Adult hemopoietic stem cell transplantation
STEVEN D. WESTBROOK, D.M.D., M.S.,
ELEONORE D. PAUNOVICH, D.D.S., M.S. and
CESAR O. FREYTES, M.D., F.A.C.P.
 |
ABSTRACT
|
|---|
Background. Hemopoietic stem cell transplantation, or HSCT, is an important tool in modern cancer treatment. Refinement of transplantation techniques and supportive care has resulted in increased posttransplantation survival rates. Dental care is a key supportive element in both pretransplantation and posttransplantation care of this patient population.
Methods. The authors provide an overview of HSCT transplantation, emphasizing the oral complications and required supportive dental care.
Conclusions. It is critical that transplantation candidates undergo dental screenings and be treated adequately before transplantation, that their care be closely managed during the transplantation process, and that they be given dental support as soon as their recovery permits. Dentists should consult with the patient’s oncologist or primary health provider to identify the appropriate timing and intensity of dental support.
Clinical Implications. Because of improved transplantation survival rates, more patients may seek supportive outpatient dental care after transplantation, which requires special management considerations. Dental professionals need to be knowledgeable about modern HSCT.
Hemopoietic stem cell transplantation, or HSCT, is the term commonly used to describe both bone marrow transplantation and peripheral stem cell transplantation.1 HSCT has become an established therapy in the modern cancer treatment armamentarium. The objective of cancer therapy is to eradicate malignant tumor cells and prevent recurrence. The majority of patients with cancer receive primary therapy in the form of conventional-dose chemotherapy, radiotherapy or surgery that results in significant tumor cell eradication and possibly full remission. Both chemotherapy and radiotherapy adversely affect not only tumor cells but normal cells as well.2 Unfortunately, tumoricidal dosages often result in myelosuppression, leaving patients susceptible to life-threatening infections, hemorrhages or both.1,3,4 The patients’ oncologists must carefully balance tumoricidal regimens with susceptibility of normal organs and tissues. Transplantation of suitable hemopoietic stem cells has proven to be a successful way of establishing a predictable bone marrow recovery after extremely toxic tumoricidal regimens.
Oral complications requiring dental supportive care are a frequent cause of morbidity in hemopoietic stem cell recipients.
Stem cell transplantation procedures have evolved, supporting a dramatic expansion in the types and numbers of patients with cancer benefiting from this intensive medical therapy. In 1994, the International Bone Marrow Transplant Registry, or IBMTR, recorded 4,000 allogeneic and 6,000 autologous transplantations in North America.5 For 2000, it estimated that 15,000 allogeneic and 25,000 autologous transplantations were completed.6 Worldwide, there were 78,022 registered allogeneic transplantations from 1970 to 2001. From 1981 to 2001, more than 69,000 autologous transplantations were registered (M.M. Horowitz, M.D., M.S., scientific director, International Bone Marrow Transplant Registry/Autologous Blood and Marrow Transplant Registry, written communication, July 2003). Presently, more than 492 institutions worldwide perform HSCT procedures.6 As a result of decreased transplantation-related toxicity along with the expansion of transplantation applications, patients older than 50 years of age now account for 10 percent of allogeneic and 50 percent of autologous transplantations.
|
SUPPORTIVE CARE
|
|---|
The refinement of medical and dental supportive care has been a major factor in improved transplantation success.7,8 Managing the dental care of patients before transplantation should be directed toward maintaining oral comfort, while eliminating dental conditions that could predispose patients to oral infections or hemorrhages. Once patients become neutropenic, oral pathological conditions may be more difficult to diagnose accurately owing to suppression of the cardinal signs of inflammation, be more difficult to treat with conventional therapies and result in treatment-altering conditions that could be life-threatening.9–11 Potential sites of oral trauma and infection must be eliminated.10,12 A clean, healthy oral environment can prevent or minimize complications that could jeopardize a successful transplantation result.2,13,14 Patients’ normal oral hygiene regimens should be evaluated carefully and modified based on their medical conditions, gingival health, manual dexterity and motivational levels. Patients must be made aware of the possible severe consequences of oral neglect on their proposed medical therapies and future quality of life.
