INTRODUCTION — Hematopoietic cell transplantation (HCT) has the potential to cure malignant (eg, leukemias, lymphomas) and nonmalignant disorders (eg, hemoglobinopathies). However, cure of the underlying disease by HCT is not necessarily associated with full restoration of health. Transplantation may be associated with life-long morbidity and survivors require monitoring for relapse of the underlying disease, management of transplantation-associated complications, and general medical care and health maintenance.
This topic will discuss the long-term care of the adult survivor of autologous or allogeneic HCT, focusing on issues that require attention from approximately one year after transplantation.
The following related topics are discussed separately:
TERMINOLOGY — Terminology related to HCT is described in the accompanying table (table 1).
GOALS — The goals of care for the adult survivor of HCT are to monitor for recurrence of the underlying disease, prevent and manage transplantation-associated complications, and integrate survivorship care with age- and gender-appropriate health maintenance.
COORDINATION OF CARE — Long-term care of the transplant survivor can be provided in a variety of clinical settings. Regardless of the setting, we suggest use of a survivorship care plan (SCP) as an effective method to define responsibilities, facilitate communication, coordinate care, and enhance patient self-management, adherence to treatment recommendations, and shared decision making. Cancer SCPs are described in more detail separately. (See "Assuring quality of care for cancer survivors: The survivorship care plan".)
●Care setting and team – Care is generally provided by the transplant team for at least 6 to 12 months after HCT. Although institutional practices vary, many transplant centers "discharge" patients after a year of transplantation to the care of the referring hematologist/oncologist, primary care clinician, or other community provider. In some settings, care is provided through a multispecialty clinic with expertise in the needs of the long-term survivor of HCT.
Responsibilities for follow-up must be clearly defined and effective communication is important to ensure that findings are reported to both the transplant team and other medical providers [1,2]. Adverse events should be reported to the transplant center, as this may inform long-term follow-up plans. Optimal management of transplant complications may require access to various medical specialties (eg, cardiology, pulmonary, endocrinology, nephrology), oral medicine (eg, dentist, otolaryngology), eye care (eg, ophthalmology), nutrition, physical medicine, cognitive and psychological services, and others.
●Survivorship care plan – A comprehensive SCP should be developed by the transplant team and shared with the patient, referring hematology/oncology specialist, primary care provider, and other caregivers. The SCP should be individualized according to age, gender, and comorbid medical conditions and it should include a summary of prior treatments and details of the transplant (eg, type of donor, graft, conditioning regimen, transplant course, early complications, GVHD, and use of corticosteroids). It should detail a schedule and protocol for follow-up care; emphasize prevention, education, and self-care; and define ongoing responsibilities of the caregivers and the patient [3,4]. Further discussion of SCPs for patients with cancer is provided separately. (See "Assuring quality of care for cancer survivors: The survivorship care plan".)
Use of a transplant SCP has been associated with improved patient-reported outcomes and may aid coordination of care, shared decision making, self-management, and adherence to treatment recommendations. In a multicenter trial, 458 adults who were relapse-free one to five years after transplantation were randomly assigned to receive an individualized SCP versus usual care . Six months after receiving the SCP, compared to usual care, use of an SCP was associated with lower treatment-related distress and improved mental health quality of life.
COMPONENTS OF CARE — Care of HCT survivors should include:
●Monitoring for relapse – Relapse is the most common cause of death in transplant survivors in the first two to four years after transplantation . Monitoring for relapse should be tailored to the underlying disease, as discussed separately in the corresponding disease topic.
●Health maintenance – Health maintenance in the transplant survivor includes age- and gender-appropriate health screening for hypertension, hyperlipidemia, diabetes, cancers, and mental health; surveillance for second cancers; encouragement of healthy behaviors; and management of psychosocial distress. Screening should recognize that transplant survivors are at higher risk for some of these conditions because of the transplant process (eg, increased risk for osteoporosis in young survivors with a history of chronic steroid use). (See 'Health maintenance' below.)
