AUTHOR INFORMATION

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Authored by E Anders Kolb, MD, Assistant Professor of Pediatrics, Division of Hematology and Oncology, Albert Einstein College of Medicine; Director, Pediatric Stem Cell Transplantation and Leukemia/Lymphoma Service, Children's Hospital at Montefiore

Coauthored by Pooja Gidwani, MD, Fellow, Department of Pediatric Hematology and Oncology, Montefiore Medical Center; Stephan A Grupp, MD, PhD, Director, Stem Cell Biology Program, Children's Hospital of Philadelphia; Assistant Professor, Department of Pediatrics, Division of Oncology, University of Pennsylvania

E Anders Kolb, MD, is a member of the following medical societies: American Association for Cancer Research, American Society of Clinical Oncology, American Society of Hematology, and Children's Oncology Group

Edited by Kathleen Sakamoto, MD, Professor, Department of Pediatrics, Division of Hematology-Oncology and Pathology and Laboratory Medicine, Mattel Children's Hospital, David Geffen School of Medicine, University of California at Los Angeles; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Timothy P Cripe, MD, PhD, Associate Professor of Pediatric Hematology/Oncology, University of Cincinnati; Director, Translational Research Trials Office, Department of Pediatrics, Cincinnati Children's Hospital Medical Center; Helen SL Chan, MBBS, FRCP(C), FAAP, Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada; and Robert J Arceci, MD, PhD, King Fahd Professor, Division of Pediatric Oncology, Johns Hopkins University School of Medicine

Author's Email:	E Anders Kolb, MD
Editor's Email:	Kathleen Sakamoto, MD

eMedicine Journal, August 18 2006, VOLUME 7, Number 8

INTRODUCTION

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As an approach to treat malignant and nonmalignant disorders, hematopoietic stem cell transplantation (HSCT), has been around for more than 50 years. The earliest work was done in animal models in the mid 1950s. In the 1960s, the first few cases of successful use of HSCT in the treatment of congenital immunodeficiency disorders and end-stage leukemia were reported. Subsequent research focused on designing conditioning regimens, decreasing transplantation-related morbidity and mortality, improving survival and our understanding of the immune mechanisms associated with both the adverse effects and the antitumoral effects of the transplanted graft.

This review summarizes the types of HSCT, methods of collection of stem cells, indications for HSCT, complications of HSCT, and survival data with emphasis on current research with particular reference to pediatrics.

TYPES OF HSCT

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Until recently, the 2 major types of HSCT have been autologous and allogeneic transplantations. A third type now being used with increasing frequency is umbilical-cord blood transplantation (CBT).

Autologous transplantation refers to the use of the patient’s own stem cells as a rescue therapy after high-dose myeloablative therapy. This is generally used in chemosensitive hematopoietic and solid tumors to eliminate all malignant cells by administering high-dose chemotherapy with subsequent rescue of the host's bone marrow with previously collected autologous stem cells. Immunosuppression is not required after autologous transplantation.

Allogeneic transplantation refers to the use of stem cells from a human leucocyte antigen (HLA)–matched related or unrelated donor. This is used for a variety of malignant and nonmalignant disorders to replace a defective host marrow or immune system with the normal donor marrow and immune system. The key to successful allogeneic transplantation is finding an HLA-matched donor because it decreases the risk of graft rejection and graft versus host disease (GVHD).

The 3 HLA loci critical for matching are HLA-A, HLA-B, and HLA-DR. HLA-C, and HLA-DQ were recently added to this list. A completely matched sibling donor is considered ideal. For unrelated donors, a completely matched or a single mismatch is considered acceptable for most transplantation protocols. Syngeneic transplantation is a form of allogeneic transplantation in which the donor is an identical twin sibling of the patient. Graft rejection is less of an issue for such transplants when compared to other allogeneic transplants.

CBT refers to the use of hematopoietic stem cells collected from the umbilical cord and placenta. The use of CBT has rapidly increased because of several favorable factors: ease of collection, expanded and prompt availability, no risk to the donors, decreased risk of adverse effects (eg, GVHD, transmission of infections), increased tolerance to HLA-mismatch, and no risk of donor loss at the time of transplantation.

