RESUMO
HLX01 (HanliKang®) is a rituximab biosimilar that showed bioequivalence to reference rituximab in untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) in the phase 3 HLX01-NHL03 study. Here, we report the 5-year follow-up results from the open-label extension part. Patients were randomised to either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or HLX01 plus CHOP (H-CHOP) every 21 days for up to six cycles. The primary efficacy endpoint was overall survival (OS), and secondary efficacy endpoint was progression-free survival (PFS). Of the 407 patients enrolled in HLX01-NHL03, 316 patients (H-CHOP = 157; R-CHOP = 159) were included in the 5-year follow-up for a median duration of 65.1 (range, 2.2-76.5) months. 96.5% of the patients had an International Prognostic Index (IPI) of 1 or 2, and 17.7% had bone marrow involvement. The 5-year OS rates were 81.0% (95% CI: 74.9-87.5%) and 75.4% (95% CI: 68.9-82.6%)( HR: 0.75, 95% CI 0.47-1.20; p = 0.23) while 5-year PFS rates were 77.7% (95% CI: 71.4-84.6%) and 73.0% (95% CI: 66.3-80.3%) (HR: 0.84, 95% CI 0.54-1.30; p = 0.43) in the H-CHOP and R-CHOP groups, respectively. Treatment outcomes did not differ between groups regardless of IPI score and were consistent with the primary analysis. H-CHOP and R-CHOP provided no significant difference in 5-year OS or PFS in previously untreated patients with low or low-intermediate risk DLBCL.
Assuntos
Medicamentos Biossimilares , Linfoma Difuso de Grandes Células B , Humanos , Medicamentos Biossimilares/efeitos adversos , Rituximab/efeitos adversos , Seguimentos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Doxorrubicina , Prednisona/efeitos adversosRESUMO
Refractory/relapsed (R/R) diffuse large B-cell lymphoma (DLBCL) patients' failure of salvage chemotherapy had extremely worse prognoses. Herein, 14 R/R DLBCL patients failed to salvage chemotherapy were exposed to dual epigenetic agents (Chidamide 30 mg biw*2w and Decitabine 10 mg/m2 qd*d1-d5) and sequential R-GemOx (rituximab 375 mg/m2 qd d6; gemcitabine 1 g/m2 d7, d14; and oxaliplatin 100 mg/m2 d7) for further salvage chemotherapy. Finally, 11/14(78.6%) patients achieved overall response with 6/14(42.9%) achieving complete remission and 2-year overall survival (OS)/progression free survival (PFS) rate was 42.7%, extremely higher than reported previously. Further subgroup analysis demonstrated that 2-year OS/PFS rate was significantly higher in patients achieved complete/partial remission or with low international prognosis index (IPI 0-2) than that in patients with steady disease or high IPI (3-5). Common grade 3-4 adverse events were hematological toxicities. All toxicities were transient and reversible. Our report implicates that combination of dual epigenetic agents and R-GemOx is a safe and promising alternative for R/R DLBCL patients.
Assuntos
Linfoma Difuso de Grandes Células B , Terapia de Salvação , Humanos , Gencitabina , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genéticaRESUMO
Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivations are common complications after allogeneic hematopoietic cell transplantation (allo-HCT), but data focusing on non-Hodgkin lymphoma (NHL) are limited. We retrospectively analyzed the prevalence of EBV and CMV reactivation post-allo-HCT and the impacts on transplant outcomes in 160 NHL patients. The 1-year incidences of EBV and CMV reactivation were 22.58% and 25.55%, respectively. Independent impactors for EBV reactivation were more than 6 lines of chemotherapy (P = 0.030), use of rituximab (P = 0.004), and neutrophil recovery within 30 days post-HCT (P = 0.022). For T-cell lymphoblastic lymphoma patients, the International Prognostic Index (IPI) (P = 0.015) and chronic GVHD (P = 0.001) increased the risk of CMV reactivation. CMV reactivation was independently related to a lower risk of relapse (P = 0.027) but higher transplant-related mortality (TRM) (P = 0.038). Although viral reactivation had no significant impact on overall survival (OS) in the whole cohort, it led to an inferior 2-year OS (67.6% versus 92.5%, P = 0.005) and TRM (20.1% versus 4.7%, P = 0.020) in recipients surviving for more than 180 days. We concluded that EBV and CMV reactivation post-allotransplant still deserved concern particularly in NHL patients with high-risk factors, since it is generally related to a deteriorated prognosis. Large-scale studies are warranted to validate our findings.
