RESUMO
PURPOSE: To compare the detection of human cytomegalovirus (HCMV) in bronchoalveolar lavage (BAL) fluid by viral culture and quantitative polymerase chain reaction (qPCR), and to establish a viral load threshold that can identify cases of HCMV replication indicative of pneumonitis. There is currently no universal viral load cut-off to differentiate between patients with and without pneumonitis, and the interpretation of qPCR results is challenging. METHODS: 176 consecutive BAL samples from immunosuppressed hosts with signs and/or symptoms of respiratory infection were prospectively studied by viral culture and qPCR. RESULTS: Concordant results were obtained in 81.25% of the BAL samples. The rest were discordant, as only 34% of the qPCR-positive BAL samples were positive by culture. The median HCMV load was significantly higher in culture-positive than in culture-negative BAL samples (5038 vs 178 IU/mL). Using a cut-off value of 1258 IU/mL of HCMV in BAL, pneumonia was diagnosed with a sensitivity of 76%, a specificity of 100%, a VPP of 100% and VPN of 98%, and HCMV was isolated in 100% of the BAL cultures. CONCLUSION: We found that a qPCR-negative was a quick and reliable way of ruling out HCMV pneumonitis, but a positive result did not always indicate clinically significant replication in the lung. However, an HCMV load in BAL fluid of ≥ 1258 IU/mL was always associated with disease, whereas < 200 IU/mL rarely so.
Assuntos
Infecções por Citomegalovirus , Transplante de Pulmão , Pneumonia , Humanos , Citomegalovirus/genética , Líquido da Lavagem Broncoalveolar , Infecções por Citomegalovirus/diagnóstico , Pneumonia/diagnóstico , DNA Viral , Hospedeiro ImunocomprometidoRESUMO
Posttransplant high-dose cyclophosphamide (PTCy) effectively prevents GvHD after haploidentical SCT. However, its use in HLA-matched SCT has been less explored. Fifty-six consecutive patients who underwent allo-SCT for hematological malignancies have been included in this prospective single-center protocol. Donors have been HLA-identical siblings, fully-matched unrelated or 1-allele-mismatched unrelated donors in 30%, 32%, and 37% of cases, respectively. Nine patients have received a TBI-containing MAC regimen, while the remaining (84%) received RIC platforms based on Fludarabine plus Busulfan/Melphalan. Due to the high graft failure (GF) rate (21%) in a preliminary analysis in the allo-RIC cohort (n = 29), protocol amendments have been implemented, with no further cases of GF after the introduction of mini-thiotepa (0/18). The overall incidence of grade II-IV acute GvHD is 24% (95% CI: 17-31%) with four steroid-refractory cases. Severe chronic GvHD has occurred in only 1 of 43 evaluable cases. The 1-year NRM and relapse are 18% (95% CI: 12-26%) and 30% (18-42%) and the OS and DFS are 78% and 64%, respectively. These outcomes support the feasibility of using PTCy as a SOC outside the haplo-setting, albeit mini-thiotepa (3 mg/kg) was incorporated in the standard allo-RIC platforms to prevent GF. Despite the limitations of a single-center experience and the short follow-up, these protocols show promising results with particular benefit in reducing the occurrence of moderate-to-severe GvHD.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Ciclofosfamida , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Recidiva Local de Neoplasia , Estudos Prospectivos , Condicionamento Pré-Transplante , Doadores não RelacionadosRESUMO
Eighty-one patients with high-risk hematological malignancies received unmanipulated haploidentical stem cell transplants (haploSCT) using the same protocol at four Spanish institutions. The conditioning regimen was thiotepa, busulfan and fludarabine; following bone marrow or peripheral blood infusion. GvHD prophylaxis with high-dose cyclophosphamide on days +3 and +4, and IV tacrolimus from day +5 was administered. 62% were in complete remission, 17% had received previous allogeneic SCT and 44% had a high-very high refined disease risk index. One patient had primary graft failure and three more died before +21. The median days to neutrophil and platelet recoveries were +18 and +23, respectively, and 93% achieved a full donor chimerism on day +30. At 1 year, cumulative incidences (CumInc) of non-relapse mortality and relapse were 27 and 19%. One-year overall survival and PFS were 61 and 51%. CumInc of grade II-IV and III-IV were 23 and 14%. At 30 months, CumInc of limited and extensive GvHD were 20 and 22%. In conclusion, patients with hematological malignancies who receive an unmanipulated haploSCT with post-transplant cyclophosphamide may benefit from less intense pharmacological prophylaxis for GvHD prophylaxis. Whether this approach potentiates the graft-versus-tumor effect and decreases relapses requires further investigation.