Dental assessment and intervention have become integral parts of the pretransplantation work-up at most transplantation centers. Through pretransplantation dental screenings, dentists have discovered a significant number of chronic oral conditions that required resolution before HSCT.9,15 Some of the problems that required immediate care included pericornitis, advanced periodontitis, moderate-to-severe carious lesions and periapical pathology.10,15 Dental treatment before transplantation must resolve any acute pathology and attempt to minimize patients’ dental problems for their extended recovery period. Dentists should be aware that after transplantation patients’ medical treatments or conditions may contraindicate definitive dental care for a prolonged period ranging from six to 12 months.7 Any required dental treatment before transplantation should be coordinated with patients’ oncologists to ensure ideal timing in the overall medical plan.
|
STEM CELL SOURCES
|
|---|
The source of the stem cells used for transplantation depends on the type of tumor, the presence of bone marrow involvement, the patient’s age and the availability of a suitable donor. Hemopoietic stem cell donors can be the patients themselves as in an autologous transplantation, a genetically identical twin in a syngeneic transplantation, or a related or nonrelated human leukocyte antigen-, or HLA, matched donor for an allogeneic transplantation. Hemopoietic stem cells also may be collected from placental or umbilical cord blood. Cord blood banks may provide donors for a larger number of patients who require allografts but do not have access to "conventional" donors. It is expected that cord blood cell use will increase because of the low incidence of immunological complications experienced by the recipients.16 The IBMTR and other bone marrow registries now list more than 4 million registered volunteer donors.16
The advantages of an autologous HSCT include lack of a need to find a suitable donor and lack of graft-versus-host disease, or GVHD, since the patient is the donor. The disadvantages of autologous HSCT include the possibility of infusing the patient’s own malignant cells as part of the transplantation and the absence of the "graft-versus-tumor" effect. Autologous transplantations most frequently are used for Hodgkin’s lymphoma, non-Hodgkin’s lymphoma and multiple myeloma, as well as some solid tumors such as testicular, ovarian and breast malignancies.1,6 More than 95 percent of autologous transplantations in adults use only peripheral blood stem cells instead of the more traditional bone marrow stem cells.6 Complications resulting from infections are the most common cause of morbidity and mortality immediately after autologous transplantation.1 Tumor recurrence is the principal cause of treatment failure after the immediate peritransplantation period. Methods are available that allow purging of the remaining tumor cells from the donor material before transplantation, but to date this process has not resulted in increased survival.1
For patients whose diseases or medical conditions contraindicate autologous transplantation, a suitable donor must be located for allogeneic transplantation. The inevitable immunological mismatch of allogeneic transplants can be beneficial to some patients owing to the resulting graft-versus-tumor effect or can generate adverse sequelae due to the resulting GVHD (Table
). Allogeneic transplantations most frequently are used for acute and chronic leukemias, myelodysplasia and nonmalignant diseases (aplastic anemia, immuno deficiencies, inherited metabolic disorders).16 Most allogeneic stem cell transplantations use stem cells from a matched or identical HLA donor.6 Complications resulting from infections are the most common cause of morbidity and mortality immediately after allogeneic transplantation. GVHD and infection followed by recurrence or progression of primary disease are the leading causes of death after the peritransplantation period.6
|
TRANSPLANTATION PROCEDURES
|
|---|
Human bone marrow transplantation first was performed in the 1950s as a procedure that was capable of rescuing the patient’s hemopoietic system after cancer therapy that produced prolonged myelosuppression or permanent marrow ablation.17 Bone marrow was used as a source of hemopoietic stem cells that could differentiate into neutrophils, red cells and platelets.17 Currently, bone marrow can be harvested while the donor is under spinal or general anesthesia. The marrow is harvested by multiple needle aspirations from both posterior iliac crests. The anterior iliac crests and sternum can be used as alternative sites if the cell yield from the posterior crests is inadequate. The total volume collected usually is 500 to 1,000 milliliters. The entire process usually takes one to two hours, and the donor is discharged after recovery. The procedure has low donor morbidity. The collected marrow is filtered and then transplanted to the recipient immediately or cryopreserved for future use.18
