Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Receptores de Antígenos Quiméricos , Humanos , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/patologia , Imunoterapia Adotiva , Custos e Análise de Custo , Atenção à Saúde , Receptores de Antígenos de Linfócitos T , Antígenos CD19RESUMO
A 52-year-old patient developed pancytopenia of unknown origin 1.5 years after allogeneic stem cell transplantation. The bone marrow aspirate showed visceral leishmaniasis (VL). Although VL is distributed world-wide, the incidence in patients after allogeneic stem cell transplantation is rare.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leishmania donovani/isolamento & purificação , Leishmaniose Visceral/diagnóstico , Pancitopenia/etiologia , Exame de Medula Óssea , Doença Enxerto-Hospedeiro , Humanos , Leishmaniose Visceral/sangue , Leishmaniose Visceral/parasitologia , Pessoa de Meia-Idade , Infecções Oportunistas/sangue , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/parasitologiaRESUMO
We screened 136 patients with myelofibrosis and a median age of 58 years who underwent allogeneic stem cell transplantation (AHSCT) for molecular residual disease for JAKV617F (n=101), thrombopoietin receptor gene (MPL) (n=4) or calreticulin (CALR) (n=31) mutation in peripheral blood on day +100 and +180 after AHSCT. After a median follow-up of 78 months, the 5-year estimated overall survival was 60% (95% confidence interval (CI): 50-70%) and the cumulative incidence of relapse at 5 years was 26% (95% CI: 18-34%) for the entire study population. The percentage of molecular clearance on day 100 was higher in CALR-mutated patients (92%) in comparison with MPL- (75%) and JAKV617F-mutated patients (67%). Patients with detectable mutation at day +100 or at day +180 had a significant higher risk of clinical relapse at 5 years than molecular-negative patients (62% vs 10%, P<0.001) and 70% vs 10%, P<0.001, respectively) irrespectively of the underlying mutation. In a multivariate analysis, high-risk diseases status (hazard ratio (HR) 2.5; 95% CI: 1.18-5.25, P=0.016) and detectable MRD at day 180 (HR 8.36, 95% CI: 2.76-25.30, P<0.001) were significant factors for a higher risk of relapse.
Assuntos
Calreticulina/genética , Janus Quinase 2/genética , Neoplasia Residual/genética , Patologia Molecular/métodos , Mielofibrose Primária/diagnóstico , Receptores de Trombopoetina/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Pessoa de Meia-Idade , Mutação , Neoplasia Residual/diagnóstico , Neoplasia Residual/mortalidade , Mielofibrose Primária/genética , Mielofibrose Primária/mortalidade , Recidiva , Taxa de Sobrevida , Transplante HomólogoAssuntos
Candida tropicalis/isolamento & purificação , Candidíase/diagnóstico , Fusariose/diagnóstico , Fusarium/isolamento & purificação , Encefalite Infecciosa/diagnóstico , RNA Fúngico/genética , Análise de Sequência de RNA , Idoso , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Candidíase/microbiologia , Coinfecção/diagnóstico , Coinfecção/microbiologia , Terapia Combinada , Evolução Fatal , Fusariose/microbiologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Hospedeiro Imunocomprometido , Encefalite Infecciosa/microbiologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/terapia , MasculinoAssuntos
Calreticulina/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Mutação , Mielofibrose Primária/terapia , Adulto , Idoso , Análise Mutacional de DNA , Humanos , Pessoa de Meia-Idade , Mielofibrose Primária/genética , Mielofibrose Primária/mortalidade , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do TratamentoRESUMO
Allogeneic hematopoieteic stem cell transplantation (HSCT) is the only curative treatment for myelofibrosis (MF), but it is still associated with significant risks and complications. One of these complications is poor graft function, but incidence and risk factors have not been studied yet. We retrospectively studied a cohort of 100 patients with primary MF or post-ET/PV MF who received a reduced-intensity HSCT in our center. The cumulative incidence of primary leukocyte engraftment was 98%. The cumulative incidence of poor graft function was 17% and all of the cases occurred before day 100 after HSCT at a median of 49 days (range 24-99 days). In the univariate analysis, age as continuous parameter (P=0.05; hazard ratio 1042) and persistence of significant splenomegaly (defined as palpable splenomegaly of ⩾10 cm under costal margin) at d+30 after HSCT (33% vs 12%; P=0.05) showed an increased cumulative incidence of poor graft function. In conclusion, the incidence of poor graft function after HSCT for MF is rather high, but did not influence survival. Persistence of splenomegaly after transplantation is a significant factor for poor graft function in myelofibrosis patients. Whether therapeutic reduction of splenomegaly before HSCT would result in a lower incidence of poor graft function should be investigated in future studies.
