a cancer, the preferred graft source is guided by the transplant recipient's age.

Adults — For adults undergoing allogeneic HCT for a malignancy, we suggest peripheral blood grafts rather than bone marrow grafts.

Compared with bone marrow, peripheral blood grafts for adults undergoing allogeneic HCT for a cancer are associated with comparable or better survival and fewer relapses but more chronic graft-versus-host disease (GVHD). Peripheral blood grafts generally provide a greater yield of HSPCs, and the donor avoids pain and general anesthesia associated with bone marrow grafts. In highly selected patients, such as when chronic GVHD must be minimized, bone marrow is an acceptable graft source.

HSPC mobilization and collection of peripheral blood grafts are discussed below. (See 'Peripheral blood grafts' below.)

Studies that compared graft sources for adults undergoing allogeneic transplantation for cancer include:

●Meta-analyses – Meta-analyses indicate that peripheral blood grafts are associated with equivalent or superior survival, better engraftment, fewer relapses, and better quality of life but more chronic GVHD.

•A Cochrane meta-analysis that compared graft sources in HCT for adults with hematologic malignancies (1521 patients in nine randomized trials; 1994 to 2009) reported that peripheral blood and bone marrow grafts were associated with similar overall survival (OS), disease-free survival (DFS), and transplant-related mortality (TRM), but peripheral blood grafts were associated with a higher risk for extensive chronic GVHD and trends toward more acute GVHD, faster engraftment, and lower rates of relapse [10].

•A meta-analysis of myeloablative allogeneic HCT using matched sibling donor (MSD) grafts (1111 adults in nine randomized trials; 1990 to 2002) reported that for adults who were transplanted for leukemia, peripheral blood grafts were associated with superior engraftment, fewer relapses, and a higher risk for extensive chronic GVHD; there were trends toward better OS and DFS [11].

•Markov analysis of HCT in adults reported that peripheral blood grafts were associated with longer overall life expectancy and quality-adjusted life expectancy (QALE) compared with bone marrow grafts [12]. There was an advantage of seven months for both life expectancy and QALE with peripheral blood grafts for all conditions in which the one-year risk probability of relapse was ≥5 percent. The advantage was reversed when the risk of relapse was lower (ie, primarily nonmalignant disorders).

●Individual studies

•Related donors – Randomized trials that compared graft sources using human leukocyte antigen (HLA)-MSD grafts for HCT in adults with malignancies report that, compared with bone marrow, peripheral blood was associated with equivalent or superior survival but more GVHD.

-A phase 3 trial of 228 patients (age 19 to 64 years) who received MSD grafts for myeloid malignancies reported better survival with peripheral blood grafts [13]. Patients who received peripheral blood grafts achieved superior 30-month OS (68 versus 60 percent; hazard ratio [HR] 0.62 [95% CI 0.39-0.97]), faster engraftment of platelets and neutrophils, and similar rates of relapse, acute GVHD, and chronic GVHD.

-A trial that randomly assigned the type of graft source to 329 patients with leukemia (18 to 55 years) reported that, with nine years of follow-up, the OS, leukemia-free survival (LFS), relapse rate, and late adverse effects (AEs) were similar between trial arms, but the incidence of chronic GVHD and duration of immunosuppression were greater with peripheral blood grafts [14].

-Long-term follow-up of a phase 3 trial of 172 patients (12 to 55 years) transplanted with MSD grafts for hematologic malignancies reported no difference in OS or GVHD between peripheral blood and bone marrow grafts [15]. After 10 years, rates of OS and LFS with peripheral blood grafts (49 and 13 percent, respectively) did not differ significantly from bone marrow grafts (57 and 28 percent, respectively). More patients who received peripheral blood grafts had GVHD (73 versus 56 percent) and required immunosuppression five years after transplantation (26 versus 12 percent), but the graft sources did not differ in performance status, return to work, incidence of bronchiolitis obliterans, or hematopoietic function.

-A phase 3 trial of 350 patients (18 to 55 years) undergoing allogeneic HCT for leukemia reported comparable two-year OS, DFS, relapse, and day-100 TRM between graft sources [16]. Peripheral blood was associated with more grade ≥2 acute GVHD (52 versus 39 percent, odds ratio [OR] 1.74 [95% CI 1.1-2.7]) and more chronic GVHD (67 versus 54 percent; OR 1.7 [95% CI 1.2-2.4])

•Unrelated donors

-A phase 3 trial that randomly assigned 551 patients to peripheral blood versus bone marrow grafts from HLA-matched unrelated donors (MUD) reported similar two-year OS, but peripheral blood grafts were associated with faster neutrophil and platelet engraftment, lower incidence of graft failure (3 versus 9 percent), higher incidence of extensive chronic GVHD (48 versus 32 percent), and a lower percentage of patients off GVHD therapy by two years (37 versus 57 percent) [17].

-A retrospective review of 214 recipients of MUD grafts reported no difference between graft sources for OS, TRM, or relapse, but peripheral blood grafts were associated with an increased risk for extensive chronic GVHD [18].

Children — For children undergoing HCT for a malignancy, we suggest bone marrow grafts rather than peripheral blood grafts, based on similar or better survival outcomes and less GVHD.

No randomized trials have compared graft sources for malignancies in children, but retrospective studies report that bone marrow grafts are associated with better outcomes.

●A retrospective study reported that for children with leukemia (ages 8 to 20 years) who received MSD grafts, survival was superior in the 630 patients who received bone marrow grafts compared with 143 patients who received peripheral blood grafts [19]. Peripheral blood grafts were associated with increased overall mortality (relative risk [RR] 1.38 [95% CI 1.07-1.79]), TRM (RR 1.89 [95% CI 1.28-2.80]), and chronic GVHD (RR 1.85 [95% CI 1.28-2.66]).

