Page 1175 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHAPTER 83 Hematopoietic Stem Cell Transplantation for Malignant Diseases 1139

to chemotherapy at the time of transplantation, with relapse HSCT or who are not candidates for auto-HSCT because of
the major cause of treatment failure. The Parma randomized aggressive, chemotherapy-refractory disease.
trial for high-dose therapy followed by auto-HSCT reported
a significantly higher event-free survival for patients treated Solid Tumors
with auto-HSCT than for the group receiving standard-dose Skin and colonic mucosa are primary targets of both acute and
treatment (46% vs 12%). Furthermore, it is notable that no cGvHD, and this would suggest that allo-HSCT would be effective
patients assigned to the conventional-dose salvage therapy therapy in the treatment of cancers of these organs. Yet allo-HSCT
could be rescued at the time of the second relapse with delayed is not effective in the control of these cancers, illustrating the
transplantation. The efficacy of auto-HSCT is diminished discrimination between target antigens of normal tissues of GvH,
for patients previously treated with rituximab, an anti–B-cell such as the colonic crypt cells, compared with antigens expressed
chimeric antibody, and who relapse within 12 months of by tumors derived from these tissues targeted by GvT. With the
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initial therapy. Other circumstances, in which HSCT may be exception of allo-HSCT in the treatment of renal cell cancer, in
indicated, include HSCT for patients who respond slowly to which a GvT effect was seen to be clinically evident in some but
initial therapy, have high-risk disease, are resistant to initial not all studies, transplantation in the treatment of solid tumors,
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therapy, or are in relapse with chemotherapy-insensitive disease. such as neuroblastoma, Wilm tumor, and germ cell tumors, is
Results for patients with truly chemotherapy-refractory disease limited to auto-HSCT with one or more cycles of dose-intensive
are, however, poor, and such patients should be considered for chemotherapy.
allo-HSCT.
Mantle cell lymphoma is known for its unremitting clinical FUTURE DIRECTIONS
course when treated conventionally and has proven relatively
resistant to dose-intensive treatment, especially when used for Advances in HLA typing, chemotherapy conditioning regimens,
management of relapsed disease. Mantle cell NHL appears to supportive care, and our understanding of the biology of the
be very sensitive to the GvT effect of allo-HSCT allowing treat- HvG and GvH reactions have greatly reduced the toxicity of
ment with reduced-intensity regimens. both auto-HSCT and allo-HSCT. Although the diseases treat-
Burkitt lymphoma, Burkitt-like lymphomas, and lymphoblastic able with HSCT are those characterized by dose sensitivity,
lymphomas are high-grade NHLs associated with relatively poor currently available dose-intensive conditioning regimens have
long-term survival rates. The role of both auto-HSCT and allo- been pushed to maximal tolerable doses. Newer approaches
HSCT in these disorders remains unclear. There are no convincing to the treatment of these malignancies will likely include the
risk models that identify clear indications for transplantation as addition of therapies that target the malignancy, such as radioim-
part of the initial therapy. The lack of an obvious GvT effect in munoconjugates that will add minimal toxicity to other organs.
these disorders suggests that auto-HSCT can provide a reasonable The availability of reduced-intensity regimens permits tandem
treatment. Transplantation registry data suggest that disease status transplantation, using dose-intensive therapy with auto-HSCT to
at the time of transplantation is the most important predictor achieve maximal tumor-cell debulking, followed, after recovery
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of outcome in patients with high-grade disease. T-cell lym- from transplantation-related toxicities, by Allo-HSCT, using a
phomas are less common than B-cell lymphomas. There is no reduced-intensity regimen to achieve an immunological GvT
well-defined management strategy for these disorders, and effect. Advancements in the field of haploidentical HSCT have
treatment is based on the disease stage and immunopathological facilitated immediate availability of donors for patients with
grade. Disease control with T cell–type treatment regimens, high-risk malignancies when selection of unrelated donors is
compared with the more common B cell–type treatment regimens, limited by ethnicity and time constraints. Finally, the ability to
is lower, although the comparison may not be appropriate, as use HSCT as a platform for protein- or cellular-based vaccination
T-cell diseases present at more advanced stages compared with strategies is the subject of considerable interest.
B-cell diseases. The GvT effect may be more evident in T-cell
NHL, particularly for virus-associated NHL, and allo-HSCT is ON THE HORIZON
the preferred treatment for some patients.
Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Hodgkin Lymphoma Development of donor selection algorithms
Many patients with Hodgkin lymphoma will achieve durable Strategies to maximize graft-versus-tumor (GvT) effect
Advent of haploidentical HSCT allows for easy donor availability
remissions with nontransplantation chemotherapy and/or radia- Refining haploidentical HSCT techniques for different diseases and use
tion therapy, and algorithms for staging and treatment of this of KIR testing for donor selection
disease are well defined. Dose-intensive therapy with auto-HSCT Combination conditioning regimens
is available to those patients who do not achieve a remission or Developing regimens with lower toxicities
who relapse after initial therapy. The outcome for patients whose Posttransplantation maintenance/treatment
remission lasted <1 year is dismal with standard dose second-line Posttransplantation maintenance/treatment for high risk of relapse after
HSCT
treatments, and approximately 40–50% of patients with Hodgkin Immune effector cell therapies
lymphoma who suffer a relapse within 1 year will achieve durable Platform for other treatments; chimeric antigen receptor (CAR) T–cell
remissions after auto-HSCT. This approach can also overcome therapy, checkpoint inhibitor blockade
drug resistance and lead to an overall survival rate of 34–50%
for patients with chemotherapy-refractory disease. Autologous HSCT
Allo-HSCT is not the first choice for the treatment of relapsed Tumor-specific conditioning regimens
Hodgkin lymphoma because of the higher transplantation-related Improve ratio of toxicity to tumor-cell cytotoxicity
complications despite the evidence of an effective GvT effect. Posttransplantation vaccination strategies
Checkpoint inhibitor blockade in clinical trials for high-risk malignancies
Allo-HSCT is offered to patients who suffer relapse after auto-