●Monitoring for transplant complications – Surveillance, prevention, and management of transplant complications are discussed below. (See 'Screening and prophylaxis' below.)
●Screening for second cancers – Second cancers (eg, hematologic malignancies, solid tumors, post-transplant lymphoproliferative disorders) account for up to 10 percent of mortality in patients who survive for two years after HCT. Second cancers and lifelong cancer screening for transplant survivors are discussed below and separately. (See 'Health maintenance' below and "Malignancy after hematopoietic cell transplantation".)
●Continued care for graft-versus-host disease (GVHD) – Evaluation and management of GVHD, which is associated with allogeneic (but not autologous) HCT, is discussed separately. (See "Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease" and "Treatment of chronic graft-versus-host disease".)
Our approach to long-term care of the transplant survivor (table 2) is consistent with guidelines of the European Group for Blood and Marrow Transplantation (EBMT), the Center for International Blood and Marrow Transplant Research (CIBMTR), the American Society of Blood and Marrow Transplantation (ASBMT), and other guidelines for survivorship care [4,7-9].
Considerations — The schedule and protocol for follow-up should be individualized and will vary according to the type of transplantation, prior treatments, age, gender, and medical comorbidities. Good medical judgment should be applied and plans may require modification based on the care setting and available resources. Development of a survivorship care plan (SCP) to coordinate care and facilitate shared decision making, adherence to treatment recommendations, and patient engagement and self-management is discussed above. (See 'Coordination of care' above.)
There is no consensus regarding an optimal schedule and protocol for follow-up. No randomized or controlled trials have directly addressed the schedule and protocol for follow-up, and most suggestions are based on expert opinion and retrospective studies.
Among the factors that we consider in developing a follow-up care plan are:
●Type of HCT (ie, allogeneic versus autologous)
●Conditioning regimen (eg, alkylator-based, total body irradiation [TBI])
●Prior treatments (eg, chemotherapy associated with cardiac or pulmonary toxicity, mantle radiation therapy)
●Severity of graft-versus-host disease (GVHD) and associated treatments
Such exposures influence the risk for cardiac, pulmonary, and liver toxicities; thyroid disorders; osteoporosis; fertility; various cancers; and other complications, as described below. (See 'Health maintenance' below and 'Screening and prophylaxis' below.)
●Schedule – The frequency and content of long-term follow-up visits should be individualized and will vary with the severity of chronic GVHD and ongoing use of immune suppression, underlying disease, age, sex, and comorbid illnesses. Following is an example:
•Every three to six months in years 2 and 3 after HCT
•Every four to six months in years 4 and 5
•Annually for life
●Protocol – Each follow-up visit should include interim history and physical examination, and laboratory studies (table 2).
●Screening and counseling – Health maintenance and counseling for healthy behaviors are described below. (See 'Health maintenance' below.)
●Medical management – Assessment and management of medical conditions that are associated with transplantation are described below. (See 'Screening and prophylaxis' below.)
●Chronic graft-versus-host-disease (cGVHD) – cGVHD can exacerbate medical complications of allogeneic transplantation, and special attention is required with regard to infectious complications, cardiovascular and pulmonary systems, liver, skin, and oral health, as discussed below. (See 'Screening and prophylaxis' below.)
Management of cGVHD, including treatment with immunosuppressive agents, is generally directed by the HCT team. With ongoing cGVHD, or for patients who continue on long-term immunosuppressant use, long-term follow-up care and cGVHD are often linked and provided at the transplant center. (See "Treatment of chronic graft-versus-host disease".)
Allogeneic HCT continues to evolve, with emerging indications, donor sources, conditioning regimens, and prevention/treatment strategies for cGVHD. As such, treatment complications and outcomes will continue to change and may affect the nature and schedule of follow-up.