●Among children and adolescents with leukemia, survival was comparable for recipients of bone marrow grafts (650 patients) versus peripheral blood grafts (222 patients) in the CIBMTR (Center for International Blood and Marrow Transplant Registry; 2000 to 2012) registry [20]. Recipients of bone marrow and peripheral blood grafts had comparable eight-year OS (47 and 42 percent, respectively) and LFS (40 percent for both groups). However, peripheral blood was associated with higher rates of late (ie, >6 months) overall mortality (HR 1.3 [95% CI 1-1.7]), late TRM (HR 1.9 [95% CI 1.3-2.9]), grade ≥2 acute GVHD (HR 1.5 [95% CI 1.2-1.8]), and chronic GVHD (HR 1.9 [95% CI 1.6-2.4]). The increased AEs with peripheral blood grafts were offset by a lower risk for relapse (HR 0.8 [95% CI 0.6-1]). There was no difference in early (ie, ≤6 months) TRM, early overall mortality, or graft failure at one year (11 percent with bone marrow versus 6 percent with peripheral blood).

●Bone marrow grafts were associated with superior survival for children (8 to 20 years) with leukemia who received bone marrow (630 patients) versus peripheral blood grafts (143 patients) in the Internation Bone Marrow Transplant Registry (1995 to 2000) [19]. Three-year OS with bone marrow grafts was 58 percent compared with 48 percent with peripheral blood grafts after adjusting for other significant factors. Peripheral blood grafts were associated with higher RR for mortality (RR 1.4 [95% CI 1.1-1.8]), TRM (RR 1.9 [95% CI 1.3-2.8]), and treatment failure (RR 1.3 [95% CI 1-1.7]). Relapse rates were similar (33 percent with bone marrow versus 38 percent with peripheral blood). Grade ≥3 chronic GVHD at three years was higher with peripheral blood (33 versus 19 percent; RR 1.8 [95% CI 1.3-2.6]), but rates of grade ≥2 acute GVHD were similar between graft sources.

●A single-institution study of allogeneic transplantation in children using unrelated donor grafts reported similar outcomes between recipients of bone marrow grafts (39 patients) versus peripheral blood grafts (35 children) [21]. OS, TRM, and relapse-free survival did not differ, but relapses were more common with bone marrow grafts than peripheral blood grafts (48 versus 24 percent).

●In a CIBMTR study of transplantation for pediatric chronic myeloid leukemia, peripheral blood grafts were associated with more early mortality and GVHD but better LFS and engraftment [22]. Peripheral blood was associated with more day-100 TRM (RR 1.96 [95% CI 1.26-3.05]), chronic GVHD (RR 1.72 [95% CI 1.28-2.32]), and acute GVHD (RR 1.97 [95% CI 1.42-2.72]) but better LFS (RR 1.64 [95% CI 1.19-2.27]) and day-28 neutrophil engraftment (RR 3.87 [95% CI 1.31-11.47]).

Collection of bone marrow grafts and peripheral blood grafts are discussed below. (See 'Bone marrow grafts' below and 'Peripheral blood grafts' below.)

Allogeneic HCT for nonmalignant disorders — For both adults and children who are undergoing HCT for a nonmalignant disorder, we suggest bone marrow grafts rather than peripheral blood grafts. Compared with peripheral blood, bone marrow grafts are associated with comparable or better survival and less GVHD; there is no need for a graft-versus-tumor effect in nonmalignant conditions.

●A study of 692 patients with aplastic anemia transplanted with MSDs reported that bone marrow grafts were associated with better outcomes for ages ≤20 years, but there was no difference in outcomes for older patients [23]. This CIBMTR and EBMT registry study included 558 patients who received bone marrow grafts and 134 who received peripheral blood grafts. For patients ≤20 years, peripheral blood grafts were associated with increased overall mortality (RR 2.04 [95% CI 1.09-3.78]), more chronic GVHD (RR 2.82 [95% CI 1.46-5.44]), and a trend toward inferior five-year OS (73 versus 85 percent). For patients ≥21 years, there were no significant differences between graft sources in overall mortality or chronic GVHD.

●Decision analysis concluded that for patients with a low risk for relapse (primarily acquired aplastic anemia, hemoglobinopathies, rheumatoid arthritis, inherited marrow failure syndromes), bone marrow grafts were associated with longer life expectancy and QALE than peripheral blood grafts [12].

Autologous HCT — For autologous HCT, we recommend peripheral blood grafts rather than bone marrow grafts based on superior outcomes and avoidance of the risks of bone marrow graft collection.

Virtually all transplant centers use peripheral blood grafts rather than bone marrow grafts for autologous HCT. Compared with bone marrow, peripheral blood grafts are associated with comparable or better survival, faster engraftment, and avoidance of pain and general anesthesia associated with bone marrow grafts. Unlike allogeneic HCT, GVHD is not a problem with autologous HCT because the patient's own cells are used for the graft.

Peripheral blood grafts achieved superior OS compared with bone marrow grafts in a phase 3 trial that randomly assigned graft source for autologous HCT to 105 patients with aggressive non-Hodgkin lymphoma [24]. Compared with bone marrow, recipients of peripheral blood grafts had superior four-year OS (61 versus 43 percent), but there was no difference in four-year event-free survival (37 percent in both arms). Peripheral blood grafts achieved faster engraftment and a trend toward more complete responses (72 versus 54 percent).

Other randomized trials reported that peripheral blood grafts for lymphomas achieved faster engraftment and provided advantages with supportive care, quality of life, and cost [25-27]. A matched-pair analysis using registry data reported no difference in OS or progression-free survival by graft source in patients with lymphomas but better engraftment with peripheral blood grafts [28].

Low levels of contaminating tumor cells can be detected in some autologous peripheral blood specimens; however, there is generally a lower level of contaminating tumor cells than that with bone marrow grafts, and its clinical significance is uncertain.

Autologous HCT is used for hematologic malignancies, solid tumors, and other conditions. Indications for autologous HCT are discussed in disease-specific topics.

PERIPHERAL BLOOD GRAFTS — HSPCs circulate at extremely low levels in peripheral blood, but mobilization can increase the yield 1000-fold or more. Mobilization protocols for peripheral blood grafts vary according to the type of transplantation (allogeneic versus autologous) and among institutions.

