RESUMO
The optimal conditioning for patients with higher risk MDS receiving potentially curative allogeneic haematopoietic stem cell transplant(allo-HCT) remains to be defined. This is particularly the case for patients with excess of blasts at time of allo-HCT. Sequential (Seq) conditioning, whereby chemotherapy is followed rapidly by transplant conditioning, offers an opportunity to decrease disease burden, potentially improving outcomes allo-HCT outcomes. Herein we present the only analysis comparing Seq to myeloablative (MAC) and reduced intensity conditioning (RIC) specifically focussed on MDS patients with excess of blasts at allo-HCT. 303 patients were identified in the EBMT registry, receiving RIC (n = 158), Seq (n = 105), and MAC (n = 40). Median follow-up was 67.2 months and median age at allo-HCT was 59.5 years (IQR 53.5-65.6). For the entire cohort, 3 y overall survival (OS) was 50% (95% CI 45-56%) and relapse free survival (RFS) 45% (95% CI 40-51%). No significant differences in OS (log-rank p = 0.13) and RFS (log-rank p = 0.18) were observed between conditioning protocols. On multivariable analysis, lower performance status, worse IPSS-R cytogenetics, sibling donor (compared to 8/8 MUD) and ≥20% blasts at allo-HCT were associated with worse outcomes. In conclusion, the Seq protocol did little to influence the outcome in this high-risk group of patients, with outcomes mostly determined by baseline disease risk and patient characteristics such as performance status.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Transplante Homólogo/métodos , Recidiva Local de Neoplasia , Síndromes Mielodisplásicas/terapia , Doença Crônica , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Doença Enxerto-Hospedeiro/etiologiaRESUMO
During simultaneous liver-kidney transplantation (SLK) in highly sensitized patients, donor specific anti-human leukocyte antigen antibodies (DSA, HLA) can be present prior to transplant leading to positive crossmatch, yet these recipients have relatively low incidences of acute rejection. The mechanisms and timing underlying immunologic changes that occur intra-operatively remain largely unknown. Therefore, we measured the intra- and peri-operative kinetics of anti-HLA antibodies in highly sensitized SLK recipients. In this study, pre- and post-operative blood samples were obtained from sensitized SLK candidates with documented DSA. Intra-operative samples were obtained from a sub-group of SLK recipients. Pretransplant anti-HLA antibody profiles were created and flow cytometry and anti-human globulin complement-dependent cytotoxic crossmatches were performed. Significant reductions in anti-HLA class I and II DSA were seen intra-operatively shortly after reperfusion of the liver allograft. This effect was most pronounced for anti-HLA class I DSA (mean change, -85%, p < 0.05); changes to anti-HLA class II DSA were less robust (mean change, -47%, p = 0.15). Importantly, non-DSA anti-HLA antibodies remained unchanged throughout the perioperative period, suggesting the mechanism(s) by which the liver lowers DSA levels are specific to the DSA. These data demonstrate the immunologic benefit of performing SLK is lasting and occurs very shortly after liver reperfusion.
