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[PMID]:29390324
[Au] Autor:Harada Y; Nishiwaki S; Sugimoto T; Onodera K; Goto T; Sato T; Kamoshita S; Kawashima N; Seto A; Okuno S; Yamamoto S; Iwasaki T; Ozawa Y; Miyamura K; Akatsuka Y; Sugiura I
[Ad] Endereço:Division of Hematology and Oncology, Toyohashi Municipal Hospital.
[Ti] Título:Successful treatment with allogeneic stem cell transplantation followed by DLI and TKIs for e6a2 BCR-ABL-positive acute myeloid leukaemia: A case report and literature review.
[So] Source:Medicine (Baltimore);96(50):e9160, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Patients with the e6a2 BCR-ABL transcript, 1 of the atypical transcripts, have been reported to have a poor prognosis, and allogeneic stem cell transplantation (ASCT) can be considered as additional therapy. However, long-term survival after ASCT for this disease is rare. PATIENT CONCERNS: This report concerns a 55-year-old female patient with e6a2 BCR-ABL-positive acute myeloid leukemia including the outcome of ASCT followed by donor lymphocyte infusion (DLI). DIAGNOSES: The breakpoint was confirmed by direct sequencing. Her minimal residual disease could be detected by nested reverse-transcription polymerase chain reaction using primers for the minor BCR-ABL (e1a2) transcript. INTERVENTIONS: Treatment with tyrosine kinase inhibitors (TKIs) and ASCT followed by DLI. OUTCOMES: Despite multiple cytogenetic and molecular relapses after ASCT, she remains in molecular remission at 46 months after ASCT. LESSONS: This case indicates the efficacy of the combination of the graft-versus-leukemia effect and TKIs for e6a2 BCR-ABL-positive acute leukemia. When the Philadelphia chromosome with an unusual chromosomal breakpoint is suggested, we should clarify the breakpoint because that information can aid molecular assessments and decisions to provide an additional or alternative therapy.
[Mh] Termos MeSH primário: Transplante de Células-Tronco Hematopoéticas
Leucemia Mieloide Aguda/terapia
[Mh] Termos MeSH secundário: Feminino
Proteínas de Fusão bcr-abl
Efeito Enxerto vs Leucemia
Seres Humanos
Transfusão de Linfócitos
Meia-Idade
Neoplasia Residual
Cromossomo Filadélfia
Proteínas Tirosina Quinases/antagonistas & inibidores
Reação em Cadeia da Polimerase Via Transcriptase Reversa
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
EC 2.7.10.1 (Protein-Tyrosine Kinases); EC 2.7.10.2 (Fusion Proteins, bcr-abl)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009160


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[PMID]:29384978
[Au] Autor:Nishiwaki S; Sugiura I; Miyata Y; Saito S; Sawa M; Nishida T; Miyamura K; Kuwatsuka Y; Kohno A; Yuge M; Kasai M; Iida H; Kurahashi S; Osaki M; Goto T; Terakura S; Murata M; Nishikawa H; Kiyoi H
[Ad] Endereço:Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya.
[Ti] Título:Efficacy and safety of autologous peripheral blood stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia: A study protocol for a multicenter exploratory prospective study (Auto-Ph17 study).
[So] Source:Medicine (Baltimore);96(52):e9568, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: The prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph + ALL) has been dramatically improved since the introduction of tyrosine kinase inhibitors (TKIs). Although allogeneic hematopoietic cell transplantation (allo-HCT) is a major treatment option, the role of autologous peripheral blood stem cell transplantation (auto-PBSCT) has been reconsidered, especially in patients who achieved early molecular remission. METHODS AND ANALYSIS: This is a multicenter exploratory study for Ph + ALL patients aged between 55 and 70 years who achieved complete molecular remission within 3 cycles of chemotherapy. The target sample size is 5, and the registration period is 2 years. The primary endpoint is Day100- mortality after transplantation, and the secondary endpoints are survival, relapse rate, nonrelapse mortality, and adverse events.This study is divided into 3 phases: peripheral blood stem cell harvest, transplantation, and maintenance. Chemomobilization is performed using a combination of cyclophosphamide (CPM), doxorubicin, vincristine (VCR), and prednisolone (PSL). As a preparative regimen, the LEED regimen is used, which consists of melphalan, CPM, etoposide, and dexamethasone. Twelve cycles of maintenance therapy using a combination of VCR, PSL, and dasatinib are performed.In association with relapse, the minimal residual disease (MRD) of BCR-ABL chimeric gene and T-cell subsets are analyzed both before and after auto-PBSCT. ETHICS AND DISSEMINATION: The protocol was approved by the institutional review board of Nagoya University Hospital and all the participating hospitals. Written informed consent was obtained from all patients before registration, in accordance with the Declaration of Helsinki. Results of the study will be disseminated via publications in peer-reviewed journals. TRIAL REGISTRATION: Trial registration number UMIN000026445.