●Schedule – The frequency and content of long-term follow-up visits should be individualized and will vary with the underlying disease, age, sex, and comorbid illnesses. Following is an example:
•Every four to six months in years 2 and 3 after HCT
●Protocol – Each follow-up visit should include interim history and physical examination, and laboratory studies (table 2).
●Screening and counseling – Health maintenance and counseling for healthy behaviors are described below. (See 'Health maintenance' below.)
●Medical management – Monitoring and management of medical conditions associated with transplantation are described below. (See 'Screening and prophylaxis' below.)
HEALTH MAINTENANCE — Long-term well-being of transplant survivors requires attention to age- and sex-related risks.
All patients — Screening, prevention (table 2), and counseling for healthy behaviors is described below:
Blood pressure — Blood pressure should be checked at least annually.
Management of hypertension is discussed separately. (See "Overview of hypertension in adults".)
Hypercholesterolemia — Cholesterol and high density lipoprotein (HDL) levels should be checked annually starting at age 35 for men and 45 for women. Lipid screening should begin at age 20 for any higher-risk patient, including those who smoke and/or have hypertension, diabetes, obesity, chronic tacrolimus, sirolimus or corticosteroid use, or a family history of heart disease (ie, male relatives ≤50 years and/or female relatives ≤60 years).
Management of hypercholesterolemia is discussed separately. (See "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease".)
Diabetes — Screening for diabetes should be performed annually after age 45 or in those with sustained higher blood pressure (eg, >135/80) or presence of other risk factors, including chronic use of corticosteroids. (See "Screening for type 2 diabetes mellitus", section on 'A suggested approach'.)
Colorectal cancer — Screening for patients without a family history of colorectal cancer (ie, a first-degree relative with colorectal at age <60) should begin at age 45. However, screening may be considered earlier (eg, age 30) for survivors whose treatment included alkylating agents. Screening for colorectal cancer is described separately. (See "Screening for colorectal cancer: Strategies in patients at average risk".)
Other cancers — In addition to screening for colorectal cancer (described above) and age- and sex-specific screening guidelines (described below), cancer screening should be tailored to the individual, as informed by pretransplant exposures and other individual risks. As examples, patients who were treated with radiation therapy may be at increased risk for cutaneous malignancies or head and neck cancer. (See "Epidemiology and risk factors for head and neck cancer" and "Prevention and management of skin cancer in solid organ transplant recipients", section on 'Post-transplantation surveillance'.)
Mental health — We suggest screening for depression at all clinical encounters, given the high prevalence following transplantation. Evaluation may utilize a depression screening instrument, but simple questions about mood and anhedonia can serve as an acceptable alternative (eg, "Over the past two weeks have you felt down, depressed, hopeless, or had little interest or pleasure in doing things?"). Screening for depression in adults is discussed separately. (See "Screening for depression in adults".)
Factors that may impair return to the status quo include issues with exercise tolerance, disturbances in taste, obesity, and sexual health. Involvement of mental health providers, exercise physiologists, nutritionists, and sexual health counselors may be appropriate in selected patients [10,11]. Attention should also be paid to the psychological health of the spouse/partner or other family providers.
Healthy behaviors — Suggestions for all patients include:
●Eat a healthy diet with a variety of foods, maintain a healthy weight, and follow age-specific guidelines for physical activity. (See "The roles of diet, physical activity, and body weight in cancer survivors".)
●No passive or active smoking exposure, tobacco chewing, or illegal drugs. (See "Overview of smoking cessation management in adults".)
●Avoid alcohol or use it only in moderation (eg, ≤2 drinks per day) .
●Avoid excessive sun exposure and wear sunscreen protection.
●Male and female survivors should be reminded that protection against sexually transmitted infections (STI) is important even when pregnancy is unlikely or impossible. Screening for STIs is described separately. (See "Screening for sexually transmitted infections", section on 'Screening recommendations'.)
Further discussion of preventive care is provided separately. (See "Overview of cancer survivorship care for primary care and oncology providers", section on 'Preventive care'.)