RESUMO
Patients with acute myeloid leukaemia (AML) who lack a matched sibling or unrelated donor commonly undergo transplantation from a donor matched at 9/10 HLA-A, -B, -C, -DRB1, -DQB1 alleles, and it is unclear if a specific locus mismatch is preferable to any other. We therefore studied 937 patients with AML in complete remission transplanted using a reduced intensity conditioning regimen from an unrelated donor mismatched at a single allele. In a multivariate analysis, patient age, adverse karyotype and patient cytomegalovirus (CMV) seropositivity were correlated with decreased leukaemia free survival (LFS) and overall survival (OS). There was no significant difference in LFS or OS between patients transplanted from donors mismatched at HLA-A, -B, -C or -DRB1 in comparison to a HLA-DQB1 mismatched transplant. In a multivariate analysis, patients transplanted with a HLA-A mismatched donor had higher rates of acute graft-versus-host disease (GVHD) and non-relapse mortality (NRM) than patients transplanted with a HLA-DQB1 mismatched donor. Patient CMV seropositivity was associated with an increase in NRM and acute GVHD and reduced LFS and OS, regardless of donor CMV status. For CMV seropositive patients lacking a fully matched donor, alternative GVHD and CMV prophylaxis strategies should be considered.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia , Estudos Retrospectivos , Doadores não RelacionadosRESUMO
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with aggressive behavior and poor prognosis. We present the first retrospective analysis mapping its incidence and therapeutic outcomes in patients diagnosed and treated from 2000 to 2017 in the Czech Republic. The cohort comprised 14 patients (10 males, 4 females) with a median age at diagnosis of 39 years (range, 5-68 years). Initially, skin involvement was noted in 10 (71%) patients and bone marrow infiltration was present in 9 (64%). The first complete remission was achieved in 6/14 (43%) patients after acute lymphoblastic leukemia/lymphoma induction therapy and in 3/14 (21%) patients after acute myeloid leukemia regimen. Nine patients underwent allogeneic hematopoietic cell transplantation, with two patients achieving the first complete remission only after allogeneic transplantation. Patients undergoing allogeneic hematopoietic cell transplantation had longer overall survival than those treated without transplantation (the median survival over the period 16.4 vs. 8.1 months). Relapse of the disease was a significant predictor of mortality (p=0.05). Over the study period, patients' survival ranged from 3.3 to 44.2 months, with a median overall survival of 13 months. Our results revealed an effectivity of allogeneic hematopoietic cell transplantation on complete remission achievement in refractory/relapsed disease. The study aimed to present the actual data from the Czech Republic and thus contribute to a global understanding of BPDCN.
Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , República Tcheca , Células Dendríticas/patologia , Feminino , Neoplasias Hematológicas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Estudos Retrospectivos , Adulto JovemRESUMO
Severe corticosteroid-refractory graft-versus-host-disease (GVHD) is a major non-relapse cause of mortality and morbidity after an allogeneic hematopoietic stem cell transplantation (allo-HSCT). One of the most promising treatment options is using advanced therapy medicinal products based on mesenchymal stem cells (MSCs) immunomodulation ability. The protocols of MSC application differ in many parameters including a source of MSC, a dose, a number of doses or way of preparation of the medicinal product. The process is limited by the need for laborious and expensive manufacturing processes fraught with batch-to-batch variability. In our study, we compared the immunomodulatory effects of different MSC batches versus pooled MSC, specifically the influence on lymphocyte proliferation, the metabolic activity, and the expression of activation markers on T cells. Our goal was to determine whether the effect depends on donor-to-donor heterogeneity and if pooling of MSCs could increase their immunomodulatory ability. All tested batches showed an immunomodulatory effect, with no significant differences between the groups. Our study suggests that immunosuppressive potential is comparable in single batches and pooled products, and the use of products got from individual donors is suitable to treat corticosteroid-refractory GVHD.