Assuntos
Infecções por Citomegalovirus/etiologia , Citomegalovirus/fisiologia , Infecções por Vírus Epstein-Barr/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 4/fisiologia , Linfoma não Hodgkin/terapia , Ativação Viral , Adulto , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Infecções por Citomegalovirus/epidemiologia , Infecções por Vírus Epstein-Barr/epidemiologia , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunoterapia Adotiva , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Condicionamento Pré-Transplante/efeitos adversos , Resultado do Tratamento , Irradiação Corporal Total/efeitos adversosRESUMO
We analyzed the outcomes of 44 patients with paroxysmal nocturnal hemoglobinuria (PNH) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) (haploidentical [haplo]-donors, 25; matched sibling donors [MSDs], 15; and matched unrelated donors, 4) between July 2007 and May 2018. All patients achieved successful donor engraftment. The median time was 12 days (range, 7 to 26) for myeloid engraftment and 13 days (range, 11 to 75) for platelets. The cumulative incidences were 15.91% and 2.27% for grades II to IV and grades III to IV acute graft-versus-host disease (GVHD), respectively, with a median follow-up time of 36 months (range, 4 to 132). The cumulative incidences were 26.73% for chronic GVHD and 9.70% for moderate to severe chronic GVHD. No patients relapsed. The probabilities of 3-year overall survival (OS) and GVHD-free, failure-free survival (GFFS) were 90.4% ± 4.6% and 85.6% ± 5.4%, respectively. The 3-year OS rates of the haplo-donor and MSD groups were 86.5% ± 7.3% versus 93.3% ± 6.4% (Pâ¯=â¯.520). The 3-year GFFS rates of the haplo-donor and MSD groups were 78.3% ± 8.6% versus 92.9% ± 6.9% (Pâ¯=â¯.250). The preliminary results indicated that allo-HSCT is a feasible option for patients with PNH; however, this should not be considered as a first-choice therapy, because the results seemed to only suggest rather than confirm that haplo-HSCT and MSD-HSCT exerted similar therapeutic efficacies.
Assuntos
Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas , Hemoglobinúria Paroxística/terapia , Irmãos , Obtenção de Tecidos e Órgãos , Doença Aguda , Adolescente , Adulto , Aloenxertos , Criança , Doença Crônica , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
HLA-mismatched stem cell microtransplantation is a new form of transplantation reported in recent years. We compared 59 patients undergoing microtransplantation to 66 patients undergoing HLA-matched sibling donor (MSD) transplantation at the same period from April 2012 to December 2016, who all suffered from intermediate/high-risk acute myelogenous leukemia (AML) in first complete remission (CR1). The estimated overall survival (OS) at 2 years was 74.1% ± 6.2% and 34.3% ± 7.9% in MSD and microtransplantation group, respectively (P = 0.001). The estimated leukemia-free survival (LFS) at 2 years was 73.3% ± 6.1% in the MSD group and 31.6% ± 7.6% in the microtransplantation group (P = 0.000). The 2-year cumulative incidence of relapse was 17.6% and 62.3% in the MSD and microtransplantation groups, respectively (P < 0.0001). The 2-year cumulative incidence of nonrelapse mortality was 10.9% in MSD group and 4.2% in the microtransplantation group (P = 0.251). Hematopoietic recovery time was shorter in the microtransplantation group than in the MSD group (P < 0.05). The infection rate was higher in the MSD group than in the microtransplantation group (P = 0.012). The preliminary results suggested that OS and LFS of microtransplantation were inferior to MSD transplantation for intermediate/high-risk AML in CR1.