More recently, it has been discovered that the peripheral circulation is a readily accessible source of a low number of hemopoietic stem cells.19 To harvest sufficient quantities of stem cells from the peripheral blood to support transplantation, additional stem cells need to be mobilized from the bone marrow to the peripheral circulation. The mobilization process involves administering recombinant hemopoietic growth factors alone or a combination of cytotoxic chemotherapy and recombinant hemopoietic growth factors to the donor that stimulate a rapid proliferation of stem cells and their release into the peripheral circulation for harvesting.1 Chemotherapeutic agents used for mobilization include cyclophosphamide or etoposide. The most commonly used growth factors are granulocyte colony-stimulating factor, or G-CSF, or granulocyte-macrophage colony-stimulating factor, or GM-CSF; both are cytokines that are capable of stimulating the growth and maturation of hematologic cells.1
After the mobilization process, the recipient’s peripheral stem cells are ready to be collected. An automated leukapheresis machine harvests the circulating progenitor cells via an indwelling catheter during the myeloid recovery phase after mobilization therapy. The leukapheresis machine centrifuges blood drawn from the patient, separating the stem cells for collection, while returning the other hematologic elements to the patient. The leukapheresis process, which normally takes two to four hours, is repeated daily until sufficient numbers of stem cells have been collected. The collection period normally lasts from one to seven days. The harvested stem cells are cryopreserved, frozen at –80 C and stored for future transplantation based on the recipient’s needs.1 Peripheral stem cell use has facilitated autologous transplantation options, especially for medically compromised patients previously not considered to be candidates for general anesthesia or the "surgical harvesting" of bone marrow.
Once the peripheral stem cells have been collected, the transplantation patient undergoes the conditioning or preparative regimen consisting of high-dose chemotherapy, irradiation or both to accomplish total tumor kill, ablate the host bone marrow and, in allogeneic transplantations, ablate the patient’s immune system. Box 1 lists commonly used cytotoxic and immunosuppressant agents that are used as conditioning or preparative regimens. This conditioning treatment usually lasts from two to seven days. The patient’s transplantation is performed as soon as the cytotoxic agents have been cleared from his or her circulation. This usually is within 24 to 48 hours after the conditioning regimen has concluded. The transplantation process consists of infusion of donor stem cells through the central venous catheter in a process similar to a blood transfusion, which is considered "Day 0" in the typical HSCT treatment regimen.20
Vascular access is a critical component of HSCT. The transplantation candidate has a large-bore, multiport, venous catheter placed into the internal jugular or subclavian vein. The catheter serves as an indwelling vascular access device from which blood samples may be drawn, medications given, parenteral feeding accomplished, as well as providing the means for giving the stem cell infusion itself. Patients with indwelling central venous catheters are candidates for prophylactic antibiotic coverage for procedures likely to induce bacteremia.2 The need for endocarditis prevention should be based on each patient’s systemic condition and current medical therapy. The patient’s oncologist should be consulted about the planned antibiotic regimen.
|
ENGRAFTMENT
|
|---|
The process of re-establishing the patient’s hemopoietic system by the production of blood cells is termed "engraftment." Once the patient is able to sustain an absolute neutrophil count of more than 500 per cubic millimeter and a platelet count of more than 20,000/mm3 that lasts more than three consecutive days without transfusions, engraftment is considered complete.12
Peripheral stem cells cause faster engraftment of neutrophils, red cells and platelets than do stem cells harvested directly from the patient’s bone marrow.1 After peripheral stem cell transplantation, hemopoietic recovery usually occurs within two to four weeks. This shortening of the critical neutropenic period can reduce posttransplantation complications significantly.
