Late complications after allogeneic hematopoietic cell transplant: What primary care physicians can do

Lauren M. Granat; Mariah Ondeck; Bennett Osantowski; Michael Sheu; Vishwanath Ganesan; Seth Rotz; Betty K. Hamilton

doi:10.3949/ccjm.90a.23006

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Figure 1
Typical course of hematopoietic cell transplant (HCT).

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TABLE 1

Chronic graft-vs-host disease: Common findings, questions to ask the patient

Organs affected	Common findings	Questions to ask the patient
Skin	Poikiloderma: erythema Sclerotic features: thickened skin Lichen planus-like features: purple polygonal plaques Lichen sclerosus-like features: wrinkled, atrophic plaques Morphea-like features: small, red or purple patches with white center Dryness Pruritus Hypopigmentation or hyperpigmentation	Have you noticed any changes to your skin?
Mouth	Lichen planus-like changes: lacy white patches Xerostomia (dry mouth) Gingivitis: swelling, redness, bleeding, or pain of the gums Mouth ulcers Mucosal atrophy Mucosal pseudomembranes Mucoceles: painless mucus-filled cysts	Do you have dryness or sensitivity of your mouth?
Eyes	Dry, gritty, painful eyes Photophobia Periorbital hyperpigmentation	Have you noticed any changes in your eyes?
Liver	Jaundice Total bilirubin, alkaline phosphatase, and alanine aminotransferase levels > 2 times the upper limit of normal
Gastrointestinal tract	Anorexia Nausea Vomiting Diarrhea Weight loss Dysphagia	Do you have any nausea, appetite changes, changes in bowel habits or appetite, or difficulty swallowing?
Lungs	Cough Dyspnea	Do you have a cough, wheezing, or shortness of breath?
Muscles and joints	Joint swelling Joint stiffness Muscle cramps Arthralgias Arthritis	Do you have any joint or muscle swelling, stiffness, or pain?
Genitalia	In women: vaginal dryness, pruritus, dyspareunia, lower urinary tract symptoms In men: burning, phimosis	Have you noticed any urinary or sexual symptoms?

Based on information in reference 9.

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TABLE 2

Screening for common adverse effects of corticosteroids in patients with chronic graft-vs-host disease

	Adverse effects	Screening
Metabolic and endocrine	Hyperglycemia Adrenal insufficiency Weight gain	Measure hemoglobin A1c every 3 months Monitor complete metabolic panel and blood pressure Weigh at every visit
Orthopedic	Osteoporosis Avascular necrosis Myopathy	Obtain dual-energy x-ray absorptiometry scan within first year after hematopoietic cell transplant Obtain radiograph if symptoms are present Ask about muscle pain and weakness
Neuropsychiatric	Insomnia, mania, psychosis	Ask about sleep and psychiatric symptoms
Cardiovascular	Hypertension Fluid retention	Check blood pressure at every visit Weigh at every visit
Gastrointestinal	Gastritis, peptic ulcer disease	Ask about gastrointestinal symptoms
Hematologic	Leukocytosis	Monitor complete blood cell count
Dermatologic	Acne, hirsutism	Perform skin examination at every visit

Based on information from reference 10.

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TABLE 3

Cardiovascular and metabolic complications after hematopoietic cell transplant

Complications	Recommendations
General	Moderate exercise 150 minutes per week Tobacco cessation counseling Maintain a healthy weight Eat a healthy diet
Diabetes mellitus	Screen with hemoglobin A1c or fasting plasma glucose 3 months after transplant for patients at high risk (on corticosteroids) Repeat every 6 months if elevated
Dyslipidemia	Check a fasting lipid panel 3 months after transplant Repeat evaluation every 3 to 6 months for patients at high risk (on sirolimus, calcineurin inhibitors, or corticosteroids)
Hypertension	Check blood pressure at every visit at least annually for all patients, regardless of age or other risk factors

Based on information in references 11–13.

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TABLE 4

Recommended vaccination schedule after allogeneic hematopoietic cell transplant

Vaccine	Time posttransplant to initiate vaccination
20-valent pneumococcal conjugate (PCV20)	3 months
Tetanus-diphtheria	≥ 6 months
Acellular pertussis	≥ 6 months
Haemophilus influenzae type B	3 months
Meningococcal disease	≥ 6 months
Inactivated polio	6–12 months
Hepatitis B	≥ 6 months
Inactivated influenza	≥ 6 months
Measles-mumps-rubella	≥ 24 months
Varicella	≥ 24 months
Human papillomavirus	6–12 months
COVID-19	3 months

Based on information in references 21–24.

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TABLE 5

Screening for solid tumors in allogeneic hematopoietic cell transplant recipients vs the general population

	General population	Allogeneic transplant recipients
	General population	Risk factors	Screening considerations
Skin cancers	Routine screening not recommended	Acute or chronic graft-vs-host disease Prolonged immunosuppression Human papillomavirus infection Total body irradiation	Annual skin self-examination
Breast cancer	Yearly mammogram beginning at age 45^a	Same as in general population
Head and neck cancer	Routine screening not recommended	Chronic graft-vs-host disease with prolonged immunosuppression Reduced-intensity conditioning	Oral evaluation at 6 months, 1 year, then annually
Colorectal cancer	Colonoscopy every 10 years beginning at age 45^b	Abdominal radiation	For patients who received radiation: colonoscopy every 5 years beginning at age 35 or 10 years after radiation, whichever occurs last
Esophageal cancer	Routine screening not recommended	Chronic graft-vs-host disease	Upper endoscopy if persistent gastroesophageal reflux disease, symptoms of dysphagia
Thyroid cancer	Routine screening not recommended	Neck radiation; chronic graft-vs-host disease	Yearly thyroid examination
Lung cancer	Annual low-dose computed tomography for high-risk cigarette smokers beginning at age 50 ^c	Busulfan and cyclophosphamide-based conditioning Pretransplant smoking	Yearly chest imaging, smoking cessation
Prostate cancer	Discuss prostate-specific antigen screening at age 50	Same as in general population
Cervical cancer	Papanicolaou smear every 3 years beginning at age 25^d	Age > 34 Chronic graft-vs-host disease	Papanicolaou smear annually posttransplant^e

↵a Patients at high risk may require earlier or more frequent screening.
↵b Patients at high risk, including those with inflammatory bowel disease (Crohn disease or ulcerative colitis), family history of colorectal cancer, or a genetic syndrome, may require earlier or more frequent screening.
↵c Current smokers or those who quit within the past 15 years with a 20-pack-year history.
↵d Starting at age 30—cotesting with human papillomavirus every 5 years or Papanicolaou testing alone every 3 years. Discontinue at age 65 if certain criteria are met.
↵e Cotesting preferred, but cytology-only acceptable. If cytology-only is done, if 3 consecutive tests are negative, can increase the interval to every 3 years. If initial cotesting with human papillomavirus is done and negative, can increase interval to every 3 years. Continue past age 65.
Based on information in references 18 and 36–42.