For allogeneic HCT

Mobilization — For mobilization of peripheral blood grafts with allogeneic HCT, we suggest filgrastim (granulocyte colony stimulating factor [G-CSF]; or a biosimilar) rather than filgrastim plus a CXCR4 inhibitor (eg, plerixafor). This suggestion is based on adequate mobilization for most allogeneic donors using filgrastim alone, and it avoids the substantial added cost of plerixafor.

We reserve the addition of plerixafor to filgrastim for allogeneic donors who do not adequately mobilize HSPCs with filgrastim alone. (See 'Plerixafor for inadequate collection' below.)

Some institutions routinely use filgrastim plus plerixafor for peripheral blood graft collection in allogeneic HCT. (See 'Other strategies' below.)

Filgrastim — Mobilization using filgrastim is the most common method for collecting peripheral blood HSPCs.

●Administration – We treat with filgrastim 10 mcg/kg subcutaneously once daily for four days prior to leukapheresis.

The preferred protocol for filgrastim mobilization varies among institutions. Some centers favor twice-daily administration of filgrastim 5 mcg/kg, but there is no persuasive evidence that this provides advantages compared with once-daily filgrastim 10 mcg/kg [29,30]. Randomized trials and other studies have reported that higher doses of filgrastim or different schedules can increase the yield of HSPCs but did not reduce the number of leukapheresis sessions and were associated with greater cost and/or more adverse effects (AEs) [31-37].

Recombinant filgrastim is approved by the US Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) for graft mobilization.

●Toxicity – Filgrastim is safe and well-tolerated by graft donors [38,39]. The most common AEs are local skin reactions at the injection site and mild to moderate bone pain after repeated administration.

Rare cases of splenic rupture, alveolar hemorrhage, acute respiratory distress, Sweet syndrome, and hemoptysis have been reported, as discussed separately. (See "Evaluation of the hematopoietic cell transplantation donor", section on 'Toxicity of PBPC donation'.)

Alternative cytokines — Other cytokines are acceptable for mobilizing HSPCs, but they are used much less often than filgrastim.

●Lenograstim – Lenograstim is a glycosylated G-CSF product that can be used to mobilize HSPCs.

Lenograstim is given at a dose of 5 mcg/kg or 10 mcg/kg, alone or in combination with chemotherapy.

A phase 3 trial reported that random assignment to lenograstim versus filgrastim achieved similar efficacy [40]. Other studies also reported comparable outcomes with lenograstim [41-53].

Lenograstim is approved by EMA and the Pharmaceuticals and Medicals Devices Agency of Japan (PMDA) for peripheral blood HSPC mobilization. Lenograstim is not approved in the United States.

●Pegfilgrastim – Pegylated recombinant G-CSF (pegfilgrastim) is a longer-acting form of G-CSF.

Pegfilgrastim 6 or 12 mg subcutaneously can be given either alone or in combination with chemotherapy.

Pegfilgrastim can safely mobilize HSPCs in adults and children with less frequent dosing than filgrastim [54-63], but it is not commonly used for graft mobilization. Mobilization using a single dose of pegfilgrastim daily G-CSF versus daily filgrastim in 64 patients with lymphoma reported that both approaches provided comparable mobilization and collection of CD34+ cells [56].

Pegfilgrastim is not approved for HSPC mobilization by the FDA or the EMA.

●Sargramostim – Granulocyte-monocyte colony stimulating factor (GM-CSF) is no longer routinely used for peripheral blood HSPC mobilization.

Although it is safe and effective for peripheral blood HSPC mobilization, there was a shift to filgrastim because GM-CSF mobilization is more often associated with fever and myalgias in the donor.

GM-CSF is approved by the FDA for mobilization of HSPCs.

Graft collection — Peripheral blood grafts are collected via leukapheresis after four days of filgrastim mobilization.

Most leukapheresis procedures can be performed using antecubital veins (ie, without the need for central venous access) in one or two leukapheresis sessions. However, up to four sessions may be needed for some collections. Leukapheresis in an adult, performed through the antecubital veins, can process up to 25 liters of blood in four hours, which usually yields enough HSPCs to ensure rapid engraftment.

The leukapheresis procedure is discussed separately. (See "Evaluation of the hematopoietic cell transplantation donor", section on 'Procedure'.)

Cell dose and infusion — The target dose for peripheral blood allogeneic grafts is generally ≥2 to 5 x 106 CD34+ cells/kg recipient body weight. Grafts are infused as a bedside procedure with little toxicity. It takes approximately 10 days for neutrophil recovery and 10 to 12 days for platelet recovery after graft infusion.

●Cell dose – The CD34+ cell dose for allogeneic HCT varies with the degree of histocompatibility, but precise targets are not well-defined:

•Human leukocyte antigen (HLA)-matched donor – A dose of 2 to 5 x 106 CD34+ cells/kg is adequate for allogeneic HCT using a graft from an HLA-matched sibling donor (MSD) or matched unrelated donor (MUD).

•Others – For HLA-mismatched or haploidentical transplantation, a dose of 10 to 20 x 106 CD34+ cells/kg is generally administered.

There is no established minimum CD34+ cell dose. Many centers will accept 1 x 106 CD34+ cells/kg, while recognizing that this may further delay platelet recovery.

Studies that evaluated outcomes according to peripheral blood graft doses have reported mixed results. Higher doses generally yield slightly faster platelet recovery and have a minimal effect on neutrophil recovery and may improve clinical outcomes, but some studies reported more graft-versus-host disease (GVHD).

•A registry study reported outcomes for 932 patients receiving peripheral blood grafts who were enrolled in prospective studies of the National Marrow Donor Program (1999 to 2003) [64]. Compared with lower doses, >4.5 x 106 CD34+ cells/kg was associated with improved three-year overall survival (OS; 39 versus 25 percent), less transplant-related mortality (TRM), more rapid engraftment, and no increase in risk for GVHD.

