RESUMO
BACKGROUND: Despite advances in the field, diagnosis and management of the wide spectrum of neurological events post allogeneic hematopoietic cell transplantation (alloHCT) remain challenging. Therefore, we investigated their incidence, diagnosis, management and long-term prognosis in alloHCT recipients. METHODS: We retrospectively recorded data from consecutive alloHCT recipients with or without neurological complications in our center. RESULTS: Among 758 alloHCT recipients, 127 (16.8%) presented with neurological complications. Complications developed in central nervous system (89.7%) during the late post-transplant period. Neurological adverse events included a wide spectrum of infectious and non-infectious etiologies. With a median follow-up of 11.4 months, incidence of chronic graft-versus-host disease (GVHD) was 52.8%, relapse mortality 48.6%, transplant-related mortality 39.1% and 5-year overall survival (OS) 25.8% in patients with neurological complications. Timing of appearance of neurological complications, early or late, was associated only with acute and chronic graft-versus-host-disease/GVHD. Independent pre-transplant risk factors of neurological complications in the multivariate model were unrelated or alternative donors, ALL diagnosis and non-myeloablative conditioning. In multivariate analysis of post-alloHCT events, favorable OS was independently associated with resolution of neurological syndromes, absence of chronic GVHD and sibling transplantation. In our cohort, 10-year OS was significantly lower in patients with neurological complications and independently associated with acute and chronic GVHD, relapse, fungal and bacterial infections and neurological complications. CONCLUSIONS: Our large study with long-term follow-up highlights the wide spectrum of neurological complications in alloHCT. Accurate recognition is required for adequate management, a major determinant of survival. Thus, long-term increased awareness and collaboration between expert physicians is warranted.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/mortalidade , Adulto , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Mortalidade/tendências , Doenças do Sistema Nervoso/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/tendências , Adulto JovemRESUMO
BACKGROUND: Graft vs host disease (GVHD) is the most severe complication of allogeneic hematopoietic cell transplantation. Conventional immunosuppressive therapy increases morbidity and mortality without improving survival. Extracorporeal photopheresis (ECP) has been introduced as an alternative treatment in steroid-dependent and steroid-refractory disease. STUDY DESIGN AND METHODS: We studied the safety and efficacy of ECP as a second- or third-line treatment in GVHD. RESULTS: ECP was administered in 21 patients with grade III-IV acute GVHD and 88 patients with extensive chronic GVHD, without ECP-related adverse events. Eight patients receiving four or less ECP sessions were not further analyzed. The majority of acute GVHD patients (84%) presented partial (15) or complete (1) response to ECP. Immunosuppression was reduced in 10 of 19 patients and ceased in 1 of 19 patients. One-year cumulative incidence (CI) of transplant-related mortality (TRM) (17.6%) was associated with the lack of response to ECP and steroid refractoriness. With a follow-up of 17.5 (1.8-58.3) months, 1-year overall survival (OS) (52.5%) was independently associated with a higher number of ECP sessions. Regarding chronic GVHD, complete response was achieved in 35 patients, whereas partial response in 25 patients, leading to an overall response rate of 73%. Cutaneous sclerosis manifestations were associated with higher response rates. With a follow-up of 68.1 (5.4-283.1) months, 5-year CI of TRM (24.1%) was associated only with a number of ECP sessions. The 5-year OS (64.5%) was independently associated with number of ECP sessions and cutaneous manifestations. CONCLUSION: Our findings suggest that ECP is safe and effective for GVHD and should be considered early in the course of GVHD, before irreversible end-organ damage has been established.
