Late Complications of Hematologic Diseases and Their Therapies

Published on 04/03/2015 by admin

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Chapter 44 Late Complications of Hematologic Diseases and Their Therapies

Neuropsychologic Sequelae After Hematopoietic Cell Transplantation in Adults

The few studies describing neurocognitive sequelae in adults undergoing hematopoietic cell transplant (HCT) suggest that these patients are at risk for developing adverse sequelae related to neuropsychologic functioning, such as slowed reaction time, reduced attention and concentration, and difficulties in reasoning and problem solving1; memory impairment25; problems with executive functioning and processing speed3; and cognitive impairment.13 Reduced memory function is associated with older age, longer interval since HCT, chronic graft-versus-host disease, and long-term cyclosporine use.6 Other predictors include fatigue and poor physical functioning. Lower education level and poorer social functioning appear to impact cognitive performance.3 It is therefore prudent to query post-HCT patients regarding perceived deficits in neuropsychologic functioning and to refer patients with these problems to a neuropsychologist who is experienced in the follow-up care of HCT patients.

Evaluating Survivors for Potential Late Effects

To diminish the incidence and severity of untoward late effects and to improve the quality of survival for patients with hematopoietic malignancies, systematic evaluation of outcomes with subsequent modification of current and future therapies is required. To decrease late morbidity and mortality rates and to meet the specialized health care needs of this group of patients, ongoing comprehensive follow-up care with attention to early detection and intervention for late effects are essential.

Patients are generally eligible to enter formal long-term follow-up care when the risk for relapse of their primary disease is minimal. For most hematologic malignancies, this occurs when a patient is at least 2 years off therapy. When a patient enters long-term follow-up, the focus of care shifts from vigilant surveillance for disease recurrence to a survivorship model of health maintenance or promotion and management of treatment-related late effects. Effective management of these late effects requires ongoing surveillance, early intervention, and when possible, prevention.

The long-term complications of treatment for which an individual survivor is at risk are determined by several factors, including the patient’s diagnosis, age at treatment, specific chemotherapeutic agents received (including cumulative doses), specific radiation fields and doses, therapy-related complications, degree of psychosocial support received, genetic predisposition, and current health-related behaviors (e.g., diet, physical activity, tobacco, and alcohol use).

Table 44-1 Late Effects Associated With Conventional Therapy for Acute Lymphoblastic Leukemia and Non-Hodgkin Lymphoma

Common Therapeutic Exposures Potential Late Effects
Vincristine Peripheral neuropathy, Raynaud phenomenon
Corticosteroids Cataracts, osteopenia, osteoporosis, avascular necrosis
Asparaginase No known late effects
Mercaptopurine Hepatic dysfunction (rare)
Thioguanine Portal hypertension, hepatotoxicity (when used continuously in maintenance therapy)
Methotrexate (systemic) Osteopenia, osteoporosis, osteonecrosis, renal dysfunction (rare), hepatic dysfunction (rare)
Methotrexate (intrathecal, high-dose), or cytarabine (high-dose) Neurocognitive deficits, clinical leukoencephalopathy
Cranial or craniospinal irradiation Neurocognitive deficits, clinical leukoencephalopathy, cataracts, hypothyroidism, second malignant neoplasm in radiation field (e.g., skin, thyroid, brain), short stature, scoliosis or kyphosis, obesity
Anthracyclines Cardiomyopathy, arrhythmias, subclinical left ventricular dysfunction, secondary AML
Cyclophosphamide Hypogonadism, hemorrhagic cystitis, dysfunctional voiding, bladder malignancy, secondary AML or MDS
Blood products Chronic viral hepatitis, HIV

AML, Acute myeloid leukemia; HIV, human immunodeficiency virus; MDS, myelodysplastic syndrome.

Table 44-2 Late Effects Associated With Conventional Therapy for Acute Myeloid Leukemia

Common Therapeutic Exposures Potential Late Effects
Anthracyclines Cardiomyopathy, arrhythmias, subclinical left ventricular dysfunction, secondary acute myeloid leukemia
Corticosteroids Cataracts, osteopenia, osteoporosis, avascular necrosis
Asparaginase No known late effects
Cytarabine (high dose) Neurocognitive deficits, clinical leukoencephalopathy
Blood products Chronic viral hepatitis, human immunodeficiency virus infection

Table 44-3 Late Effects Associated With Conventional Therapy for Hodgkin Lymphoma

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Common Therapeutic Exposures Potential Late Effects