Practical Aspects of Hematologic Stem Cell Harvesting and Mobilization

Published on 04/03/2015 by admin

Filed under Hematology, Oncology and Palliative Medicine

Last modified 22/04/2025

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 1320 times

Chapter 45 Practical Aspects of Hematologic Stem Cell Harvesting and Mobilization

Scott D. Rowley, Michele L. Donato

Choice of Hematologic Stem Cell Product for Transplantation

Virtually all patients undergoing autologous HSC transplantation will have PBSC as the source of HSC, based on the following advantages: ease of collection, greater quantities of HSC (resulting in faster hematologic recovery and shorter and less costly hospital stays), and potentially lower risks for tumor cell contamination of the graft.

The allogeneic donor has a wider range of options, including marrow, PBSC, or UCB products from HLA-compatible or partially compatible related or unrelated donors. The transplant recipient may request a source of cells, but the donor has the right to decide about the method of donation. PBSC products have the greatest quantity of HSC and will result in faster hematologic recovery compared with marrow or UCB transplants. In some reports, PBSC transplantation also results in a survival advantage. However, PBSC transplantation is also associated with a higher risk for difficult-to-control chronic GVHD and may not be appropriate for use in patients who would not benefit from a robust GVL effect, such as those treated for nonmalignant diseases. Umbilical cord blood has the advantage of being immediately available, reducing the time to transplantation. Targeted collection of UCB products from ethnic populations not well represented in donor registries will facilitate treatment of ethnic minority patients. The relative immature immunity of the cord blood donor allows use of HLA mismatched products without an undue increase in GVHD risk. Infusion of two cord blood units may achieve a greater graft-versus-tumor effect, even though one unit will be rejected. The much smaller quantity of HSC in the cord blood product results in slower hematologic recovery, and the adult patient, in particular, may be at greater risk for posttransplant infections because of the relative immature immune system of the donor.

Table 45-1 Randomized Studies Comparing Marrow and PBSC as HSC Sources*

image

ANC, Absolute neutrophil count; BM, bone marrow, G-BM, granulocyte colony-stimulated bone marrow; NS, not significant; PBSC, peripheral blood stem cell.

* Shown are number of patients enrolled in each arm of the study, quantity of CD34+ cells × 106/kg (CFU-GM × 104/kg for reports by Beyer and Hartmann), days after transplantation to achieve a peripheral blood absolute neutrophil count >500/µL and platelet count >20,000/µL (25,000/µL for report by Blaise and 30,000/µL for report by Hartmann), and percentage of patients developing acute graft-versus-host disease.

Evaluation of the Marrow or Peripheral Blood Stem Cell Donor

HSC transplantation involves the infusion of a “blood product,” and all donors must be evaluated for risks for disease transmission as per the current criteria for blood donation. Exemptions from criteria that specifically address the risk for disease transmission are permissible, if the risks of excluding an otherwise appropriate donor outweigh the risks for disease transmission to the transplant recipient, who may not have an alternate donor. Informed consent must be obtained for the evaluation and collection procedures. Informed consent also must be specifically obtained for the release of protected donor health information to the transplant recipient, allowing proper informed consent for the transplant to be obtained. Minors and donors not competent to provide consent must be represented by a third party not involved in the care of the recipient. Ideally, similar courtesy will be provided to the adult donor. Donors must also be evaluated for health issues that would increase the risks resulting from the collection procedures. For marrow donors, this includes the risks of anesthesia; for PBSC donors, evaluation should include the risks of mobilization medications and apheresis.

The donor collection facility’s standard operating procedures for evaluation of HSC donors must meet FACT/JACIE or AABB guidelines and FDA (or other regulatory agency) standards, and include policies and procedures for the following:

• Education of donor, including education regarding procedures, risks, alternatives, and possible future collections

• Medical history, including special attention to history of autoimmune disorders, arthritis, cardiac and vascular diseases, and history of cancer

• History of high-risk behaviors, such as recent tattoos, body piercing, sexual practices, and travel

• Physical examination, including vein assessment (PBSC donors) and oral examination (marrow donors undergoing inhalational anesthesia)

• Laboratory studies, including verification HLA typing, ABO typing, CBC, chemistry panel, infectious disease panel, urinalysis, ECG, CXR

• Consent for collection procedures and the release of protected health information to the stem cell recipient

Table 45-2 Relationship Among Mobilization Therapy, Dose of Progenitor Cells, and Engraftment Kinetics for Autologous Peripheral Blood Stem Cell Transplantation

image

Shown are mean values for progenitor cell quantities infused and median times to achieve the particular endpoint of engraftment. ANC, Absolute neutrophil count; G-CSF, granulocyte colony-stimulating factor; ND, not measured; NR, not reached.