Assuntos
Doença Enxerto-Hospedeiro/terapia , Fotoferese/métodos , Adulto , Resistência a Medicamentos , Seguimentos , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Terapia de Imunossupressão/métodos , Terapia de Imunossupressão/mortalidade , Pessoa de Meia-Idade , Fotoferese/efeitos adversos , Fotoferese/mortalidade , Indução de Remissão , Esteroides/farmacologia , Análise de Sobrevida , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Anti-thymocyte globulin (ATG)-based immunosuppressive therapy is often used in allogeneic hematopoietic cell transplantation to reduce incidence and severity of graft-versus-host disease (GVHD). PATIENTS AND METHODS: In our observational study, ATG (rabbit, Thymoglobulin; Sanofi, 5 mg/kg) was administered as a standardized part of the conditioning in 97 patients with a median age of 34 years (range, 14-58 years), allotransplanted for hematologic malignancies from matched (8/8; n = 52) and allele or antigen mismatched (7/8; n = 43 and 6/8; n = 2) unrelated donors. RESULTS: Five-year overall survival (OS) was 46.9%, disease-free survival was 46.5%, and treatment-related mortality was 20.6%, with a median follow-up of 29 months (range, 1-145 months). Acute GVHD (grade ≥ II) cumulative incidence was 26.9% in matched versus 50.5% in mismatched patients (P = .060), whereas extensive chronic GVHD was 45.6% versus 50%, respectively (P = .310). Five-year OS was 62.2% for the matched patients and 27.9% for the mismatched patients (P = .003) owing to a higher treatment-related mortality rate in mismatched patients (P = .032). In multivariate analysis including age, gender, time until transplantation, disease phase, mismatched donor, ABO mismatch, number of CD34+ infused, acute and chronic GVHD, the significant unfavorable factors for OS were HLA mismatch and advanced disease phase. CONCLUSION: A relatively low-dose ATG is effective in acute GVHD prophylaxis, leading to promising survival rates in matched transplants. Further comparative studies with adjusted ATG dose depending on Human leukocyte antigen disparity or alternative donors are warranted.
Assuntos
Soro Antilinfocitário/administração & dosagem , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Imunossupressores/administração & dosagem , Transplante de Células-Tronco de Sangue Periférico , Doadores não Relacionados , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/mortalidade , Teste de Histocompatibilidade , Humanos , Infecções/etiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Recidiva , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Adulto JovemAssuntos
Candida/patogenicidade , Candidíase/epidemiologia , Candidíase/microbiologia , Doenças Hematológicas/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neutropenia/etiologia , Candidíase/patologia , Doenças Hematológicas/terapia , Humanos , Incidência , Neutropenia/patologia , Prognóstico , Transplante HomólogoRESUMO
Treosulfan has been incorporated in conditioning regimens for sustained remission without substantial toxicity and treatment-related mortality (TRM). We aimed to analyze the safety and efficacy of a fludarabine 150 mg/m2 and treosulfan 42 g/m2 (FluTreo) conditioning regimen in medically infirm patients. Outcomes were compared with those of a similar historical group treated with fludarabine 150 mg/m2 to 180 mg/m2, busulfan 6.4 mg/kg, and antithymocyte globulin (ATG) 5 mg/kg to 7.5 mg/kg (FluBuATG). Thirty-one consecutive patients with acute myeloid leukemia (AML; n = 21), myelodysplastic syndrome (MDS; n = 6), or treatment-related AML (n = 4) received FluTreo conditioning. The historical group consisted of 26 consecutive patients treated with FluBuATG. In the FluTreo group, engraftment was prompt in all patients and 74% achieved >99% donor chimerism by day +30. No grades III or IV organ toxicities were noted. One-year cumulative incidences (CI) of acute and chronic graft-versus-host disease (GVHD) were 19.4% and 58.4%. The groups were similar for age, disease risk, lines of treatment, hematopoietic cell transplantation-specific comorbidity index, and acute or chronic GVHD incidence, except that there were more matched unrelated donor recipients in the FluTreo group (P < .001). With 20 (range, 2 to 36) months follow-up for FluTreo and 14 (range, 2 to 136) for FluBuATG, the 1-year cumulative overall survival (OS) probability was 76% versus 57%, respectively (P = .026); 1-year disease-free survival (DFS) was 79% versus 38% (P < .001). In multivariate analysis, the only significantly favorable factor for OS and DFS was FluTreo (P = .010 and P = .012). The CI of relapse mortality was markedly decreased in FluTreo versus FluBuATG (7.4% versus 42.3%, P < .001). In conclusion, the treosulfan-based regimen resulted in favorable OS and DFS with acceptable toxicity and low relapse rates compared with busulfan-based conditioning.
