# 30 - SECTION 2 Hematopoietic Disorders

## SECTION 2 Hematopoietic Disorders

traditionally been performed by oncologists, but the magnitude of the 
problem mandates that primary care providers and preventive medi­
cine specialists be trained in the follow-up of treated cancer patients 
in remission or undergoing chronic therapy. All former cancer patients 
should undergo surveillance for recurrence and second malignancies 
and be monitored for long-term effects of treatment; however, nearly 
all recurrences are detected because of symptoms. Health promotion 
and disease prevention with age- and sex-specific routine screening 
tests (e.g., colonoscopy, Pap smears, mammography, human papillo­
mavirus vaccination, dual-energy x-ray absorptiometry scans) should 
be a focus of survivorship care along with psychosocial well-being. 
Annual mammography should start no later than 10 years after breast 
radiation. Patients receiving radiation fields encompassing thyroid tis­
sue should have regular thyroid examinations and TSH testing. Local­
ized pain or palpable abnormality in a previously radiated field should 
prompt radiographic evaluation. Patients treated with alkylating agents 
or topoisomerase inhibitors should have a complete blood count every 
6–12 months, and cytopenias, abnormal cells on peripheral smear, or 
macrocytosis should be evaluated with bone marrow biopsy and aspi­
rate and include cytogenetics, flow cytometry, or fluorescence in situ 
hybridization (FISH) studies as appropriate.

As the population of cancer survivors increases and patients live 
longer, cancer survivorship has become increasingly important, and 
the Institute of Medicine and National Research Council have pub­
lished a monograph entitled From Cancer Patient to Cancer Survivor: 
Lost in Transition. The monograph proposes a plan that would inform 
clinicians caring for cancer survivors of the complete details of patients’ 
previous treatments, complications thereof, signs and symptoms of late 
effects, and recommended screening and follow-up procedures.
PART 4
Oncology and Hematology
OUTLOOK
Survivorship care is a burgeoning problem facing oncologists today. 
The challenge is to develop cancer treatments that maximize clini­
cal benefit including cure of disease while also mitigating the risks 
of long-term toxicity. As cancer treatments continue to improve, the 
prevalence of cancer survivors increases along with an increase in life 
expectancy. Further, since emerging therapies often have improved 
tolerability profiles, a greater number of patients with advanced age or 
comorbid medical conditions will become cancer survivors with per­
sistent treatment-related toxicities. As treatment paradigms continue to 
evolve, the nature and biologic basis for toxicities will change and phar­
macovigilance of new therapies is critical. Advances in genomic medi­
cine may allow for more risk-stratified personalized care. The choice of 
therapy needs to be tailored to the type of cancer, expected outcomes, 
and patient-related risk factors for both acute and long-term toxicities. 
After therapy is complete, longitudinal monitoring of the health and 
health-related quality of life of cancer survivors is critical since the inci­
dence of late effects of treatment does not appear to plateau over time.
Acknowledgment
We would like to acknowledge the contribution of Carl E. Freter who 
coauthored a previous version of this chapter; material from his chapter 
was retained in this version.
■
■FURTHER READING
Armenian SH et al: Cardiovascular disease in survivors of childhood 
cancer: Insights into epidemiology, pathophysiology, and prevention. 
J Clin Oncol 36:2135, 2018.
Brinkman TM et al: Psychological symptoms, social outcomes, 
socioeconomic attainment, and health behaviors among survivors 
of childhood cancer: Current state of the literature. J Clin Oncol 
36:2190, 2018.
Chow EJ et al: New agents, emerging late effects, and the development 
of precision survivorship. J Clin Oncol 36:2231, 2018.
Ehrhardt MJ et al: Health care transitions among adolescents and 
young adults with cancer. J Clin Oncol 42:743, 2024.
Lustberg MB et al: Mitigating long-term and delayed adverse events 
associated with cancer treatment: Implications for survivorship. Nat 
Rev Clin Oncol 20:527, 2023.

Rowland JH et al: Survivorship science at the NIH: Lessons learned 
from grants funded in fiscal year 2016. J Natl Cancer Inst 111:109, 
2019.
Shapiro CL: Cancer survivorship. N Engl J Med 379:2438, 2018.
Shapiro CL et al: ReCAP: ASCO core curriculum for cancer survivor­
ship education. J Oncol Pract 12:e08, 2016.
Shree T et al: Impaired immune health in survivors of diffuse large 
B-cell lymphoma. J Clin Oncol 38:1664, 2020.
Turcotte LM et al: Risk, risk factors, and surveillance of subsequent 
malignant neoplasms in survivors of childhood cancer: A review. J Clin 
Oncol 36:2145, 2018.
Section 2	 Hematopoietic Disorders
David T. Scadden, Dan L. Longo

Hematopoietic Stem 

Cells
All of the cell types in the blood and some cells in every tissue of the 
body are derived from hematopoietic (hemo: blood; poiesis: creation) 
stem cells. If the hematopoietic stem cell is damaged and can no longer 
function (e.g., due to a nuclear accident), a person would survive 
2–4 weeks in the absence of extraordinary support measures. With the 
clinical use of hematopoietic stem cells, tens of thousands of lives are 
saved each year (Chap. 119). Stem cells produce hundreds of billions 
of blood cells daily from a stem cell pool that is estimated to be only 
20,000–200,000. How stem cells do this, how they persist for many 
decades despite the production demands, and how they may be better 
used in clinical care are important issues in medicine.
The study of blood cell production has become a paradigm for how 
other tissues may be organized and regulated. Basic research in hema­
topoiesis includes defining stepwise molecular changes accompanying 
functional changes in maturing cells, aggregating cells into functional 
subgroups, and demonstrating hematopoietic stem cell regulation by 
a specialized microenvironment; these concepts are worked out in 
hematology and offer models for other tissues. Moreover, these con­
cepts may not be restricted to normal tissue function but extend to 
malignancy.
CARDINAL FUNCTIONS OF 
HEMATOPOIETIC STEM CELLS
All stem cell types have two cardinal functions: self-renewal and dif­
ferentiation (Fig. 101-1). Stem cells exist to generate, maintain, and 
repair tissues. They function successfully if they can replace a wide 
variety of shorter-lived mature cells over prolonged periods. The pro­
cess of self-renewal (see below) assures that a stem cell population can 
be sustained over time. Without self-renewal, the stem cell pool would 
become exhausted and tissue maintenance would not be possible. The 
process of differentiation leads to production of the effectors of tissue 
function: mature cells. Without proper differentiation, the integrity of 
tissue function would be compromised and organ failure or neoplasia 
would ensue.
In the blood, mature cells have variable average life spans, ranging 
from hours for mature neutrophils to a few months for red blood cells 
to many years for memory lymphocytes. However, the stem cell pool is 
the central, durable source of all blood and immune cells, maintaining 
a capacity to produce a broad range of cells from a single cell source, 
yet keeping itself vigorous over decades of life. As an individual stem 
cell divides, it has the capacity to accomplish one of three division 
outcomes: two stem cells, two cells destined for differentiation, or one 
stem cell and one differentiating cell. The former two outcomes are the