RESUMO
BACKGROUND: Infants are subjected to hematopoietic stem cell transplantation (HSCT) due to malignant and non-malignant diseases. However, specific data concerning the outcome and transplantation-related complications in infants, as a separate age group, are limited. Our aim was to evaluate the impact of infancy on the outcome, toxicity, and complications after HSCT. METHODS: We retrospectively analyzed data of 55 infants that underwent HSCT in our unit from May 1997 until February 2020, emphasizing on the probability of overall survival (OS) and the cumulative incidence (CI) of transplantation-related mortality (TRM) and complications. RESULTS: We report a probability of OS of 61%, a CI of TRM at day 100 and 365 post transplantation of 22% and 30%, respectively, and additionally a CI of graft failure, acute graft-versus-host disease (GvHD), and infectious complications, 18%, 44%, and 39%, respectively. No statistically significant association was detected between the above mentioned parameters and diagnosis, the use of myeloablative or non-myeloablative/reduced toxicity conditioning regimens or the type of donor. CONCLUSIONS: We conclude that HSCT in infancy is associated with significant mortality and morbidity. This is possibly attributed to endogenous, age-related factors. More specifically, infants may be at a higher risk of toxicities due to the immaturity of developing vital organs and the deficiency of the newly adopted immune system that predisposes them to infectious complications. The development of GvHD further augments the danger of infections, in a potential vice-versa relationship. Moreover, there are few data on pharmacokinetics of chemotherapy agents, making safe and efficacious drug administration hard.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Morbidade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversosAssuntos
Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/epidemiologia , Paraproteinemias/complicações , Gerenciamento Clínico , Feminino , Humanos , Incidência , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , Masculino , Paraproteinemias/diagnóstico , Paraproteinemias/epidemiologia , Avaliação de Resultados da Assistência ao Paciente , Prognóstico , Vigilância em Saúde Pública , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Rituximab/uso terapêuticoRESUMO
The coexistence of a myeloid and a lymphoid neoplasm in the same patient is a rare finding. We retrospectively searched the records of the Hematology Division of the Second Department of Internal Medicine and Research Institute at Attikon University General Hospital of Athens from 2003 to 2018. Nine cases have been identified in a total of 244 BCR-/ABL1- negative MPN and 25 MDS/MPN patients and 1062 LPD patients referred to our institution between 2003 and 2018. Each case is distinct in the diversity of myeloid and lymphoid entities, the chronological occurrence of the two neoplasms, and the patient clinical course. All of them exhibit myeloproliferative (6 JAK2 V617F-positive cases) and lymphoproliferative features, with 1 monoclonal B-cell lymphocytosis (MBL), 3 B-chronic lymphocytic leukemias (B-CLL), 3 B-non-Hodgkin lymphomas (B-NHL), 1 multiple myeloma (MM), and 1 light and heavy deposition disease (LHCDD), while in three cases myelodysplasia is also present. The challenges in identifying and dealing with these rare situations in everyday clinical practice are depicted in this article.
RESUMO
The aim of the present study was to identify biomarkers predictive of the outcome of patients with high-risk myelodysplastic syndrome and oligoblastic acute myeloid leukemia (AML) treated with 5-azacytidine (AZA). We prospectively examined the association between NK-cytotoxic activity, myeloid-derived suppressor cells (MDSCs), and T-regulatory cells (Tregs) on the overall survival (OS) of patients. Patients with NK-cytotoxicity above a critical threshold had a longer duration of response and survived longer than patients with severe impairment of NK-cytotoxicity. The numbers of MDSCs, and Tregs in the PB of patients after a short exposure to AZA were not different from normal donors. In conclusion, the results of our study suggest that the therapeutic activity of AZA is at least partly mediated by an immunomodulatory effect. To our knowledge, this is the first study reported so far, that shows a positive correlation between NK cytotoxicity and OS of AZA-treated patients.
Assuntos
Citotoxicidade Imunológica , Células Matadoras Naturais/imunologia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/mortalidade , Síndromes Mielodisplásicas/imunologia , Síndromes Mielodisplásicas/mortalidade , Idoso , Idoso de 80 Anos ou mais , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Azacitidina/uso terapêutico , Biomarcadores , Linhagem Celular Tumoral , Feminino , Humanos , Células Matadoras Naturais/metabolismo , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/tratamento farmacológico , Prognóstico , Curva ROCRESUMO
Plasmablastic lymphoma (PBL) is a rare, aggressive type of B-cell non-Hodgkin lymphoma with the vast majority of patients responding poorly to treatment or progressing shortly thereafter. Cyclophosphamide-doxorubicin-vincristine-prednisolone (CHOP) or CHOP-like regimens have disappointing results in this setting. We report a case of PBL arising in a previously diagnosed myelodysplastic/myeloproliferative (MDS/MPN) with ring sideroblasts and thrombocytopenia (RS-T), HIV-negative patient treated with the combination of CHOP and bortezomib. The patient achieved complete metabolic response, which has lasted one year, longer by far than would have been expected with the sole use of CHOP.