Assuntos
Antígenos HLA , Teste de Histocompatibilidade , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Irmãos , Doadores de Tecidos , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante de Células-Tronco , Taxa de SobrevidaRESUMO
The aim of this study is to determine whether the modified BuCy (semustine, cytarabine, busulfan, and cyclophosphamide, mBuCy) conditioning regimen can be safely used as an alternative to the SEAM (semustine, etoposide, cytarabine, and melphalan) regimen by comparing the efficacy and toxicity of the mBuCy and SEAM regimens. We matched 34 pairs of patients with regard to disease status at the time of autologous stem cell transplantation (auto-SCT). We found no significant difference in the time of platelet engraftment between the two groups. Furthermore, neutrophil engraftment was somewhat faster in the mBuCy group than in the SEAM group (median: 9 days vs 10 days, p = 0.015). With regard to toxicity, the incidence of nausea/vomiting, hepatic impairment, renal impairment, pulmonary infection, and treatment-related mortality (TRM) was similar between the two groups. In addition, compared to patients conditioned with SEAM, patients conditioned with mBuCy were less likely to develop mucositis and diarrhea (p = 0.027; p = 0.050). The 2-year progression-free survival (PFS) rates in the mBuCy and SEAM groups were 79% and 70% (p = 0.378), respectively, and the 2-year overall survival (OS) rates were 81% and 78.0%, respectively (p = 0.789). These analyses showed that the mBuCy conditioning regimen was well tolerated and can be used as an alternative to the SEAM regimen for lymphoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Linfoma/mortalidade , Linfoma/terapia , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Autoenxertos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Semustina/administração & dosagem , Semustina/efeitos adversos , Taxa de SobrevidaAssuntos
Infecções por Adenovirus Humanos , Transplante de Células-Tronco Hematopoéticas , Falência Hepática Aguda , Humanos , Infecções por Adenovirus Humanos/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/terapiaRESUMO
Peripheral T cell lymphomas (PTCLs) often carry poor outcomes with conventional chemotherapy, and hematopoietic cell transplantation (HCT) can benefit patients with PTCL. We conducted a retrospective review of 67 patients with PTCL who underwent autologous HCT (autoHCT, n = 43; median age, 40 years) or allogeneic HCT (alloHCT, n = 24; median age, 36.5 years) from 2004 to 2016. With a median follow-up of 27 months, 5-year progression-free survival (PFS) and overall survival (OS) of autoHCT patients were 49% and 57%, respectively. Among alloHCT recipients, the 5-year PFS and OS were 54% and 55%, respectively. When considering incidence of disease relapse or progression (CIR) and nonrelapse mortality (NRM), the 5-year CIR and 1-year NRM of alloHCT recipients were 38% and 18%, respectively, and 58% and 7% for autoHCT patients, respectively. There were no differences between autoHCT and alloHCT in 5-year PFS (P = .499), OS (P = .566), CIR (P = .555), and NRM (P = .202). When specifically examining recipients in primary refractory disease, 3-year PFS rates of autoHCT and alloHCT were 20% and 49% (P = .054); 3-year OS rates were 20% and 53% (P = .042), respectively. Based on these results, we favor proceeding to alloHCT in patients with PTCL in primary refractory disease.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/terapia , Adolescente , Adulto , Aloenxertos , Autoenxertos , Criança , China , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de TempoAssuntos
Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Quimioterapia de Indução , Leucemia Mieloide Aguda , Proteínas de Neoplasias/sangue , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Cariótipo , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Fatores de Transcrição MEF2/sangue , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
OBJECTIVE: To explore the therapeutic efficacies of decitabine application prior to hematopoietic cell transplantation (HSCY) in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). METHODS: Retrospective reviews were conducted for 46 patients with MDS (n = 14) and AML (n = 32) on a therapy of decitabine prior to allo-HSCT between September 2009 and February 2013. RESULTS: In MDS patients, complete remission (CR, n = 10), partial remission (PR, n = 2) and stable disease (SD, n = 1) were achieved prior to HSCT. And the remission rate of one course was 10/14. After decitabine dosing, 17/32 patients achieved CR in 32 with AML and the remission rate of one course was 53.1ï¼ (17/32) and effective rate of one course (CR+PR) achieves 78.1ï¼ (25/32). Successful engraftment was attained in all MDS patients and 12/14 patients survived disease-free and one died of pneumonia after relapse. And 28 patients with AML attained successful engraftment after using decitabine prior to allo-HSCT and there were 20 disease-free survivors. Ten patients died and another lived with tumor. The incidences of acute and chronic graft-versus-host disease (GVHD) among evaluable patients were 4.3% (2/26) and 23.9% (11/46) respectively. After a median follow-up of 8 months for survivors, the treatment-related mortality was 23.9% (11/46). The 30-month disease-free survival (DFS) rate was 53.1% and 30-month overall survival rate after decitabine dosing 61.9%. CONCLUSION: Thus decitabine is an effective therapy during bridge time to HSCT in patients with MDS and AML.
Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Azacitidina/análogos & derivados , Decitabina , Intervalo Livre de Doença , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Recidiva , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Transplante HomólogoRESUMO
Extramedullary relapse (EMR) of acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a contributor to post-transplantation mortality and remains poorly understood, especially the different characteristics of EMR in patients with acute myelogenous leukemia (AML) and those with acute lymphoblastic leukemia (ALL). To investigate the incidence, risk factors, and clinical outcomes of EMR for AML and ALL, we performed a retrospective analysis of 362 patients with AL who underwent allo-HSCT at the First affiliated Hospital of Soochow University between January 2001 and March 2012. Compared with patients with AML, those with ALL had a higher incidence of EMR (12.9% versus 4.6%; P = .009). The most common site of EMR was the central nervous system, especially in the ALL group. Multivariate analyses identified the leading risk factors for EMR in the patients with AML as advanced disease status at HSCT, hyperleukocytosis at diagnosis, history of extramedullary leukemia before HSCT, and a total body irradiation-based conditioning regimen, and the top risk factors for EMR in the patients with ALL as hyperleukocytosis at diagnosis, adverse cytogenetics, and transfusion of peripheral blood stem cells. The prognosis for EMR of AL is poor, and treatment options are very limited; however, the estimated 3-year overall survival (OS) was significantly lower in patients with AML compared with those with ALL (0 versus 18.5%; P = .000). The characteristics of post-allo-HSCT EMR differed between the patients with AML and those with ALL, possibly suggesting different pathogenetic mechanisms for EMR of AML and EMR of ALL after allo-HSCT; further investigation is needed.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Adulto JovemAssuntos
Antígenos CD19/imunologia , Imunoterapia Adotiva , Cuidados Pós-Operatórios , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos Quiméricos/metabolismo , Terapia Combinada , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunoterapia Adotiva/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Prognóstico , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genética , Transplante Homólogo , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the efficacies of hematopoietic stem cell transplantation (HSCT) for severe aplastic anemia (SAA). METHODS: A total of 43 SAA patients (SAA-I, n = 29; SAA-II, n = 14) underwent HSCT from 2002 January to 2013 December. There were 22 males and 21 females with a median age of 31 (12-49) years. And 35 patients received HLA-matched sibling HSCT (Sib-HSCT) while another 8 had unrelated donor HSCT (UD-HSCT). The hematopoietic stem cells were collected from bone marrow (n = 10), peripheral blood (n = 23) and bone marrow & peripheral blood (n = 10). Conditioning regimens were mostly composed of Fludarabine, antihuman thymocyte gloBulin and cyclophosphamide. Cyclosporine and methotrexate (including mycophenolate mofetil for UD) were offered for preventing graft-versus-host disease (GVHD). The median counts of mononuclear cell and CD34(+) stem cell were 8.1 (2.4-13.5) ×10(8)/kg and 3.7 (2.3-14.7) ×10(6)/kg respectively. RESULTS: Hematopoiesis reconstitution was achieved in 42 patients. The median periods for neutrophils to 0.5×10(9)/L and platelets to 20×10(9)/L were +10 (+8-+25) days and +14 (+8-+80) days respectively. The median of survival time was not reached. Overall survival (OS) and failure-free survival (FFS) at 5 years had no differences between UD-HSCT and Sib-HSCT groups (OS: 87.6% vs 84.5%, P = 0.87; FFS: 86.2% vs 79.5%, P = 0.64). The same results also were seen between age ≤ 20 group and > 20 group (OS: 92.0% vs 82.5%, P = 0.39; FFS: 91.0% vs 77.3%, P = 0.38). The median follow-up time was 17.0 (0.4-140.0) months. And 8/43 patients died from thrombotic microangiopathy (TMA) (n = 1), TMA associated with capillary leak syndrome (n = 1), pulmonary infection (n = 3), acute GVHD of grade IV (n = 1) and unknown causes (n = 2). CONCLUSIONS: Sib-HSCT is preferred for SAA patients under 40 years. Searching of HLA-matched unrelated donor should be performed soon after diagnosis if HLA-matched sibling is unavailable.
