Mirosław Majewski

Publications of Mirosław Majewski

• Frequency of BCR-ABL gene mutations in Polish patients with chronic myeloid leukemia treated with imatinib: a final report of the MAPTEST study.

  Authors: Krzysztof Lewandowski, Krzysztof Warzocha, Andrzej Hellmann, Aleksander Skotnicki, Witold Prejzner, Kajetana Foryciarz, Tomasz Sacha, Michał Gniot, Mirosław Majewski, Iwona Solarska, Grazyna Nowak, Bartosz Wasag, Mikołaj Kobelski, Cezary Scibiorski, Marek Siemiatkowski, Maria Lewandowska, Mieczysław Komarnicki

  Polskie archiwum medycyny wewnȩtrznej. 12/2009; 119(12):789-94.

  INTRODUCTION: The presence of BCR-ABL oncogene mutations in patients with chronic myeloid leukemia (CML) may be responsible for the failure of tyrosine kinase inhibitor treatment. OBJECTIVES: The aimINTRODUCTION: The presence of BCR-ABL oncogene mutations in patients with chronic myeloid leukemia (CML) may be responsible for the failure of tyrosine kinase inhibitor treatment. OBJECTIVES: The aim of the study was to evaluate the frequency of BCR-ABL gene mutations in patients with CML (the MAPTEST study) treated with imatinib (IM). PATIENTS AND METHODS: Direct sequencing analysis of BCR-ABL gene was performed in 92 patients treated with IM for more than 3 months. The mean time of IM treatment was 18 months. At the time of the analysis, 75 patients were in the first chronic phase (CP), 4 in the second CP, 5 in the acceleration and 8 in the blastic phase. Fifty-seven patients (62%) were treated with IM at a daily dose of 400 mg and 35 patients with higher doses (600 or 800 mg daily). Inclusion criteria were based on the European Leukemia Net definitions for failure and suboptimal response to IM. RESULTS: Twelve mutations were detected in 11 of 92 patients, including 4 mutations (36.7%) diagnosed during CP, 3 (27.3%) in acceleration, and 4 (36.7%) in blast crisis. In 1 patient with lymphoid blast crisis of CML coexisting F359V and Y253F mutations were detected. In the whole group mutations were detected in 2 of 5 patients (40%) with primary resistance (M351T, F359V + Y253F) and in 9 of 87 patients (10.3%) (E255K, T315I-3x, M351T, E355G, F359V-2x) with acquired resistance to IM. CONCLUSIONS: The study confirmed the usefulness of BCR-ABL gene mutation screening in patients with CML resistant to IM therapy.

• A diagnostically difficult case of chronic myeloid neoplasm with eosinophilia and abnormalities of PDGFRA effectively treated with imatinib in accelerated phase: case report.

  Authors: Marek Rodzaj, Krystyna Gałazka, Mirosław Majewski, Andrzej Zduńczyk

  Polskie archiwum medycyny wewnȩtrznej. 12/2009; 119(12):838-41.

  Chronic myeloid neoplasm with eosinophilia and abnormalities of platelet-derived growth factor receptor alpha (PDGFRA), referred to until 2008 as chronic eosinophilic leukemia, is distinguished fromChronic myeloid neoplasm with eosinophilia and abnormalities of platelet-derived growth factor receptor alpha (PDGFRA), referred to until 2008 as chronic eosinophilic leukemia, is distinguished from hypereosinophilic syndrome (HES), if accompanied by genetic abnormalities that enable to determine eosinophil clonality. Typically, HES has a benign course and glucocorticosteroids suffice to achieve remission. In chronic myeloid neoplasm with eosinophilia and abnormalities of PDGFRA the FIP1L1-PDGFRA fusion gene can be detected. Its product is a protein showing tyrosine kinase activity leading to malignant proliferation of eosinophil precursors. Differential diagnosis of HES is often difficult because hypereosinophilia may also be reactive and may occur in many nonhematological as well as hematological disorders. Thus, reverse-transcription polymerase chain reaction (RT-PCR)is indicated in all patients with HES in order to detect the FIP1L1-PDGFRA transcript. Traditional treatment of chronic myeloid neoplasm with cytostatic drugs results in a short-term and transient remission or stabilization of the disease. We present the case of a 52-year-old patient with chronic myeloid neoplasm with eosinophilia and abnormalities of PDGFRA, in whom acceleration occurred after a year of cytostatic therapy with hydroxyurea and was successfully treated with imatinib. It was impossible to unequivocally determine the type of bone marrow disease based on histologic criteria, and a wide spectrum of molecular tests differentiating the type of myeloid proliferation were necessary to establish the diagnosis. RT-PCR did not reveal BCR-ABL or JAK2 V617F mutation. Further molecular testing showed rearrangement involving the FIP1L1 gene, thus enabling implementation of targeted therapy.

• Characteristics of T-cell large granular lymphocyte proliferations associated with neutropenia and inflammatory arthropathy.