•In another registry study, among 511 recipients of peripheral blood grafts, compared with lower doses, patients who received >6 x 106 CD34+ cells/kg had a lower risk for relapse, less treatment failure, and faster neutrophil and platelet engraftment [65].

•In a study of 146 patients who underwent peripheral blood allogeneic HCT (1997 to 2004), the median OS was better in patients who received 4 to 8 x 106 CD34+ cells/kg compared with those who received either lower or higher doses [66]. A retrospective study of 130 patients reported that outcomes were better for patients who received 6 to 8 x 106 CD34+ cells/kg compared with those who received higher or lower doses; multivariable analysis suggested that increasing numbers of infused cells were associated with an improved OS in a continuous fashion [67].

•A single-institution study reported that engraftment, GVHD, and OS did not vary according to CD34+ dose among 101 patients (1995 to 2002) who underwent allogeneic HCT with peripheral blood grafts [68]. In a study of 181 patients who received MSD grafts, compared with lower doses, infusion of >8 x 106 CD34+ cells/kg was associated with no difference in OS, rate of relapse, or engraftment, but there was increased extensive chronic GVHD [69].

●Graft infusion – Peripheral blood grafts are infused as a bedside procedure. Infusions are generally well-tolerated.

•Administration – Peripheral blood grafts can be either fresh or cryopreserved. The graft is thawed at the bedside and infused over several minutes [70].

•Toxicity – Graft administration is typically associated with minimal toxicity. Significant infusional AEs, such as hypotension, cardiac arrhythmias, and electrolyte disturbances, are rare.

Infusion of cryopreserved peripheral blood products may be associated with minor AEs, such as fever, cough, nausea, vomiting, flushing, headache, and occasional bronchospasm. Most such reactions disappear rapidly following the completion of the infusion. These reactions may be related to the cryoprotectant dimethyl sulfoxide (DMSO) or the quantity of granulocytes or nonmononuclear cells in the leukapheresis product [71,72]. DMSO gives off an odor for one to two days after infusion.

Plasma depletion can be performed in cases of major ABO incompatibility, but we do not routinely do this. Instead, we use significant hydration to avoid complications of the mild hemolytic transfusion reaction.

Plerixafor for inadequate collection — When filgrastim alone yields inadequate levels of circulating CD34+ cells or insufficient peripheral blood HSPC collection, we suggest adding plerixafor rather than other approaches.

Targets for levels of circulating CD34+ cells and peripheral blood HSPC collection are discussed above. (See 'Cell dose and infusion' above.)

Some centers routinely mobilize peripheral blood HSPCs using filgrastim plus plerixafor. Other methods of mobilization for peripheral blood grafts are discussed below. (See 'Other strategies' below.)

●Administration – Plerixafor 240 mcg/kg is given subcutaneously when ≥4 days of filgrastim treatment does yield adequate peripheral blood HSPC mobilization. Graft collection generally begins the following day.

Plerixafor may be repeated for up to four consecutive days until an adequate specimen is collected.

●Toxicity – The most common AEs are mild diarrhea, nausea, fatigue, injection site reactions, headache, arthralgias, dizziness, and vomiting.

Plerixafor mobilizes functional HSPCs into the circulation within hours of injection [73-75]. Plerixafor inhibits interactions between stromal-cell-derived factor 1 (SDF-1) and its receptor, CXCR4, which plays a key role in HSPC trafficking [76,77].

The US Food and Drug Administration has approved plerixafor in combination with G-CSF to mobilize HSPCs for collection and subsequent autologous transplantation in patients with non-Hodgkin lymphoma (NHL) or multiple myeloma (MM).

For autologous HCT — Many patients who are undergoing autologous HCT are heavily pretreated. As many as one-third of patients may have an inadequate yield of peripheral blood HSPCs using filgrastim alone.

Risk-adapted mobilization — For peripheral blood grafts in autologous HCT, we suggest filgrastim plus the risk-adapted addition of plerixafor rather than other approaches. This strategy treats the patient with daily filgrastim and adds plerixafor in cases where the level of circulating CD34+ cells is insufficient and/or the collection of HSPCs is inadequate. This approach places a high value on reducing the cost of HSPC mobilization for autologous HCT.

The preferred approach for HSPC mobilization in autologous HCT varies among institutions. Some centers routinely treat with filgrastim plus plerixafor and/or chemotherapy when mobilizing HSPCs. Although a phase 3 trial found that filgrastim plus plerixafor achieved higher HSPC yields than filgrastim plus placebo, this did not affect survival for patients with NHL or MM. The routine addition of plerixafor to filgrastim and other strategies for HSPC collection with autologous HCT are discussed below. (See 'Other strategies' below.)

Our approach to risk-adapted mobilization follows. Details may differ according to institutional practice and the underlying disease.

●Treat with filgrastim 10 mcg/kg daily by subcutaneous injection for four consecutive days.

●Measure circulating CD34+ cells on day 4.

●For <10 CD34+ cells/microL on day 4, treat with plerixafor 240 mg in the evening and initiate leukapheresis the following day.

●If the first day of leukapheresis (ie, day 5) yielded <1.5 x 106 CD34+ cells/kg, or if the subsequent daily yield was <0.5 x 106 CD34+ cells/kg/day, add plerixafor daily and continue leukapheresis.

A dose of ≥2 to 5 x 106 CD34+ cells/kg recipient body weight is adequate for autologous HCT in most settings; this yield correlates with 10 CD34+ cells/microL on day 4 of filgrastim mobilization [78-81]. Note that autologous HCT for MM may apply different targets; in some patients with MM, there may be two potential rounds of autologous HCT (ie, one for consolidation therapy and another as salvage therapy for possible future relapse). Graft collection for patients with MM is discussed separately. (See "Multiple myeloma: Use of hematopoietic cell transplantation", section on 'G-CSF-based stimulation'.)