The traditional source of hematopoietic stem cells for use in autologous and allogeneic transplantations was bone marrow. Use of peripheral blood as a source of these cells later replaced bone marrow for all autologous and most allogeneic transplantations. Table 1 lists the differences in the cellular characteristics of these commonly used sources of stem cells, and Table 2 lists the clinical differences.

Table 1. Cellular Characteristics of Various Sources of Stem Cells

Cellular Characteristics	Source
	Bone Marrow	Peripheral Blood	Cord Blood
Stem-cell content	Adequate	Good	Low
Progenitor-cell content	Adequate	High	Low*
T-cell content	Low	High	Low, functionally immature
Risk of tumor cell contamination	High	Low	Not applicable

^*Studies have shown that the cord-blood progenitor cells have greater proliferative potential than that of peripheral blood and marrow progenitor cells.

Table 2. Clinical Characteristics With Various Sources of Stem Cells

Cellular Characteristics	Source
	Peripheral Blood	Bone Marrow	Cord Blood
HLA matching	Close matching required	Close matching required	Less restrictive than others
Engraftment	Fastest	Faster than cord blood but slower than peripheral blood	Slowest
Risk of acute GVHD	Same as in bone marrow	Same as in peripheral blood	Lowest
Risk of chronic GVHD	Highest	Lower than peripheral blood	Lowest

COLLECTION OF STEM CELLS

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Bone marrow

Stem cells are obtained from the bone marrow by repeated aspirations of the posterior iliac crests of the donor under general or local anesthesia. Adverse effects are generally rare and include discomfort at the harvesting site that typically lasts 1-2 weeks. This can be a difficult procedure in donors who are smaller than the recipient, such as sibling donors, and several aspirations may be required for an adequate mononuclear cell dose.

Bone marrow primed with granulocyte colony-stimulating factor (G-CSF, filgrastim [Neupogen]) have been used both in pediatric and adult patients to increase the stem cell count and thus reduce the number of aspirations from the donor and speed engraftment in the recipient. Filgrastim and chemotherapy can be used alone or in combination to mobilize stem cells. Interleukin-2 increases T-cell function but is not a stem-cell mobilizer.

Recent literature also shows that the risk of chronic GVHD from G-CSF primed bone marrow may be less than that from G-CSF–primed peripheral-blood stem cells. Randomized trials are being conducted to study the risks versus benefits of using G-CSF in healthy pediatric donors. The potential risks include increased bone pain, rare events like splenic rupture and the theoretical risk of leukemia.

Peripheral blood

Stem cells in the bone marrow can be mobilized into the peripheral blood and then collected. Stem cells are collected after the patient recovers after a cycle of chemotherapy, and their number can be increased by using hematopoietic growth factors like G-CSF. Along with increasing the number of cells, G-CSF also causes the release of proteases that degrade the proteins that anchor the stem cells to the marrow stroma, causing their release into the peripheral blood. Recent literature has shown that combination of G-CSF and AMD3100, an inhibitor of chemokine receptor 4 (CXCR4), is superior to G-CSF alone in mobilizing stem cells.

The dosage of G-CSF dose is 5-20 mcg/kg/day. In most regimens, 10 mcg/kg/day is used until harvesting. After mobilization, an apheresis machine collects the cells. Two ports of venous access are necessary to allow for continuous blood processing. In most adults, venous access is accomplished by using 2 antecubital lines. In 5-10% of adults and in most children, percutaneous antecubital large-bore access is not possible, and an apheresis catheter is used instead. Apheresis catheters can be used in children as light as 10 kg. Lighter children generally require a femoral catheter.

The WBC count, or recently the CD34 count, in the peripheral blood determines the timing of collection. CD34 is a cell surface marker on hematopoietic stem cells. Studies have shown a good correlation between the CD34 count in the peripheral blood and the number of cells harvested. The recommended CD34 count is 20-50 cells/mL of blood.

Collected stem cells are counted by flow cytometric analysis. Although the minimum number required for engraftment is considered to be 1 X 10⁶ cells per kilogram of body weight, the preferred number is 2-2.5 X 10⁶ cells/kg. Most people prefer to have a collection goal of 5-10 X 10⁶ cells/kg to freeze the extra cells for potential future use.