Assuntos
Imunomodulação , Células-Tronco Mesenquimais/imunologia , Proliferação de Células , Separação Celular , Células Cultivadas , Técnicas de Cocultura , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Ativação Linfocitária , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Linfócitos T/citologia , Linfócitos T/imunologia , Doadores de TecidosRESUMO
BACKGROUND: Allogeneic hematopoietic stem cell transplantation is one of the therapeutic options for patients with relapsed or refractory classic Hodgkins lymphoma (cHL). In the case of dis-ease relapse after transplant, other treatment options are still limited (for example donor lymphocyte infusion, and chemother-apy with brentuximab, bendamustine, or other agents) with uncertain outcomes in terms of patient tolerance and long-term dis-ease remission. One way to achieve remission is administration of the PD-1 inhibitor nivolumab, a PD-1 checkpoint inhibitor. Nivolumab is also indicated for the treatment of cHL relapses after autologous hematopoietic stem cell transplantation. Since September 2018, nivolumab has been approved by the State Institute for Drug Control in the Czech Republic for treatment of cHL autologous hematopoietic stem cell transplantation relapse; however, treatment with nivolumab is accompanied by an increased risk of develop-ing fatal, acute graft-versus-host dis-ease. CASE: The article describes the development of resistant acute graft-versus-host disease in a patient who had received allogeneic-unrelated transplantation and nivolumab treatment for Hodgkins lymphoma relapse. CONCLUSION: Our case study, as well as the literature review, demonstrates the excellent efficacy of PD-1 inhibitors, but also cautions against the administration of these agents in patients follow-ing allogeneic hematopoietic stem cell transplantation. Administration of nivolumab to these patients should be done on a strictly individual basis in the context of known risks, and consideration should be given to other treatment options. Key words Hodgkins lymphoma - PD-1 inhibitor - nivolumab - GvHD - transplantation.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Doença Enxerto-Hospedeiro , Doença de Hodgkin/terapia , Nivolumabe/uso terapêutico , Transplante Homólogo , Humanos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , RecidivaRESUMO
BACKGROUND: The selection of optimal donor is crucial for successful hematopoietic stem cell transplantation (HSCT). Thereby, it is appropriate to know, in addition to basic human leukocyte antigen (HLA) gene matches, other immunogenic or nonimmunogenic parameters predicting the outcome of transplant. OBJECTIVE: A unified approach is necessary to provide a comprehensive view of the patient-donor compatibility characterization outside of standard HLA genes. The approach should be applicable as a tool for optimizing procedures for extended donor typing and/or verification typing of a donor. METHODS: The study used the summary, unification, and innovation of existing practical knowledge and experience of the Czech National Marrow Donor Registry of various factors beyond HLA matching with impact on transplant outcome. RESULTS: An information technology system-implemented procedure (a verification algorithm) is presented as the decision support approach for prematurely discarding less suitable donors from the transplantation process. It is intended primarily for the transplant specialist to help establish optimal procedures for verifying and determining donor critical factors. CONCLUSIONS: A process defining HLAs, killer cell immunoglobulin-like receptors, and cytokine typing strategies was proposed to provide support to a transplant specialist in refining the choice of a suitable donor.
Assuntos
Algoritmos , Sistemas de Apoio a Decisões Clínicas , Seleção do Doador/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Tchecoslováquia , Antígenos HLA/imunologia , Teste de Histocompatibilidade/métodos , Humanos , Receptores KIR/imunologia , Sistema de RegistrosRESUMO
Multiple myeloma is a malignant hemato-oncological malignancy that affects up to 600 people in the Czech Republic every year. Treatment options are under constant improvement and the autologous hematopoietic cell transplantation (Tx) remains a part of treatment protocols. Despite modern drug administration, the autologous Tx keeps its irreplaceable position and when ensuring two autologous Tx, the studies confirm a survival time more than twice as long as in non-transplant patients. However, there are no standardized procedures specifying the period in between the transplantations in more detail. Within our group, we compared the total of 66 patients who were administered a double transplant. One group underwent both planned tandem autologous Tx within a median of six months and mostly achieved just partial remission (PR) and less after the first transplant and out of disease progression. The other group only underwent the second Tx within a median of up to 14 months during a progression period or disease relapse. Both groups were comparable as far as basic parameters are concerned (age, type of induction therapy and cytogenetic risk). A significantly better treatment free survival (TFX) and overall survival (OS) were observed in the group where tandem Tx was administered. TFS was 18 months and median OS was not reached for the group of patients who received tandem Tx, while TFS was 10 months (p=0.04) and median OS was 57 months (p=0.005) for those who received delayed second Tx. In the group of patients who received second Tx during relapse, we observed that TFS and OS were shorter in those with a higher paraprotein level, thus suggesting the potential role of paraprotein level as a prognostic marker. The TFS in the subgroup with a high initial level was 4 months vs. 11 months (p=0.0016) and OS 44 months vs. 65 months (p=0.03).