Women — In addition to the general suggestions above, specific care for female transplant survivors includes (see 'Health maintenance' above):
●Breast cancer – Screening for breast cancer should begin at age 40 and occur every one to two years. For women treated with radiation, screening should begin at age 25 or eight years after radiation exposure, whichever is later, but no later than age 40 . (See "Screening for breast cancer: Strategies and recommendations".)
●Cervical cancer – Screening for cervical cancer with Pap test and human papillomavirus (HPV) testing should generally be performed in women ≥21 years every one to three years. Screening for cervical cancer is discussed separately. (See "Screening for cervical cancer in resource-rich settings".)
●Osteoporosis – All women should be screened for bone mineral density with dual-energy X-ray absorptiometry (DXA) one year after HCT [8,9,13]. Some experts also suggest vitamin D measurement, as the prevalence of vitamin D deficiency after allogeneic HCT is high . Ongoing screening is influenced by risk for osteoporosis; prior treatments and other exposures (eg, corticosteroids for chronic graft-versus-host disease [cGVHD]) are important risk factors for osteoporosis in transplant survivors. (See "Screening for osteoporosis in postmenopausal women and men", section on 'Fracture risk assessment'.)
Management of osteoporosis in women is discussed separately. (See "Evaluation and treatment of premenopausal osteoporosis", section on 'Management'.)
●Hypogonadism/fertility – Premature menopause (ie, secondary oligo-amenorrhea) is common and should be evaluated with a pregnancy test and follicle-stimulating hormone (FSH); an elevated FSH is consistent with ovarian insufficiency .
For women with ovarian insufficiency we suggest:
•Women <40 years with premature ovarian insufficiency should receive estrogen replacement therapy through the age of natural menopause, regardless of menopausal symptoms.
•Women ≥40 years with menopausal symptoms should be engaged in shared decision making with discussion of the benefits and risks of estrogen therapy; selective estrogen receptor-modulating drugs can be considered in lieu of estrogen in women with excess risks of breast cancer . (See "Management of primary ovarian insufficiency (premature ovarian failure)", section on 'Importance of estrogen therapy' and "Treatment of menopausal symptoms with hormone therapy".)
In general, spontaneous or assisted pregnancies should be delayed for at least two to five years after HCT since this is the period when the risk of relapse is greatest . Contraception is advised if the woman is fertile or potentially fertile and pregnancy is not desired. Even if infertile, barrier contraception should be used with new partners to prevent STIs. (See "Contraception: Counseling and selection".)
For women who underwent allogeneic HCT, it is important to emphasize the role of cGVHD in low libido and other aspects of sexual health in this population. (See "Overview of sexual dysfunction in females: Management".)
Evaluation and management of specific fertility issues may require referral to a reproductive endocrinologist. (See "Treatment of menopausal symptoms with hormone therapy".)
●Sexually transmitted infections – All HCT survivors should be counseled regarding safe sexual practices, and patients should be questioned about their sexual health and referred for sexual health counseling, if appropriate [16-18]. Routine screening for STIs is similar to that in the general population and is described separately. (See "Screening for sexually transmitted infections", section on 'Females'.)
Men — In addition to the general suggestions above, specific suggestions for male survivors of HCT include (see 'Health maintenance' above):
●Prostate cancer – Routine screening for prostate cancer in HCT survivors is similar to that in the general population, as discussed separately. (See "Screening for prostate cancer", section on 'Approach to screening'.)
●Screening for genital chronic GVHD – Genital cGVHD occurs in 5 to 20 percent of men with systemic cGVHD. Balanoposthitis, lichen sclerosis or lichen planus type features may be present, along with phimosis, urethral or meatal scarring or stenosis . Women may experience vulvovaginal dryness, ulcers, lichen planus-like features, vaginal stenosis or complete obliteration, and/or dyspareunia. (See "Treatment of chronic graft-versus-host disease", section on 'Vagina'.)