Peripheral-blood stem cells can be cryopreserved for infusion months to years after collection.

Peripheral-blood stem cells have 10-fold more T cells than bone marrow and increase of chronic GVHD. Peripheral-blood stem cells speed engraftment and reduce toxicity in patients undergoing autologous transplantation.

Issues in the collection of peripheral-blood stem cells

Two issues in the collection of peripheral-blood stem cells require special consideration in children. First is the issue of priming. Even when devices to minimize extracorporeal volume are used, priming of the apheresis machine with RBCs is required for children younger than 6 years. This step prevents unacceptable dilutional anemia during the procedure and fluid overload associated with the return of red cells from the centrifuge chamber at the end of the procedure.

Second is the issue of anticoagulation. In older patients, anticoagulation required for the apheresis procedure is accomplished using anticoagulant citrate dextrose (ACD). Although ACD does not result in systemic anticoagulation, the citrate component of ACD increases the risk of symptomatic hypocalcemia in young patients. Citrate toxicity often limits the rate of blood processing, prolonging the procedure. Pediatric patients can also be treated with a combination of ACD and heparin. The heparin can allow use of decreased amounts of ACD, making symptomatic hypocalcemia rare. However, the patient treated with heparin and ACD may be fully anticoagulated by the end of the procedure, slightly increasing the bleeding risk and possibly requiring reversal of heparinization at the end of the procedure.

Cord blood

Blood from umbilical cord and placenta is rich in hematopoietic stem cells. Cord blood has relatively immature donor T cells compared with allogeneic stem cells; therefore, they are more immunotolerant to host’s immune system. This property decreases the risk of graft versus host disease and graft rejection. About 40-70 mL of fetal cord blood is collected immediately after the cord is clamped and cut. These units are cryopreserved and stored in private and public cord blood banks worldwide until future use. This type of collection has no risk to the donor if the cord is clamped appropriately.

INDICATIONS FOR HSCT

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More than 30,000 autologous and 15,000 allogeneic transplantation procedures are performed every year worldwide. The list of diseases for which HSCT is being used is rapidly increasing. More than half of the autologous transplantations are performed for multiple myeloma and non-Hodgkin lymphoma, and a vast majority of allogeneic transplants are performed for hematologic and lymphoid cancers.

Table 3 summarizes the common indications for HSCT. Cord-blood transplants are being used for many of the allogeneic transplant indications whenever a suitable HLA-matched donor is unavailable or whenever time for identifying, typing, and harvesting a transplant from an unrelated donor is limited.

Table 3. Common Indications for HSCT

Autologous Transplantation		Allogeneic Transplantation
Malignant Disorders	Nonmalignant Disorders	Malignant Disorders	Nonmalignant Disorders
Multiple myeloma Neuroblastoma Non-Hodgkin lymphoma Hodgkin disease Acute myeloid leukemia (AML) Medulloblastoma Germ-cell tumors	Autoimmune disorders Amyloidosis	AML Non-Hodgkin lymphoma Hodgkin disease Acute lymphoblastic leukemia (ALL) Chronic myeloid leukemia (CML) Myelodysplastic syndromes Multiple myeloma Chronic Lymphocytic Leukemia	Aplastic Anemia Fanconi anemia Severe combined immunodeficiency Thalassemia major Diamond-Blackfan anemia Sickle cell anemia Wiskott-Aldrich Syndrome Osteopetrosis Inborn errors of metabolism Autoimmune disorders

CONDITIONING REGIMENS

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Conditioning regimens can be classified as myeloablative, nonmyeloablative, and reduced intensity.

Myeloablative regimens are designed to kill all residual cancer cells in autologous or allogeneic transplantation and to cause immunosuppression for engraftment in allogeneic transplantation. Total-body irradiation (TBI) and cyclophosphamide or busulfan and cyclophosphamide are the commonly used myeloablative therapies. These regimens are especially used in aggressive malignancies, such as leukemias.

