Asthma management: A new phenotype-based approach using presence of eosinophilia and allergy.

Asthma is a heterogeneous disease. The Czech Pneumology and Allergology Societies commissioned 10 experts to review the literature and create joint national guidelines for managing asthma, reflecting this heterogeneity. The aim was to develop an easy-to-use diagnostic strategy as a rational approach to the widening opportunities for the use of phenotype-targeted therapy. The guidelines were presented on websites for public comments by members of both the societies. The reviewers' comments contributed to creating the final version of the guidelines. The key hallmark of the diagnostic approach is the pragmatic concept, which assesses the presence of allergy and eosinophilia in each asthmatic patient. The guidelines define three clinically relevant asthma phenotypes: eosinophilic allergic asthma, eosinophilic nonallergic asthma and noneosinophilic nonallergic asthma. The resulting multifunctional classification describing the severity, level of control and phenotype is the starting point for a comprehensive treatment strategy. The level of control is constantly confronted with the intensity of the common stepwise pharmacotherapy, and the concurrently included phenotyping is essential for phenotype-specific therapy. The concept of the asthma approach with assessing the presence of eosinophilia and allergy provides a way for more precise diagnosis, which is a prerequisite for using widening options of personalized therapy.

Long-term follow-up of chimerical state of the patients transplanted for different haematologic diseases.

Long-term follow-up of peripheral cellular chimerism in patients treated with BMT or PBSCT revealed the usefulness of their continuous monitoring at molecular level. Our results are based on monitoring of 120 patients, who were followed for at least 24 months. Comparison of the patients treated for chronic myelogenous leukemia (CML), acute myelocytic leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndromes (MDS) and aplastic anaemia (AA) revealed that mixed chimerism was practically absent in MDS and relatively long-lasting in ALL and AA (regardless to substantially different post-transplantation treatment). The first disease relapses signalized by molecular checking of mixed peripheral chimerism were observed also after a period of remission lasting for several years. Molecular watching enables us to detect relapses at their very beginning that would remain hidden to less sensitive methods. We believe that all of the transplanted patients ought to be monitored for residual disease i.e. cellular chimerism using molecular methods without time limits. On the other hand low level of mixed cellular chimerism is not necessarily a sign of disease progression and can remain unchanged as "status quo" for a very long period.

Prediction and reversion of post-transplant relapse in patients with chronic myeloid leukemia using mixed chimerism and residual disease detection and adoptive immunotherapy.

In the prospective study, we examined hematopoietic mixed chimerism (using polymerase chain reaction (PCR) of variable number of tandem repeat-VNTR sequences) and minimal residual disease (MRD) status (using qualitative and in the case of positivity quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for the BCR/ABL fusion mRNA) in serial peripheral blood samples taken from 25 patients after bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). Increasing mixed chimerism in correlation with increasing signal of MRD was detected in 10 patients. In two patients mixed chimera status and BCR/ABL rearrangement led to hematologic relapse, in five patients molecular relapse was followed by reappearance of Ph chromosome and three patients developed molecular relapse only. Adoptive immunotherapy-donor lymphocyte infusion (DLI), interferon (INF) and discontinuation of post-transplant immunosupression-separately or in different combinations was used in nine patients with molecular, cytogenetic or hematologic relapse of CML. The results demonstrate that significant response at the molecular level can be achieved for a majority of CML patients and that using of all forms of adoptive immunotherapy controlled by MC and MRD is more efficient in patients treated in early molecular relapse-with minimal disease burdens.

[DNA polymorphism, allogenic bone marrow transplantation and peripheral cell chimerism]. / DNA polymorfismy, alogenní transplantace kostní drene a periferní bunecný chimérismus.

BACKGROUND: Bone marrow transplantation or transplantation of peripheral stem cells is an effective treatment of a number of diseases. Its increasing success and expanding use in associated with the development of molecular diagnostic methods which enable to follow up the graft from its engraftment in a recipient and then during the whole posttransplantation period at the level extremely small numbers of cells. METHODS AND RESULTS: In peripheral blood of patients, genotypes of the following loci were examined by polymerase chain reaction (PCR): APOB, COL2A1, D17S20, D1S80, HVR/1G, SRY and AMXY. Technique of restriction analysis was used for loci DXYS20 and DXYS75. 1. The first signs of donor bone marrow activity were observed in 50% of patients already at the beginning of the second week after transplantation, while in the second half of patients increasing number of donor cells in peripheral blood was noticed in the second and third week. 2. Engraftment with full and permanent substitution of own bone marrow without presence of recipients cells in peripheral blood--complete chimerism--was achieved only in a part of patients (cca 50%). 3. Peripheral blood of other patients did not contain only donor cells but also recipients cells--mixed chimerism. With regard to its onset, the authors have divided mixed chimerism into early and late, taking into account that some patients can develop both types. In patients under study, early chimerism was found more frequently, which apparently resulted from a shorter period of observation of lately transplanted patients. 4. In cases of oncohaematologic patients, which allowed to study specifically the presence of a pathologic clone, the follow-up of chimerism enabled to distinguish between relapse of the original disease and "biologic" recovery--resurrection of original disease-free haematopoiesis. 5. Regression of mixed chimerism was supposed to be the result of treatment focused at the original disease (CML), in some patients, however, it was a spontaneous process. CONCLUSIONS: Follow-up of cellular chimerism in transplanted patients by means of molecular genetic methods provides substantial information about patient's shape which can be utilized it is necessary to decide on treatment procedures. For this reason it is desirable that examination of chimerism by molecular methods should form integral part of care of these patients.