  Authors: Monika Prochorec-Sobieszek, Grzegorz Rymkiewicz, Hanna Makuch-Łasica, Mirosław Majewski, Katarzyna Michalak, Robert Rupiński, Krzysztof Warzocha, Renata Maryniak

  Arthritis research & therapy. 06/2008; 10(3):R55.

  ABSTRACT: INTRODUCTION: The purpose of this study was to analyze the data of patients with T-cell large granular lymphocyte (T-LGL) lymphocytosis associated with inflammatory arthropathy or with noABSTRACT: INTRODUCTION: The purpose of this study was to analyze the data of patients with T-cell large granular lymphocyte (T-LGL) lymphocytosis associated with inflammatory arthropathy or with no arthritis symptoms. METHODS: Clinical, serological as well as histopathological, immuhistochemical, and flow cytometric evaluations of blood/bone marrow of 21 patients with T-LGL lymphocytosis were performed. The bone marrow samples were also investigated for T-cell receptor (TCR) and immunoglobulin (IG) gene rearrangements by polymerase chain reaction with heteroduplex analysis. RESULTS: Neutropenia was observed in 21 patients, splenomegaly in 10, autoimmune diseases such as rheumatoid arthritis (RA) in 9, unclassified arthritis resembling RA in 2, and autoimmune thyroiditis in 5 patients. T-LGL leukemia was recognized in 19 cases. Features of Felty syndrome were observed in all RA patients, representing a spectrum of T-LGL proliferations from reactive polyclonal through transitional between reactive and monoclonal to T-LGL leukemia. Bone marrow trephines from T-LGL leukemia patients showed interstitial clusters and intrasinusoidal linear infiltrations of CD3+/CD8+/CD57+/granzyme B+ lymphocytes, reactive lymphoid nodules, and decreased or normal granulocyte precursor count with left-shifted maturation. In three-color flow cytometry (FCM), T-LGL leukemia cells demonstrated CD2, CD3, and CD8 expression as well as a combination of CD16, CD56, or CD57. Abnormalities of other T-cell antigen expressions (especially CD5, CD7, and CD43) were also detected. In patients with polyclonal T-LGL lymphocytosis, T cells were dispersed in the bone marrow and the expression of pan-T-cell antigens in FCM was normal. Molecular studies revealed TCRB and TCRG gene rearrangements in 13 patients and TCRB, TCRG, and TCRD in 4 patients. The most frequently rearranged regions of variable genes were Vbeta-Jbeta1, Jbeta2 and Vgamma If Vgamma10-Jgamma. Moreover, in 4 patients, additional rearrangements of IG kappa and lambda variable genes of B cells were also observed. CONCLUSION: RA and neutropenia patients represented a continuous spectrum of T-LGL proliferations, although monoclonal expansions were most frequently observed. The histopathological pattern and immunophenotype of bone marrow infiltration as well as molecular characteristics were similar in T-LGL leukemia patients with and without arthritis.

• Screening for JAK2 V617F point mutation in patients with hypereosinophilic syndrome-in response to 'Hypereosinophilic syndrome: Another face of janus?' by Dahabreh et al. published in Leukemia Research, in press.

  Authors: Grzegorz Helbig, Mirosław Majewski, Agata Wieczorkiewicz, Grażyna Bober, Janina Grzegorczyk, Joanna Dziaczkowska-Suszek, Anna Soja, Aleksandra Bartkowska-Chrobok, Małgorzata Krawczyk, Sławomira Krzemień

  Leukemia research. 06/2008;

• Biclonal T-cell receptor gammadelta+ large granular lymphocyte leukemia associated with rheumatoid arthritis.

  Authors: Monika Prochorec-Sobieszek, Monika Chełstowska, Grzegorz Rymkiewicz, Mirosław Majewski, Krzysztof Warzocha, Renata Maryniak

  Leukemia & lymphoma. 05/2008; 49(4):828-31.

• A single weekly dose of imatinib is sufficient to induce and maintain remission of chronic eosinophilic leukaemia in FIP1L1-PDGFRA-expressing patients.

  Authors: Grzegorz Helbig, Beata Stella-Hołowiecka, Mirosław Majewski, Małgorzata Całbecka, Jolanta Gajkowska, Ryszard Klimkiewicz, Andrzej Moskwa, Janina Grzegorczyk, Monika Lewandowska, Jerzy Hołowiecki

  British journal of haematology. 05/2008; 141(2):200-4.