With nonmyeloablative regimens, use doses of chemotherapy drugs and radiation substantially lower than those of myeloablative regimens. These regimens are immunosuppressive but not myeloablative and rely on a graft-versus-tumor effect to kill tumor cells with donor T lymphocytes. Because of their decreased acute and chronic toxicity, these regimens can be used in patients aged 55 years or older and in patients with notable comorbidities.

Such regimens are usually beneficial for slow-growing tumors, such as those of chronic lymphocytic leukemia or chronic myelogenous leukemia, and are also beneficial for a variety of nonmalignant disorders, such as thalassemia and autoimmune disorders. At present, a combination of autologous transplantation followed by nonmyeloablative allogeneic transplantation is being studied for both pediatric and adult tumors, the most common being multiple myeloma.

Reduced-intensity regimens are between myeloablative and nonmyeloablative regimens and involve drugs such as fludarabine, melphalan, antithymocyte globulin, and busulfan. Such regimens also reduce acute and chronic toxicity compared with myeloablative regimens, though the incidence of GVHD is comparable to that of myeloablative regimens. The onset of GVHD is delayed with this compared with other regimens.

OUTCOME DATA

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Over the years, transplantation-related mortality and morbidity rates have considerably decreased because of improved conditioning regimens, HLA typing, supportive care, and prevention and treatment of serious infections. However, overall and event-free survival rates are based on the individual's disease pathology and on the stage of disease. Table 4 lists the survival rates of different diseases after HSCT.

Patients undergoing HLA-matched sibling allogeneic transplantation have the best 5-year survival rate of all treated patients.

Table 4. Five-Year Survival Data by Disease^*

Disease	Stage	Survival Rate, %
		Autologous Transplantation	Allogeneic Transplantation
			Sibling Donor	Unrelated Donor
ALL	CR1	NA	65	45
	CR2	NA	55	35
AML	CR1	60	65	30
	CR2	40	45	50
	No remission	20	NA	25
CML	Chronic phase <1 y	NA	70	55
	Chronic phase > 1 y	NA	60	50
Hodgkin disease	CR1	80	NA	NA
	CR2	70	NA	NA
	No remission	45	NA	NA
Diffuse large-cell lymphoma	CR1	65	25	30
		50	25	NA
		45	20	NA
Neuroblastoma		40	NA	NA

Note.—CR = complete response; NA = not applicable.

^*Based on Kaplan-Meier curves of data from the Center for International Blood and Marrow Transplant Research (CIBMTR) and the National Marrow Donor Program (NMDP) data.

Acute lymphoblastic leukemia

HSCT is recommended in high-risk ALL in the following situations: ALL with poor cytogenetics (Philadelphia chromosome positive, hypodiploidy), infant ALL (with 11q23 rearrangement), induction failure, and relapsed ALL.

According to the survival data from CIBMTR, an allogeneic transplant from an HLA-matched sibling donor in CR 1 has the best overall survival.

Acute myelogenous leukemia

HSCT is recommended in pediatric patients with AML in the following circumstances: (1) in CR1, if a HLA-matched sibling donor is available; (2) in CR1, with an unrelated transplant if poor cytogenetics (monosomy 5, monosomy 7) or induction failure are present; (3) in CR2, for all patients with relapse; (4) in CR1 or CR2, with an autologous transplant if the cytogenetics are good.

According to the NMDP data, allogeneic transplantation with an HLA-matched sibling donor in CR1 results in the best overall prognosis in pediatric patients with AML. In patients with no sibling donor, the decision and timing of transplantation depends on other risk factors, such as cytogenetics. Patients with good cytogenetics might be followed up after standard chemotherapy, or they might receive autologous transplantation after CR1 or CR2. Patients with poor cytogenetics should undergo unrelated HLA-matched donor transplantation in CR1 because the survival rate substantially decreases in CR2.

Chronic myeloid leukemia

Allogeneic transplantation has been the standard of care for patients with CML because it offers the only potential for cure. In statistical analysis, the likelihood of cure is better for patients in the chronic phase who underwent transplantation within 1 year of diagnosis than for those undergoing transplantation after 1 year. However, drugs such as imatinib have challenged this finding because it offers potential remission for long periods. This possibility must be weighed against transplantation-related morbidity and mortality.