Assuntos
Aloenxertos/fisiopatologia , Transplante de Células-Tronco Hematopoéticas/métodos , Mielofibrose Primária/terapia , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mielofibrose Primária/complicações , Estudos Retrospectivos , Fatores de Risco , Esplenomegalia , Condicionamento Pré-Transplante/métodosAssuntos
Calreticulina/genética , Transplante de Células-Tronco Hematopoéticas , Reação em Cadeia da Polimerase , Mielofibrose Primária/genética , Alelos , Calreticulina/metabolismo , Humanos , Imunoterapia/métodos , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Mutação , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/metabolismo , Recidiva , Indução de Remissão , Fatores de TempoRESUMO
TBI-based preparative regimens are considered as standard conditioning therapy for allogeneic stem cell transplantation (AHSC) in patients with ALL. We investigated toxicity and efficacy of a non-TBI-based regimen consisting of treosulfan, etoposide and cyclophosphamide for ALL within a prospective study. Major inclusion criteria were CR and non-eligibility for TBI. Fifty patients with a median age of 46.5 years (range, 18-64) were included. Donors were HLA-identical sibling (n=8), matched (n=42) or mismatched (n=10) unrelated. The toxicity was moderate, resulting in a cumulative incidence of non-relapse mortality (NRM) at 1 year of 8% (90% confidence interval: 2-15%). Acute GvHD grade II-IV and grade III/IV was noted in 53% and 14%, respectively. Chronic GvHD at one year was seen in 41%. After a median follow-up of 24 months the cumulative incidence of relapse was 36% (90% confidence interval: 24-48) and 51% (90% confidence interval: 37-65) at 1 and 2 years, respectively. The estimated 2-year disease-free and overall survivals were 36 and 48%, respectively. Treosulfan, etoposide and cyclophosphamide followed by AHSC has a favorable toxicity profile with low NRM and therefore represents a potential alternative regimen for ALL in 1. CR (NCT00682305).
Assuntos
Agonistas Mieloablativos/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Transplante de Células-Tronco , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Aloenxertos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Bussulfano/análogos & derivados , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Condicionamento Pré-Transplante/efeitos adversosRESUMO
Despite major improvements in allogeneic hematopoietic cell transplantation over the past decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Preclinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n=54, all grades III or IV) or SR-cGVHD (n=41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1-7) and SR-cGVHD (1-10). The overall response rate was 81.5% (44/54) in SR-aGVHD including 25 complete responses (46.3%), while for SR-cGVHD the ORR was 85.4% (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was 6.8% (3/44) and 5.7% (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (67.3-90.7%, 95% confidence interval (CI)) and 97.4% (92.3-100%, 95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and cytomegalovirus-reactivation were observed during ruxolitinib treatment in both SR-aGVHD (30/54, 55.6% and 18/54, 33.3%) and SR-cGVHD (7/41, 17.1% and 6/41, 14.6%) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial.
Assuntos
Corticosteroides/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Neoplasias Hematológicas/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pirazóis/uso terapêutico , Terapia de Salvação , Adulto , Idoso , Animais , Modelos Animais de Doenças , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Janus Quinases/antagonistas & inibidores , Masculino , Camundongos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nitrilas , Prognóstico , Pirimidinas , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo , Adulto JovemAssuntos
Transplante de Células-Tronco Hematopoéticas , Janus Quinases/antagonistas & inibidores , Mielofibrose Primária/tratamento farmacológico , Pirazóis/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Pirazóis/efeitos adversos , Pirimidinas , Transplante HomólogoRESUMO
To investigate the impact of anti-lymphocyte globulin (ATG-Fresenius) as part of the HLA-sibling transplantation, we evaluated 238 patients (median age 48 years) with different diagnoses (AML, ALL, CML and lymphoproliferative disorders). A total of 79 patients received ATG and 159 patients did not. In the ATG group, there were more HLA-mismatched donors (6% vs 1%, p=0.02), bad risk patients (70% vs 55%, P=0.04), reduced intensity conditioning (RIC) regimens (65% vs 34%, P=<0.001) and older patients (median age 51 vs 48 years, P=0.002). The median time to leukocyte engraftment was significantly faster in the non-ATG group (13 vs 15 days, P < 0.001). EBV reactivation was more often seen in the ATG group (9% vs 2%, P=0.05). Cumulative incidence of acute and chronic GVHD was less observed in the ATG group (27% vs 40%, P=0.004, and 33% vs 54%, P=0.002). The cumulative incidence rates of non-relapse mortality and of relapse at 5 years were 20 and 34%, respectively, for ATG and 34 and 29%, respectively, for non-ATG (P=0.06 and P=0.3). ATG can prevent GVHD without an obvious risk of relapse but should be confirmed in a randomized study.