Failure to achieve an adequate HSPC collection with filgrastim alone has been reported in up to one-third of patients undergoing autologous HCT [47,82]. By contrast, the risk-adapted strategy was associated with only 1 percent failure rate and reduced the cost and number of days of collection [83].

Other strategies — The preferred method of mobilization for autologous HCT varies among institutions.

Mobilization with filgrastim and risk-adapted addition of plerixafor is discussed above. (See 'Risk-adapted mobilization' above.)

Other approaches include:

●Filgrastim alone – Filgrastim alone has been reported to yield an inadequate collection in up to one-third of patients undergoing autologous HCT [47,82].

Mobilization using filgrastim is discussed above. (See 'Mobilization' above.)

●Filgrastim plus routine addition of plerixafor – Some institutions routinely add plerixafor after four days of filgrastim when collecting peripheral blood grafts for autologous HCT.

A phase 3 trial reported that filgrastim plus plerixafor on day 4 and continuing daily for up to four days achieved higher HSPC yields than filgrastim plus placebo in 302 patients undergoing autologous HCT for MM [43]. However, the routine addition of plerixafor did not affect long-term survival for patients with NHL or MM [84].

The administration of plerixafor is discussed above. (See 'Plerixafor for inadequate collection' above.)

●Filgrastim plus motixafortide – The use of the cyclic CXCR4 inhibitor, motixafortide, is discussed separately. (See "Multiple myeloma: Use of hematopoietic cell transplantation", section on 'G-CSF-based stimulation'.)

●Cyclophosphamide with or without filgrastim and/or plerixafor – Some centers favor the use of cyclophosphamide (or other disease-specific chemotherapy) plus filgrastim, with or without plerixafor, when collecting peripheral blood grafts for autologous HCT.

Note that the use of chemotherapy mobilization is not appropriate for HSPC mobilization in allogeneic donors. (See 'For allogeneic HCT' above.)

We generally reserve the use of cyclophosphamide for autologous HSPC mobilization in patients who are unable to achieve an adequate autologous collection with G-CSF and plerixafor, especially if there was an inadequate response (eg, partial response) to induction chemotherapy.

Filgrastim plus cyclophosphamide provides higher HSPC yields than filgrastim alone, but it also the delays the start of collection and carries the risk of neutropenic fever, hemorrhagic cystitis, and possible hospitalization [85].

In a phase 3 trial of 47 heavily pretreated patients with relapsed or refractory lymphomas, mobilization was more effective with cyclophosphamide 5 g/m2 followed by filgrastim compared with filgrastim alone [86]. After a median follow-up of 21 months, OS, progression-free survival, and engraftment did not differ between the two trial arms.

●Filgrastim plus stem cell factor – Stem cell factor (SCF; ancestim; recombinant methionyl human stem cell factor) has limited activity as a single agent for mobilizing HSPCs, but it can enhance HSPC yield with little toxicity when combined with filgrastim for mobilization.

SCF is not available in the United States or Europe.

A phase 3 trial of 203 patients undergoing autologous HCT for breast cancer reported that the addition of SCF to filgrastim was more effective than filgrastim alone for mobilization and reducing the number of leukaphereses, but it did not affect the rate of engraftment [87].

BONE MARROW GRAFTS — Collection of bone marrow grafts requires general anesthesia and is associated with substantial postoperative pain.

●Procedure – Bone marrow grafts are obtained from the posterior iliac crests under general anesthesia. Other anatomic sites (eg, anterior iliac crests) do not provide sufficient HSPCs for successful engraftment with HCT.

Multiple aspirations (approximately 5 to 10 mL of marrow from each puncture) are performed with the goal of collecting up to 2 x 108 cells of marrow/kg of recipient body weight. This corresponds to 700 and 1500 mL of bone marrow for an adult recipient.

Guidelines established by the National Marrow Donor Program (NMDP) limit the volume of bone marrow removed to 20 mL/kg of donor weight. Either heparin or acid-citrate-dextran-A can be used to anticoagulate bone marrow products. If the product is to be cryopreserved, red cells are washed off prior to freezing. (See "Evaluation of the hematopoietic cell transplantation donor", section on 'Bone marrow collection'.)

●Complications – Bone marrow donors frequently experience back or hip pain, fatigue, and transient changes in peripheral blood cell counts.

Serious complications, such as mechanical injury, complications of anesthesia, infection, and bleeding, are extremely rare, as discussed separately. (See "Evaluation of the hematopoietic cell transplantation donor", section on 'Complications'.)

Bone marrow cell dose and infusion

●Cell dose – The dose of a bone marrow graft is generally calculated according to the number of nucleated cells/kg of recipient body weight. A dose of 2 x 108 nucleated cells/kg is considered adequate for stable long-term engraftment.

Retrospective studies have reported better outcomes in association with CD34+ cell dose ≥3 x 106/kg, but cell doses of as low as 1 x 108/kg have been used.

•Clinical outcomes were associated with bone marrow graft dose in recipients of human leukocyte antigen (HLA)-matched sibling donor (MSD) grafts for leukemia (1995 to 1998) in the IBMTR (International Bone Marrow Transplant Registry) [65]. Transplant-related mortality (TRM; relative risk [RR] 0.60 [0.37–0.96]) and treatment failure (RR 0.69 [0.56–0.97]) were lower with doses above the median (3 x 106 CD34+ cells/kg) compared with lower doses.

•In a retrospective single-center study of 97 patients who underwent autologous HCT for lymphomas, there was an inverse correlation between the infused CD34+ cell dose and better clinical outcomes [88]. With a median follow-up of 44 months, compared with those who received doses <8.2 x 106 CD34+ cells/kg, patients who received larger doses had a better overall survival (OS; not reached versus 12 months) and longer event-free survival (not reached versus five months) in multivariate analysis. Patients who received higher doses also had faster recovery of neutrophils, platelets, and lymphocytes.

•Other retrospective studies identified lower, better five-year OS and lower TRM in recipients of CD34+ cell doses ≥3 x 106/kg [89,90]. In another study, hematopoietic recovery was worse when the CD34+ cell dose was <1.2 x 106/kg [91].

