Page 1684 - Hematology_ Basic Principles and Practice ( PDFDrive )

1502 Part VIII Comprehensive Care of Patients with Hematologic Malignancies

of hearing loss has been reported in survivors of HCT performed in primary cancer were at a 1.7-fold increased risk for developing a
childhood, the risk is elevated threefold to fourfold over that in the second cancer. Another cohort of 633,964 cancer patients diagnosed
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general population. Data are beginning to emerge regarding genetic between 1958 and 1996 in Sweden and followed for the development
polymorphisms associated with increased susceptibility to platinum- of subsequent cancers revealed a modestly increased risk (less than
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related hearing loss; these data may prove useful in identifying future twofold), when compared with the general population. The
patients who are at increased risk for hearing loss as a consequence Swedish family-cancer database was used to analyze site-specific risk
of platinum-based chemotherapy. 202 of second primary malignancies following 53,159 hematologic
malignancies diagnosed between 1958 and 1996. Among 18,960
patients with NHL, there was a 1.2-fold significant increase in risk
Dental Effects of subsequent malignancies. Among the 5353 patients with HL, there
was a 1.7-fold significant increase in subsequent malignancies. Among
Children whose teeth have not completely developed at the time of the 8098 patients with ALL, there was a 1.3-fold increased risk of
cancer treatment are most vulnerable to dental complications and subsequent malignancies. 218
treatment with chemotherapy during early childhood may result in However, when we examine the risk of subsequent neoplasms
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qualitative problems with enamel and root development. However, among childhood cancer survivors, a somewhat different picture
patients of all ages who received RT involving the head or neck emerges. The cumulative incidence of subsequent malignant neo-
(including cranial irradiation and TBI) are susceptible to dental plasms (SMNs) exceeds 20% at 30 years after diagnosis of the primary
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complications, most often manifesting as increased susceptibility to cancer. The cumulative incidence is 9% for nonmelanoma skin
dental caries and gingivitis as a result of diminished salivary gland cancer (NMSC) and 3% for meningioma. The cumulative incidence
function. Patients who have undergone HCT are at increased risks is 8% for SMNs excluding NMSC; this represents a sixfold increased
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for dental caries, gum disease, and xerostomia ; abnormalities of risk of SMNs among cancer survivors compared with the general
tooth development are seen in survivors who underwent HCT during population. HL survivors demonstrate the highest risk of subsequent
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childhood. Younger age at transplantation (especially under 6 malignancies (8.7-fold compared with the general population). Treat-
years) and TBI doses above 10 Gy are associated with the greatest ment with RT and specific chemotherapeutic agents is associated with
risk. 205 increased risk of subsequent malignancies; female sex, older age at
diagnosis, and earlier treatment era modify that association. Breast
cancer is the most common subsequent malignancy, followed by
Hepatic Effects thyroid cancer. Subsequent malignancies are the leading cause of
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nonrelapse late mortality. The risk of subsequent malignancies
Although acute hepatic dysfunction may be seen with certain che- remains elevated for more than 20 years from diagnosis of the primary
motherapeutic agents, including antimetabolites and anthracyclines, cancer. Multiple subsequent neoplasms are common among aging
there has generally been a low reported incidence of delayed hepato- survivors of childhood cancer. Cumulative incidence of a second
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toxicity in patients receiving these agents. However, reports of subsequent malignancy was reported as 47% at 20 years after the first
chronic hepatotoxicity and portal hypertension have emerged in SMN. A first SMN of NMSC identifies a population at high risk for
survivors of childhood ALL who received 6-thioguanine–based a subsequent invasive SMN. 221
maintenance therapy, 207–210 and these survivors require long-term The magnitude of risk for subsequent malignant neoplasms after
surveillance for this complication. 82,211 Chronic viral hepatitis, result- HCT ranges from fourfold to 11-fold that of the general population.
ing from transfusion of contaminated blood or serum products, Several host and clinical factors are associated with an increased risk
should be considered in the differential diagnosis of all survivors with for subsequent malignant neoplasms after HCT. These include age
persistently elevated alanine aminotransferase levels. Hepatitis C is at HCT, pre-HCT exposure to chemotherapy and radiation, exposure
the most prevalent type of hepatitis seen in survivors transfused before to TBI as part of conditioning, infection with oncogenic viruses
universal screening of the blood supply for this infection (imple- (Epstein-Barr virus and hepatitis B and C viruses), prolonged immu-
mented in the United States in July 1992). 212,213 Cirrhosis and nosuppression after HCT, autologous versus allogeneic HCT, and
hepatocellular carcinoma are potential sequelae of untreated chronic original cancer.
viral hepatitis and potential causes of morbidity and mortality in this The cumulative incidence of solid tumors after allogeneic HCT
population. In addition, iron overload associated with HCT for ranges from 7% to 11% at 15 years posttransplantation. 222–225 The
hematopoietic malignancies may also be a contributing factor to magnitude of risk of solid tumors exceeds twofold that of an age-
hepatotoxicity in survivors. 214,215 matched and sex-matched general population; the risk reaches
threefold among patients followed for 15 or more years after HCT.
Solid tumors are unequivocally related to the RT used to treat the
Second and Subsequent Malignancies primary cancer, typically have a long latency, and the risk is high
among those exposed to irradiation at a young age. Thus among
Second or subsequent malignancies are defined as histologically dis- patients exposed to radiation at an age less than 30 years, the risk is
tinct cancers developing after the occurrence of a first cancer. Subse- ninefold that of the general population, whereas for those older than
quent malignancies are conventionally categorized into two major 30 years it approaches that of the general population. Solid tumors
types: therapy-related myelodysplastic syndrome/acute myeloid leu- commonly seen after HCT include melanoma, cancers of the oral
kemia (t-MDS/AML) and solid tumors. The latency between diag- cavity and salivary glands, brain, liver, cervix, thyroid, breast, bone,
nosis and treatment of the primary cancer and the development of and connective tissue.
t-MDS/AML is generally short, whereas nonhematopoietic malig- t-MDS/AML is the major cause of nonrelapse mortality in patients
nancies or solid tumors seem to have a longer latency, and the risk undergoing autologous HCT for patients with a primary diagnosis
continues to rise for three or more decades. A wide variety of factors of HL or NHL. 226,227 The cumulative probability of t-MDS/AML
influence the risk for subsequent malignancies. ranges from 1.1% at 20 months to 24.3% at 43 months after autolo-
Several large epidemiologic studies have attempted to determine gous HCT, with a median latency of 12–24 months after HCT
the magnitude of the burden of subsequent malignancies after adult- (range: 4 months to 6 years). Using the World Health Organization
onset primary cancer. For example, 470,000 cancer patients registered classification, two types of t-MDS/AML are recognized, related
between 1953 and 1991 in Finland were followed for the develop- closely to the therapeutic exposure: alkylating agent/radiation and
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ment of a second cancer. Overall, the cohort was not at an increased topoisomerase II inhibitor. The alkylating agent-related t-MDS/
risk for developing a second cancer when compared with the risk for AML typically develops 4–7 years after exposure. Cytopenias are
cancer in an age-matched and sex-matched healthy population. common. Roughly 65% of the patients present with myelodysplasia;
However, patients less than 50 years of age at the diagnosis of their the remaining present with AML but carry myelodysplastic features.