Assuntos
Soro Antilinfocitário/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Doenças Hematológicas/terapia , Depleção Linfocítica , Transplante de Células-Tronco de Sangue Periférico , Linfócitos T/citologia , Adolescente , Adulto , Idoso , Criança , Ensaios Clínicos como Assunto , Intervalo Livre de Doença , Feminino , Antígenos HLA/imunologia , Humanos , Incidência , Leucócitos/citologia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Risco , Irmãos , Condicionamento Pré-Transplante , Transplante Homólogo , Adulto JovemAssuntos
Antígenos CD19/imunologia , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/cirurgia , Síndromes Mielodisplásicas/imunologia , Síndromes Mielodisplásicas/cirurgia , Neprilisina/imunologia , Células Precursoras de Linfócitos B/imunologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
In a retrospective study of 168 patients with AML in CR who underwent allo-SCT, we compare the impact of young unrelated donors (UD) vs older matched related donors (MRD) on 5-year OS (5-yr OS). Median follow-up was 59 months and median donor age was 39 years, which was used as cutoff for young vs older donors. Kaplan-Meier-estimated 5-yr OS was better with UD ≤39 years vs MRD >39 years (66% vs 34%, P=0.001). In multivariate analysis, only donor age and cytogenetic risk impacted 5-yr OS. Compared with UD ≤39 years, both MRD >39 years (relative risk (RR): 4.31, P=0.001) and UD >39 years (RR: 2.14, P=0.03) were associated with poorer 5-yr OS. Standard-risk cytogenetics was associated with better 5-yr OS compared with bad-risk cytogenetics, (RR: 0.53, P=0.02). Subgroup analyses of patients ≥50 years (n=76) revealed similar results, with 5-yr OS of 62% for UD ≤39 yrs and 26% for MRD >39 yrs (P=0.022). In patients undergoing allo-HSCT for AML, young UD may improve outcome as compared with older MRD.
Assuntos
Seleção do Doador/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/cirurgia , Doadores Vivos , Adulto , Fatores Etários , Seleção do Doador/normas , Feminino , Transplante de Células-Tronco Hematopoéticas/normas , Humanos , Masculino , Indução de Remissão , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoAssuntos
Medula Óssea/patologia , Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas/patologia , Adulto , Idoso , Feminino , Humanos , Leucemia Mielomonocítica Crônica/patologia , Leucemia Mielomonocítica Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/cirurgia , Condicionamento Pré-TransplanteRESUMO
Relapse after dose-reduced allograft in advanced myeloma patients remains high. To reduce the risk of relapse, we investigated a myeloablative toxicity-reduced allograft (aSCT) consisting of i.v. BU and CY followed by lenalidomide maintenance therapy in 33 patients with multiple myeloma (MM) who relapsed following an autograft after a median of 12 months. The cumulative incidence of non-relapse mortality at 1 year was 6% (95% confidence interval (CI): 0-14). After a median interval of 168 days following aSCT, 24 patients started with a median dose of 5 mg (r, 5-15) lenalidomide without dexamethasone. During follow-up, 13 patients discontinued lenalidomide owing to progressive disease (n=6), GvHD (n=3), thrombocytopenia (n=2), or fatigue (n=2). Major toxicities of lenalidomide were GvHD II-III (28%), viral reactivation (16%), thrombocytopenia (III-IV°,16%), neutropenia (III/IV°, 8%), peripheral neuropathy (I/II°, 16%), or other infectious complication (8%). Cumulative incidence of relapse at 3 years was 42% (95% CI: 18-66). The 3-year estimated probability of PFS and OS was 52% (95% CI: 28-76) and 79% (95% CI: 63-95), respectively. Toxicity-reduced myeloablative allograft followed by lenalidomide maintenance is feasible and effective in relapsed patients with MM, but the induction of GvHD should be considered.