[Mh] Termos MeSH primário: Transplante de Células-Tronco de Sangue Periférico/mortalidade
Transplante de Células-Tronco de Sangue Periférico/métodos
Cromossomo Filadélfia
Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade
Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
[Mh] Termos MeSH secundário: Idoso
Progressão da Doença
Feminino
Genes abl/fisiologia
Seres Humanos
Imunossupressores/administração & dosagem
Masculino
Meia-Idade
Transplante de Células-Tronco de Sangue Periférico/efeitos adversos
Estudos Prospectivos
Proteínas Proto-Oncogênicas c-bcr/biossíntese
Projetos de Pesquisa
Análise de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Immunosuppressive Agents); EC 2.7.11.1 (BCR protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins c-bcr)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009568


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[PMID]:29025593
[Au] Autor:Seol CA; Cho YU; Jang S; Park CJ; Lee JH; Lee JH; Lee KH; Seo EJ
[Ad] Endereço:Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea.
[Ti] Título:Prognostic significance of recurrent additional chromosomal abnormalities in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.
[So] Source:Cancer Genet;216-217:29-36, 2017 Oct.
[Is] ISSN:2210-7762
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL), additional chromosomal abnormalities (ACAs) are frequently observed. We investigated the cytogenetic characteristics and prognostic significance of ACAs in Ph-positive ALL. We reviewed the clinical data and bone marrow cytogenetic findings of 122 adult Ph-positive ALL patients. The ACAs were examined for partial or whole chromosomal gains or losses, and structural aberrations. The overall survival (OS) and disease-free survival (DFS) of patients who received hematopoietic cell transplantation were compared between the isolated Ph group and ACA group. ACAs were present in 73.0% of all patients. The recurrent ACAs were extra Ph (24.7%), 9/9p loss (20.2%), and 7/7p loss (19.1%). Complex karyotype was found in 28.1% of patients in the ACA group. Younger patients (19-30 years) in the ACA group showed the highest frequency of extra Ph (54%) compared to other age groups. The OS in the ACA group was significantly shorter than in the isolated Ph group. The presence of an extra Ph chromosome or 9/9p loss was significantly associated with shorter OS and DFS, whereas 7/7p loss and complex karyotype were not associated with poorer prognosis. We suggest that subclassification of ACAs could be applied to prognostic investigation of Ph-positive ALL.
[Mh] Termos MeSH primário: Aberrações Cromossômicas
Cromossomo Filadélfia
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Análise Citogenética
Intervalo Livre de Doença
Feminino
Transplante de Células-Tronco Hematopoéticas
Seres Humanos
Masculino
Meia-Idade
Análise Multivariada
Ploidias
Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
Prognóstico
Modelos de Riscos Proporcionais
Recidiva
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171014
[St] Status:MEDLINE


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[PMID]:29025581
[Au] Autor:Wasilewska EM; Panasiuk B; Gniot M; Sawicka A; Kozlowska K; Lewandowski K; Kloczko J; Midro AT
[Ad] Endereço:Department of Hematology, Medical University of Bialystok, 24A Sklodowskiej-Curie Street, 15-276 Bialystok, Poland. Electronic address: emewa79@gmail.com.
[Ti] Título:Clonal chromosomal aberrations in Philadelphia negative cells such as monosomy 7 and trisomy 8 may persist for years with no impact on the long term outcome in patients with chronic myeloid leukemia.
[So] Source:Cancer Genet;216-217:1-9, 2017 Oct.