RESUMO
MicroRNA-20b-5p (miR-20b-5p) is part of the miR-106a/363 cluster and a member of the cancer-related miR-17 family. miR-20b-5p regulates important transcription factors, including hypoxia-inducible factor 1 (HIF1) and signal transducer and activator of transcription 3 (STAT3). Recently, the dysregulation of miR-20b-5p expression has been observed in many B-cell lymphomas and T-cell leukemias. In this research study, we examined the putative prognostic value of miR-20b-5p in CLL. Therefore, total RNA was isolated from peripheral blood mononuclear cells (PBMCs) collected from 88 CLL patients; next, total RNA was polyadenylated and first-strand cDNA was synthesized, using an oligo-dT-adapter primer. miR-20b-5p expression was quantified using an in-house-developed real-time quantitative PCR assay. Kaplan-Meier OS analysis and bootstrap univariate Cox regression showed that high miR-20b-5p expression predicts better OS for CLL patients (pâ¯<â¯0.001). Interestingly, miR-20b-5p overexpression retains its favorable prognostic role in CLL patients of intermediate risk or stratified according to established prognostic factors [CD38 expression and mutational status of the immunoglobulin heavy chain variable (IGHV) region]. In conclusion, miR-20b-5p is a potential independent molecular biomarker of favorable prognosis in CLL.
Assuntos
Biomarcadores Tumorais , Regulação Leucêmica da Expressão Gênica , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucócitos Mononucleares/metabolismo , MicroRNAs/genética , Idoso , Linhagem Celular Tumoral , Feminino , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Estimativa de Kaplan-Meier , Leucemia Linfocítica Crônica de Células B/diagnóstico , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
The hypoxia inducible factor 1 (HIF1) is a heterodimeric transcription factor that ultimately regulates cellular responses to changes in oxygen tension. In this study, we examined the potential diagnostic and prognostic potential of the mRNA expression of HIF1 regulatory α-subunit (HIF1A) in chronic lymphocytic leukemia (CLL). For this purpose, total RNA was isolated from peripheral blood mononuclear cells collected from 88 CLL patients and 33 non-leukemic blood donors, and poly(A)-RNA was reversely transcribed. HIF1A mRNA levels were quantified using real-time PCR. Kaplan-Meier survival analysis showed that high HIF1A mRNA expression predicts inferior overall survival for CLL patients (p=0.001). Bootstrap univariate Cox regression analysis confirmed that HIF1A mRNA overexpression is a significant unfavorable prognosticator in CLL (hazard ratio=3.75, bias-corrected and accelerated 95% confidence interval=1.43-24.36, bootstrap p<0.001), independent of other established prognostic factors, including CD38 expression, the mutational status of the immunoglobulin heavy chain variable region (IGHV), and the clinical stage (Binet or Rai stage) or risk group (p<0.001 in all cases). Interestingly, HIF1A mRNA positivity retains its unfavorable prognostic value in distinct subgroups of patients, stratified according to established prognostic factors. Thus, HIF1A mRNA overexpression can be regarded as a promising, independent molecular biomarker of unfavorable prognosis in CLL.
Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Leucemia Linfocítica Crônica de Células B/diagnóstico , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Prognóstico , RNA Mensageiro/análise , Taxa de SobrevidaRESUMO
Accumulated data indicate a significant role of T cell dysfunction in the pathogenesis of chronic lymphocytic leukemia. In CLL, regulatory T cells are significantly higher and show lower apoptotic levels compared to healthy donors. We demonstrate that CLL derived CD4+CD25-CD127- and CD4+CD25lowCD127- subpopulations share a common immunophenotypic profile with conventional Tregs and are associated with advanced stage disease. We further provide evidence that the increased number of Tregs contributes indirectly to the proliferation of the CLL clone, by suppressing the proliferation of Teffs which in turn suppress CLL cells. These data are further supported by our observations that CLL derived Tregs appear rather incapable of inducing apoptosis of both normal B cells and CLL cells, in contrast to normal Tregs, suggesting an immunoediting effect of CLL cells on Tregs which negatively affects the functionality of the latter and contributes to the failure of Tregs in CLL to efficiently eliminate the abnormal clone.