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362 Part V: Therapeutic Principles Chapter 23: Hematopoietic Cell Transplantation 363

such as heart, lung, kidney, and liver disease, is particularly important available, and widely used by cancer patients to combat chemother-
in older patients, and allotransplantation in patients 70 years of age and apy-related nausea and anorexia. Anecdotally, an increasing number
older remains somewhat controversial. Existing data suggest that allo- of patients referred for transplantation consultation are actively using
geneic HCT can be safely performed in selected patients age 60 to 75 marijuana to control these symptoms during their pretransplantation
years, with a 5-year overall survival of 35 percent. 202,203 Some investiga- chemotherapy. Cases of severe or fatal pulmonary aspergillosis from
tors have proposed that age is a poor and imprecise prognostic marker, inhaled spores have been reported in immunosuppressed patients using
and instead advocate the use of comorbidity assessment and scoring to marijuana. 219,220 Transplant center policies regarding medical marijuana
204
determine eligibility for allogeneic HCT. However, caution is war- use and abstinence have lagged behind the rapidly changing legal status
ranted since this approach has not been prospectively validated; retro- of marijuana in the United States, creating a challenge in assessing and
spective cohort studies necessarily suffer severely from patient selection counseling patients.
bias, as they include only those older patients who were deemed appro-
priate candidates to proceed to allogeneic HCT. Outcomes for this
selected group of older patients cannot be generalized to the population DISEASES TREATED WITH
of older adults as a whole. TRANSPLANTATION
In contrast to allogeneic HCT, autologous HCT relies on high-dose
conditioning for its antitumor efficacy. Thus, there is no way to reduce Numerous malignant and nonmalignant hematologic disorders, as well
conditioning intensity without sacrificing some degree of efficacy. As as selected solid tumors, may be treated with HCT. The results obtained
a result, age limitations are often stricter for autologous HCT than for with transplantation are reviewed in detail in the disease-specific chap-
allogeneic HCT, as candidates for the former must be able to tolerate ters of this book, and are discussed only briefly here.
intensive, high-dose chemotherapy. It is unusual for autologous HCT to In general terms, autologous HCT is recommended for patients
be offered to patients older than 75 years of age. 205,206 whose malignancy exhibits chemosensitivity to conventional dose ther-
apy and does not extensively involve the marrow; included are most
lymphomas, germ cell tumors, and other selected pediatric tumors. In
COMORBID MEDICAL CONDITIONS these instances, tumor eradication is a result of dose escalation of cyto-
Comorbid medical conditions have a significant impact on trans- toxic therapy in the conditioning regimen, and the autograft serves as
plantation outcomes. Routine screening of heart and lung function to hematopoietic cell rescue. In contrast, allogeneic transplantation is gen-
detect occult abnormalities is of critical importance, especially in older erally pursued for hematologic malignancies and disorders that primar-
patients. Evaluation of liver and kidney function, as well as exposure to ily originate in the marrow, such as acute and chronic leukemias, aplastic
potential pathogens such as CMV, hepatitides B and C, herpes viruses, anemia, MDSs, and myeloproliferative neoplasms. For some diseases
and HIV are routine and should be performed in all patients. Another with extensive marrow involvement, such as the low-grade lympho-
major factor is the nutritional status of the patient, as extremes such as mas and myeloma, the decision to pursue autologous versus allogeneic
cachexia or obesity require special considerations and adversely impact HCT is more complex. In these settings, allogeneic transplantation has
TRM. 207,208 generally been more successful in controlling disease recurrence and
Several scoring instruments have been devised to allow quantifi- reducing relapse risk. However, the associated risks, including GVHD
cation and comparison of pretransplantation comorbidities. The most and prolonged immunosuppression, result in a higher TRM compared
widely used of these are the EBMT Risk Score, the Pretransplant to autologous HCT. Thus, the decision to pursue an allogeneic or autol-
209
Assessment of Mortality (PAM) score, and the HCT-specific Comor- ogous HCT for patients with these diseases depends on the combination
210
bidity Index (HCT-CI; later modified to incorporate age). 204,211 A num- of patient characteristics such as comorbidities and age, availability of
ber of efforts have been made to validate, revise, or combine these scores a suitable donor, disease-specific characteristics, and often patient pref-
in diverse populations, with variable success. 212–216 Several caveats are erence. For some hematologic conditions, such as MDSs, myeloprolif-
important when considering quantitative scoring of pretransplantation erative neoplasms, and aplastic anemia, only allogeneic transplants are
comorbidities. First, because these scoring instruments were derived generally appropriate.
from retrospective cohorts of patients, they suffer from an inescapable In addition, patients with selected solid tumors, such as testicular
selection bias, as only patients who were deemed fit for transplantation cancer, neuroblastoma, and other pediatric tumors, have had successful
were included in their derivation. This selection bias limits the ability outcomes with autologous HCT. 221–224 Extensive studies in women with
to generalize their use to unselected patient populations. Second, trans- breast and ovarian carcinoma, and more limited studies in patients with
plantation outcomes have not remained stable over time; instead, TRM renal cell carcinoma and small cell lung cancer, have failed to demon-
has steadily decreased over time with the availability of better support- strate a role for HCT. 225,226 Outside of the investigational setting, there
ive care and other refinements. 217,218 Thus, it is conceivable that the rel- are no currently accepted indications for allogeneic HCT to treat non-
ative impacts of specific comorbidities on transplantation outcomes are hematologic solid tumors.
not fixed, but may vary over time. Efforts are currently underway to A variety of congenital and acquired nonmalignant disorders can
prospectively validate these comorbidity scoring instruments. be successfully treated with HCT. The most well-established nonmalig-
Every effort should be made to encourage potential patients to nant indication is for allogeneic HCT in patients with severe aplastic
maintain good health practices, including discontinuation of alcohol anemia, where outstanding results have been achieved, particularly for
use, tobacco smoking, and illicit drug use (if applicable). Centers vary in younger patients with HLA-matched sibling donors, where long-term
their approach to abstinence, but it is common to require that patients disease-free survival rates of 88 to 100 percent have been reported. 227,228
cease all tobacco use permanently as a condition of proceeding to Hematopoietic cell transplantation for patients with clinically signifi-
autologous or, especially, allogeneic HCT. The risk of pulmonary com- cant hemoglobin disorders, such as thalassemia major, has been very
plications from chemotherapy (e.g., BCNU) or from chronic GVHD successful, especially in patients without significant liver disease. 229,230
involving the lung is potentiated by smoking, as is the risk of second- Likewise, allogeneic HCT is considered a treatment option for young
ary cancers of the lung and other organs. A special situation deserv- patients with severe forms of sickle cell disease. 231,232 Guidelines for
ing consideration is the use of marijuana, which is increasingly legal, patient selection and management of patients with thalassemia or sickle

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