[Is] ISSN:2210-7762
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The appearance of clonal chromosomal aberrations in Philadelphia negative cells (CCA/Ph-) during the treatment of chronic myeloid leukemia (CML) was recently confirmed. Importance of these findings has not been clearly defined. We present data on the time of appearance, persistence, size of the CCA/Ph- clone in terms of drugs used and hematological, cytogenetic and molecular response rates. The focus was on the peripheral blood cytopenias and myelodysplastic changes in the bone marrow microscopic evaluation. In 5 out of 155 (3,2%) CML patients, the persistent presence (up to nine years) of CCA/Ph- was found (monosomy 7 and trisomy 8 in unrelated clones in two patients treated with tyrosine kinase inhibitors; trisomy 8 in two patients on imatinib; trisomy 21 in one patient on interferon alfa treatment). Aberrations were present in median 24% Ph- cells in 3-15 subsequent analyses at different cytogenetic and molecular response time points. No evident myelodysplastic changes nor transformation to MDS/AML occurred in patients with CCA/Ph-. All the patients achieved major molecular response (MMR). It seems that CCA/Ph- presence does not affect the long term outcome in patients with chronic myeloid leukemia. Further complex monitoring of the CML patients with CCA/Ph- is still needed.
[Mh] Termos MeSH primário: Leucemia Mielogênica Crônica BCR-ABL Positiva/genética
Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia
Cromossomo Filadélfia
Trissomia/genética
[Mh] Termos MeSH secundário: Idoso
Deleção Cromossômica
Cromossomos Humanos Par 7/genética
Cromossomos Humanos Par 8/genética
Células Clonais
Análise Citogenética
Feminino
Seres Humanos
Masculino
Meia-Idade
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171014
[St] Status:MEDLINE


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[PMID]:28866095
[Au] Autor:Sadras T; Heatley SL; Kok CH; Dang P; Galbraith KM; McClure BJ; Muskovic W; Venn NC; Moore S; Osborn M; Revesz T; Moore AS; Hughes TP; Yeung D; Sutton R; White DL
[Ad] Endereço:Cancer Theme, South Australian Health & Medical Research Institute, Adelaide, SA, Australia; Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia.
[Ti] Título:Differential expression of MUC4, GPR110 and IL2RA defines two groups of CRLF2-rearranged acute lymphoblastic leukemia patients with distinct secondary lesions.
[So] Source:Cancer Lett;408:92-101, 2017 Nov 01.
[Is] ISSN:1872-7980
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:CRLF2-rearrangements (CRLF2-r) occur frequently in Ph-like B-ALL, a high-risk ALL sub-type characterized by a signaling profile similar to Ph + ALL, however accumulating evidence indicates genetic heterogeneity within CRLF2-r ALL. We performed thorough genomic characterization of 35 CRLF2-r cases (P2RY8-CRLF2 n = 18; IGH-CRLF2 n = 17). Activating JAK2 mutations were present in 34% of patients, and a CRLF2-F232C mutation was identified in an additional 17%. IKZF1 deletions were detected in 63% of cases. The majority of patients (26/35) classified as Ph-like, and these were characterized by significantly higher levels of MUC4, GPR110 and IL2RA/CD25. In addition, Ph-like CRLF2-r samples were significantly enriched for IKZF1 deletions, JAK2/CRLF2 mutations and increased expression of JAK/STAT target genes (CISH, SOCS1), suggesting that mutation-driven CRLF2/JAK2 activation is more frequent in this sub-group. Less is known about the genomics of CRLF2-r cases lacking JAK2-pathway mutations, but KRAS/NRAS mutations were identified in 4/9 non-Ph-like samples. This work highlights the heterogeneity of secondary lesions which may arise and influence intracellular-pathway activation in CRLF2-r patients, and importantly presents distinct therapeutic targets within a group of patients harboring identical primary translocations, for whom efficient directed therapies are currently lacking.
