[Chronic myelogenous leukemia: diagnosis and treatment]. / A krónikus myeloid leukaemia korszeru diagnosztikája és kezelése.

Chronic myelogenous leukemia is a clonal myeloproliferative neoplasm caused by reciprocal translocation involving chromosomes 9 and 22 resulting in the expression of a constitutively activated BCR-ABL1 tyrosine kinase that leads to the malignant transformation of the hematopoietic stem cells. The condition was previously known as a relentlessly progressive disease, but the treatment was revolutionalized by the efficacy of tyrosine kinase inhibitors. Therapeutic success is thus currently determined by the depth of molecular response achieved on therapy. Multiple tyrosine kinase agents are available even for the first line treatment. This guideline summarizes current focal points of the treatment of chronic myelogenous leukemia specific to Hungary and provides definitions for optimal molecular responses in this condition. Orv. Hetil., 2016, 157(37), 1459-1468.

First and second line imatinib treatment in chronic myelogenous leukemia patients expressing rare e1a2 or e19a2 BCR-ABL transcripts.

During the formation of the Philadelphia (Ph) chromosome, in the majority of chronic myelogenous leukemia (CML) patients, the chromosome 22 breakpoint is located in the major breakpoint cluster region of the BCR gene (M-bcr). Minor and micro breakpoint cluster regions (m-bcr with e1a2 transcript and micro-bcr with e19a2 transcript) are rarely affected and have been suggested to be associated with peculiar CML phenotypes. Despite the different clinical characteristics, it is currently not established, whether different therapeutic options are preferably recommended for the treatment of e1a2 or e19a2 CML. Here we report two patients with e1a2 and one patient with e19a2 translocations, treated with different approaches including imatinib. First and second line imatinib treatments induced haematologic response in all of the three patients, and major cytogenetic response in one patient with e1a2, as well as in the patient with e19a2 CML. However, relapse occurred in the patient with e19a2 CML, possibly caused by the presence of additional chromosomal abnormalities such as an extra Ph chromosome, and loss of chromosome Y. Stem cell transplantation (SCT) therapy caused complete haematologic response with molecular remission; however, the patient died of infectious complication. We conclude that in patients with rare BCR-ABL variants, the effectiveness of imatininb treatment may be influenced by the CML stage besides the actual molecular type of the rare transcript. However, this conclusion cannot be generalized to larger patient groups with rare BCR-ABL variants for which further studies may be needed.

[The role of imatinib in the treatment of acute lymphoid leukemias]. / Az imatinib szerepe az akut lymphoid leukaemiák kezelésében.

The paper reviews current data on the use of imatinib in acute lymphoid leukemia. A brief description of classification of acute lymphoid leukemia and the therapeutic developments of the last 30 years are presented with particular emphasis on the clinical and biological features of Philadelphia positive acute lymphoid leukemia. The main therapeutic principles of acute lymphoid leukemia and the role of minimal residual disease in therapeutic indications are summarized. In Philadelphia positive acute lymphoid leukemia, in addition to chemotherapy and bone marrow transplantation, the tyrosine kinase inhibitor imatinib mesylate has been increasingly administered. The results of major clinical studies are presented along with the author's own clinical experience. Based on the above considerations the current indications of imatinib treatment in Philadelphia positive acute lymphoid leukemia can be summarized as follows: a) during the induction phase along with chemotherapy; b) alternating with cycles of consolidation or maintenance treatment; c) before stem cell transplantation to eradicate minimal residual disease; d) in relapsed or refractory cases; e) after stem cell transplantation for the treatment of minimal residual disease and/or relapse, alone or in combination with donor lymphocyte immunotherapy.

[Familial adenomatous polyposis coli--case report]. / A familiaris adenomatosus polyposisról egy eset kapcsán.

