Reduced-intensity conditioning (RIC) is widely used for allogeneic stem cell transplantation (SCT). Here we present our long-term experience with RIC regimen consisting of fludarabine (30 mg/m2/day on days -10 to -5), busulfan (4mg/kg/day on days -6 and -5) and antithymocyte globulin (ATG Fresenius, 10 mg/kg/day on days -4 to -1) (Flu-Bu-ATG) in a cohort of 71 patients with various hematological malignancies including chronic myeloid leukemia (24 patients), acute myeloid leukemia (19 patients), lymphoma (20 patients), multiple myeloma (3 patients), myelodysplastic syndrome (3 patients), and myelofibrosis (2 patients). The median age was 50 years. The overall response rate was 87%, including 83% CR and 4% PR. The incidence of acute and chronic GVHD was 35% and 52% and the cumulative incidence of non-relapse mortality at 1 year and 4 years was 8% and 14%. With the median follow-up of 55.0 months, the 2- and 4-year event-free survival (EFS) was 49.0% and 40.3%, and the overall survival (OS) was 73.2% and 62.6%, respectively. Gender, age at SCT, type of donor, disease status at SCT, previous autologous transplantation, and complete chimerism by day +100 did not significantly influence EFS and OS. In a multivariate analysis, no presence of chronic GVHD (p=0.029, HR: 2.5),and diagnosis other than CML (p=0.018, HR: 4.6), and CD34+ dose < 5x106/kg (p=0.010, HR: 2.8) were significant predictors of poor OS. Flu-Bu-ATG protocol is a RIC regimen that combines effective disease control with low non-relapse mortality and acceptable toxicity profile. Keywords: reduced-intensity conditioning, fludarabine, busulfan, antithymocyte globulin.
- MeSH
- antilymfocytární sérum terapeutické užití MeSH
- busulfan terapeutické užití MeSH
- časové faktory MeSH
- dospělí MeSH
- hematologické nádory mortalita terapie MeSH
- homologní transplantace MeSH
- imunosupresiva terapeutické užití MeSH
- kohortové studie MeSH
- kombinovaná farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- mladiství MeSH
- mladý dospělý MeSH
- následné studie MeSH
- nemoc štěpu proti hostiteli prevence a kontrola MeSH
- příprava pacienta k transplantaci MeSH
- senioři MeSH
- transplantace hematopoetických kmenových buněk MeSH
- vidarabin analogy a deriváty terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
INTRODUCTION: The reoccurrence or increase in autologous hematopoiesis after allogeneic transplantation has been linked to incipient leukemia relapse. However, the importance of such an emergency regarding microchimerism (i.e. mixed chimerism below 1% of autologous cells) still remains controversial, as fluctuating microchimerism can be observed for a very long time after transplantation. METHODS: Using real-time PCR (RQ-PCR), we compare peripheral blood samples obtained from patients with acute myeloid leukemia (AML) before hematological relapse and those taken during complete remission (i.e. either complete cytogenetic remission or complete molecular remission where applicable). By comparison of these two groups, we describe microchimerism dynamics clearly connected with imminent AML relapse. Additionally, we compare applicability of RQ-PCR and conventional PCR with fragment analysis. RESULTS: Mere reappearance of autologous hematopoiesis within patients with complete donor chimerism is alarming, and another sample with further increase confirms ongoing relapse. In case of patients with continuous microchimerism, another two consecutive samples with increasing trend are required. RQ-PCR predicted a significantly higher number of hematological relapses (87%vs. 39%) with a median anticipation period of 33 days, 26 days earlier than conventional PCR (P= 0.0002). Moreover, the outcome of microchimerism dynamics was in complete agreement with monitoring of minimal residual disease when analyzed from the same cell compartment. CONCLUSION: Within this paper, we emphasize the importance of microchimerism monitoring as a reliable indicator of incipient AML relapse, especially in patients where no other specific molecular marker is available.
- MeSH
- akutní myeloidní leukemie diagnóza genetika MeSH
- dospělí MeSH
- genetické markery MeSH
- genetické testování MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru diagnóza MeSH
- mladý dospělý MeSH
- translokace genetická genetika MeSH
- transplantace hematopoetických kmenových buněk MeSH
- transplantační chiméra genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Vyšetření chimerismu se stalo nedílnou součástí sledování pacientů po alogenní transplantaci krvetvornýchbuněk. Předkládaná publikace nejprve seznamuje s různými metodami jeho stanovení.Ve druhé části je pak detailně uvedena charakteristika metody kapilární elektroforézy s fluorescenčnídetekcí (fragmentační analýzy) produktů amplifikace vysoce polymorfních mikro- a mini- satelitníchoblastí genomové DNA, metody, která je v současnosti považována za „gold standard“ metodu stanovení.
Examination of chimerism has become an integral element of the monitoring of patients after allogenichematopoietic cell transplantation. Presented publication initially describes different methods ofchimerism evaluation. In the second part, there is detailed characterization of the capillary electrophoresiswith fluorescence detection (fragment analysis) of amplification products of high polymorficmicro- and mini- satellite DNA regions, technique, which become the gold standard for quantitativeevaluation.