Current recommendations are to perform transplantation as soon as possible in the first chronic phase if HLA-matched sibling donor is available or to continue surveillance for relapse during imatinib therapy and to perform transplantation when early relapse or resistance to imatinib therapy occurs if no HLA-matched sibling donor is available.

Hodgkin disease

Autologous transplantation is the standard of care for relapsed Hodgkin disease and primary refractory Hodgkin disease.

CIBMTR data about survival for patients with Hodgkin disease suggest that the outcome is improved after CR1 and decreases with subsequent remissions or partial remissions. The role of allogeneic transplantation in Hodgkin disease is being evaluated.

Non-Hodgkin lymphoma

Autologous transplantation is the standard of care for relapsing or refractory diffuse, large B-cell lymphoma and relapsing or refractory follicular lymphoma. Allogeneic transplantations with HLA-matched sibling donors are comparable to autologous transplantations but are associated with increased related morbidity and mortality rates.

Neuroblastoma

Autologous transplantation is the standard of care for patients with high-risk neuroblastoma in CR1. A children’s cancer group study, CCG 3891, showed that 3-year event free survival is significantly better for patients undergoing high-dose chemotherapy followed by autologous transplantation than for those undergoing chemotherapy alone. Allogeneic transplantation is reported in patients with relapsing or refractory disease, but no standard guidelines for its use are currently available.

COMPLICATIONS

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HSCT related complications can be classified as early and late effects.

Early effects

Mucositis

Mucositis is one of the most common adverse effects of transplantation. It can involve the entire gastrointestinal tract, leading to painful mouth sores, diarrhea, nausea, and abdominal pain. It is usually managed symptomatically with narcotics and topical anesthetics. A novel keratinocyte growth factor, palifermin, reduces the incidence of mucositis in adults.

Graft versus host disease

Acute GVHD is a common complication of allogeneic transplantation and occurs within first 100 days of the procedure. It is an immune response of donor T lymphocytes against host cells. The skin, gastrointestinal tract, and liver are the organs typically involved. HLA mismatch and myeloablative conditioning regimens are important risk factors.

Preventive and therapeutic measures include immunosuppression with drugs such as cyclosporine, corticosteroids, tacrolimus, mycophenolate mofetil (MMF), and methotrexate. Nonmyeloablative regimens and graft T-cell depletion are other techniques used to decrease the incidence of GVHD. Current research is focusing on improving our understanding of the pathophysiologic pathways of GVHD to design targeted therapies and genetic modifications of donor T-cells to prevent and treat GVHD.

The severity of GVHD is inversely related to the risk of relapse because GVHD and graft versus leukemia (GVL) effect are interrelated. Therefore, strategies reducing GVHD may increase relapse rates. New strategies are being developed to separate these 2 effects to decrease the incidence and severity of GVHD without increasing the risk of relapse.

Veno-occlusive disease

Veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome, is a potentially fatal syndrome of tender hepatomegaly, direct hyperbilirubinemia, ascites, and weight gain. VOD is caused by damage to the sinusoidal endothelium, which results in sinusoidal obstruction. TBI and drugs, such as oral busulfan and cyclophosphamide, predispose people to this syndrome. Preexisting liver disease and certain genetic mutations that alter drug metabolism may increase the risk of VOD. No standard effective therapy is currently available. Defibrotide is a novel agent that elicits responses in severe VOD; it is under investigation in a phase III trial.

Transplantation-related lung injury

Transplantation-related lung injury (TRLI) is an acute inflammatory response that leads to severe lung injury. TRLI is seen in allogeneic transplants. Early treatment with corticosteroids and etanercept, an anti–tumor-necrosis factor (TNF) agent, can reduce the extent of this injury.