  Hypereosinophilic syndrome (HES) is defined as chronic, unexplained hypereosinophilia with organ involvement. A subset of HES patients presents an interstitial deletion in chromosome 4q12, whichHypereosinophilic syndrome (HES) is defined as chronic, unexplained hypereosinophilia with organ involvement. A subset of HES patients presents an interstitial deletion in chromosome 4q12, which leads to the expression of an imatinib-responsive fusion gene, FIP1L1-PDGFRA. These patients are diagnosed as chronic eosinophilic leukaemia (CEL). We treated seven CEL and HES patients, six of which expressed FIP1L1-PDGFRA, with imatinib using initial daily doses ranging from 100 to 400 mg. In a remission maintenance phase, the patients were treated with imatinib once weekly. All imatinib-treated patients achieved a complete haematological remission (CHR), and five of the six patients with FIP1L1-PDGFRA expression exhibited molecular remission. The decreased imatinib doses were as follows: 200 mg/week in three patients, 100 mg/week in two patients and 100 mg/d in the remaining two patients. For remission maintenance, imatinib doses were set at 100 mg/week in five patients and 200 mg/week in two patients. At a median follow-up of 30 months all patients remained in CHR and FIP1L1-PDGFRA expression was undetectable in five of the six FIP1L1-PDGFRA-expressing patients. These data suggest that a single weekly dose of imatinib is sufficient to maintain remission in FIP1L1-PDGFRA- positive CEL patients.

• Predictive value of RT-PCR PML-RARA transcript monitoring for extramedullary relapse of acute promyelocytic leukemia in the pleura, heart and pericardium after allogeneic SCT.

  Authors: Barbara Nasilowska-Adamska, Mirosław Majewski, Ilona Seferynska, Andrzej Szczepinski, Agnieszka Tomaszewska, Monika Prochorec-Sobieszek, Katarzyna Guz, Adam Torbicki, Krzysztof Warzocha, Bozena Marianska

  Annals of transplantation : quarterly of the Polish Transplantation Society. 02/2007; 12(3):33-8.

  BACKGROUND: We report a patient with acute promyelocytic leukemia (APL) relapse in extremely rare sites--the pleura, heart and pericardium without evidence of bone marrow infiltration and withBACKGROUND: We report a patient with acute promyelocytic leukemia (APL) relapse in extremely rare sites--the pleura, heart and pericardium without evidence of bone marrow infiltration and with molecular evidence of disease after allogeneic stem cell transplantation (alloSCT). CASE DESCRIPTION:Presented patient underwent alloSCT in second complete hematological and cytogenetic remission with presence of promyelocytic leukemia-retinoic acid receptor A (PML-RARA) detected in reverse transcription-polymerase chain reaction (RT-PCR) with sensitivity of 10(-2). After transplant, this patient remained in complete hematological and cytogenetic remission but nested RT-PCR assays with detection thresholds of 10(-3)/10(-4) were positive for PML-RARA rearranged gene even chimerism tests showed 100% of donor profile. He was in a very good clinical condition and presented symptoms of transient limited chronic graft vs. host disease. Twenty one months after transplant, the leukemic relapse in the pleura, heart and pericardium was diagnosed. At that time, PML-RARA transcript detected in RT-PCR assay (10(-2)) was positive for the first time after transplant. During salvage chemotherapy he died because of cardiogenic shock. CONCLUSIONS: We conclude that detection of PML-RARA after alloSCT should be indication insightful diagnosis of medullary or extramedullary (EM) relapse. The imaging techniques of all possible sites of APL EM relapse have to be included.

• Localized gastric diffuse large B-cell lymphoma and Hodgkin's lymphoma as secondary neoplasms in two patients with chronic lymphocytic leukemia.

  Authors: Monika Prochorec-Sobieszek, Mirosław Majewski, Anna Sikorska, Kinga Kos, Sławomir Huszcza, Renata K Maryniak

  Leukemia & lymphoma. 11/2006; 47(10):2244-6.

• Transformation in lymphomas--morphological, immunophenotypic and molecular features.

  Authors: Monika Prochorec-Sobieszek, Mirosław Majewski, Anna Sikorska, Piotr Centkowski, Joanna Tajer, Elzbieta Lampka-Wojciechowska, Grzegorz Rymkiewicz, Lech Konopka, Janusz Meder, Krzysztof Warzocha, Renata K Maryniak

  Polish journal of pathology : official journal of the Polish Society of Pathologists. 02/2006; 57(2):63-70.

  During the course of lymphoma, a clinically more aggressive process with different morphology may develop, referred to as lymphoma transformation. Clonal relationship and pathogenic mechanism of thisDuring the course of lymphoma, a clinically more aggressive process with different morphology may develop, referred to as lymphoma transformation. Clonal relationship and pathogenic mechanism of this process are widely debated. The aim of the study was to evaluate morphology, immunophenotype (including EBV status) and clonal relationship in nine cases of lymphoma transformation. Among the six patients with low grade B-cell lymphomas three transformed into high grade B-cell lymphomas (two into diffuse large B-cell lymphoma, one into Burkitt lymphoma) and three into Hodgkin lymphoma. Three other patients with Hodgkin lymphoma presented with transformation into diffuse large B-cell lymphoma in two patients and peripheral T-cell lymphoma in one patient. In all cases there was a sudden clinical change as well as change in morphology and phenotype. In five of the nine patients studied EBV-LMP1 was demonstrated by immunohistochemistry in large transformed lymphoma cells. In two cases molecular studies revealed a different pattern of immunoglobulin gene rearrangement in the large transformed cells as compared to the small cells of primary indolent lymphoma. Thus, they represented secondary, arising de novo neoplasm.