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Chapter 109 Complications After Hematopoietic Cell Transplantation 1679

TABLE Selected Late Complications of Hematopoietic increase with time and continued surveillance for these problems
109.5 Cell Transplantation indicated in all HCT survivors.
Complication Risk Factors Monitoring and Prevention
Endocrine Second Cancers
Hypothyroidism TBI/radiation Periodic assessment of
thyroid and gonadal Secondary cancers are a rare, but devastating complication of HCT.
function They account for 5% to 10% of deaths among greater than 2 year
survivors. These malignancies can be broadly categorized as post-
Hypogonadism Chronic GVHD transplant lymphoproliferative disorders (PTLD), hematologic
Growth retardation Chemotherapy malignancies, and solid cancers. 36,37
Ocular PTLD comprise a heterogeneous group of lymphoid prolifera-
Cataracts TBI/radiation Periodic eye exam tions, primarily involving B-lymphocytes that develop as a result of
Keratoconjunctivitis Corticosteroids uncontrolled Epstein-Barr virus (EBV) infection. (Chapter 54) They
sicca occur almost exclusively in allogeneic HCT recipients, with an overall
Chronic GVHD incidence of 1% to 2%. They typically manifest soon after transplan-
Oral tation with more than 80% of cases diagnosed within the first year.
Dental caries TBI/radiation Periodic dental Since T cells play an important role in preventing proliferation of
assessment EBV-infected lymphocytes, removal of T cells from the hematopoietic
Dry mouth Chronic GVHD graft or anti–T-cell serotherapy with ATG or alemtuzumab are strong
Cardiovascular risk factors for PTLD. A greater degree of immunosuppression, such
Coronary artery TBI/radiation Periodic clinical as that resulting from GVHD and use of grafts from unrelated or
disease evaluation HLA-mismatched donors, also increases the risk for PTLD. Treat-
Cerebrovascular Chemotherapy Modification of risk ment of PTLD is often challenging, and available treatments are not
disease factors very effective. Withdrawal of immunosuppression is usually attempted
Respiratory first, but can be difficult in patients with active GVHD. Treatment
Bronchiolitis TBI/radiation Periodic clinical options include anti-CD20 monoclonal antibody rituximab, antiviral
obliterans evaluation therapy with acyclovir or ganciclovir, multiagent chemotherapy, or
Interstitial Chronic GVHD Smoking cessation infusion of EBV-specific cytotoxic T lymphocytes. Since PTLD is
pneumonitis associated with high mortality rates, active surveillance for EBV
Infections reactivation in high-risk settings and initiation of preemptive therapy,
Hepatic often with rituximab, is important.
Secondary MDS and acute myeloid leukemia (AML) can be seen
Cirrhosis Hepatitis B or C Periodic liver function in 5% to 15% of autologous HCT recipients, but is extremely rare
tests
Iron overload Transfusions Serum ferritin level among allogeneic HCT recipients. They usually occur following a
36
latency period of 2–5 years. Bone marrow evaluation can show
Renal cytogenetic abnormalities characteristic of other treatment-induced
Nephropathy TBI/radiation Periodic serum AML/MDS (e.g., balanced translocations to 11q23, monosomy of
creatinine and 5q and 7q or multiple, complex chromosomal aberrations). Risk
urinalysis factors for secondary MDS/AML include older age at transplant, the
Chemotherapy Control hypertension type, intensity and duration of pre-HCT chemotherapy (especially
Cyclosporine alkylating agents), and use of TBI. Outcomes are very poor and
Skeletal long-term survival rates are less than 20%, sometimes following a
Osteoporosis TBI/radiation Periodic bone second allograft for this new malignancy.
densitometry Secondary solid cancers have a latency period of 3–5 years follow-
Avascular necrosis Corticosteroids ing HCT. Subsequently, their incidence continues to rise with time
Second cancers TBI/radiation Periodic cancer and is higher than what may be expected in age- and gender-matched
screening general populations. Their cumulative incidence ranges from 1% to
Chemotherapy 2% at five years, 2% to 6% at 10 years, and 4% to 15% at 15 years
36
Chronic GVHD posttransplantation. Younger age at transplantation, use of TBI and
GVHD, Graft-versus-host disease; TBI, total body irradiation. chronic GVHD are important risk factors for solid cancers. Solid
cancers at variety of sites have been reported, including cancers of the
head and neck, liver, brain and nervous system, thyroid, and bone
and connective tissue. Since there is no plateau in the incidence of
and second malignancies, especially those associated with chronic secondary solid cancers after HCT, their overall risk has not been
immunodeficiency. completely realized, and longer follow up than what is currently
Although any organ system can be involved, certain organs have available is needed before the true magnitude of risk will become
a greater predilection for late-onset problems post-HCT. Cataracts apparent. Lifelong cancer screening is recommended for all HCT
develop in more than one-third of patients by 5-years posttransplan- survivors according to established guidelines (Table 109.6). 4,35
tation and often require surgical therapy. Hypothyroidism can be seen
in up to 50% and hypogonadism in up to 90% of HCT survivors.
The majority of HCT survivors become permanently sterile, although Quality of Life After Transplantation
HCT without TBI can be fertility-sparing in nearly one-third of men
and women. Prepubertal children may retain fertility, although sec- Despite the early morbidity associated with HCT, the majority of
ondary sexual development may be delayed. Up to 50% of children transplant survivors attain high levels of physical and psychologic
undergoing HCT also develop growth retardation. Musculoskeletal QOL and return to full-time employment by 3–5 years posttrans-
complications including osteoporosis and avascular necrosis of plant. However, up to 20% to 40% of long-term survivors continue
weight-bearing joints can be particularly debilitating. An increased to have functional, psychological, and cognitive impairments years
incidence of cardiovascular events and diabetes has also been reported. after HCT. 38,39 The major risk factors for compromised QOL are
The risk for most organ-specific late complications continues to older age and advanced disease at transplantation, chronic GVHD