[Mh] Termos MeSH primário: Regulação Leucêmica da Expressão Gênica
Rearranjo Gênico
Subunidade alfa de Receptor de Interleucina-2/metabolismo
Mucina-4/metabolismo
Proteínas Oncogênicas/metabolismo
Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
Receptores de Citocinas/genética
Receptores Acoplados a Proteínas-G/metabolismo
[Mh] Termos MeSH secundário: Feminino
Seres Humanos
Subunidade alfa de Receptor de Interleucina-2/genética
Janus Quinase 2/genética
Janus Quinase 2/metabolismo
Mucina-4/genética
Mutação/genética
Proteínas Oncogênicas/genética
Cromossomo Filadélfia
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo
Prognóstico
Receptores Acoplados a Proteínas-G/genética
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CRLF2 protein, human); 0 (GPR110 protein, human); 0 (IL2RA protein, human); 0 (Interleukin-2 Receptor alpha Subunit); 0 (MUC4 protein, human); 0 (Mucin-4); 0 (Oncogene Proteins); 0 (Receptors, Cytokine); 0 (Receptors, G-Protein-Coupled); EC 2.7.10.2 (JAK2 protein, human); EC 2.7.10.2 (Janus Kinase 2)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170904
[St] Status:MEDLINE


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[PMID]:28790105
[Au] Autor:Lafage-Pochitaloff M; Baranger L; Hunault M; Cuccuini W; Lefebvre C; Bidet A; Tigaud I; Eclache V; Delabesse E; Bilhou-Nabéra C; Terré C; Chapiro E; Gachard N; Mozziconacci MJ; Ameye G; Porter S; Grardel N; Béné MC; Chalandon Y; Graux C; Huguet F; Lhéritier V; Ifrah N; Dombret H; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)
[Ad] Endereço:Department of Genetics, University Hospital, Assistance Publique-Hôpitaux de Marseille, INSERM 1104, Aix-Marseille University, Marseille, France.
[Ti] Título:Impact of cytogenetic abnormalities in adults with Ph-negative B-cell precursor acute lymphoblastic leukemia.
[So] Source:Blood;130(16):1832-1844, 2017 Oct 19.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Multiple cytogenetic subgroups have been described in adult Philadelphia chromosome (Ph)-negative B-cell precursor (BCP) acute lymphoblastic leukemia (ALL), often comprising small numbers of patients. In this study, we aimed to reassess the prognostic value of cytogenetic abnormalities in a large series of 617 adult patients with Ph-negative BCP-ALL (median age, 38 years), treated in the intensified Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/2005 trials. Combined data from karyotype, DNA index, fluorescence in situ hybridization, and polymerase chain reaction screening for relevant abnormalities were centrally reviewed and were informative in 542 cases (88%), allowing classification in 10 exclusive primary cytogenetic subgroups and in secondary subgroups, including complex and monosomal karyotypes. Prognostic analyses focused on cumulative incidence of failure (including primary refractoriness and relapse), event-free survival, and overall survival. Only 2 subgroups, namely t(4;11)/ and 14q32/ translocations, displayed a significantly worse outcome in this context, still observed after adjustment for age and after censoring patients who received allogeneic stem cell transplantation (SCT) in first remission at SCT time. A worse outcome was also observed in patients with low hypodiploidy/near triploidy, but this was likely related to their higher age and worse tolerance to therapy. The other cytogenetic abnormalities, including complex and monosomal karyotypes, had no prognostic value in these intensive protocols designed for adult patients up to the age of 60 years.
[Mh] Termos MeSH primário: Aberrações Cromossômicas
Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico
Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Aberrações Cromossômicas/estatística & dados numéricos
Ensaios Clínicos como Assunto/estatística & dados numéricos
Análise Citogenética
Feminino
Seres Humanos
Cariotipagem
Masculino
Meia-Idade
Estudos Multicêntricos como Assunto/estatística & dados numéricos
Cromossomo Filadélfia
Leucemia-Linfoma Linfoblástico de Células Precursoras B/epidemiologia
Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia
Valor Preditivo dos Testes
Prognóstico
Estudos Retrospectivos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170810
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2017-05-783852


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[PMID]:28654842
[Au] Autor:Chen H; Liu KY; Xu LP; Chen YH; Zhang XH; Wang Y; Qin YZ; Liu YR; Lai YY; Huang XJ
[Ad] Endereço:Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
[Ti] Título:Haploidentical hematopoietic stem cell transplantation for pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia in the imatinib era.
[So] Source:Leuk Res;59:136-141, 2017 Aug.