The patient’s hemopoietic recovery can be monitored by means of complete blood counts. The speed of the hemopoietic recovery has been correlated with the length of the hospital stay, the severity of illness during the stay and the patient’s survival.1 Engraftment may be slowed in allogeneic transplant recipients owing to GVHD or from methotrexate that is used to combat GVHD. Retarded granulocyte recovery is an unwanted side effect of ganciclovir, a potent antiviral agent used against the cytomegalovirus.21
|
SIDE EFFECTS
|
|---|
Severe side effects of the patient’s conditioning regimen begin to appear within three to five days after the myeloablative agents have been given. The exact course and form these will take depend on which chemotherapeutic agents were given and their dosages, as well as the patient’s overall medical condition, prior cancer therapy and disease status. Pancytopenia is a common hematologic toxicity that significantly increases the patient’s risk of developing a neutropenic infection, thrombocytopenic hemorrhage or both until the time of marrow recovery. Acute nonhematologic toxicities include fluid and electrolyte imbalance, mucositis, nausea or vomiting, diarrhea, veno-occlusive disease of the liver and interstitial pneumonitis.
Many HSCT centers use hemopoietic growth factors such as G-CSF or GM-CSF immediately posttransplantation for five to seven days to accelerate hemopoietic recovery, thus minimizing the duration of neutropenia.1 The growth factors speed up the engraftment process, decrease the number of days of fever and reduce the total amount of antibiotics used, though the overall incidence of infection has remained unchanged.22 During their neutropenic phase, most transplant recipients will require transfusions of irradiated, leukopoor-filtered blood products when their hemoglobin is less than 8 grams per deciliter or their platelet counts fall to less than 10,000/mm3. These laboratory values should be considered in concert with the patient’s tolerance, side effects and comfort to determine the need for transfusion.
|
ORAL COMPLICATIONS
|
|---|
Mucositis is the most frequent and obvious oral complication seen in HSCT patients.7 Both radiotherapy and chemotherapeutic agents have direct effects on the mucosal progenitor cells, which can lead to loss of mucosal integrity. The degree of severity can range from mild erythema to severe mucosal ulcerative breakdown.7,23 Severe mucositis can cause intense pain that interferes with eating and significantly affects the patient’s quality of life, frequently leading to the need for opioid analgesics.24,25 Patients who had ulcerative mucositis were found to be up to three times more likely to develop alpha hemolytic streptococcal bacteremias than were patients without ulcerative mucositis.9,26 This complication, though rarely fatal, can result in the increased need for antibiotics, narcotics, longer hospital stays and costs.26 Life-threatening infections may result from other opportunistic or acquired, gram-positive bacteria; herpes simplex virus, or HSV; or fungal organisms.22 This susceptibility has led to standard transplantation protocols that dictate prophylactic use of antiviral agents, antifungal agents and various antimicrobial agents, resulting in a much lower complication rate in the transplantation patient with febrile neutropenia (Box 2).7
Mucositis typically becomes clinically evident shortly after transplantation and peaks five to seven days posttransplantation.27,28 If uncomplicated by trauma or infections, mucositis usually will resolve spontaneously approximately 15 to 22 days after transplantation.27,28 There is a direct correlation between the patient’s neutrophil count and the course of oral mucositis.23 Therefore, successful engraftment will enhance oral health and comfort.