●Osteoporosis – Screening for osteoporosis is influenced by prior treatments and other exposures (eg, corticosteroids for cGVHD). Some experts suggest that all men should be screened for bone mineral density with DXA one year after HCT, while others suggest such screening only for men at higher risk [8,9,13].
Risk factors include myeloablative conditioning, clinical manifestations of low bone mass (eg, radiographic osteopenia, history of low-trauma fractures, loss of more than 1.5 inches in height), and risk factors for fracture (eg, chronic glucocorticoid therapy, androgen deprivation therapy for prostate cancer, hypogonadism, primary hyperparathyroidism, gastrointestinal cGVHD) (table 3). Some experts also suggest vitamin D measurement, as the prevalence of vitamin D deficiency after allogeneic HCT is high . Additional information regarding evaluation for osteoporosis in men is presented separately. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in men".)
Management of osteoporosis in men is discussed separately. (See "Treatment of osteoporosis in men".)
●Hypogonadism – Men with symptoms worrisome for hypogonadism (eg, diminished libido, erectile dysfunction) should have serum testosterone and prolactin measured. In men who received cranial radiation, FSH should also be measured. Testosterone replacement therapy with transcutaneous testosterone preparations or long-acting implantable pellets is indicated in men with very low testosterone levels, as discussed separately. (See "Clinical features and diagnosis of male hypogonadism" and "Testosterone treatment of male hypogonadism".)
●Sexually transmitted infections – All HCT survivors should be counseled regarding safe sexual practices, and patients should be questioned about sexual health and referred for sexual health counseling, if appropriate. Routine screening for STIs is similar to that in the general population and is described separately. (See "Screening for sexually transmitted infections", section on 'Males'.)
SCREENING AND PROPHYLAXIS — Organ-specific late complications of HCT increase over time and active surveillance is required in all transplant survivors. Some long-term complications (eg, cardiovascular, pulmonary, renal) contribute to nonrelapse mortality (NRM), while others (eg, dry eyes, xerostomia, avascular necrosis) may not cause NRM but are a source of substantial morbidity and impaired quality of life (QOL).
Infection/immunity — Transplantation can impair immunity and increase the risk for infections. Infections are an important cause of late morbidity and mortality in both autologous and allogeneic transplant recipients. All HCT survivors should be educated about the need for prompt medical attention for febrile illnesses.
Our approach follows:
●Allogeneic HCT – Recipients are vulnerable to various bacterial, fungal, and viral infections for extended periods after transplantation. Immune reconstitution can take two years or longer and the risk for infections is greatest in the first two years after HCT. The increased risk for infections may continue long-term, especially in patients with chronic graft-versus-host disease (cGVHD), extended immunosuppressive therapy, and recipients of human leukocyte antigen (HLA)-mismatched, T cell-depleted, or umbilical cord blood grafts . (See "Overview of infections following hematopoietic cell transplantation".)
•Antibiotic prophylaxis targeting encapsulated organisms should be given for at least as long as immunosuppressive therapy is administered, or lifelong for those patients who have undergone splenectomy. Suggestions for antibiotic prophylaxis are presented separately. (See "Prevention of infections in hematopoietic cell transplant recipients", section on 'Antimicrobial prophylaxis or pre-emptive therapy'.)
•Immunization following the return of immune competence (table 4) is discussed separately. (See "Prevention of infections in hematopoietic cell transplant recipients", section on 'Immunization'.)
•T-helper cell (CD4) count is useful as a marker of immune reconstitution and to guide the duration of viral or other infection prophylaxis. We generally continue antibiotic prophylaxis for encapsulated organisms and antiviral prophylaxis while CD4 counts remain abnormally low. (See "Overview of infections following hematopoietic cell transplantation", section on 'Late postengraftment period'.)