●Infusion – Allogeneic bone marrow products are generally used fresh and infused through a central vein over several hours to reduce infusion reactions.

These products are associated with occasional fever, but most patients tolerate the infusion like a blood transfusion. Hemolytic reactions can occur when the ABO type of a bone marrow donor is a mismatch with the recipient. Red blood cells should be depleted prior to infusion in patients with major ABO incompatibilities [92].

Acute hemolytic transfusion reactions are treated in standard fashion by administering fluids and diuretics. (See "Hemolytic transfusion reactions".)

Mobilized bone marrow — Filgrastim-primed bone marrow can hasten hematologic recovery in heavily pretreated patients, but this is not often used for clinical transplantation.

Filgrastim 10 to 16 mcg/kg subcutaneously daily for three days can be used to prime bone marrow.

There is no evidence that bone marrow priming with filgrastim improves outcomes in transplant recipients:

●Compared with historical controls, there was no difference in OS, graft-versus-host disease, or platelet recovery among 17 patients who received filgrastim-primed bone marrow, but neutrophil recovery was faster, and hospitalization was shorter [93].

●Filgrastim-primed bone marrow enabled effective hematologic recovery among heavily pretreated patients with poor peripheral blood mobilization [94,95].

UMBILICAL CORD BLOOD — Umbilical cord blood (UCB) refers to the blood remaining in the umbilical cord and placenta following the birth of an infant.

Although HSPCs are abundant in UCB, many centers routinely use two separate specimens to provide an adequate dose. Cryopreserved specimens in cord blood banks are identified based on immunologic compatibility with the recipient, thawed at the bedside, and infused over several minutes. (See "Collection and storage of umbilical cord blood for hematopoietic cell transplantation".)

The expanded donor pool, ease of procurement, lack of donor attrition, and decreased rate of graft-versus-host disease are practical advantages for UCB grafts. Limitations include an increased risk of graft failure, delayed immune reconstitution, and unavailability of the donor for additional donations (ie, donor lymphocyte infusions). Other aspects of UCB grafts for allogeneic HCT are presented separately. (See "Selection of an umbilical cord blood graft for hematopoietic cell transplantation", section on 'Features of UCB grafts'.)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Hematopoietic cell transplantation (bone marrow transplantation) (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Description – In hematopoietic cell transplantation (HCT), a graft of hematopoietic stem and progenitor cells (HSPCs) is infused to restore hematopoiesis following the administration of conditioning therapy (intensive chemotherapy and/or radiation therapy). The graft can be the patient's own cells (autologous HCT), or the donor can be another individual (allogeneic HCT).

●Sources of HSPCs – Potential sources for HSPC grafts for HCT are peripheral blood, bone marrow, and umbilical cord blood (UCB). Peripheral blood grafts are collected by leukapheresis, while bone marrow grafts require general anesthesia. Preferred graft sources vary with transplantation technique (allogeneic versus autologous), underlying disease (malignant versus nonmalignant), and recipient age. (See 'Preferred graft sources' above.)

•Allogeneic HCT for malignant diseases

-Adults – For adults undergoing HCT for a malignancy, we suggest a peripheral blood graft rather than a bone marrow graft (Grade 2C). (See 'Adults' above.)

-Child – For children undergoing HCT for a malignancy, we suggest a bone marrow graft rather than a peripheral blood graft (Grade 2C). (See 'Children' above.)

•Nonmalignant diseases – For both adults and children undergoing HCT for a nonmalignant disorder, we suggest a bone marrow graft rather than a peripheral blood graft (Grade 2C). (See 'Allogeneic HCT for nonmalignant disorders' above.)

•Autologous HCT – For autologous HCT, we recommend a peripheral blood graft rather than a bone marrow graft (Grade 1B). (See 'Autologous HCT' above.)

●Peripheral blood grafts – Peripheral blood grafts are obtained by leukapheresis after mobilization of HSPCs. Preferred mobilization techniques vary among institutions and applications.

•Allogeneic HCT – For mobilization of peripheral blood grafts in allogeneic HCT, we suggest filgrastim rather than filgrastim plus plerixafor (Grade 2C). (See 'For allogeneic HCT' above.)

-Filgrastim – Filgrastim administration for peripheral blood mobilization in allogeneic HCT is discussed above. (See 'Filgrastim' above.)

-Alternative cytokines – Other cytokines can be used for mobilization. (See 'Alternative cytokines' above.)

-Inadequate yield – When filgrastim alone yields inadequate levels of circulating CD34+ cells or insufficient peripheral blood HSPC collection, we suggest adding plerixafor rather than other approaches (Grade 2C). (See 'Plerixafor for inadequate collection' above.)

•Autologous HCT – For peripheral blood grafts in autologous HCT, we suggest filgrastim plus the risk-adapted addition of plerixafor rather than other approaches (Grade 2C). Details of risk-adapted strategy for HSPC collection are discussed above. (See 'Risk-adapted mobilization' above.)

●Bone marrow grafts – Collection of bone marrow grafts requires general anesthesia and is associated with substantial postoperative pain. (See 'Bone marrow grafts' above.)

•Dose – A dose of ≥2 x 108 nucleated cells/kg recipient body weight is considered adequate. (See 'Bone marrow cell dose and infusion' above.)

•Mobilized bone marrow – There is no evidence that bone marrow priming with filgrastim improves clinical outcomes. (See 'Mobilized bone marrow' above.)

●Umbilical cord blood – HCT using UCB grafts is discussed separately. (See "Selection of an umbilical cord blood graft for hematopoietic cell transplantation".)

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Topic 3537 Version 38.0

References

1 : A direct measurement of the radiation sensitivity of normal mouse bone marrow cells.

2 : The biology of hematopoietic stem cells.

3 : Hematopoietic Stem Cells and Their Roles in Tissue Regeneration.

4 : Purification and characterization of mouse hematopoietic stem cells.