Once patients become neutropenic, modifications in their oral hygiene regimens must be instituted to avoid trauma to oral tissues. Generally, patients will require increased monitoring for intraoral trauma and potential hemorrhage if platelet counts are less than 50,000/mm3 or white blood cell counts are less than 2,000/mm3. Once the patient’s platelet counts reach less than 20,000/mm3 or the absolute neutrophil count is less than 500/mm3, the patient must discontinue regular toothbrushing and use of dental floss. Instead, gauze squares, cotton swabs or sponge swabs can be moistened with chlorhexidine or sodium bicarbonate and be used to reduce gross plaque accumulation, and thus reduce the patient’s risk of developing septicemia.7,29 Each patient must be evaluated to determine an acceptable oral care regimen that will be used faithfully throughout the neutropenic period. Frequent use of bland oral rinses of sodium bicarbonate or lukewarm saline solutions is encouraged to combat the dryness of xerostomia, dilute mucinous secretions, rinse away debris and provide some measure of comfort to the sensitive oral mucosa.2 A neutropenic diet containing soft, bland, nutritious foods likewise should be initiated to prevent trauma and irritation to susceptible oral mucosa. Symptomatic oropharyngeal mucositis may prevent oral intake completely and lead to the need for parenteral hyperalimentation.2
Approximately 30 to 50 percent of allogeneic graft recipients may experience adverse immunological responses that lead to the development of acute GVHD within the first 100 days after transplantation.30 GVHD is initiated by donor T lymphocytes that recognize histocompatibility antigens in the recipient that differ from those in the donor.31 Donor T cells react against the recipient’s cells, which results in clinical manifestations in the skin, liver, intestinal tract, eyes, salivary glands and oral mucosa. Not only are the resulting tissue injuries painful and debilitating for the patient, but they may prolong critical hematologic and immunological recovery. Chronic GVHD, or cGVHD, develops after day 100 but may not manifest itself until years after transplantation.30 Some sequelae of cGVHD have been reported to be resistant to treatment and, therefore, may persist for years.32,33 The intraoral clinicopathologic manifestations of cGVHD may mimic features of other autoimmune connective-tissue disorders such as Sjögren’s syndrome, scleroderma or systemic lupus erythematosus.34
Oral manifestations of GVHD may include xerostomia, mucosal lichenoid and papular lesions, erythema, atrophy and ulcerations.32,33 Resolution of these oral complications may occur once the patient is treated with conventional immunosuppressant agents such as a short course of methotrexate or corticosteriods combined with cyclosporine.16 Chronic oral effects of GVHD include mucosal erythema, tongue-surface atrophy, lichenoid changes of the buccal mucosa and an increased incidence of oral cancer in the form of squamous cell carcinoma.7,35 Being male and having a history of cGVHD are risk factors that are strongly linked to the higher incidence of squamous cell carcinomas of the oral cavity and skin.35 Another serious long-term complication of high-dose conditioning therapy is the increased risk of developing acute myelogenous leukemia and other solid tumors.1 It is recommended that transplant recipients be closely followed indefinitely by all members of the health care team so they can detect early cancerous or precursor lesions.35
In allogeneic transplant recipients the development of cGVHD has serious systemic and oral adverse effects. Because of the role of allogeneic T cells in GVHD, attempts have been made to eliminate grafted T cells or block their activation.16 These efforts, however, have been tempered because they have resulted in higher rates of graft failure and an increased incidence of relapse.12 Patients who have received allogeneic transplants and who developed GVHD after either bone marrow or peripheral blood transplantation have fewer relapses due to an immunologically mediated, graft-versus-tumor response. Donor T cells mediate this immunological response by reacting against tumor antigens contributing to tumor eradication. This immunological antineoplastic effect has been proven beneficial for certain patients with leukemias, myelomas and breast cancer.36
Salivary gland dysfunction is reported commonly due to the direct toxicity of the conditioning agent, as well as the frequent use of anti-cholinergic medications.7 Clinical manifestations include parotitis, increasingly mucinous saliva and marked xerostomia. These features may persist for months after transplantation. Full recovery of salivary gland function in a two- to five-month period has been observed in patients receiving only chemotherapy or total lymphoid irradiation (avoiding parotid glands).37 Unfortunately, patients who have received significant radiation to their salivary glands or developed GVHD after allogeneic transplantation can experience chronic persistence of salivary gland hypofunction.2 Consequently, these patients are more susceptible to dental caries, have altered taste sensation and frequently have a decreased palatability for a normal diet.