●Autologous HCT – Reconstitution of the cellular and humoral immune systems generally occurs within 6 to 12 months after autologous HCT, but transplant recipients typically lose immunity to pathogens against which they were previously immunized. Immunization following the return of immune competence (table 4) is discussed separately. (See "Prevention of infections in hematopoietic cell transplant recipients", section on 'Immunization'.)
An overview of infections following HCT and management of suspected infections are described separately. (See "Overview of infections following hematopoietic cell transplantation".)
Cardiovascular — Cardiovascular (CV) complications are a significant source of morbidity and mortality after transplantation and can appear years or even decades after HCT. CV complications vary with age, underlying risk factors, type of transplantation, and prior treatment with cardiotoxic drugs and/or radiation therapy. Patients with the metabolic syndrome are at significantly higher risk for CV complications than those without . (See "Survival, quality of life, and late complications after hematopoietic cell transplantation in adults", section on 'Cardiovascular disease'.)
Screening and management for CV complications (table 2) for all HCT survivors should include:
●History and focused physical examination for CV complications at each visit.
●Regular measurement and control of blood pressure, lipid screening, nutritional counseling and weight control, smoking cessation, and control of diabetes, as described above. (See 'All patients' above.)
●For patients with CV clinical findings, we suggest performing electrocardiogram, echocardiogram with assessment of ventricular function, and/or exercise stress testing as clinically indicated. We generally obtain a cardiac echocardiogram for all patients five years after transplantation. Some transplant centers perform annual electrocardiography to screen for asymptomatic coronary disease and refer patients with one or more CV risk factors for echocardiography and/or exercise stress testing.
Our suggestions for CV surveillance are consistent with clinical practice guidelines [4,7-9,22]. Evaluation and management of specific CV diseases are discussed in those topics. (See "Overview of primary prevention of cardiovascular disease" and "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults: Our approach".)
Pulmonary — Chronic respiratory failure can occur following autologous or allogeneic HCT. (See "Pulmonary complications after allogeneic hematopoietic cell transplantation: Causes" and "Pulmonary complications after autologous hematopoietic cell transplantation".)
For all transplant survivors, we suggest:
●Annual history and physical examination for pulmonary complications.
●Smoking history should be assessed in all HCT survivors; smokers and those at risk for passive (secondary) exposure should be counseled regarding smoking cessation. (See "Overview of smoking cessation management in adults".)
●There is no role for screening asymptomatic patients with routine radiologic imaging (table 2). Care should be taken to limit radiographic and CT imaging studies (particularly in younger individuals) to reduce the risk for second malignancies. (See "Radiation-related risks of imaging".)
●For patients with active cGVHD, we suggest pulmonary function tests (PFT; including FEV1 and FEV1/FVC) at 1, 5, and 10 years, or more frequently depending on cGVHD activity. For abnormal pulmonary function, we suggest repeat testing every three months until stability in airflow is documented.
●Even in patients without active cGVHD, PFTs should be performed at least once at 12 months following transplantation. Routine PFTs during the first year following transplantation is also recommended.
For transplant recipients with respiratory findings (eg, dyspnea, tachypnea, hypoxemia), radiologic abnormalities, and/or abnormal pulmonary function, evaluation and management are discussed separately. (See "Pulmonary complications after allogeneic hematopoietic cell transplantation: Causes" and "Pulmonary complications after autologous hematopoietic cell transplantation".)
Liver disease — Transplant survivors are at risk for liver dysfunction, as described separately. (See "Survival, quality of life, and late complications after hematopoietic cell transplantation in adults", section on 'Liver disease'.)
Our suggestions for long-term follow-up of liver function in HCT survivors (table 2) include:
●Screening tests – For all patients, liver function tests (LFT), including total bilirubin, alkaline phosphatase, and transaminases should be performed at least annually for several years, and continued as warranted by the individual's status.
●History of viral hepatitis – We suggest repeat screening using DNA-based techniques for viral hepatitis in all patients one year after transplantation.