Assuntos
Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/terapia , Imunossupressores/uso terapêutico , Tacrolimo/uso terapêutico , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/métodos , Adolescente , Adulto , Idoso , Ciclofosfamida/farmacologia , Feminino , Neoplasias Hematológicas/patologia , Humanos , Imunossupressores/farmacologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tacrolimo/farmacologia , Adulto JovemRESUMO
This study aimed to characterize the incidence, etiology and outcome of infectious episodes in patients with steroid refractory acute GvHD (SR-GvHD). The cohort included 127 adults treated with inolimomab (77%) or etanercept (23%) owing to acute 2-4 SR-GvHD, with a response rate of 43% on day +30 and a 4-year survival of 15%. The 1-year cumulative incidences of bacterial, CMV and invasive fungal infection were 74%, 65% and 14%, respectively. A high rate (37%) of enterococcal infections was observed. Twenty patients (15.7%) developed BK virus-hemorrhagic cystitis and five percent had an EBV reactivation with only one case of PTLD. One-third of long-term survivors developed pneumonia by a community respiratory virus and/or encapsulated bacteria, mostly associated with chronic GvHD. Infections were an important cause of non-relapse mortality, with a 4-year incidence of 46%. In multivariate analysis, use of rituximab in the 6 months before SCT (hazard ratio; HR 4.2; 95% confidence interval; CI 1.1-16.3), severe infection before SR-GvHD onset (HR 5.8; 95% CI 1.3-26.3) and a baseline C-reactive protein >15 UI/mL (HR 2.9; 95% CI 1.1-8.5) were associated with infection-related mortality. High rates of opportunistic infections with remarkable mortality warrant further efforts to optimize long-term outcomes after SR-GvHD.
Assuntos
Doença Enxerto-Hospedeiro/mortalidade , Infecções/mortalidade , Doença Aguda , Adolescente , Adulto , Idoso , Aloenxertos , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Intervalo Livre de Doença , Etanercepte/administração & dosagem , Etanercepte/efeitos adversos , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Infecções/etiologia , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco , Taxa de SobrevidaAssuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunossupressores/uso terapêutico , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Sirolimo/uso terapêutico , Análise de Sobrevida , Tacrolimo/uso terapêutico , Transplante HomólogoRESUMO
We monitored 133 high-risk allo-SCT recipients for 6 months after transplant for EBV reactivation by quantitative real-time PCR. Rituximab was given as pre-emptive therapy for viremia >1000 copies/mL. The 1-year cumulative incidence of EBV reactivation was 29.4% (95% confidence interval (CI): 18-40) in patients monitored due to initial high-risk characteristics (n=93) and 31.8% (95% CI: 19.7-44) in those followed because of the development of refractory GVHD (n=40). Overall response rate to Rituximab was 83%. Nine patients (9.6%) developed post-transplant lymphoproliferative disorder (PTLD) at a median of +62 days after SCT. Eight of them showed a concomitant CMV reactivation. Second SCT was the only risk factor associated with EBV infection and PTLD in multivariate analysis (hazard ratio (HR) 2.6 (95% CI: 1.1-6.4; P=0.04) and HR 6.4 (95%CI: 1.3-32; P=0.02)). The development of EBV reactivation was not associated with non-relapse mortality or OS (P=0.97 and P=0.84, respectively).
Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Hematológicas/terapia , Herpesvirus Humano 4/fisiologia , Fatores Imunológicos/administração & dosagem , Rituximab/administração & dosagem , Transplante de Células-Tronco , Ativação Viral/efeitos dos fármacos , Adolescente , Adulto , Idoso , Aloenxertos , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/etiologia , Infecções por Vírus Epstein-Barr/prevenção & controle , Feminino , Neoplasias Hematológicas/epidemiologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Umbilical cord blood (CB) is increasingly used as an alternative source of stem cells in adult unrelated transplantation. Although registry studies report similar overall outcomes in comparison with BM/PB, comparative studies focusing on severe infections and infection-RM (IRM) with a long follow-up are scarce. A total of 434 consecutive unrelated transplants (1997-2009) were retrospectively analyzed to compare overall outcomes, incidence and risk factors of severe viral and invasive fungal infections in CB (n=65) vs BM/PB recipients (n=369). The 5-year OS was 38 vs 43%, respectively (P=0.2). CB transplantation (CBT) was associated with a higher risk of invasive aspergillosis (100-days-cumulative incidence 16 vs 6%, P=0.04) and CMV infection without differences in RM. No statistically significant differences were found regarding NRM (NRM of 38% in CB vs 37% in BM/PB at 1 year) nor IRM (30% in CB vs 27% in BM/PB at 1 year). In the overall population, NRM and IRM improved in more recent years. In adults who receive a single CBT, the risk of severe infections is increased when compared with unrelated BM/PB recipients, but mortality from infections is similar, leading to similar NRM and survival.