[Is] ISSN:1873-5835
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains an important curative option for children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who have a poor response to chemotherapy plus imatinib. For such children, if there are no matched related or unrelated donors, alternative donor transplantation may be a choice. The role of haploidentical donor (HID) HSCT in pediatric patients with Ph+ ALL has not been reported. The study population included pediatric patients with Ph+ ALL who underwent HID-HSCT. BCR-ABL transcript levels were analyzed using real-time quantitative reverse transcription polymerase chain reaction. At a median follow-up of 34 months, the 5-year probabilities of event-free survival (EFS) and overall survival (OS) were 61.0% and 70.0%, respectively in HID HSCT. The 3-year incidence of relapse and non-relapse mortality was 22.7% and 16.4%. Multivariate analysis showed that the post-HSCT BCR-ABL transcript level on +30day was a significant factor affecting relapse rate. HID HSCT for the treatment of pediatric patients with Ph+ ALL yielded promising long-term survival. Post-HSCT BCR-ABL transcript positivity was a significant factor for clinical relapse after allo-HSCT in the imatinib era.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Haplótipos/genética
Transplante de Células-Tronco Hematopoéticas/métodos
Mesilato de Imatinib/uso terapêutico
Cromossomo Filadélfia
Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
[Mh] Termos MeSH secundário: Adolescente
Criança
Pré-Escolar
Intervalo Livre de Doença
Feminino
Proteínas de Fusão bcr-abl/genética
Transplante de Células-Tronco Hematopoéticas/mortalidade
Seres Humanos
Lactente
Masculino
Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade
RNA Mensageiro/sangue
Recidiva
Taxa de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (RNA, Messenger); 8A1O1M485B (Imatinib Mesylate); EC 2.7.10.2 (Fusion Proteins, bcr-abl)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170628
[St] Status:MEDLINE


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[PMID]:28644853
[Au] Autor:Alexander PM; Caudell DL; Kucera GL; Pladna KM; Pardee TS
[Ad] Endereço:Internal Medicine, Section on Hematology and Oncology, Wake Forest Baptist Health, Winston-Salem, North Carolina, United States of America.
[Ti] Título:The novel phospholipid mimetic KPC34 is highly active against preclinical models of Philadelphia chromosome positive acute lymphoblastic leukemia.
[So] Source:PLoS One;12(6):e0179798, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Philadelphia chromosome positive B cell acute lymphoblastic leukemia (Ph+ ALL) is an aggressive cancer of the bone marrow. The addition of tyrosine kinase inhibitors (TKIs) has improved outcomes but many patients still suffer relapse and novel therapeutic agents are needed. KPC34 is an orally available, novel phospholipid conjugate of gemcitabine, rationally designed to overcome multiple mechanisms of resistance, inhibit the classical and novel isoforms of protein kinase C, is able to cross the blood brain barrier and is orally bioavailable. KPC34 had an IC50 in the nanomolar range against multiple ALL cell lines tested but was lowest for Ph+ lines. In mice bearing either naïve or resistant Ph+ ALL, KPC34 treatment resulted in significantly improved survival compared to cytarabine and gemcitabine. Treatment with KPC34 and doxorubicin was more effective than doxorubicin and cytarabine. Mice with recurrence of their ALL after initial treatment with cytarabine and doxorubicin saw dramatic improvements in hind limb paralysis after treatment with KPC34 demonstrating activity against established CNS disease. Consistent with this KPC34 was better than gemcitabine at reducing CNS leukemic burden. These promising pre-clinical results justify the continued development of KPC34 for the treatment of Ph+ALL.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Desoxicitidina/análogos & derivados
Glicerofosfatos/farmacologia
Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/toxicidade
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade
Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Citarabina/farmacologia
Dano ao DNA/efeitos dos fármacos
Desoxicitidina/farmacologia
Desoxicitidina/toxicidade
Relação Dose-Resposta a Droga
Doxorrubicina/farmacologia
Resistência a Medicamentos Antineoplásicos
Ensaios de Seleção de Medicamentos Antitumorais
Glicerofosfatos/toxicidade
Seres Humanos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Transplante de Neoplasias
Cromossomo Filadélfia
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo
Proteína Quinase C/antagonistas & inibidores
Proteína Quinase C/metabolismo
Distribuição Aleatória
Carga Tumoral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Glycerophosphates); 0 (KPC34 compound); 04079A1RDZ (Cytarabine); 0W860991D6 (Deoxycytidine); 80168379AG (Doxorubicin); B76N6SBZ8R (gemcitabine); EC 2.7.11.13 (Protein Kinase C)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170624
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179798


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[PMID]:28580853
[Au] Autor:Dombi P; Illés Á; Demeter J; Homor L; Simon Z; Kellner Á; Karádi É; Valasinyószki E; Udvardy M; Egyed M
[Ad] Endereço:Szent Borbála Kórház Tatabánya.