Assuntos
Bussulfano/análogos & derivados , Bussulfano/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Bussulfano/toxicidade , Quimerismo , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Recidiva , Análise de Sobrevida , Condicionamento Pré-Transplante/mortalidade , Transplante Homólogo , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Vidarabina/toxicidadeRESUMO
Optimal conditioning remains a challenge in lymphomas. We designed a regimen consisting of Busulfex, etoposide and melphalan (BuEM). We retrospectively analyzed the outcome of patients conditioned with carmustine, etoposide, cytarabine and melphalan (BEAM) or BuEM in matched-pair analysis on a planned 2:1 ratio. Eighty-seven patients treated with BEAM who fulfilled the matching criteria were randomly selected. Two-year progression-free survival/overall survival (PFS/OS) were 63.2%/76.7% for BEAM vs. 65.6%/79.8% for BuEM after 64.7 and 42.7 months, respectively. Furthermore, marginally better PFS and OS were noted in Hodgkin lymphoma (HL) after BuEM. In multivariate analysis, PFS was superior in HL, chemosensitive disease and complete remission post-transplant. BEAM correlated with faster engraftment, reduced infections, less mucositis and liver toxicity, and BuEM with less need for blood cell and platelet transfusions and granulocyte colony-stimulating factor administration. In conclusion, BuEM was well tolerated and equally highly efficacious as BEAM for non-Hodgkin lymphoma and offered marginally significantly improved PFS and OS in HL with acceptable toxicity and zero mortality.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Condicionamento Pré-Transplante , Adulto , Bussulfano/administração & dosagem , Carmustina/uso terapêutico , Citarabina/uso terapêutico , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/mortalidade , Humanos , Linfoma não Hodgkin/mortalidade , Masculino , Análise por Pareamento , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Podofilotoxina/uso terapêutico , Estudos Retrospectivos , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento , Adulto JovemRESUMO
The genus Acremonium (formerly known as Cephalosporium) is a large polyphyletic fungal genus that comprises approximately 150 phylogenetically distant species, commonly isolated from the environment. Clinical cases concern mostly superficial infections after traumatic inoculation, but there are reports of opportunistic invasive infections in immunocompromised patients. Acremonium kiliense has been described as a cause of mycetoma, keratitis, endophthalmitis, endocarditis, and continuous ambulatory peritoneal dialysis-associated peritonitis. We describe an unusual cluster of possible catheter-related bloodstream infections due to this pathogen in patients who underwent haematopoietic cell transplantation.
Assuntos
Acremonium/isolamento & purificação , Fungemia/microbiologia , Transplante de Células-Tronco Hematopoéticas , Micoses/sangue , Acremonium/efeitos dos fármacos , Acremonium/patogenicidade , Adulto , Antifúngicos/farmacologia , Farmacorresistência Fúngica Múltipla , Feminino , Fungemia/tratamento farmacológico , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Hospedeiro Imunocomprometido , Leucemia Mieloide/patologia , Leucemia Mieloide/terapia , Masculino , Testes de Sensibilidade Microbiana , Micoses/tratamento farmacológico , Micoses/microbiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Transplante Homólogo , Adulto JovemAssuntos
Infecção Hospitalar/virologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/virologia , Leucemia/virologia , Adulto , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/epidemiologia , Surtos de Doenças , Feminino , Hematologia , Unidades Hospitalares , Humanos , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Radiografia Torácica , Estados Unidos/epidemiologiaAssuntos