For patients with a history of viral hepatitis:
•Hepatitis B – Monitoring for reactivation should include annual hepatitis B surface antigen (HbsAg) or hepatitis B viral load by polymerase chain reaction (PCR). Intensified monitoring is warranted for patients on chronic immunosuppressive therapy or in those who receive B cell depleting agents following transplantation. (See "Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis", section on 'Diagnosis'.)
•Hepatitis C – Monitoring for reactivation should include measuring hepatitis C viral load at least annually. Patients should be referred to appropriate specialists for further management, as needed, and liver biopsy may be appropriate to determine the extent of cirrhosis.
Liver and/or infectious disease specialists should also be consulted if hepatitis C virus was not previously treated. Management of hepatitis C virus is discussed separately. (See "Overview of the management of chronic hepatitis C virus infection".)
●Ferritin – Ferritin should be assessed one year after HCT in patients who received red blood cell (RBC) transfusions pre- or post-transplant :
•For patients who have normal ferritin levels and no longer need blood product support, further ferritin testing is not necessary.
•Ferritin should be monitored regularly for patients with elevated serum ferritin and/or elevated transferrin saturation, continued RBC transfusion, or hepatitis C infection. In the absence of acute inflammation, elevated ferritin suggests iron overload, which should be confirmed with imaging and/or liver biopsy. Therapeutic phlebotomy is well tolerated and is effective in the management of the post-transplantation patient with iron overload. Further discussion regarding the diagnosis of iron overload is presented separately. (See "Approach to the patient with suspected iron overload" and "Iron chelators: Choice of agent, dosing, and adverse effects".)
Diabetes/metabolic syndrome — Screening for diabetes is described above. (See 'Health maintenance' above.)
●Hypothyroidism – The risk for hypothyroidism is influenced by prior exposures (eg, radiation therapy). Our suggestions for monitoring for hypothyroidism follow:
•All HCT survivors should have thyroid-stimulating hormone (TSH) measured one year after HCT and at least annually thereafter. If TSH is elevated, the TSH measurement should be repeated along with a free T4 to make the diagnosis of hypothyroidism. (See "Diagnosis of and screening for hypothyroidism in nonpregnant adults" and "Thyroid function in nonthyroidal illness".)
•For patients who received cranial irradiation (eg, total body irradiation in the preparative regimen, treatment of central nervous system leukemia), TSH screening may be insufficient; these patients should also be monitored annually with free T4.
●Hypoadrenalism – No routine screening for hypoadrenalism is required.
Chronic administration of glucocorticoids (eg, for treatment of cGVHD) can suppress the hypothalamic-pituitary-adrenal function and result in adrenal insufficiency. Adrenal crisis is a life-threatening emergency that may occur in patients who are abruptly withdrawn from exogenous glucocorticoids or who are under acute stress; patients who have had prolonged exposure to glucocorticoids should be tapered slowly. Evidence of adrenal crisis requires immediate treatment (table 5) as described separately. (See "Treatment of adrenal insufficiency in adults".)
Bone and joint health — Transplant survivors may be at risk of osteopenia, osteoporosis, and avascular necrosis of the hip or other joints. Patients with cGVHD also require screening by history and physical examination for glucocorticoid-induced myopathy and sclerotic changes in the skin and fascia that can limit joint mobility.
Patients should be encouraged to take advantage of preventative measures commonly used in other patient populations to prevent osteoporosis, including regular physical activity, supplemental calcium and vitamin D, avoidance of smoking and excess alcohol, bisphosphonates to patients receiving prolonged courses of corticosteroids, and estrogen replacement for women with premature ovarian failure or testosterone replacement for men with documented abnormal serum levels . Management of osteoporosis after HCT is discussed separately. (See "Overview of the management of osteoporosis in postmenopausal women" and "Treatment of osteoporosis in men".)