* Time to achieve >50,000 platelets/µL

† Colony-forming unit granulocyte-macrophage (CFU-GM) cultures performed on thawed cells.

‡ Median value.

Mobilization and Collection of Peripheral Blood Stem Cell for Autologous Transplantation

Four important considerations when prescribing a mobilization regimen for collection of PBSC for autologous transplantation are as follows: (1) A regimen of chemotherapy followed by G-CSF results in higher numbers of circulating CD34+ cells than will be found with G-CSF alone. (2) The choice of chemotherapy (or cytokine alone mobilization) should be appropriate to the disease and stage of disease for the patient. (3) Each cycle of prior chemotherapy and any previous treatment with radiotherapy will decrease the response to mobilization therapy. (4) Tumor infiltration of the marrow will increase the probability of circulating tumor cells and will decrease the response to mobilization therapy. With these considerations in mind, elective collection of PBSC either before extensive treatment or after a limited number of cycles of debulking chemotherapy should be considered. If tumor contamination is found, additional components can be collected after additional rounds of chemotherapy. The timing of apheresis after chemotherapy and G-CSF mobilization is best guided by measurement of the level of peripheral blood CD34+ cells. Daily or every-other-day quantification of these cells can be initiated after the WBC count reaches 1000/µL. Patients with poor mobilization of CD34+ cells should be considered for large-volume apheresis or addition of plerixafor to reduce the costs associated with daily doses of G-CSF, laboratory testing, apheresis procedures, and cryopreservation. Patients who fail to mobilize may have successful collections if given a short drug holiday before undergoing mobilization with high-dose G-CSF with plerixafor.

Table 45-3 Incidence of Somatic Complaints for Normal Donors Treated With Granulocyte Colony-Stimulating Factor

image

G-CSF, Granulocyte colony-stimulating factor; NR, particular complaint not reported in this series.

* Shown are reported proportions of donors experiencing the listed somatic complaint.

Physician Prescription for Apheresis and Peripheral Blood Stem Cell Processing

The attending physician should be aware of apheresis and laboratory procedures in order to maximize the value of PBSC components. The choices of venous access, anticoagulant(s), blood volume processed, target dose of CD34+ cells, and cryopreservation volumes can be individualized. Apheresis unit staff may ask for guidance regarding pain medications, concurrent medications, and blood transfusions (although it is advisable to avoid transfusion during the apheresis procedure because of citrate or other reactions and because changes in the hematocrit may affect the efficiency of the collection). Adequate numbers of CD34+ cells can be collected for more than one cycle of chemotherapy. It is important to communicate with the cryopreservation facility if PBSC components will be used to support more than one cycle of chemotherapy or if DMSO toxicity is of concern, in order to facilitate appropriate packaging of each product. Current cytometric techniques for quantification of CD34+ cells require at least 1 hour of processing, so it may not be practical to prescribe the number of CD34+ cells to be frozen in each bag. However, it is possible to divide the component into the number of bags equaling the number of anticipated infusions so that equal numbers of CD34+ cells will be available for each.

References

1 Beyer J, Schwella N, Zingsem J, et al. Hematopoietic rescue after highdose chemotherapy using autologous peripheral-blood progenitor cells or bone marrow: A randomized comparison. J Clin Oncol. 1995;13:1328.

2 Schmitz N, Linch DC, Dreger P, et al. Randomised trial of filgrastimmobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients. Lancet. 1996;347:353.

3 Hartmann O, Le Corroller AG, Blaise D, et al. Peripheral blood stem cell and bone marrow transplantation for solid tumors and lymphomas: Hematologic recovery and costs. A randomized, controlled trial. Ann Intern Med. 1997;126:600.