Transplantation-related infections

Life-threatening bacterial, fungal, and viral infections (eg, those due to Aspergillus or Cytomegalovirus) are common in patients undergoing HSCT. Causes include prolonged neutropenia, use of steroids, and immunodeficiency associated with GVHD. Bacterial sepsis occurs early in the course of transplantation whereas viral infections such as those caused by cytomegalovirus usually occur after engraftment. Fungal infections such as those caused by aspergillus may occur anytime after 7-10 days of onset of neutropenia until engraftment. Early recognition and treatment are vital. Following engraftment, the ongoing risk of infection relates to the degree of immunosuppression.

Late effects

Chronic GVHD

Chronic GVHD is most common in patients who develop acute GVHD, but it can develop in its absence. Chronic GVHD is characterized by an immune phenomenon that clinically resembles lupus, scleroderma, or Sjögren syndrome. It is thought to result from 2 potential mechanisms: thymic injury during conditioning resulting in loss of negative selection of autoreactive T- cells and the alloreactivity of mature post thymic donor T lymphocytes.

Immunosuppression with corticosteroids, tacrolimus, and MMF are the mainstays of treatment. Hydroxychloroquine, an antimalarial drug, is effective in several autoimmune disorders, including chronic GVHD. The use of keratinocyte growth factors prevents chronic GVHD presumably by preventing host thymic injury.

Ocular effects

Posterior subcapsular cataract formation is common in HSCT recipients. TBI is the predisposing risk factor. Fractionation of the dose substantially decreases the risk. Keratoconjunctivitis sicca, or dry eyes, is part of the chronic GVHD syndrome. Other adverse effects include retinopathy, infectious retinitis, and hemorrhage. Treatment includes the use of topical lubricants and steroids.

Endocrine effects

Infertility is common in both male and female individuals. Secondary amenorrhea affects most women after HSCT. In children, growth and development are impaired, and they may require growth-hormone supplements. Hypothyroidism is also common in these patients, and they should be screened for low levels of thyroid hormone.

Pulmonary effects

Pulmonary effects include restrictive and chronic obstructive lung disease. Conditioning regimens, infections and GVHD are important risk factors. Bronchiolitis obliterans is a specific form of obstructive lung disease seen in HSCT recipients and has a fatality rate of 50%. Corticosteroids are generally not helpful. Some patients respond to azathioprine and MMF.

Musculoskeletal effects

Osteoporosis and avascular necrosis are common adverse effects in HSCT recipients.

Neurocognitive and neuropsychological effects

A low intelligence quotient (IQ), sleep disorders, fatigue, memory problems, and developmental delays have all been reported in HSCT recipients. These issues must be addressed appropriately to improve the person's overall quality of life.

Immune effects

Host immunity is suppressed for months to years after HSCT. This effect is more pronounced in allogeneic transplantation than in autologous transplantations. Factors responsible for depressed immunity include severe myelosuppression due to the myeloablative conditioning of the host, acute GVHD that further suppresses host immunity, and the use of immunosuppressants to prevent or treat GVHD.

In allogeneic transplant recipients, complete immune reconstitution takes a few years and depends on the ability of naïve prethymic donor T cells to mature in the host's thymus and to become host tolerant and antigen specific. This process is most efficient in children and young adults because they have an active thymus. Older patients may never completely recover their immunity because their thymic tissue might not be fully functional.

These immune effects in HSCT patients should be kept in mind, as these patients are prone to serious infections long after the initial HSCT procedure. It also raises the issue of revaccinating these patients after HSCT. No formal guidelines for revaccinating HSCT patients are established, though the current literature suggests that most vaccine-acquired immunity wanes after HSCT. Most killed vaccines are considered safe, but use of live virus vaccines is generally contraindicated. Appropriate timing for revaccinating is 12-18 months after the HSCT, though this period may need to be individualized on the basis of the patient's immune function. Vaccinations earlier than this do not result in an appropriate immune response.

FUTURE OF HSCT

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Substantial progress has been made in the field of HSCT since its inception 50 years ago. HSCT currently offers the only potential cure for a large number of malignant and nonmalignant disorders. Future research will focus on decreasing the transplantation-related morbidity and mortality and on increasing relapse-free survival. The work will include designing effective, reduced-intensity conditioning regimens; discovering targeted therapies to prevent and treat GVHD (eg, cytokine antagonists and genetically modified donor T cells); in-depth HLA-typing at the allelic level; advances in CBT; in vitro expansion and modification of stem cells; and, ultimately, performing HSCT with embryonic stem cells to eliminate the need for HLA typing and other conditioning therapies.