In addition to salivary effects, mucosal color changes with increased whiteness or erythema, atrophy, vascularity and ulceration were reported during the first five weeks posttransplantation.38 The most notable intraoral locations included the ventral tongue, buccal and labial mucosa, and marginal gingiva.38 Possible etiologic factors were chemoradiation conditioning regimens, post-transplantation immunosuppressive chemoherapy, xerostomia, local trauma, oral infections (especially HSV) and acute GVHD.38
|
IMMUNOLOGICAL RECOVERY
|
|---|
Immunosuppression, including defects in both cellular and humoral immunity, will develop owing to the effects of the cytotoxic conditioning regimens given to patients who receive autologous or allogeneic transplants. Immunocompetence is established slowly over the first year after successful engraftment.33 A combination of clinical signs and lymphocyte function tests usually are used to determine the patient’s level of immunocompetence. Type of stem cell graft, conditioning regimen and use of antirejection agents will affect the rate of recovery significantly. During this critical period, the patient is at increased risk of developing bacterial, viral and fungal infections and may develop an altered healing response. Immunosuppression leads to compromised host response and may mask or alter early signs and symptoms of oral infection, making early diagnosis more difficult.11
Once transplantation patients become afebrile with stable blood counts, have adequate fluid loss control and have an oral intake of at least 50 percent of baseline, they are candidates for being discharged from the hospital. Extensive medical counseling is provided to the caregivers responsible for the patients’ homecare. Some centers now perform autologous transplantations in an outpatient setting.1
|
POSTTRANSPLANTATION DENTAL CARE MANAGEMENT
|
|---|
As for most medically compromised patients, outpatient dental care becomes essential for patients’ comfort and quality of life posttransplantation. Frequent dental evaluations with a strong emphasis on prevention and early detection of any soft- or hard-tissue pathology can be an invaluable service for patients. Atypical presentations of oral pathological conditions, as well as adverse sequelae related to continued medication regimens, must be considered constantly. All health care providers must emphasize the need for the transplantation patient to avoid exposure to carcinogens such as tobacco and sunlight. Patients’ oral hygiene regimens must be reinforced, their salivary functions monitored and the health of their soft tissues assessed. Salivary hypofunction should be treated aggressively with salivary stimulants, artificial saliva and fluoride applications to decrease adverse sequelae. Abnormal oral findings should be discussed with patients’ oncologists, as they may be indicators of chronic GVHD or recurrence of the original cancer or a new tumor. Elective, definitive dental care, even dental prophylaxis and restorative procedures, may need to be postponed until immunocompetence has been re-established.7 Immune function normally returns within six to nine months after receiving autologous transplants and nine to 12 months after receiving allogeneic transplants. Emergency dental treatment during this first post-transplantation year should be planned carefully, and patients’ primary medical providers should be consulted.
|
PREDICTIONS
|
|---|
HSCT has evolved rapidly from simply "marrow rescue" after high-dose cytotoxic therapy in patients with leukemia to a predictable treatment modality with broad applications. HSCT has improved survival rates in many patients who have "historically incurable" diseases or who have failed to respond to more conventional therapy. For example, patients with multiple myeloma who were given conventional-dose chemotherapy had a 5 percent complete remission response with median survival in the 36-month range. Now, with high-dose chemotherapy followed by an autologous HSCT, complete remission rates have risen to 25 to 30 percent, with median survival exceeding five years.39 Non-Hodgkin’s lymphoma and multiple myeloma are the most common indications for HSCT in North America and account for more than one-third of all transplantations.6 The only therapy with known curative potential for chronic myelogenous leukemia is allogeneic bone marrow transplantation.1 For these reasons, the use of HSCT will continue to increase.
|
CONCLUSION
|
|---|
Dental professionals should be familiar with HSCT, since oral complications requiring dental supportive care are a frequent cause of morbidity in hemopoietic stem cell recipients.
View larger version (30K):
[in this window]
[in a new window]
|
Dr. Westbrook was a clinical research fellow, Department of Veterans Affairs, South Texas Veterans Health Care System when this article was written. He now is a dental geriatric fellow, Department of Medicine, University of Texas Health Science Center at San Antonio. Address reprint requests to Dr. West-brook at 13614 Inwood Park, San Antonio, Texas 78216, e-mail "westbrooks{at}uthscsa.edu".
| |
View larger version (50K):
[in this window]
[in a new window]
|
Dr. Paunovich is the director, Clinical Oral Health Care Programs for Geriatrics and Extended Care, South Texas Veterans Health Care System, San Antonio, and an associate professor, Dental Diagnostic Science, University of Texas Health Science Center at San Antonio.