4 Blaise D, Kuentz M, Fortanier C, et al. Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: A report from the Societe Francaise de Greffe de Moelle. J Clin Oncol. 2000;18:537.

5 Bensinger WI, Martin PJ, Storer B, et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med. 2001;344:175.

6 Couban S, Simpson DR, Barnett MJ, et al. A randomized multicenter comparison of bone marrow and peripheral blood in recipients of matched sibling allogeneic transplants for myeloid malignancies. Blood. 2002;100:1525.

7 Schmitz N, Beksac M, Hasenclever D, et al. Transplantation of mobilized peripheral blood cells to HLA-identical siblings with standard-risk leukemia. Blood. 2002;100:761.

8 Morton J, Hutchins C, Durrant S. Granulocyte-colony-stimulating factor (G-CSF)-primed allogeneic bone marrow: Significantly less graftversus-host disease and comparable engraftment to G-CSF-mobilized peripheral blood stem cells. Blood. 2001;98:3186.

9 Damiani D, Fanin R, Silvestri F, et al. Randomized trial of autologous filgrastim-primed bone marrow transplantation versus filgrastimmobilized peripheral blood stem cell transplantation in lymphoma patients. Blood. 1997;90:36.

10 To LB, Roberts MM, Haylock DN, et al. Comparison of haematological recovery times and supportive care requirements of autologous recovery phase peripheral blood stem cell transplants, autologous bone marrow transplants and allogeneic bone marrow transplants. Bone Marrow Transplant. 1992;9:277.

11 Fermand J-P, Levy Y, Gerota J, et al. Treatment of aggressive multiple myeloma by high-dose chemotherapy and total body irradiation followed by blood stem cells autologous graft. Blood. 1989;73:20.

12 Juttner CA, To LB, Ho JQK, et al. Early lympho-hemopoietic recovery after autografting using peripheral blood stem cells in acute nonlymphoblastic leukemia. Transplant Proc. 1988;20:40.

13 Kessinger A, Armitage JO, Landmark JD, et al. Autologous peripheral hematopoietic stem cell transplantation restores hematopoietic function following marrow ablative therapy. Blood. 1988;71:723.

14 Nadamanee A, Sniecinski I, Schmidt GM, et al. High-dose therapy followed by autologous peripheral-blood stem-cell transplantation for patients with Hodgkin’s disease and non-Hodgkin’s lymphoma using unprimed and granulocyte colony-stimulating factor-mobilized peripheral-blood stem cells. J Clin Oncol. 1994;12:2176.

15 Sheridan WP, Begley CG, To LB, et al. Phase II study of autologous filgrastim (G-CSF)-mobilized peripheral blood progenitor cells to restore hemopoiesis after high-dose chemotherapy for lymphoid malignancies. Bone Marrow Transplant. 1994;14:105.

16 Weaver CH, Hazelton B, Birch R, et al. An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myeloablative chemotherapy. Blood. 1995;86:3961.

17 Bensinger W, Appelbaum F, Rowley S, et al. Factors that influence collection and engraftment of autologous peripheral-blood stem cells. J Clin Oncol. 1995;13:2547.

18 Anderlini P, Przepiorka D, Seong D, et al. Clinical toxicity and laboratory effects of granulocyte-colony-stimulating factor (filgrastim) mobilization and blood stem cell apheresis from normal donors, and analysis of charges for the procedure. Transfusion. 1996;36:590.

19 Bishop MR, Tarantolo SR, Jackson JD, et al. Allogeneic-blood stem-cell collection following mobilization with low-dose granulocyte colonystimulating factor. J Clin Oncol. 1997;15:1601.

20 Stroncek DF, Clay ME, Petzoldt ML, et al. Treatment of normal individuals with granulocyte-colony stimulating factor: Donor experiences and the effects on peripheral blood CD34+ cell counts and on the collection of peripheral blood stem cells. Transfusion. 1996;36:601.

Related posts:

Anemia of Chronic Diseases Lysosomal Storage Diseases: Perspectives and Principles Chronic Myeloid Leukemia Chronic Lymphocytic Leukemia Hemophilia A and B Complications After Hematopoietic Stem Cell Transplantation