Assuntos
Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Mieloma Múltiplo/terapia , Transplante de Células-Tronco/métodos , Talidomida/análogos & derivados , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Lenalidomida , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/cirurgia , Recidiva , Terapia de Salvação , Transplante de Células-Tronco/efeitos adversos , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo , Adulto JovemRESUMO
Estimation of relapse risk in AML after allo-SCT is critical. The negative impact of increased blast count post transplant is widely accepted. Here, we studied cellularity and dysplasia in BM cytomorphology on days 30 and 100 in 112 AML patients who achieved haematological CR after SCT. Overall cellularity on day 30 was normal in 45.3%, reduced in 37.3% and increased in 17.3% of samples (day 100: normal: 54.8%; reduced: 38.7%; and increased: 6.5%). Dysplasia in ≥10% of cells was frequent on day 30 (granulopoiesis: 25.0% of samples; erythropoiesis: 34.6%; and megakaryopoiesis: 47.7%) and also on day 100. Relapses were less frequent in patients with normal BM cellularity on day 30 (7/34; 20.6%) when compared with reduced (9/28; 32.1%) or increased cellularity (10/13; 76.9%; P = 0.001). Estimated 2-year OS was 59.0% for patients with normal overall cellularity, followed by patients with increased (44.0%) and reduced cellularity (31.4%, P = 0.009). In contrast, cellularity at day 100 and dysplasia at days 30 and 100 did not correlate with outcome measures. Thus, in the cohort studied, BM cellularity represents a prognostic parameter for the post-transplant period in AML patients. Dysplasia seems to be an unspecific phenomenon in the cohort analysed.
Assuntos
Células da Medula Óssea/patologia , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/cirurgia , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Idoso , Células da Medula Óssea/metabolismo , Citodiagnóstico/métodos , Citogenética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Fatores de Risco , Quimeras de Transplante , Resultado do Tratamento , Adulto JovemAssuntos
Antígenos CD34/sangue , Mielofibrose Primária/sangue , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/terapia , Transplante de Células-Tronco , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mielofibrose Primária/genética , Prognóstico , Estudos Retrospectivos , Transplante HomólogoRESUMO
Mannan-binding lectin (MBL) deficiency is determined by MBL gene polymorphisms and is associated with an increased infection risk. To clarify the role of MBL in Allo-SCT, 131 recipients-donors were analysed. MBL genotypes were determined by PCR and heteroduplex analyses, MBL serum levels by ELISA, and MBL oligomers by western blotting. MBL levels <400 ng/ml were associated with increased susceptibility to fungal pneumonia (7/12 vs 35/111; P=0.04, adjusted P=0.002), HSV/VZV (7/12 vs 26/111; P=0.03), CMV reactivation and acute GVHD. Donor genotypes had no influence. Pre-SCT MBL levels corresponded to recipients' genotypes (P<0.001), changed significantly post-SCT, but were not influenced by donors' genotypes. MBL oligomer profiles were similar pre-/post-SCT. Cultured CD34+ cells were found not to synthesise MBL. In conclusion, low MBL levels pre-transplant predisposed patients to sepsis, fungal and viral infection. Donors' MBL genotypes did not influence infection rates. Prospective studies should clarify the importance of MBL as a prelude for MBL replacement after SCT.
Assuntos
Lectina de Ligação a Manose/genética , Transplante de Células-Tronco/efeitos adversos , Adolescente , Adulto , Idoso , Suscetibilidade a Doenças , Feminino , Genótipo , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/genética , Humanos , Masculino , Lectina de Ligação a Manose/sangue , Pessoa de Meia-Idade , Micoses/etiologia , Fenótipo , Estudos Prospectivos , Estudos Retrospectivos , Sepse/etiologia , Transplante de Células-Tronco/mortalidade , Doadores de Tecidos , Transplante HomólogoRESUMO
We investigated efficacy and toxicity of lenalidomide in 24 heavily pretreated myeloma patients with a median age of 59 years (range: 37-70) and relapse after allo-SCT. Lenalidomide was given at a dose of 15 mg (n=4), or 25 mg (n=20), orally once daily on day 1 to day 1 every 28 days, with (n=20) or without (n=4) DHAP. The median number of lenalidomide cycles was five (range: 2-17). Major side effects were leukopenia (grade 4: 4%, grade 3: 21% and grade 2: 17%) and thrombocytopenia (grade 3: 17% and grade 2: 29%); infectious complications were observed in 50%. Non-hematological toxicity consisted of muscle cramps (n=9), fatigue (n=5) and constipation (n=2). Mild grade I-II GVHD was seen in three patients. Response was achieved in 66%: CR in 8%, VGPR in 8%, PR in 50% and SD in 13%. The median time to progression was 9.7 months (95% confidence interval (CI): 7.5-11.9), and median OS was 19.9 months (95% CI: 17.3-22.5). Immunomonitoring after lenalidomide showed significant increase of activated NK (NKp44(+)) and T (HLA-DR(+)) cells, as well as regulatory T cells (CD4(+), CD25(+), CD127(lo)), supporting an immunomodulating anti-myeloma effect of lenalidomide.