Biomedical Engineering Reference
In-Depth Information
center with major experience in SC transplants. It encompasses many rare disorders
and the paucity of data relating to transplant, variability in transplant procedures,
and contribution of many patient risk factors such as co-morbidities. The third
category incorporate developing SC transplants with little experience, like in some
autoimmune diseases. Finally, generally non-recommended category includes SC
transplant in early stages of disease when results of conventional treatment do not
normally justify the additional risk of transplant-related mortality (TRM), or when
the disorder is so advanced that the chance of success is too small (blast crisis of
chronic myeloid leukemia (CML)).
Acute Leukemia
Acute myeloid leukemia (AML)
. AML is a heterogeneous clonal disease of
hematopoietic progenitor cells which lose the ability for differentiation and for
response to normal regulators of proliferation. Induction chemotherapy is necessary
to induce complete remission (CR) in AML. Postinduction chemotherapy is aimed
to eradicate/reduce residual disease. Combined chemotherapy induces CR in an
average 60-80% of adult patients aged less than 60 years. After achieving remis-
sion, further chemotherapy is needed to prevent disease relapse. Postremission ther-
apy for patients under the age 60 includes chemotherapy or SC transplant. Generally,
SC transplant is performed after two or three cycles of chemotherapy. Patients are
stratified into three main risk factors based on cytogenetics, molecular biology, and
response to induction chemotherapy. About 40-50% adult AML patients have nor-
mal karyotype as intermediate risk factor. Unfavorable prognosis is associated with
several entities including Wilms tumor gene 1, bcl-2, bax, the brain and acute leu-
kemia cytoplasmic gene (BAALC), FMS-like tyrosine kinase-3 (FLT3), and mixed
lineage leukemia gene (MLL). Some mutations of specific genes confer a more
favorable prognosis, like mutations in the CCAT enhancer binding protein-a (C/
EBP-a), CEBPA, and nucleophosmin NPM1 [
50
] .
Concerning autologous SC transplant, better outcome is achieved when cells are
harvested after the second or third course of chemotherapy. There are several advan-
tages over allogeneic SC transplant due to unnecessary matched donor and lack of
risk of complications such as graft versus host disease (GvHD). Also, immunologi-
cal reconstitution is much faster and more complete. The major disadvantages are
higher relapse rate due to lack of GvL effect and the contamination of graft with
leukemic cells. In high-risk AML the role of autologous SC transplant is minimal,
since the final clinical outcome is poor. The data of the Acute Leukemia Working
Party (ALWP) registry indicate results as follows: leukemia-free survival (LFS)
43%, overall survival (OS) 51%, and response rate (RR) 53% [
51
] .
Allogeneic SC transplant has had an extreme relevance in AML, since so many
patients have been cured. In the last 10 years it has been shown that the results of
MUD transplants as well as the results of cord blood transplantations are improved.