| |
View larger version (34K):
[in this window]
[in a new window]
|
Dr. Freytes is an associate professor of medicine, University of Texas Health Science Center at San Antonio, and the director, Adult Bone Marrow Transplant Program, South Texas Veterans Health Care System, San Antonio.
| |
|
REFERENCES
|
|---|
- Saba N, Abraham R, Keating A. Overview of autologous stem cell transplantation. Crit Rev Oncol Hematol 2000;36(1):27–38.[Medline]
- Committee on Research, Science and Therapy of the American Academy of Periodontology. Periodontal considerations in the management of the cancer patient. J Periodontol 1997;68(8):791–801.[Medline]
- Mossad SB, Longworth DL, Goormastic M, Serkey JM, Keys TF, Bolwell BJ. Early infectious complications in autologous bone marrow transplantation: a review of 219 patients. Bone Marrow Transplant 1996;18(2):265–71.[Medline]
- Marcovich CK, Davis MJ. Bone marrow transplants: current applications and implications for oral health. N Y State Dent J 1999;65(4):28–31.[Medline]
- International Bone Marrow Transplant Registry/Autologous Blood and Marrow Transplant Registry. New IBMTR/ABMTR slides summarize current use and outcome of allogeneic and autologous transplants. IBMTR/ABMTR Newsletter 1995;2(1):3.
- International Bone Marrow Transplant Registry/Autologous Blood and Marrow Transplant Registry. Report on state of the art in blood and marrow transplantation: the IBMTR/ABMTR summary slides with guide. IBMTR/ABMTR Newsletter 2002;9(1):1, 4–11.
- Majorana A, Schubert MM, Porta F, Ugazio AG, Sapelli PL. Oral complications of pediatric hematopoietic cell transplantation: diagnosis and management. Support Care Cancer 2000;8(5):353–65.[Medline]
- Little JW, Falace DA, Miller CS, Rhodus NL. Dental management of the medically compromised patient. 6th ed. St. Louis: Mosby; 2002:501–2.
- Heimdahl A, Mattsson T, Dahllof G, Lonnquist B, Ringden O. The oral cavity as a port of entry for early infections in patients treated with bone marrow transplantation. Oral Surg Oral Med Oral Pathol 1989;68(6):711–6.[Medline]
- Barker GJ. Current practices in the oral management of the patient undergoing chemotherapy or bone marrow transplantation. Support Care Cancer 1999;7(1):17–20.[Medline]
- Epstein JB, Chow AW. Oral complications associated with immunosuppression and cancer therapies. Infect Dis Clin North Am 1999;13(4):901–23.[Medline]
- CDC, The Infectious Disease Society of America and the American Society of Blood and Marrow Transplantation. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant 2000;6(6a):659–734.[Medline]
- Semba SE, Mealey BL, Hallmon WW. Dentistry and the cancer patient, part 2: oral health management of the chemotherapy patient. Compendium 1994;15(11):1378–87.[Medline]
- Pattni R, Walsh LJ, Marshall RI, Cullinan MP, Seymour GJ, Bartold PM. Changes in the periodontal status of patients undergoing bone marrow transplantation. J Periodontol 2000;71(3):394–402.[Medline]
- Woods P, Sonis S. Dental problems among BMT recipients requiring pretreatment (abstract 574). J Dent Res 1989;68(special issue):253.
- Ringden O. Allogeneic bone marrow transplantation for hematological malignancies: controversies and recent advances. Acta Oncol 1997;36(6):549–64.[Medline]
- Thomas E, Lochte H, Lu W, Ferrebee J. Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N Engl J Med 1957;257(11):491–6.[Medline]
- Meagher RC, Herzig RH. Techniques of harvesting and cryopreservation of stem cells. Hematol Oncol Clin North Am 1993;7(3): 501–33.[Medline]
- Hong DS, Deeg HJ. Hemopoietic stem cells: sources and applications. Med Oncol 1994;11(2):63–8.[Medline]
- Kelley CH, McBride LH, Randolph SR, Leum EW, Lonergon JN, eds. Home care management of the blood cell transplant patient. 3rd ed. Sudbury, Mass.: Jones and Bartlett; 1998:5–9, 26.