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Recidiva Local de Neoplasia , Protocolos de Quimioterapia Combinada Antineoplásica , Intervalo Livre de Doença , Humanos , Prognóstico , Indução de Remissão , Transplante Autólogo , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: Alloimmune antibodies against red-blood-cell (RBC) antigens induced in susceptible individuals (responders) by transfusion, pregnancy or transplantation may have serious clinical consequences. The aim of this study was to investigate association of alloimmunization against selected RBC antigens with HLA-Class II. MATERIALS AND METHODS: A total of 230 responders (106 monoresponders and 124 multiresponders) were enrolled into the study. HLA-DRB1 and HLA-DQB1 variants were determined by PCR-SSO and their frequencies compared between the patients (patient subgroups) and 375 ethnically and regionally matched controls. RESULTS: Development of multiple RBC antibodies was associated with HLA-DRB1*15 and HLA-DQB1*06 allelic groups in the patients, with the relationship being particularly apparent in those with anti-C+D antibodies. Furthermore, DRB1*13 and DQB1*06 were more frequent in multiresponders with anti-E+c antibodies and DRB1*03 and DQB1*02 in those with anti-E+Cw. CONCLUSION: For the first time, we confirmed the association of HLA-DRB1*15 with RBC antibody multiresponder status and found HLA-Class II associations for three frequent RBC antibody combinations. Our data support the concept that HLA restriction plays an important role in the response to RBC alloantigens.
Assuntos
Eritrócitos/imunologia , Cadeias beta de HLA-DQ/imunologia , Cadeias HLA-DRB1/imunologia , Adulto , Alelos , República Tcheca , Feminino , Frequência do Gene , Genótipo , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Haplótipos , Humanos , Isoanticorpos/sangue , Masculino , GravidezRESUMO
Submitted: 27. 2. 2016.
RESUMO
Mesenchymal stromal cells (MSC) represent a promising treatment of graft-versus-host disease (GVHD) in patients after allogeneic haematopoietic stem cell transplantation. We performed co-cultivation experiments with non-specifically stimulated lymphocytes to characterize the immunosuppressive activity of MSC. MSC influenced expression of some activation antigens. CD25 expression was lower with MSC and reached 55.2 % vs. 84.9 % (CD4+, P = 0.0006) and 38.8 % vs. 86.6 % (CD8+, P = 0.0003) on day +4. Conversely, CD69 antigen expression remained higher with MSC (73.3 % vs. 56.8 %, P = 0.0009; 59.5 % vs. 49.7 %, ns) and its down-regulation along with the culture time was less pronounced. MSC reduced proliferation of the stimulated lymphocytes. The cell percentages detected in daughter generations were decreased (32.82 % vs. 10.68 % in generation 4, P = 0.0004 and 29.85 % vs. 10.09 % in generation 5, P = 0.0008), resulting in a lower proliferation index with MSC (1.84 vs. 3.65, P < 0.0001). The addition of MSC affected expression of some cytokines. Production of pro-inflammatory cytokines was decreased: IL-6 (19.5 vs. 16.3 MFI; P < 0.0001 in CD3+/CD4+ and 14.5 vs. 13.2 MFI; P = 0.0128 in CD3+/CD8+), IFN-γ (13.5 vs. 12.0 MFI; P = 0.0096 in CD3+/CD4+). Expression of anti-inflammatory IL-10 was only slightly increased after the addition of MSC (ns). The analysis confirmed the immunomodulatory activity of MSC. The functional tests have proved to be an important part of the quality control of the advanced therapy cellular product intended for GVHD treatment. Future research should focus on the interaction between MSC and the patient immune environment more closely.