Humanos , Masculino , Adulto , Proteinose Alveolar Pulmonar/complicações , Proteinose Alveolar Pulmonar/diagnóstico , Citomegalovirus/imunologia , Citomegalovirus/isolamento & purificação , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Dispneia/complicações , /métodos , Proteinose Alveolar Pulmonar/imunologia , Proteinose Alveolar Pulmonar/microbiologia , Proteinose Alveolar Pulmonar/terapia , Hospedeiro Imunocomprometido , Hospedeiro Imunocomprometido/imunologia , Hospedeiro Imunocomprometido/fisiologiaAssuntos
Nefropatias/etiologia , Plasmocitoma/complicações , Neoplasias Ósseas/patologia , Dilatação Patológica , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias dos Seios Paranasais/patologia , Plasmocitoma/patologia , Espaço Retroperitoneal , Tomografia Computadorizada por Raios X , Ureter/patologiaRESUMO
Fresh frozen plasma (FFP) contains natural anticoagulants, such as antithrombin (AT) and Protein C (Prot-C). We hypothesized that FFP given in addition to heparin, could potentially replace the consumption of endogenous anticoagulants occurring during conditioning and moreover, corrected AT levels could augment heparin's anticoagulant function. This could therefore result in an effective anti-VOD prophylaxis. In this study, we retrospectively analyzed the incidence of hepatic VOD in 403 consecutive bone marrow transplants (BMTs) comparing 2 prophylactic regimens and no prophylaxis. Patients received no prophylaxis (70/403), heparin-only (27/403) or heparin+2FFP daily during conditioning (306/403). VOD was significantly lower in the heparin+FFP group (5.9%) compared to heparin (20%) and no prophylaxis group (15.7%) [p<0.01]. Day 8 AT and Prot-C levels, were lower in the VOD- compared to the non-VOD group (AT: 69+/-26% vs. 89+/-19%, Prot-C:68+/-26% vs. 91+/-29%, respectively, p=0.001). In a multivariate logistic regression, risk factors for developing VOD were: the administration of >2 hepato-nephrotoxic drugs, previous history of hepatitis B or C and number of BMT. Multivariate analysis in a subset of 198 patients (all having recorded AT, Prot-C), demonstrated as VOD-related factors, the low day 8 Prot-C, number of BMT>1 and prior abdominal radiotherapy. Our study implies that FFP during conditioning, in addition to heparin, potentially has an anti-VOD prophylactic effect, presumably by minimizing the drop of natural anticoagulants around day 8. In order to evaluate if there truely is a beneficial effect of heparin+FFP in VOD prophylaxis, we have initiated a prospective randomized trial.
Assuntos
Anticoagulantes/administração & dosagem , Transfusão de Sangue/métodos , Transplante de Medula Óssea/efeitos adversos , Heparina/administração & dosagem , Hepatopatia Veno-Oclusiva/etiologia , Hepatopatia Veno-Oclusiva/prevenção & controle , Plasma , Adulto , Terapia Combinada , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Gonadal dysfunction in adult long-term survivors of hematopoietic stem cell transplantation (HSCT) is an adverse effect of conditioning regimens consisting of chemotherapy and total body irradiation (TBI). The impact of conditioning regimens consisting of chemotherapy alone on the function of the hypothalamic-pituitary-gonadal (HPG) axis was evaluated in a series of 41 female and 31 male patients who had undergone either autologous or allogeneic bone marrow/peripheral blood stem cell transplantation; mean age at transplantation was 32.6 years and mean time interval from transplantation was 1.5 years (range 0.2-9.8 years). Provocative testing of the HPG axis by administration of luteinizing hormone-releasing hormone was included in the first endocrinological evaluation. The follow-up period extended to three consecutive years. Gonadal dysfunction was not reported by any of the patients prior to their underlying illness. Hypergonadotrophic hypogonadism was observed in 97% of female and 19% of male patients. Leydig cell strain (normal testosterone, high luteinizing hormone levels) was evident in 32% and spermatogenesis damage (high follicle-stimulating hormone levels) in 68% of the male population. At the conclusion of the study four women (10%) had regained spontaneous menses and all hypogonadal men had resumed normal testosterone levels. Our results indicate a high incidence of gonadal dysfunction due to target organ failure in HSCT recipients not treated by TBI.