TEST QUESTIONS

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CME Question 1: What is the advantage of cord-blood transplantation over allogeneic transplantation?

A: Increased stem-cell count
B: Decreased risk of graft versus host disease
C: Speeded engraftment and marrow recovery
D: Prolonged overall survival
E: All of the above

The correct answer is B: Cord blood has relatively immature donor T cells compared with allogeneic stem cells; therefore, they are more immunotolerant to host`s immune system. This property decreases the risk of graft versus host disease and graft rejection.

CME Question 2: Which treatment can be used to mobilize stem cells to improve the collection of peripheral-blood stem cells?

A: Filgrastim (granulocyte colony-stimulating factor)
B: Interleukin-2
C: Myelosuppressive chemotherapy
D: A, B, and C
E: Only A and C

The correct answer is E: Filgrastim and chemotherapy can be used alone or in combination to mobilize stem cells. Interleukin-2 increases T-cell function but is not a stem-cell mobilizer.

Pearl Question 1 (T/F): Bone marrow improves hematopoietic support for autologous high-dose chemotherapy compared with peripheral-blood stem cells.

The correct answer is False: Peripheral-blood stem cells speed engraftment and reduce toxicity in patients undergoing autologous transplantation.

Pearl Question 2 (T/F): In allogeneic transplantation, peripheral-blood stem cells reduce the risk of graft-versus-host disease compared with bone marrow.

The correct answer is False: Peripheral-blood stem cells have 10-fold more T cells than bone marrow and increase of chronic graft-versus-host disease.

Pearl Question 3 (T/F): Patients with acute myeloid leukemia in a first complete remission should undergo allogeneic transplantation if a human leukocyte antigen (HLA)–matched sibling donor is available.

The correct answer is True: Patients undergoing HLA-matched sibling allogeneic transplantation have the best 5-year survival rate of all treated patients.

Pearl Question 4 (T/F): Peripheral-blood stem cells must be infused within 24 hours of their collection.

The correct answer is False: Peripheral-blood stem cells can be cryopreserved for infusion months to years after collection.

BIBLIOGRAPHY

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• Grupp SA, Frangoul H, Wall D, et al: Use of G-CSF in matched sibling donor pediatric allogeneic transplantation: a consensus statement from the Children's Oncology Group (COG) Transplant Discipline Committee and Pediatric Blood and Marrow Transplant Consortium (PBMTC) Executive Committee. Pediatr Blood Cancer 2006 Apr; 46(4): 414-21[Medline].
• Iwasaki T: Recent advances in the treatment of graft-versus-host disease. Clin Med Res 2004 Nov; 2(4): 243-52[Medline].
• Koh LP: Unrelated umbilical cord blood transplantation in children and adults. Ann Acad Med Singapore 2004 Sep; 33(5): 559-69[Medline].
• Kolb EA, Pan Q, Ladanyi M, Steinherz PG: Imatinib mesylate in Philadelphia chromosome-positive leukemia of childhood. Cancer 2003 Dec 15; 98(12): 2643-50[Medline].
• Matthay KK, Villablanca JG, Seeger RC, et al: Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis- retinoic acid. Children's Cancer Group. N Engl J Med 1999 Oct 14; 341(16): 1165-73[Medline].
• Schroeder H, Kamperis K, Grunnet N, Hokland P: Prediction of target CD34 positive cells following leukopheresis in children with neuroblastoma. Pediatr Blood Cancer 2006 Jun; 46(7): 786-92[Medline].
• Siena S, Schiavo R, Pedrazzoli P, Carlo-Stella C: Therapeutic relevance of CD34 cell dose in blood cell transplantation for cancer therapy. J Clin Oncol 2000 Mar; 18(6): 1360-77[Medline].
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Author Information | Introduction | Types Of Hsct | Collection Of Stem Cells | Indications For Hsct | Conditioning Regimens | Outcome Data | Complications | Future Of Hsct | Test Questions | Bibliography