5 : Transplantation of highly purified CD34+Thy-1+ hematopoietic stem cells in patients with metastatic breast cancer.

6 : Indications for Autologous and Allogeneic Hematopoietic Cell Transplantation: Guidelines from the American Society for Blood and Marrow Transplantation.

7 : Indications for haematopoietic cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2022.

8 : NCCN Guidelines®Insights: Hematopoietic Cell Transplantation, Version 3.2022.

9 : Peripheral blood progenitor cell mobilization for autologous and allogeneic hematopoietic cell transplantation: guidelines from the American Society for Blood and Marrow Transplantation.

10 : Bone marrow versus peripheral blood allogeneic haematopoietic stem cell transplantation for haematological malignancies in adults.

11 : Allogeneic peripheral blood stem-cell compared with bone marrow transplantation in the management of hematologic malignancies: an individual patient data meta-analysis of nine randomized trials.

12 : Decision analysis of peripheral blood versus bone marrow hematopoietic stem cells for allogeneic hematopoietic cell transplantation.

13 : A randomized multicenter comparison of bone marrow and peripheral blood in recipients of matched sibling allogeneic transplants for myeloid malignancies.

14 : Long-term outcome and late effects in patients transplanted with mobilised blood or bone marrow: a randomised trial.

15 : Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers.

16 : Transplantation of mobilized peripheral blood cells to HLA-identical siblings with standard-risk leukemia.

17 : Peripheral-blood stem cells versus bone marrow from unrelated donors.

18 : Increased risk of extensive chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation using unrelated donors.

19 : Higher mortality after allogeneic peripheral-blood transplantation compared with bone marrow in children and adolescents: the Histocompatibility and Alternate Stem Cell Source Working Committee of the International Bone Marrow Transplant Registry.

20 : Bone Marrow versus Peripheral Blood from Unrelated Donors for Children and Adolescents with Acute Leukemia.

21 : Similar outcome after unrelated allogeneic peripheral blood stem cell transplantation compared with bone marrow in children and adolescents.

22 : Outcomes of Allogeneic Hematopoietic Cell Transplantation in Children and Young Adults with Chronic Myeloid Leukemia: A CIBMTR Cohort Analysis.

23 : Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia.

24 : Autologous transplantation for aggressive non-Hodgkin's lymphoma: results of a randomized trial evaluating graft source and minimal residual disease.

25 : Improved immune reconstitution after allotransplantation of peripheral blood stem cells instead of bone marrow.

26 : Autologous peripheral blood stem cell transplantation in patients with relapsed lymphoma results in accelerated haematopoietic reconstitution, improved quality of life and cost reduction compared with bone marrow transplantation: the Hovon 22 study.

27 : Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients.

28 : Peripheral-blood stem-cell transplantation versus autologous bone marrow transplantation in Hodgkin's and non-Hodgkin's lymphomas: a new matched-pair analysis of the European Group for Blood and Marrow Transplantation Registry Data. Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.

29 : Current status of stem cell mobilization.

30 : A comparative study of once-daily versus twice-daily filgrastim administration for the mobilization and collection of CD34+ peripheral blood progenitor cells in normal donors.

31 : Stem cell mobilisation with 16 microg/kg vs 10 microg/kg of G-CSF for allogeneic transplantation in healthy donors.

32 : Granulocyte colony-stimulating factor alone at 20 micrograms/kg vs. 10 micrograms/kg for peripheral blood stem cell mobilization in children.

33 : The role of diagnosis in patients failing peripheral blood progenitor cell mobilization.

34 : Mobilization and harvesting of peripheral blood stem cells: randomized evaluations of different doses of filgrastim.

35 : A double-blind low dose-finding phase II study of granulocyte colony-stimulating factor combined with chemotherapy for stem cell mobilization in patients with non-Hodgkin's lymphoma.

36 : A randomised study of 10 microg/kg/day (single dose) vs 2 x 5 microg/kg/day (split dose) G-CSF as stem cell mobilisation regimen in high-risk breast cancer patients.

37 : A randomized comparison of once versus twice daily recombinant human granulocyte colony-stimulating factor (filgrastim) for stem cell mobilization in healthy donors for allogeneic transplantation.

38 : Three to six year follow-up of normal donors who received recombinant human granulocyte colony-stimulating factor.

39 : Efficacy and safety of peripheral blood stem cell mobilization and collection: a single-center experience in 190 allogeneic donors.

40 : A randomized study comparing filgrastim versus lenograstim versus molgramostim plus chemotherapy for peripheral blood progenitor cell mobilization.

41 : Mobilization of hematopoietic stem cells with lenograstim in multiple myeloma patients: Prospective multicenter observational study (KMM122).

42 : Comparison of biosimilar filgrastim, originator filgrastim, and lenograstim for autologous stem cell mobilization in patients with multiple myeloma.

43 : Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma.

44 : A randomised study comparing peripheral blood progenitor mobilisation using intermediate-dose cyclophosphamide plus lenograstim with lenograstim alone.

45 : Lenograstim reduces the incidence of febrile episodes, when compared with filgrastim, in multiple myeloma patients undergoing stem cell mobilization.

46 : Successful mobilization of peripheral blood stem cells in heavily pretreated myeloma patients with G-CSF alone.

47 : Impact of mobilization and remobilization strategies on achieving sufficient stem cell yields for autologous transplantation.

48 : Comparison of lenograstim vs filgrastim administration following chemotherapy for peripheral blood stem cell (PBSC) collection: a retrospective study of 126 patients.

49 : Incidence and risk factors of poor mobilization in adult autologous peripheral blood stem cell transplantation: a single-centre experience.

50 : Superior mobilisation of haematopoietic progenitor cells with glycosylated G-CSF in male but not female unrelated stem cell donors.

51 : Prospective randomized comparative observation of single- vs split-dose lenograstim to mobilize peripheral blood progenitor cells following chemotherapy in patients with multiple myeloma or non-Hodgkin's lymphoma.