- Haley NR. HPC engraftment. In: Snyder EL, Haley NR, eds. Hematologic progenitor cells: A primer for medical professionals. Bethesda, Md.: AABB Press; 2000:127–9.
- Leather HL, Wingard JR. Infections following hematopoietic stem cell transplantation. Infect Dis Clin North Am 2001;15(2):483–520.[Medline]
- Blijlevens NM, Donnelly JP, De Pauw BE. Mucosal barrier injury: biology, pathology, clinical counterparts and consequences of intensive treatment for haematological malignancy: an overview. Bone Marrow Transplant 2000;25(12):1269–78.[Medline]
- Wardley AM, Jayson GC, Swindell R, et al. Prospective evaluation of oral mucositis in patients receiving myeloablative conditioning regimens and haemopoietic progenitor rescue. Br J Haematol 2000; 110(2):292–9.[Medline]
- Bellm LA, Epstein JB, Rose-Ped A, Martin P, Fuchs HJ. Patient reports of complications of bone marrow transplantation. Support Care Cancer 2000;8(1):33–9.[Medline]
- Ruescher TJ, Sodeifi A, Scrivani SJ, Kaban LB, Sonis ST. The impact of mucositis on alpha-hemolytic streptococcal infection in patients undergoing autologous bone marrow transplantation for hematologic malignancies. Cancer 1998;82(11):2275–81.[Medline]
- Garfunkel AA, Tager N, Chausu S, Chausu G, Haze C, Galili D. Oral complications in bone marrow transplantation patients: recent advances. Isr J Med Sci 1994;30(1):120–4.[Medline]
- Woo SB, Sonis ST, Monopoli MM, Sonis AL. A longitudinal study of oral ulcerative mucositis in bone marrow transplant recipients. Cancer 1993;72(5):1612–7.[Medline]
- Lefkoff MH, Beck FM, Horton JE. The effectiveness of a disposable tooth cleansing device on plaque. J Periodontol 1995;66(3): 218–21.[Medline]
- Antin JH. Long-term care after hematopoietic-cell transplantation in adults. N Engl J Med 2002;347(1):36–42.[Free Full Text]
- Deeg HJ, Klingemann HG, Phillips GL, Van Zant G. A guide to blood and marrow transplantation. 3rd ed. New York: Springer; 1999:1–2.
- Redding SW, Callander NS, Haveman CW, Leonard DL. Treatment of oral chronic graft-versus-host disease with PUVA therapy: case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;86(2):183–7.[Medline]
- Guillaume T, Rubinstein DB, Symann M. Immune reconstitution and immunotherapy after autologous hematopoietic stem cell transplantation. Blood 1998;92(5):1471–90.[Free Full Text]
- Sullivan KM, Reid CD. Introduction to a symposium on sickle cell anemia: current results of comprehensive care and the evolving role of bone marrow transplantation. Semin Hematol 1991;28(3):177–9.[Medline]
- Curtis RE, Rowlings PA, Deeg HJ, et al. Solid cancers after bone marrow transplantation. N Engl J Med 1997;336(13):897–904.[Abstract/Free Full Text]
- Champlin R, Khouri I, Kornblau S, et al. Allogeneic hematopoietic transplantation as adoptive immunotherapy: induction of graft-versus-malignancy as primary therapy. Hematol Oncol Clin North Am 1999; 13(5):1041–57.[Medline]
- Chaushu G, Itzkovitz-Chaushu S, Yefenof E, Slavin S, Or R, Garfunkel AA. A longitudinal follow-up of salivary secretion in bone marrow transplant patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;79(2):164–9.[Medline]
- Kolbinson DA, Schubert MM, Flournoy N, Truelove EL. Early oral changes following bone marrow transplantation. Oral Surg Oral Med Oral Pathol 1988;66(1):130–8.[Medline]
- Zaidi A, Vesole D. Multiple myeloma: an old disease with new hope for the future. CA Cancer J Clin 2001;51(5):273–85.[Abstract/Free Full Text]
TOP
ABSTRACT
SUPPORTIVE CARE