Assuntos
Imunomodulação , Células-Tronco Mesenquimais/imunologia , Controle de Qualidade , Linfócitos T , Antígenos/genética , Proliferação de Células , Citocinas/metabolismo , Regulação da Expressão Gênica , Humanos , Ativação Linfocitária , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Transplante HomólogoRESUMO
Despite advances in immunochemotherapy CLL remains an incurable disease.. Allogeneic haematopoietic cell transplantation (HCT) has proven curative potential with ability to overcome adverse prognostic factors, however due to its toxicity it is generally perceived as the last option. We performed retrospective study to explore the outcomes and possible determinants of survival in the unselected consecutive cohort of 68 CLL patients (median age 59 years) receiving reduced intensity HCT as a part of salvage therapy in 2 Czech centers. The median interval from diagnosis to HCT was 69 months with median 3 of prior regimens, all patients were refractory to purine analogues. 49% of patients were transplanted with advanced (i.e. refractory or progressive disease or CR/PR>3), 38% had high risk cytogenetics. With median follow-up of 35 months the 3-year Kaplan-Meier survival probability for OS and PFS were 39% and 26%, respectively. Altogether 18 patients (26%) have relapsed or progressed. During the follow-up 41 patients died, 32 (78%) of transplant related factors (NRM), the others of relapse or disease progression.Univariate analysis failed to identify any clinical and pre- or post-transplant variables having clear prognostic significance for OS or PFS. The marginal OS advantage favoring HCT performed recently was detected (3-year OS: 31% for HCT until 2006 and 47% thereafter, p=0.0923). In multivariable hazards model only the female donors were associated with shorter OS (HR 2.278, p=0.016) whereas transplanted T-cell> 2.75x108/kg predicted inferior PFS(HR 1.957, p=0.035). No prognostic impact of donor type, age of donor and recipient, HLA mismatch, disease status pre-HCT, number of previous therapy lines, interval from dg. to HCT and number of transplanted hematopoietic cells was found. Our findings support the conclusion that alloHCT is able to overcome well known negative cytogenetic prognostic factors and that preferring male to female donors could be beneficial.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Linfocítica Crônica de Células B/terapia , Estudos de Coortes , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Estimativa de Kaplan-Meier , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The impact of in vivo T-cell depletion on transplantation outcomes in patients transplanted with reduced-intensity conditioning (RIC) remains controversial. This study assessed the outcome of 1250 adult patients with de novo AML in first CR (CR1) given PBSC from HLA-identical siblings after chemotherapy-based RIC. A total of 554 patients did not receive any form of in vivo T-cell depletion (control group), whereas antithymocyte globulin (ATG) and alemtuzumab were given in 444 and 252 patients, respectively. The incidences of grade II-IV acute GVHD were 21.4, 17.6 and 10.2% in control, ATG and alemtuzumab patients, respectively (P<0.001). In multivariate analysis, the use of ATG and the use of alemtuzumab were each associated with a lower risk of chronic GVHD (P<0.001 each), but a similar risk of relapse, and of nonrelapse mortality, and similar leukemia-free survival and OS. Further, among patients given BU-based RIC, the use of <6 mg/kg ATG did not increase the risk of relapse (hazard ratio, HR=1.1), whereas there was a suggestion for higher relapse risk in patients given î¶6 mg/kg ATG (HR=1.4, P=0.08). In summary, these data suggest that a certain amount of in vivo T-cell depletion can be safely used in the conditioning of AML patients in CR1 given PBSC after chemotherapy-based RIC.