For patients who underwent allogeneic HCT, we suggest evaluation of the skin and skin-derived structures (ie, nail beds, hair) for the signs of graft-versus-host disease (follicular erythema, dyspigmentation, focal induration, joint contracture). Patients should be counseled to prevent sun burn and damage (dermatoheliosis) and to prevent severe dryness (xerosis), which may exacerbate cGVHD and cutaneous infections. (See "Clinical manifestations and diagnosis of chronic graft-versus-host disease", section on 'Mucocutaneous'.)
Oral health — Screening for the chronic oral complications of transplantation and cancer by an oral medicine specialist or dentist is recommended 12 months after transplantation, and at least twice a year thereafter (table 6) .
Presenting features of intraoral malignancy (eg, nonhealing ulcers, mucosal growths, induration) may be difficult to distinguish from oral cGVHD and may be identifiable as malignancies only with tissue biopsy.
Symptomatic management of chronic xerostomia and dry, cracked lips is described separately. (See "Treatment of dry mouth and other non-ocular sicca symptoms in Sjögren’s disease".)
Ocular complications — An ophthalmologic evaluation should be performed at one year by an ophthalmologist knowledgeable in the potential complications of transplantation, including cataracts, dry eye, elevated intraocular pressure, and ischemic microvascular retinopathy. Ophthalmologic examination should include measurement of visual acuity, ocular pressure, and fundus examination, with subsequent evaluation based on findings and risk factors [9,26-29].
Management of chronic dry eye (keratoconjunctivitis sicca) in the long-term HCT survivor is described separately. (See "Treatment of dry eye in Sjögren’s disease: General principles and initial therapy".)
Neurocognitive — Neurocognitive dysfunction is common in transplant survivors and is a significant source of concern for patients and caregivers [30,31].
History and focused neurologic examination are sufficient to screen for neurologic complications of HCT (table 2). There is no consensus regarding routine use of screening tests for neurocognitive dysfunction or a preferred screening instrument . When possible, pre-transplant evaluation should be performed at baseline, for comparison with post-transplantation testing.
Further evaluation in patients with evidence of neurocognitive dysfunction is described separately. (See "Evaluation of cognitive impairment and dementia".)
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)")
●Hematopoietic cell transplantation (HCT) can cure malignant and nonmalignant disorders, but cure of the underlying disease is not necessarily associated with full restoration of health. HCT may be associated with life-long morbidity and survivors require monitoring for relapse of the underlying disease, management of potential transplantation-associated complications, and general medical care.
●Goals of care – The goals of care for the HCT survivor are to monitor, prevent, and manage transplant-associated complications; monitor for recurrence of the underlying disease; and integrate survivorship care with age-appropriate health maintenance. (See 'Goals' above.)
●Survivorship care plan – Long-term care of the transplant survivor may be provided in a variety of clinical settings. A comprehensive survivorship care plan (SCP) should be developed by the HCT team and shared with the patient, referring hematology/oncology specialist, primary care provider, and other caregivers to clearly define responsibilities and communicate regularly regarding care. (See 'Coordination of care' above.)
●Components of care – Care of HCT survivors should include (see 'Components of care' above):
•Monitoring for relapse – Monitoring for relapse of the underlying disease is discussed separately, in the corresponding disease topic.
•Health maintenance – Age- and gender-appropriate health screening for hypertension, hyperlipidemia, diabetes, cancers, and mental health; surveillance for second cancers; encouragement of healthy behaviors; and management of psychosocial distress are discussed below. (See 'Health maintenance' above.)
•Transplant complications – Surveillance, prevention, and management of medical consequences of HCT (eg, cardiovascular, respiratory, endocrine, and other systems) are discussed below. (See 'Screening and prophylaxis' above.)
•Chronic graft-versus-host disease (cGVHD) – For patients who underwent allogeneic HCT, evaluation and management of cGVHD is discussed separately. (See "Treatment of chronic graft-versus-host disease".)
●HCT complications can affect nearly all organ systems. Evaluation and management are discussed in the sections above. (See 'Screening and prophylaxis' above.)
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