RESUMO
INTRODUCTION: Chromosome 17 abnormalities, especially disorders of the 17p region and including TP53 gene mutations, result in very low rates of cure for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) treated with conventional chemotherapy or allogeneic hematopoietic cell transplant (allo-HCT). Our retrospective study analyzed outcomes in patients with chromosome 17 (ch17) abnormalities who received conventional chemotherapy followed by allo-HCT versus those who did not receive a transplant. We analyzed whether poor outcomes extend to patients with all types of ch17 abnormalities and the impact of concomitant TP53 gene mutations assessed by next-generation sequencing (NGS) on prognosis. METHODS: We retrospectively analyzed diagnostic and outcome data on 98 patients treated at our institution from 2012 to 2018 with AML or MDS who possessed ch17 abnormalities by cytogenetic analysis. The presence of TP53 mutations was analyzed by NGS. Primary endpoint of our study was overall survival (OS). RESULTS: 61 patients with AML and 37 with MDS were included. Complete remission (CR) with first line treatment was similar between induction chemotherapy or hypomethylating agents (HMA), 22.9 % versus 21.6 % (p = 0.33). Median OS for all patients (with or without transplant) was 10 months. Patients with abnormal ch17 in conjunction with any TP53 mutation(s) exhibited worse OS compared to patients without a TP53 mutation (10 versus 23 months, p = 0.02). 30 patients (19 AML, 11 MDS) underwent HCT, with a median OS of 11 months. For AML patients who underwent allo-HCT, 18 were in CR (13 with cytogenetic remission) and 1 had persistent disease at transplant. In the MDS cohort, 3 patients were in CR (2 with cytogenetic remission) and 8 had stable disease. Post allo-HCT survival of AML and MDS cohorts did not differ (p = 0.6), although cytogenetic CR at time of HCT trended towards improved OS (17 versus 8 months; p = 0.6). CONCLUSIONS: AML/MDS patients with ch17 abnormalities have poor outcomes with or without HCT. Our results show that patients with ch17 abnormalities and TP53 mutations have a significantly poorer survival compared to patients who have ch17 abnormalities but no TP53 mutations. Drugs targeting abnormalities of the p53 pathway, improvement in depth of response prior to HCT, and novel maintenance strategies are needed for improved outcomes in these patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aberrações Cromossômicas , Cromossomos Humanos Par 17 , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Prognóstico , Estudos Retrospectivos , Proteína Supressora de Tumor p53/genéticaRESUMO
Low-grade follicular lymphomas are genetically characterized by the translocation t(14; 18)(q32;q21) with BCL2 gene rearrangements. Marginal zone lymphomas are often associated with translocations or transcriptional deregulations of the MALT gene. We report 2 cases of lymphomas which harbor both the t(14;18)(q32;q21) translocation and MALT gene upregulation. Patients presented with numerous circulating atypical lymphocytes. Lymph node biopsy in both cases on HE staining demonstrated vague nodularity readily highlighted by CD10, CD23, or BCL6. Staining with CD20 and BCL2 demonstrated monotonous diffuse effacement of normal architecture with tumor cells without obvious follicular structures. Morphologically, tumor cells were consistent with centrocytes. Bone marrow biopsy demonstrated a combined peritrabecular and interstitial distribution of the tumor cells. These cases present substantial difficulties for diagnosis and classification. Clinical and morphological features were mostly consistent with follicular lymphoma, with a few features more often seen in marginal zone lymphomas (leukemic presentation, no CD10 in circulating cells, interstitial location of tumor cells in bone marrow); therefore, these cases were finally classified as follicular lymphoma grade I. Both patients were treated with standard chemotherapy regimens for follicular and nongastric MALT lymphomas with a good response to date.
Assuntos
Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Células B/diagnóstico , Linfoma Folicular/diagnóstico , Adulto , Biomarcadores , Biópsia , Medula Óssea/patologia , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfonodos/patologia , Linfoma de Células B/genética , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma Folicular/genética , Pessoa de Meia-Idade , Avaliação de Sintomas , Translocação GenéticaRESUMO
Chronic myeloid leukaemia (CML) is a clonal haematological disease which is characterized by a diagnostic karyotypic abnormality t (9;22)(q34;q11) called as Philadelphia (Ph) chromosome. Occurrence of additional chromosomal abnormalities besides the Ph chromosome is defined as clonal evolution (CE) and considered to be a marker of disease progression. A 67-year-old male who was initially evaluated at a private hospital where a diagnosis of acute promyelocytic leukaemia was made on bone marrow aspirate with ambiguous RT-PCR report referred to our centre for further evaluation and treatment. On conventional karyotyping, Ph chromosome along with translocations t(5;13)(q12;p13), t(15;20)(q22;p13) and monosomy 13 was observed in all 20 metaphases. A final diagnosis of CML-myeloid blast crisis with complex cytogenetics was made. Patient succumbed to death within one month of initiation of imatinib therapy.