Assuntos
Antígenos HLA/imunologia , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/terapia , Células-Tronco/citologia , Linfócitos T/citologia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Alemtuzumab , Anticorpos Monoclonais Humanizados/uso terapêutico , Soro Antilinfocitário/metabolismo , Intervalo Livre de Doença , Europa (Continente) , Feminino , Doença Enxerto-Hospedeiro , Humanos , Incidência , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Recidiva , Indução de Remissão , Estudos Retrospectivos , Irmãos , Doadores de Tecidos , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
For adults with acute leukemia, it is important to know whether the therapeutic schemes initially planned were actually implemented. The European Group for Blood and Marrow transplantation Acute Leukemia Working Party prospectively followed 695 consecutive patients who were registered at the time of HLA typing. Of 304 patients with an available matched sibling donor (MSD), SCT was planned in 264, chemotherapy in 33 and autografting in 7. For the rest, an unrelated donor (UD) search was initiated in 198. Among these, 117 were transplanted, 114 received chemotherapy and 77 underwent autografting. Probabilities of receiving a planned treatment were 60 and 65% at 1 and 2 years, respectively. Patients scheduled to receive MSD SCT had an 82% probability, whereas those scheduled to undergo UD SCT had a 57% probability, of receiving their transplant at 1 year. The only factor associated with a lower probability of MSD SCT in first remission was delayed HLA typing (HR=0.82; P=0.03). One year after enrollment, 40% of patients did not follow their initial treatment plan. Because OS was 50% only at 3 years and only 57% of the patients without a MSD underwent SCT, this suggests room for improvement in outcomes for adults with acute leukemia.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Idoso , Progressão da Doença , Intervalo Livre de Doença , Europa (Continente) , Feminino , Antígenos HLA/química , Humanos , Masculino , Pessoa de Meia-Idade , Probabilidade , Estudos Prospectivos , Sistema de Registros , Indução de Remissão , Irmãos , Resultado do Tratamento , Adulto JovemRESUMO
Chronic lymphocytic leukemia (CLL) is the most common form adult leukemia in western world. The disease is typically cha-racterized by heterogeneous clinical behavior ranging from indolent course to rapidly progressive disease. Using clinical and bio-logical factors we can stratify patients with CLL and prospectively identify those who can be expected unfavorable course. There is a special group known as ultra highrisk chronic lymphocytic leukemia with an extremely poor prognosis. These are about 10-â15% of all patients with CLL. They do not respond to standard treatment and their survival is short with a median of 2-â3 years. For highrisk patients are considered: patients with a proven TP53 defect, refractory to purine analogues or with early relapse after chemoimmunotherapy based on fludarabine ( 24 months). While the standard 1st line treatment protocol in younger patients is chemoimmunotherapy FCR, in case of ultraâhighrisk CLL other methods like allogeneic hematopoietic stem cell transplantation or clinical trials testing the new drugs should be considered. In particular, allogeneic hematopoietic stem cell transplantation is a very promising treatment modality that offers longterm disease control and cure regardless of the unfavorable CLL subtype. Transplantation treatment should be therefore considered in all younger patients with ultraâhighrisk CLL, who should be without delay referred to a center for intensive hematological treatment.
Assuntos
Leucemia Linfocítica Crônica de Células B/terapia , Antineoplásicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Vidarabina/análogos & derivados , Vidarabina/uso terapêuticoRESUMO
BACKGROUND: The Non-âHodgkin-lymphoma (NHL) brain infiltration carries a poor prognosis. Because of relatively rare incidence, we decided to share our experience. PATIENTS AND METHODS: Retrospective analysis of patients with NHL brain infiltration dia-gnosed in 2001-â2011 at our university hospital. RESULTS: Twentyâ-seven patients with median age of 61 (range 42-â82) years were analyzed. The primary diffuse large cell Bâcell lymphoma of CNS was defined in 22/â27 (81%) patients, in the others systemic NHL was present. Median positivity of the proliferative marker Kiâ67 was 80%, the number of NHL lesions 1 (1-â8), diameter 28 × 30 × 29 (11 × 16 × 20 to 85 × 76 × 65) mm. The fundamental finding in brain lymphoma MRI imaging was lesion with predominantly homogenous contrast enhancement, diffusion restriction and collateral edema. Thirteen out of 27 (48%) patients underwent lumbar puncture, and lymphoma presence in fluid was detected in only two of them. The most frequent symptoms were limb paresis or hemiparesis (55%), bradypsichysm (22%), expressive aphasia (22%), cephalea (18%). Corticosteroid therapy, as a primary treatment option, was indicated in 15% of patients with a median overall survival of one month, CNS radiotherapy in 37% with a median survival of three months, and chemotherapy in 48% patients with a median overall survival 10 (2-â45) months. CONCLUSION: The brain lymphomas are rare and prognostically very unfavorable affection. When specifying brain focal lesions on MRI, it is necessary to consider this etiology and to elect imaging protocols with contrast agents and diffusion weighted sequence. Biopsy should be performed prior to start of corticosteroid therapy. Intensive chemotherapy or radiotherapy indication must be individually considered, and proposed treatment should be initiated immediately with a potential for somewhat prolonged survival.