Page 1174 - Clinical Immunology_ Principles and Practice ( PDFDrive )

1138 PART NINE Transplantation

DLI. CML is a stem cell disease, and the collection of normal melphalan with auto-HSCT can achieve about a 40% complete
HSCs is unlikely for most patients, precluding auto-HSCT. Of response rate. Tandem auto-HSCT with two cycles of dose-
speculative interest is the collection of autologous cells after intensive therapy at 2- to 6-month intervals can improve progres-
cytogenetic remission is achieved with the use of a TK inhibitor, sive free survival and in some studies, overall survival. This
for subsequent use at the time of disease relapse. approach to treatment is still debated. Ultimately, most patients
experience relapse and succumb to the disease. Although auto-
Myeloproliferative Diseases HSCT is not considered curative for this disease, the median
MPDs are clonal stem cell diseases and include CML (discussed duration of time without treatment is 2–3 years, and ≈15% of
above), polycythemia vera, primary myelofibrosis, essential patients may not need treatment for progressive disease for 5
thrombocytosis, chronic myelomonocytic leukemia, and MPD years or longer, which greatly improves their quality of life.
not otherwise characterized. These disorders display overlapping Allo-HSCT with use of a reduced-intensity conditioning regimen
clinical features and may also show features more characteristic decreases the risk of TRM to <10%, but patients with advanced
of MDS, but they exhibit different natural histories and different disease are unlikely to respond to this treatment. The lower risk
therapeutic requirements. Allo-HSCT is effective in ablating the of complications with nonmyeloablative conditioning regimens
abnormal clone in these disorders. The timing of treatment is has led to studies of tandem auto-HSCT, using an intensive
important because of the frequently long natural history of these chemotherapy regimen to achieve tumor debulking, followed
diseases. Anemia, older age, and cytogenetic abnormalities all 2–6 months later by allo-HSCT using a reduced-intensity regimen
predict poor survival in primary myelofibrosis, suggesting that to achieve the GvT effect. This approach to the treatment of
patients with anemia and an abnormal karyotype should proceed MM is being studied in large multicenter trials, with some studies
to allo-HSCT. showing a survival advantage for recipients of allo-HSCT.
Acute Lymphoblastic Leukemia Non-Hodgkin Lymphoma
In contrast to treatment of the pediatric patient with ALL The lymphomas (Chapter 79) represent a diverse group of
(Chapter 78), only very few adults with ALL are cured with malignant diseases of B and T lymphocytes, comprising some
nontransplantation induction and consolidation regimens. As of the slowest- to the fastest-growing human malignancies, with
with AML, adverse risk features include certain cytogenetic a range of curability achieved by nontransplantation therapies.
changes and the inability to achieve remission with initial induc- As a group, the lymphomas exhibit a strong dose–response
tion chemotherapy. Allo-HSCT in first remission is clearly effective relationship to chemotherapy or radiotherapy, and the benefit
in the management of patients with defined adverse risk cyto- of dose-intensive treatment with auto-HSCT has been well
genetics, such as translocation involving chromosome 4 and 11, established. Auto-HSCT avoids the morbidity of allo-HSCT and
or 9 and 22 (Philadelphia chromosome). Recent randomized is the preferred approach for the majority of patients, with some
studies also demonstrate a survival advantage for patients who prominent exceptions discussed below. Popular chemotherapy
have intermediate risk of disease and are undergoing allo-HSCT, regimens include cyclophosphamide, BCNU, and etoposide (CBV)
especially since current salvage regimens for patients in relapse or BEAM (BCNU, etoposide, cytarabine, and melphalan).
have a very low likelihood of achieving a second remission. There However, no single chemotherapeutic or radiation-based regimen
is little evidence to support the effectiveness of auto-HSCT despite has emerged as a superior treatment.
its theoretical potential.
Low-Grade NHL
Chronic Lymphocytic Leukemia Low-grade NHL, in general, exhibits a variable and prolonged
Many patients and physicians are reluctant to support aggressive natural course, with many patients not requiring treatment until
treatment of CLL with allo-HSCT because of the frequently symptoms or organ toxicity appear. Therefore most of the experi-
indolent nature and long natural history of this disease, as well ence with HSCT has been in patients after initial relapse rather
as the advanced age of most patients at time of diagnosis. Yet than at the time of initial diagnosis. Few randomized studies
disease progression is inevitable, and the aggressiveness of this comparing auto-HSCT with nontransplantation therapies for
disease can be predicted by various features, including chromo- patients have been reported. A number of phase II and registry
some 17p and 11q deletions and detection of ZAP-70 mutation data have been published for auto-HSCT, and although response
and CD38 expression. Therefore HSCT should be considered a rates are high, a continuing pattern of relapse has been observed.
treatment choice, especially for younger patients or those with In contrast, patients who undergo allo-HSCT experience a higher
adverse risk features. probability of TRM but a lower risk of relapse after transplanta-
The exquisite sensitivity of the CLL cells to the GvT effect tion. Indolent B-cell NHL, similar to other low-grade diseases,
allows for the use of reduced-intensity regimens with lower risks such as CLL, appears to be very sensitive to the GvT effect of
of regimen-related mortality in these, generally, older patients. allo-HSCT, and using reduced-intensity regimens will result in
Durable control of disease can be achieved for about 50% of lower transplantation-related complications. The difference in
patients. The extensive infiltration of bone marrow by malignant relapse rates between auto-HSCT and allo-HSCT could result
lymphocytes and the lack of the GvT effect preclude auto-HSCT. from the possible reintroduction of lymphoma cells in the HSC
In the few clinical studies that have been reported, high CR product but is more likely from the lack of a GvT effect of
responses have been obtained with auto-HSCT, but relapses were auto-HSCT.
the frequent cause of treatment failure.
Aggressive NHL
Multiple Myeloma Auto-HSCT is the standard of care for patients with B-cell NHL
MM is a malignancy of plasma cells (Chapter 80), with a median in first “chemotherapy-sensitive” relapse. The success of this
patient age of 65 years at time of diagnosis. In MM, dose-intensive therapy reflects the extent and the responsiveness of the disease