Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. To identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. We demonstrate that the causal variant must be at least 91% different in frequency between West Africans and European Americans. An excellent candidate is the Duffy Null polymorphism (SNP rs2814778 at chromosome 1q23.2), which is the only polymorphism in the region known to be so differentiated in frequency and is already known to protect against Plasmodium vivax malaria. We confirm that rs2814778 is predictive of WBC and neutrophil count in African Americans above beyond the previously described admixture association (P = 3.8×10−5), establishing a novel phenotype for this genetic variant.

Success of hematopoietic-cell transplantation (HCT) can vary by race, but the impact of socioeconomic-status (SES) is not known. To evaluate the role of race and SES, we studied 6207 unrelated-donor myeloablative HCT recipients transplanted between 1995–2004 for acute or chronic leukemia or myelodysplastic syndrome. Patients were reported by transplant center to be White (n=5253), African-American (n=368), Asian/Pacific-Islander (n=141), or Hispanic (n=445). Patient income was estimated from residential ZIP Code at time of HCT. Cox-regression analysis adjusting for other significant factors showed that African-American (but not Asian or Hispanic) recipients had worse overall survival (OS) (relative-risk [RR] 1.47 (95% CI 1.29–1.68), P<0.001) compared to Whites. Treatment-related mortality (TRM) was higher in African-Americans (RR 1.56, (1.34–1.83), P<0.001) and in Hispanics (RR 1.30, (1.11–1.51), P=0.001). Across all racial groups, patients with median incomes in the lowest quartile (<$34,700) had worse OS (RR 1.15 (1.04–1.26), P=0.005) and higher risks of TRM (RR 1.21 (1.07–1.36), P=0.002). Inferior outcomes among African-Americans are not fully explained by transplant-related factors or SES. Potential other mechanisms such as genetic polymorphisms that impact drug metabolism or unmeasured co-morbidities, socioeconomic factors and health behaviors may be important. Low SES, regardless of race, has a negative impact on unrelated donor HCT outcomes.

White blood cell count (WBC) is an important clinical marker that varies among different ethnic groups. African Americans are known to have a lower WBC than European Americans. We surveyed the entire genome for loci underlying this difference in WBC by using admixture mapping. We analyzed data from African American participants in the Health, Aging, and Body Composition Study and the Jackson Heart Study. Participants of both studies were genotyped across >or= 1322 single nucleotide polymorphisms that were pre-selected to be informative for African versus European ancestry and span the entire genome. We used these markers to estimate genetic ancestry in each chromosomal region and then tested the association between WBC and genetic ancestry at each locus. We found a locus on chromosome 1q strongly associated with WBC (p < 10(-12)). The strongest association was with a marker known to affect the expression of the Duffy blood group antigen. Participants who had both copies of the common West African allele had a mean WBC of 4.9 (SD 1.3); participants who had both common European alleles had a mean WBC of 7.1 (SD 1.3). This variant explained approximately 20% of population variation in WBC. We used admixture mapping, a novel method for conducting genetic-association studies, to find a region that was significantly associated with WBC on chromosome 1q. Additional studies are needed to determine the biological mechanism for this effect and its clinical implications.

The incidence, clinical features, histogenesis, and treatment of extramammary Paget's disease (EMPD) are reviewed. This unusual skin lesion is associated with an underlying adnexal neoplasm in about 50% of cases. Also, the incidence of distant organ malignancies of EMPD is higher than expected by chance. Even in the absence of a recognizable underlying cancer, EMPD may occasionally produce distant metastases, indicating the malignant potential of this condition. Histochemical, immunohistological, and lectin binding studies demonstrate that the cell of origin of EMPD is the exocrine cell of sweat glands. Although EMPD may arise from eccrine cells, derivation from apocrine cells appears more common. The treatment of the primary lesion, by wide margin excision, is fraught by a high recurrence rate. Chemosurgery may reduce local relapse of EMPD. The value of adjuvant radiation therapy is unestablished. Chemotherapy has induced remission in 2 cases of advanced EMPD and needs testing in clinical trials.

Alternative approaches to the prevention of hemopoietic complications may include more conservative use of growth factors (later initiation of treatment and earlier termination), prophylactic antibiotics in patients at risk for prolonged neutropenia, and biological treatment. Dose-reduction of chemotherapy may lead to inferior outcomes and is not recommended for patients with good functional status.

Aging is associated with a progressive decline in the functional reserve of multiple organ systems, which may lead to enhanced susceptibility to stress such as that caused by cancer chemotherapy. Myelodepression is the most common and the most commonly fatal complication of antineoplastic drug therapy and may represent a serious hindrance to the management of cancer in older individuals. This is already a common and pervasive problem and promises to become more so. Currently 60% of all neoplasms occur in persons aged 65 years and older, and this percentage is expected to increase as the population ages. This well-known phenomenon, sometimes referred to as squaring or the age pyramid, is caused by the combination of an increasing life expectancy and a decreasing birth rate. This article explores the use of hematopoietic growth factors in the older cancer patient after reviewing the influence of age on hemopoiesis and chemotherapy-related complications. The issue is examined in terms of effectiveness and cost. An outline of the assessment of the older cancer patient is provided at the end of the chapter as a frame of reference for clinical decisions.

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