Page 1687 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 93 Late Complications of Hematologic Diseases and Their Therapies 1505

including anxiety, depression, posttraumatic stress disorder, and bar- significantly because of differences in therapy, age at exposure to
riers to accessing the healthcare system because of problems obtaining therapy, or pharmacogenetics. General associations of late effects with
health insurance coverage. The impact of cancer therapy on psycho- conventional treatment for common hematologic malignancies are
social functioning is dependent on many variables, including intensity reviewed in Tables 93.1–93.3. The risk for specific late effects in
and duration of therapy, treatment-related complications, family survivors who have undergone HCT depends on the conditioning
functioning, developmental processes, and treatment-specific sequelae regimen, donor source, complications experienced during the trans-
such as altered cognitive or physical functioning. 286 plantation process, presence or absence of GVHD, and prior cancer
Results from an analysis of 5736 long-term survivors of childhood therapy. Transplantation-related sequelae have been reviewed
leukemia and lymphoma demonstrated that although a relatively low throughout the text of this chapter.
proportion reported symptoms indicative of depression (4.6%) and
somatic distress (10.8%), they were significantly more likely to report
287
these symptoms when compared with sibling controls. In a study Acute Lymphoblastic Leukemia
of 6542 childhood cancer survivors (55% of whom were survivors of
leukemia/lymphoma), the risk for posttraumatic stress disorder was ALL is a heterogeneous disease. Therapy for ALL ranges from a rela-
increased by 4.6-fold, 4.1-fold, and 3.8-fold for survivors of HL, tively innocuous, antimetabolite-based approach for low-risk child-
297
NHL, and leukemia respectively, compared with sibling controls; hood ALL to marrow-ablative therapy followed by HCT for very
increased risk was associated with lower educational level (high school high-risk disease in all age groups. 298,299 The risk for long-term
or less), lower income (<$20,000 annually), being unmarried, being complications for individual survivors varies widely and is dependent
288
unemployed, and having had more intensive treatment. Long-term on the specific therapy received as well as the patient’s age at time of
survivors of adult-onset HL report poorer health-related quality of treatment. 300,301 Potential late effects that may occur as a consequence
life, primarily in physical health, when compared with a healthy of conventional therapy for ALL are listed in Table 93.1.
289
general population. Survivors of HL also appear to be at increased
risk for psychosocial distress when compared with acute leukemia
survivors; areas of greatest impact for these patients include impaired Acute Myeloid Leukemia
290
family and sexual functioning. There is growing interest in the
reported occurrences of fatigue and sleep disturbances among cancer Therapy for AML is generally more intense and of shorter duration
survivors, particularly those with HL, 291–293 which may contribute to than that used for treatment of ALL. Higher doses of anthracycline
depression. chemotherapy are often employed, as is consolidation therapy
Fatigue, psychological distress, psychiatric symptoms, mood distur-
bances, and sexual difficulties are commonly reported by HCT survi-
294
vors. Risk factors for impaired health-related quality of life include Late Effects Associated With Conventional Therapy for
older age, advanced disease at transplantation, presence of chronic TABLE Acute Lymphoblastic Leukemia and Non-Hodgkin
GVHD, and lower level of education. Fatigue and sleep disturbances 93.1 Lymphoma
295
have been reported in up to 65% of the patient cohorts studied, and
296
sexual disturbances are prevalent in 25% of HCT survivors (see box Common Therapeutic Exposures Potential Late Effects
on Evaluating Survivors for Potential Late Effects). Vincristine Peripheral neuropathy, Raynaud
phenomenon
POTENTIAL LATE EFFECTS BY DIAGNOSIS Corticosteroids Cataracts, osteopenia, osteoporosis,
avascular necrosis
Therapeutic approaches to hematologic malignancies vary widely Asparaginase No known late effects
depending on the patient’s age at diagnosis, biologic subtype and Mercaptopurine Hepatic dysfunction (rare)
staging of disease, year (era) of diagnosis, initial response to therapy,
and physician/institutional preference. Even though two patients may Thioguanine Portal hypertension, hepatotoxicity
share an identical diagnosis, their risks for late effects may differ (when used continuously in
maintenance therapy)
Methotrexate (systemic) Osteopenia, osteoporosis,
Evaluating Survivors for Potential Late Effects osteonecrosis, renal dysfunction
(rare), hepatic dysfunction (rare)
To diminish the incidence and severity of untoward late effects and to
improve the quality of survival for patients with hematopoietic malignan- Methotrexate (intrathecal, Neurocognitive deficits, clinical
cies, systematic evaluation of outcomes with subsequent modification high dose), or cytarabine leukoencephalopathy
of current and future therapies is required. To decrease late morbidity (high dose)
and mortality rates and to meet the specialized healthcare needs of this Cranial or craniospinal Neurocognitive deficits, clinical
group of patients, ongoing comprehensive follow-up care with attention
to early detection and intervention for late effects are essential. irradiation leukoencephalopathy, cataracts,
Patients are generally eligible to enter formal long-term follow-up hypothyroidism, second malignant
care when the risk for relapse of their primary disease is minimal. For neoplasm in radiation field (e.g.,
most hematologic malignancies, this occurs when a patient is at least skin, thyroid, brain), short stature,
2 years off therapy. When a patient enters long-term follow-up, the scoliosis or kyphosis, obesity
focus of care shifts from vigilant surveillance for disease recurrence to Anthracyclines Cardiomyopathy, arrhythmias,
a survivorship model of health maintenance or promotion and manage-
ment of treatment-related late effects. Effective management of these subclinical left ventricular
late effects requires ongoing surveillance, early intervention, and when dysfunction, secondary AML
possible, prevention. Cyclophosphamide Hypogonadism, hemorrhagic cystitis,
The long-term complications of treatment for which an individual dysfunctional voiding, bladder
survivor is at risk are determined by several factors, including the malignancy, secondary AML or
patient’s diagnosis, age at treatment, specific chemotherapeutic agents MDS
received (including cumulative doses), specific radiation fields and
doses, therapy-related complications, degree of psychosocial support Blood products Chronic viral hepatitis, HIV
received, genetic predisposition, and current health-related behaviors AML, Acute myeloid leukemia; HIV, human immunodeficiency virus; MDS,
(e.g., diet, physical activity, tobacco, and alcohol use). myelodysplastic syndrome.