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/patologia , Encéfalo/patologia , Linfoma não Hodgkin/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Feminino , Humanos , Linfoma não Hodgkin/mortalidade , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de SobrevidaRESUMO
Older patients with AML have poor prognosis after chemotherapy and allo-SCT was historically limited to the young patients. In the multicentre retrospective study we analyzed 96 consecutive AML patients ≥ 50 years allografted with related (n=59) or unrelated (n=37) donor. The 2- year OS and DFS rates were 45 % and 42 % for the whole group. The corresponding figures for related patients were 48% and 42% whereas for unrelated 42% and 42%, respectively (OS p=0,721, DFS p= 0,896). The cumulative incidences of relapse (28% of all patients) and NRM mortality (26%) were low with no significant differences among related and unrelated cohorts. Multivariate analysis revealed the only major independent variables associated with an inferior OS were unfavourable cytogenetics (RR 3.36; CI 1.66-6.83; p=0.001) and advanced disease status (RR 2.30; CI 1.21-4.37; p=0.011). Unfavourable cytogenetics (RR 3.00; CI 1.50-5.99; p=0.002) and advanced disease at SCT (RR 2.27; CI 1.22-4.22; p=0.009) were also the only independent variables associated with inferior DFS. In conclusion, our analysis indicates that outcomes of allografted AML patients aged ≥ 50 years are determined by cytogenetic risk category and disease status at transplantation and not by the type of donor.
Assuntos
Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Doadores de Tecidos , Idoso , Tchecoslováquia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Transplante Homólogo , Resultado do TratamentoRESUMO
BACKGROUND: Acute myeloid leukemia is a malignant disease characterized by clonal expansion of immature hematopoietic cells - myeloblasts - in the bone marrow. Intensive chemotherapy treatment in elderly patients (over 60) has disappointing results. In these patients, conservative treatment, including compensation of deficiency of red blood cells and platelets by transfusions and treatment of infectious complications is recommended. Also, relatively new treatment with hypometyl agents (azacytidine, decitabine) could be used. DESIGN: The idea of this article is to present a spontaneous remission phenomenon, which has not been published in Czech literature yet. In this article, we present 2 case studies of our patients who were diagnosed with acute myeloid leukemia, were not treated with chemotherapy and spontaneously reached remission of acute myeloid leukemia. CONCLUSION: The mechanisms of the spontaneous remission remain unclear, but we assume positive effect of a severe systemic infection or previous applications of blood transfusions. Antibodies in blood transfusions and a strong immune response to sepsis may have contributed to spontaneous remission.
Assuntos
Leucemia Mieloide Aguda , Remissão Espontânea , Idoso , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The new HLA-A*02:395N allele differs from A*02:01:01 at one nucleotide position in the exon 2.
Assuntos
Alelos , Códon de Terminação/genética , Antígeno HLA-A2/genética , Códon sem Sentido/genética , República Tcheca , Bases de Dados Genéticas , Éxons/genética , Feminino , Teste de Histocompatibilidade , Humanos , Polimorfismo de Nucleotídeo Único , Doadores de TecidosRESUMO
Induction of molecular chimerism through genetic modification of bone marrow is a powerful tool for the induction of tolerance. Here, we demonstrate for the first time that expression of an allogeneic MHC class II gene in autologous bone marrow cells, resulting in a state of molecular chimerism, induces tolerance to MHC class II mismatched skin grafts, a stringent test of transplant tolerance. Reconstitution of recipients with syngeneic bone marrow transduced with retrovirus encoding H-2I-A(b) (I-A(b)) resulted the long-term expression of the retroviral gene product on the surface of MHC class II-expressing bone marrow-derived cell types. Mechanistically, tolerance was maintained by the presence of regulatory T cells, which prevented proliferation and cytokine production by alloreactive host T cells. Thus, the introduction of MHC class II genes into bone marrow-derived cells through genetic engineering results in tolerance. These results have the potential to extend the clinical applicability of molecular chimerism for tolerance induction.