Late Complications of Hematologic Diseases and Their Therapies

Published on 04/03/2015 by admin

Filed under Hematology, Oncology and Palliative Medicine

Last modified 22/04/2025

Print this page

This article have been viewed 1352 times

Chapter 44 Late Complications of Hematologic Diseases and Their Therapies

Wendy Landier, Smita Bhatia

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 solving ¹; memory impairment²^–⁵; problems with executive functioning and processing speed³; and cognitive impairment.¹^–³ 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

Common Therapeutic Exposures	Potential Late Effects
Anthracyclines	Cardiomyopathy, arrhythmias, subclinical left ventricular dysfunction, secondary AML or MDS
Corticosteroids	Cataracts, osteopenia, osteoporosis, avascular necrosis
Bleomycin	Pulmonary dysfunction
Vincristine, vinblastine	Peripheral neuropathy, Raynaud phenomenon
Procarbazine, mechlorethamine, dacarbazine	Hypogonadism, infertility, secondary AML or MDS
Cyclophosphamide	Hypogonadism, infertility, hemorrhagic cystitis, dysfunctional voiding, bladder malignancy, secondary AML or MDS
Mantle irradiation	Hypothyroidism, premature cardiovascular disease, cardiac valvular disease, cardiomyopathy, arrhythmias, carotid artery disease, scoliosis or kyphosis, second malignant neoplasm in radiation field (e.g., thyroid, breast), pulmonary dysfunction
Inverted Y irradiation	Hypogonadism, infertility, adverse pregnancy outcome, second malignant neoplasm in radiation field (e.g., gastrointestinal)
Splenectomy	Acute life-threatening infections
Blood products	Chronic viral hepatitis, HIV

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

Late Effects Research: What Is Needed

Major Clinical and Research Challenges

Cancer survivorship research continually changing because of new:

Therapeutic agents or combinations of agents

Radiation oncology techniques

Surgical procedures

Supportive care techniques

Future Directions

Much of the available information relates to outcomes within the first decade after treatment, and only minimal data address the longer-term outcomes that may occur later.

Research is needed to more clearly define the survivors at greatest risk for specific outcomes.

Research is needed to identify genetic predispositions to certain key outcomes and the roles of gene-environment interactions.

Research is needed to identify the role of lifestyle choices (e.g., alcohol, tobacco, diet, exercise) in terms of modification of the risks for these late outcomes.

Research is needed to understand the potential long-term impact of cancer therapy to effectively counsel survivors and offer effective intervention strategies to prevent or minimize the impact of adverse late effects.

Interventions are needed to include scientifically valid, evidence-based recommendations for clinical follow-up of survivors, which should include screening for potential late effects and application of proven approaches for health promotion.

Figure 44-1 ANNUAL COMPREHENSIVE MULTIDISCIPLINARY HEALTH EVALUATION FOR THE CANCER SURVIVOR.

Table 44-4 Comprehensive Treatment Summary

Topic	Specific Information to Include
Demographics	Name
	Record number or patient identification number
	Date of birth
	Sex
	Race or ethnicity
Diagnosis	Date or age at diagnosis
	Referring physician or institution
	Treating physician or institution
	Presenting symptoms
	Past medical history
	Family history (including cancer in first- or second-degree relatives)
	Physical examination findings at presentation
	Initial diagnostics (complete blood cell count, chemistry panel, radiographic studies)
	Diagnostic procedures (biopsies, cytologic studies)
	Pathology (morphology, histology, cytochemistry, flow cytometry)
	Cytogenetics
	Central nervous system status (if applicable)
	Stage (if applicable)
	Metastatic sites (if applicable)
	Initial response to therapy (e.g., rapid early response [RER], slow early response [SER], date first complete remission achieved)
	Relapse(s) dates, age at relapse(s), relapse site(s)
Treatment	Date of initial treatment (initiated and completed)
	Date(s) for treatment of relapse (initiated and completed)
	Final off-therapy date
	Chemotherapy agents received, including route of administration (list all)
	Cumulative doses (in mg/m²) and age at treatment for all alkylators, anthracyclines, and heavy metals
	Dose ranges for cytarabine and methotrexate (e.g., standard dose versus high dose >1000 mg/m²)
	Radiation fields, doses, shielding, age at treatment
	Surgical procedure(s)
	Transfusion(s), including all blood or serum products
	Stem cell transplantation(s), including donor source, preparative regimen, GVHD prophylaxis or treatment
Acute complications	Significant therapy-related complications (e.g., tumor lysis, septic shock, typhlitis, acute GVHD)
	Significant treatment required for complications (e.g., hemodialysis, amphotericin, aminoglycosides)
Complications after therapy	Significant complications after completion of therapy (e.g., herpes zoster, acute life-threatening infection after splenectomy)

GVHD, Graft-versus-host disease.

Modified from Children’s Oncology Group Summary of Cancer Treatment, 2008. http://www.survivorshipguidelines.org.

Table 44-5 Monitoring for Potential Late Effects

AFP, α-Fetoprotein; ALT, alanine aminotransferase; AML, acute myeloid leukemia; AST, aspartate aminotransferase; BMI, body mass index; BP, blood pressure; BUN, blood urea nitrogen; CBC, complete blood cell count; CT, computed tomography; DEXA, dual-energy x-ray absorptiometry; ECG, electrocardiogram; ECHO, echocardiogram; FSH, follicle-stimulating hormone; GFR, glomerular filtration rate; GVHD, graft-versus-host disease; HCT, hematopoietic cell transplantation; HCV, hepatitis C virus; HIB, Haemophilus influenzae type B; HIV, human immunodeficiency virus; LH, luteinizing hormone; MRI, magnetic resonance imaging; NHL, non-Hodgkin lymphoma; PCR, polymerase chain reaction; T₄, thyroxine; TBI, total body irradiation; TSH, thyroid-stimulating protein; yr, year.

Modified from Children’s Oncology Group: Long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers, version 3.0, 2008, Children’s Oncology Group. http://www.survivorshipguidelines.org.

References

1 Andrykowski MA, Altmaier EM, Barnett RL, et al. Cognitive dysfunction in adult survivors of allogeneic marrow transplantation: Relationship to dose of total body irradiation. Bone Marrow Transplant. 1990;6:269.

2 Andrykowski MA, Schmitt FA, Gregg ME, et al. Neuropsychologic impairment in adult bone marrow transplant candidates. Cancer. 1992;70:2288.

3 Harder H, Cornelissen JJ, Van Gool AR, et al. Cognitive functioning and quality of life in long-term adult survivors of bone marrow transplantation. Cancer. 2002;95:183.

4 Syrjala KL, Dikmen S, Langer SL, et al. Neuropsychologic changes from before transplantation to 1 year in patients receiving myeloablative allogeneic hematopoietic cell transplant. Blood. 2004;104:3386.

5 Meyers CA, Weitzner M, Byrne K, et al. Evaluation of the neurobehavioral functioning of patients before, during, and after bone marrow transplantation. J Clin Oncol. 1994;12:820.

6 Padovan CS, Yousry TA, Schleuning M, et al. Neurological and neuroradiological findings in long-term survivors of allogeneic bone marrow transplantation. Ann Neurol. 1998;43:627.