52 : Reduced dose of lenograstim is as efficacious as standard dose of filgrastim for peripheral blood stem cell mobilization and transplantation: a randomized study in patients undergoing autologous peripheral stem cell transplantation.

53 : Comparison between filgrastim and lenograstim plus chemotherapy for mobilization of PBPCs.

54 : Single-dose pegfilgrastim for the mobilization of allogeneic CD34+ peripheral blood progenitor cells in healthy family and unrelated donors.

55 : Phase II study of a single pegfilgrastim injection as an adjunct to chemotherapy to mobilize stem cells into the peripheral blood of pretreated lymphoma patients.

56 : A single dose of Pegfilgrastim versus daily Filgrastim to evaluate the mobilization and the engraftment of autologous peripheral hematopoietic progenitors in malignant lymphoma patients candidate for high-dose chemotherapy.

57 : Successful transplantation of peripheral blood stem cells mobilized by chemotherapy and a single dose of pegylated G-CSF in patients with multiple myeloma.

58 : Efficacy of single-dose pegfilgrastim after chemotherapy for the mobilization of autologous peripheral blood stem cells in patients with malignant lymphoma or multiple myeloma.

59 : Efficacy of single dose pegfilgrastim in enhancing the mobilization of CD34+ peripheral blood stem cells in aggressive lymphoma patients treated with cisplatin-aracytin-containing regimens.

60 : A phase 2 pilot study of pegfilgrastim and filgrastim for mobilizing peripheral blood progenitor cells in patients with non-Hodgkin's lymphoma receiving chemotherapy.

61 : Mobilization of peripheral blood stem cells in myeloma with either pegfilgrastim or filgrastim following chemotherapy.

62 : Hematopoietic progenitor cell mobilization and harvesting in children with malignancies: do the advantages of pegfilgrastim really translate into clinical benefit?

63 : Pegfilgrastim for peripheral CD34+ mobilization in patients with solid tumours.

64 : Donor, recipient, and transplant characteristics as risk factors after unrelated donor PBSC transplantation: beneficial effects of higher CD34+ cell dose.

65 : Decreased treatment failure in recipients of HLA-identical bone marrow or peripheral blood stem cell transplants with high CD34 cell doses.

66 : Efficacy of CD34+ stem cell dose in patients undergoing allogeneic peripheral blood stem cell transplantation after total body irradiation.

67 : Optimizing the CD34 + cell dose for reduced-intensity allogeneic hematopoietic stem cell transplantation.

68 : CD34, CD4, and CD8 cell doses do not influence engraftment, graft-versus-host disease, or survival following myeloablative human leukocyte antigen-identical peripheral blood allografting for hematologic malignancies.

69 : CD34 cell dose in granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell grafts affects engraftment kinetics and development of extensive chronic graft-versus-host disease after human leukocyte antigen-identical sibling transplantation.

70 : Cryopreservation of hematopoietic stem cells.

71 : Occurrence and severity of adverse events after autologous hematopoietic progenitor cell infusion are related to the amount of granulocytes in the apheresis product.

72 : Adverse events after infusions of cryopreserved hematopoietic stem cells depend on non-mononuclear cell in infused suspention and on patient age (abstract)

73 : Chemokine-mobilized adult stem cells; defining a better hematopoietic graft.

74 : BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem and progenitor cells.

75 : Advances in mobilization for the optimization of autologous stem cell transplantation.

76 : It's moving day: factors affecting peripheral blood stem cell mobilization and strategies for improvement [corrected].

77 : Current mechanistic scenarios in hematopoietic stem/progenitor cell mobilization.

78 : Safety and efficacy assessment of plerixafor in patients with multiple myeloma proven or predicted to be poor mobilizers, including assessment of tumor cell mobilization.

79 : Advances in stem cell mobilization.

80 : Poor mobilizer: a retrospective study on proven and predicted incidence according to GITMO criteria.

81 : Predicting PBSC harvest failure using circulating CD34 levels: developing target-based cutoff points for early intervention.

82 : Clinical impact and resource utilization after stem cell mobilization failure in patients with multiple myeloma and lymphoma.

83 : Cost-effectiveness analysis of a risk-adapted algorithm of plerixafor use for autologous peripheral blood stem cell mobilization.

84 : Plerixafor Plus Granulocyte Colony-Stimulating Factor for Patients with Non-Hodgkin Lymphoma and Multiple Myeloma: Long-Term Follow-Up Report.

85 : Comparison of high-dose CY and growth factor with growth factor alone for mobilization of stem cells for transplantation in patients with multiple myeloma.

86 : Randomized trial of filgrastim versus chemotherapy and filgrastim mobilization of hematopoietic progenitor cells for rescue in autologous transplantation.

87 : A randomized phase 3 study of peripheral blood progenitor cell mobilization with stem cell factor and filgrastim in high-risk breast cancer patients.

88 : Higher infused CD34+ hematopoietic stem cell dose correlates with earlier lymphocyte recovery and better clinical outcome after autologous stem cell transplantation in non-Hodgkin's lymphoma.

89 : CD34+ cell dose predicts relapse and survival after T-cell-depleted HLA-identical haematopoietic stem cell transplantation (HSCT) for haematological malignancies.

90 : Association of CD34 cell dose with hematopoietic recovery, infections, and other outcomes after HLA-identical sibling bone marrow transplantation.

91 : Engraftment of autologous and allogeneic marrow HPCs after myeloablative therapy.

92 : Immunohematologic consequences of major ABO-mismatched bone marrow transplantation.

93 : A pilot study of allogeneic bone marrow transplantation using related donors stimulated with G-CSF.

94 : Autologous transplantation of granulocyte colony-stimulating factor-primed bone marrow is effective in supporting myeloablative chemotherapy in patients with hematologic malignancies and poor peripheral blood stem cell mobilization.

95 : G-CSF-stimulated BM progenitor cells supplement suboptimal peripheral blood hematopoietic progenitor cell collections for auto transplantation.

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