[Ti] Título:[Hungarian Philadelphia negative chronic myeloproliferative neoplasia registry. Evaluation of the Polycythemia vera patients].
[Ti] Título:Philadelphia-negatív krónikus Myeloproliferativ Neoplasia Magyarországi Regiszter. Polycythaemia verás betegeink adatainak elemzése..
[So] Source:Orv Hetil;158(23):901-909, 2017 Jun.
[Is] ISSN:0030-6002
[Cp] País de publicação:Hungary
[La] Idioma:hun
[Ab] Resumo:Intruduction and aim: The Hungarian National Registry for Philadelphia chromosome negative myeloproliferative neoplasms has been developed. The aim of the recent study is to assess the clinical characteristics of Hungarian patients with polycythemia vera. METHOD: Data of 351 JAK2 and exon 12 mutation positive polycythemia vera patients were collected online from 15 haematology centres reporting epidemiologic, clinical characteristics, diagnostic tools, therapeutic interventions, thromboembolic complications, disease transformations. Vascular events prior to and after diagnosis were evaluated upon the Landolfi risk assessment scale. RESULTS: 116 thromboembolic events were reported in 106 PV patients prior to diagnosis and 152 occasions in 102 patients during follow-up. The frequency of major arterial events were significantly reduced (p<0.0001) and the minor venous events were significantly elevated (p<0.0001) after the diagnosis. Major hemorrhagic complications were found in 25 and transformation in 26 cases. CONCLUSIONS: Our registry allows to collect and evaluate the features of patients with polycythemia vera. The Landolfi risk stratification was proven to be useful. Based on evaluated data, accuracy of diagnostic criteria and compliance to risk-adapted therapeutic guidelines are needed. Orv Hetil. 2017; 158(23): 901-909.
[Mh] Termos MeSH primário: Policitemia Vera/epidemiologia
Mielofibrose Primária/epidemiologia
Sistema de Registros
[Mh] Termos MeSH secundário: Distribuição por Idade
Idoso
Feminino
Seres Humanos
Hungria
Masculino
Meia-Idade
Cromossomo Filadélfia
Medição de Risco
Fatores de Risco
Distribuição por Sexo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170606
[St] Status:MEDLINE
[do] DOI:10.1556/650.2017.30766


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[PMID]:28576259
[Au] Autor:Boissel N; Ducassou S
[Ad] Endereço:Hôpital Saint-Louis, unité d'hématologie adolescents et jeunes adultes, 1, avenue Claude-Vellefaux, 75010 Paris, France. Electronic address: nicolas.boissel@aphp.fr.
[Ti] Título:[Adolescents and young adults with acute lymphoblastic leukemia. A specific management].
[Ti] Título:Les leucémies aiguës lymphoblastiques de l'adolescent et du jeune adulte. Spécificités de la prise en charge..
[So] Source:Bull Cancer;104(7-8):683-689, 2017 Jul - Aug.
[Is] ISSN:1769-6917
[Cp] País de publicação:France
[La] Idioma:fre
[Ab] Resumo:The acute lymphoblastic leukemia (ALL) is one of the first cancer for which emerged the particularity of the adolescent and young adult population. After decades of poorly concerted approaches, adult and pediatric haematologists found out that adolescents treated according to pediatric approaches had a better outcome than those treated in adult protocols. Therefore, pediatric-inspired therapies have been successfully implemented in the young adult population, leading to decreased criteria for allogeneic stem cell transplantation. More recently, a high prevalence of Philadelphia-like ALL has been identified in the AYA population, which opens the door to the combination of target therapy similar to Philadelphia-positive ALL. AYA patients require specific care programs including fertility counselling, adhesion evaluation, and long-term survivor follow-up. They are to be optimally treated by multidisciplinary teams, exploring their personal needs and determining the best management of the "whole patient".
[Mh] Termos MeSH primário: Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
[Mh] Termos MeSH secundário: Adolescente
Fatores Etários
Aloenxertos
Feminino
Transplante de Células-Tronco Hematopoéticas
Seres Humanos
Infertilidade/prevenção & controle
Masculino
Terapia de Alvo Molecular
Cromossomo Filadélfia
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
Recidiva
Indução de Remissão
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170815
[Lr] Data última revisão:
170815
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170604
[St] Status:MEDLINE



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