Biomedical Engineering Reference
In-Depth Information
patient supportive care, including new biologic response modifiers is the mainstay
of therapy. A therapeutic dilemma exists in MDS due to the multifactorial etiopatho-
genesis and various stages of the disease, as well as elderly age of patients at diag-
nosis. The therapeutic approach vary from low-intensity treatment plus supportive
therapy to intensive chemotherapy combined with SC transplant. High-intensity
therapies generally aim to alter the disease's natural history—improving survival,
and decreasing progression to acute leukemia—and are mainly used for high-risk
disease. However, unfortunately most patients with MDS are too old to be consid-
ered for intensive treatment, such as SC transplant [
36
]. In older age comorbidities
are common, so the RIC regimens have been widely used in MDS [
55
] . In a multi-
variate analysis, the 3-year relapse rate was significantly increased after RIC, but
the 3-year non-relapse mortality was decreased [
56
] .
Myeloproliferative Disorders
CML
. CML is a rare disorder with an incidence of 1-2 patients per 100,000 popula-
tion each year. The translocation t(9;22) leads to chromosomal abnormality Ph
chromosome that is present in more than 90% of this patients. Previously, the only
curative option for CML patients was allogeneic SC transplant, and for those unsuit-
able for SC transplant, interferon (IFN)-a with or without cytosine-arabinoside.
Imatinib as tyrosine kinase inhibitor (TKI) is much more superior than previous
therapies in terms of hematological, cytogenetic, and molecular genetic responses
[
57
]. However a significant minority of patients (15-20%) will fail to achieve com-
plete cytogenetic responses, or proportion of 15-20% will lose their response [
58
] .
The allogeneic SC transplant would be second-line therapy for that group of patients
[
59
]. Also, there are the new generations of TKI like nilotinib or dasatinib used in
terms of resistance on first generations of TKI [
60
]. The decision regarding the use
of allogeneic SC transplant must now take into consideration prognostic factors like
age, duration of CML, and nature of donor stem cells, but also the response to TKI.
Within the EBMT recommendations, allogeneic SC transplant from sibling and
well-matched donors remains a standard of care for the chronic and accelerated
phases of CML, representing the only curative treatment for CML. Data relating to
the incidence and risk of relapse after allografting were derived from qualitative
RT-PCR for bcr-abl transcript. But, positive MRD for years post transplant without
clinical progression may not always herald relapse. Donor lymphocyte infusion
(DLI) has become the therapy of choice for patients who relapse after allogeneic SC
transplant, especially for patients transplanted and relapsing in chronic phase [
61
] .
Comparing the use of imatinib to DLI in this group of patients who relapsed after
allogeneic SC transplant (31 pt), molecular remission is even better in the patients
who received TKI [
62
] .
Other myeloproliferative disorders.
In other myeloproliferative disorders (MPD)
including primary osteomyelofibrosis (OMF), myelofibrosis secondary to polycythemia
