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Chronic myeloid leukemia treatment guidelines: Brazilian Association of Hematology, Hemotherapy and Cell Therapy. Brazilian Medical Association Guidelines Project – 2012
Rev Bras Hematol Hemoter. 2012;34(5):367-82
Recommendation:
The monitoring of CML patients
treated with TKIs can be accomplished by bone marrow
cytogenetics and qPCR for the BCR-ABL gene in
peripheral blood, thereby allowing an estimation of
prognosis and the definition of therapeutic strategies.
Mutational analysis should be performed in patients with
suboptimal response or loss of response to TKIs.
When should bone marrow transplantation be
indicated for CML patients?
Imatinibmay be used as treatment for relapse after allogeneic
hematopoietic stem cell transplantation, the prevalence of which
ranges from 40% to 70% at 5 months. In the chronic phase,
the cytogenetic and hematologic response rates obtained and
survival at 9 months are 58%, 84% and 100%, respectively
(93,94)
(B). Imatinib came to be used as first-line treatment in the chronic
phase of CML demonstrating increased survival when used
before bone marrow transplant
(95)
(B).
Due to the lower cost, resistance to imatinib or advanced stages
of the disease (accelerated and blast crisis phases), some series of
cases of transplant in CML have been reported with comparative
results or in association to imatinib, demonstrating similar disease-
free survival, overall survival and cardiotoxicity
(96)
(C).
The previous use (before transplantation) of imatinib in
patients with advanced stages of CML, produces hematological
response in 73% and cytogenetic response in 40% of patients,
and 3 years after the transplant, 66.7% of patients have complete
molecular response
(97)
(C).
In a prospective study, Jiang et al. compared accelerated
phase patients treated either with imatinib (n = 87) or allogeneic
transplantations (n = 54). In this study, multivariate analysis
established hemoglobin < 10.0 g/dL, blasts in peripheral blood ≤
5% and disease duration of less than 12 months as independent
risk factors for survival. High-risk (two risk factors or more)
or intermediate-risk patients (one risk factor) had better overall
survival and progression-free survival with allogeneic transplant.
No difference was seen with low-risk patients
(98)
(BII).
The mortality of CML patients on imatinib treatment
associated to hematopoietic stem cell transplant is 9.7% and the
relapse rate is 5.0% at one year
(99)
(C).
Despite the new options in imatinib-resistant patients,
such as dasatinib and nilotinib, non-comparative case series that
associate TKIs and transplant are still being performed
(100)
(C).
Data are still limited for the pediatric population, but the
results with imatinib are similar to those seen in adults. Millot
et al. published their experience in 44 children with newly
diagnosed CML treated with imatinib. With a median follow-
up of 31 months, the estimated progression-free survival at 36
months was 98%. The rates of complete cytogenetic response
and major molecular response at 12 months were 61% and 31%,
respectively. About 30% of the children discontinued the use of
medication, mainly due to lack of effectiveness. There are adverse
effects of TKIs on the growth of children and this aspect should
be monitored
(101)
(BII).
Moreover, researchers reported the results of a prospective
study involving 200 CML children and adolescents treated by
allogeneic transplantation according to donor availability. The
probability of survival at five years was 87 ± 11% for matched
related donors, 52 ± 9% for matched unrelated donors and 45 ±
16% for unmatched donors. The likelihood of relapse at 5 years
was 20 ± 12%
(102)
(BII).
Recommendation:
Bone marrow transplantation is a
therapeutic option to treat CML but it should be reserved for
cases resistant to TKI treatment and patients in the advanced
stages of the disease after an initial course of TKIs.
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