The authors report the case of a young 35 year-old male patient, investigated due to thrombocytosis for three years. First the diagnosis of chronic myeloproliferative disease was made. The diagnosis of familial adenomatous polyposis was only evident in advanced stage of the disease. Upper abdominal US, abdominal CT, double-contrast barium enema examination and colonoscopy proved advanced synchronous colorectal cancers (sigmoid and descending colon) with liver metastases along with polyposis throughout the whole large bowel. Days after the diagnosis was made the patients condition deteriorated rapidly and he died with septic symptoms suggesting bowel perforation and pneumonia. Beside the case report the authors try to give a short overview of the current literature of relatively rare but potentially fatal hereditary colon cancer syndromes to awake the attention of the clinicians to investigate more cautiously the background of unexplained clinical-laboratory signs in young adults.

[Prognostic significance of age and karyotype in the treatment of acute myeloid leukemia: results at our center]. / Az életkor és a karyotypus prognosztikai jelentósége az akut myeloid leukaemia kezelésében: centrumunk eredményei.

INTRODUCTION: Treatment outcome in patients with acute myeloid leukemia are determined by prognostic factors. AIM AND METHODS: Between January 1996 and December 2001 160 patients were treated with newly diagnosed acute myeloid leukemia. Treatment results were analysed according to the age and cytogenetics. Different types of induction and postremission protocols were applied. The median age was 42.2 +/- 12.8 (16-60) years. RESULTS: Complete remission was reached in 113 (70.6%) patients. 25/160 (15.6%) individuals were refractory to treatment, 22/160 (13.8%) patients died within one month. One hundred and ten out of 113 who went into remission were given postremission therapy. Twelve out of 50 relapsed patients achieved a second complete remission. The complete remission rate and cumulative survival of patients below the age of forty years were significantly higher than of those above the age of 40 years. Four fifths of refractory patients as well as nearly all patients with secondary leukemia were older than 40 years. Similarly to studies published in the literature, the expected survival was the best in patients who had a favourable cytogenetics. In contrast, all patients who fell into the unfavourable cytogenetic group died within three years. Intensification of the postremission treatment resulted in an improved survival. CONCLUSION: Classification of acute myeloid leukemia and careful determination of prognostic factors are necessary at the time of diagnosis. This predicts outcome, as well as provides means for application of individualized therapy.

Donor-cell myelodysplastic syndrome developing 13 years after marrow grafting for aplastic anemia.

Donor-cell-derived hematopoietic malignancy is a rare event after bone marrow transplantation. Most cases in the literature occurred within the first year. We present a rare case of a female patient who had a bone marrow transplant for severe aplastic anemia (SAA) at the age of two and a half years from her human leukocyte antigen-identical brother. She developed a myelodysplastic syndrome (refractory cytopenia with multilineage dysplasia) 12 years later. Initially, the malignant clone was of recipient origin, but within several months, progression to a clinically more aggressive refractory anemia with excess blasts (RAEB) was accompanied by the outgrowth of a new clone of donor origin. In this report we provide evidence proving that the patient's final malignant clone arose in donor cells: cytogenetic analysis of the marrow showed a male karyotype and a t(3;21)(q26;q21) in all 62 metaphases analyzed. Interphase fluorescence in situ hybridization showed that all identifiable cells contained the Y chromosome. We conclude that donor-cell-derived hematopoietic malignancy after bone marrow transplantation can occur even after many years. We believe that the 13 years that elapsed between the transplant and the development of RAEB in our case represent the longest latency period in the literature.

Gaucher disease type I complicated with Parkinson's syndrome.

Gaucher disease type I is the so-called non-neuronal adult form of the autosomally inherited lysosomal storage disease. The simultaneous occurrence of Gaucher disease with Parkinson's syndrome has been reported to aggravate both disorders, leading to an unusually early onset and therapy resistance. Neurological alterations in Gaucher disease type I are mostly related to CNS bleeding and skeletal complications. The patient presented here was sensitive to combination therapy for 5 years.