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Survivors of hematopoietic stem cell transplantation (HSCT) generally have multiple long term health problems related to:

• Therapy:
  • Chemotherapy and/or radiation therapy
• Chronic graft versus host disease (cGvHD)
• Other factors may also play a role:
  • Previous malignancy
  • Complications during transplant (such as septicaemia and hypotension)
  • Supportive therapy (such as nephrotoxic antibiotics and antifungal therapy) 

Usually these side effects overlap and produce significant morbidity.

Armenian et al compared the risk of chronic health problems in cancer survivors treated only with conventional chemotherapy, those treated with HSCT and in the siblings of cancer survivors. Severe, chronic health conditions were far more common in survivors treated with HSCT. Undergoing HSCT from an unrelated donor or a conditioning regime that included TBI (whole body RT) was associated with an increased risk of severe  adverse health conditions. Survivors after HSCT were more likely to have endocrine problems (especially gonadal failure in women), neurosensory impairments, second malignant neoplasms (6.9%) and cardiovascular disease (4.8%).

 

Late Effects of therapy:

Radiation therapy (RT):

Whole body low dose RT (often called Total Body Irradiation or TBI) can affect many organs and lead to multiple late effects.  These side effects are exacerbated by the high dose chemotherapy also given as part of the conditioning regime.

Examples of long term health problems related to RT component of conditioning regime:

Region affected by TBI	Long-term health Risk
General	Increased risk for the development of a second malignant neoplasm2, 3 Leukemia – usually AML Solid tumor – often a sarcoma or brain tumor
	Reduced growth of all the structures within the RT field Significantly worse for young patients
Skeletal	Increased risk of osteoporosis (early onset) Increased risk of avascular necrosis
Brain	Leukoencephalopathy Long term neurocognitive problems
	Increased long term risk of cerebrovascular event (stroke)
Eyes	Cataracts
Pituitary Hypothalamus	Metabolic syndrome Growth hormone abnormalities
Oral	Reduced salivary output with xerostomia and increased risk of dental caries
	In young children abnormal development of teeth
Thyroid	Hypothyroidism
	Thyroid cancer
Lungs	Interstitial disease and pulmonary fibrosis
Heart	Increased risk of coronary vascular disease
Kidneys	Renal damage and dysfunction
	Hypertension
Gonads	Delayed puberty Infertility Early onset of menopause in females
Immune system	Increased risk of infection

 

Chemotherapy:

Examples of late health problems related to the chemotherapy component of conditioning regime:

• Cyclophosphamide is directly responsible for:
  • Infertility
  • Increased risk of secondary leukemia
• Bleomycin is directly responsible for:
  • Pulmonary damage

 

Chronic graft versus host disease (cGvHD):

cGvHD affects many organs, but the major targets are:

• Skin
• GI tract
• Lung