Assuntos
Anemia Aplástica , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Criança , Ciclofosfamida , Ciclosporina , Feminino , Doença Enxerto-Hospedeiro , Humanos , Masculino , Metotrexato , Pessoa de Meia-Idade , Ácido Micofenólico/análogos & derivados , Irmãos , Condicionamento Pré-Transplante , Vidarabina/análogos & derivados , Adulto JovemRESUMO
From October 2017 to June 2022, we retrospectively report outcomes of R/R DLBCL patients with failure of CAR-T therapy, then receiving allo-HSCT. Among 10 patients, 5 were males and 5 females, with a median age of 43.5 (27-52) years. All patients were diagnosed refractory/relapsed diffuse large B cell lymphoma. The median time from CAR-T treatment to transplantation was 84.5 (31-370) days. The median follow-up was 21 (3-69) months. 5/10 patients attained CR and 1/10 patient attained PR during the follow up. The objective response rate (ORR) was 60%. The 1-year overall survival (OS) and progression-free survival (PFS) were 70% and 40%, respectively. At the time of the analysis, 6 patients were still living. During the follow up, four patients have died and the causes were disease relapses and progressions (2 patients), acute renal failure (1 patient), severe pulmonary infection (1 patient). Non-relapse was 20.0%.
RESUMO
PURPOSE: Patients with peripheral T-cell lymphomas (PTCL) in the relapsed or refractory (r/r) setting have only a limited number of therapies available, and the prognosis is extremely poor. SHR2554 is an oral inhibitor against EZH2, a rational therapeutic target for lymphomas. PATIENTS AND METHODS: This was a multicenter, two-part, phase I study of SHR2554 in r/r mature lymphoid neoplasms. In part I, 350 mg twice daily was established as the recommended phase II dose (RP2D) based on the findings during dose escalation and expansion; subsequently, selected lymphoma subtypes were recruited in clinical expansion cohorts to receive SHR2554 at RP2D. Here, we provide an in-depth assessment of SHR2554 at RP2D in subpopulation with r/r PTCL. RESULTS: Twenty-eight patients were included for analysis (17 angioimmunoblastic T-cell lymphoma and 11 not otherwise specified). Eighteen (64%) patients had received ≥2 lines of previous anticancer therapies. The objective response rate was 61% [95% confidence interval (CI), 41-78]. Responses were still ongoing in 59% (10/17) of the responders; estimated median duration of response was 12.3 months (95% CI, 7.4-not reached). Median progression-free survival was 11.1 months (95% CI, 5.3-22.0), and 12-month overall survival rate was 92% (95% CI, 72-98). The most common grade 3 or 4 treatment-related adverse events were decreased platelet count [nine (32%)] as well as decreased white blood cell count, decreased neutrophil count, and anemia [four (14%) for each]. No treatment-related deaths were reported. CONCLUSIONS: This extended follow-up analysis further supports SHR2554 as a therapeutic opportunity for patients with r/r PTCL.
Assuntos
Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/patologia , Resultado do Tratamento , Proteína Potenciadora do Homólogo 2 de Zeste , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Inibidores Enzimáticos/uso terapêuticoRESUMO
Cytomegalovirus (CMV) reactivation increases treatment-related mortality (TRM) after allogeneic hematopoietic cell transplantation (allo-HCT). We analyzed 141 adult acute leukemia (AL) patients suffered allo-HCT between 2017 and 2021, who developed CMV viremia post-HCT and treated with valganciclovir or foscarnet, to evaluate effectiveness and safety of both drugs. Viremia clearance rates (14 and 21 d post treatment) and toxicities were similar in two groups. However, valganciclovir was associated with a lower cumulative incidence of CMV recurrence within 180 days (16.7% vs. 35.7%, p=0.029) post CMV clearance. Finally, 2-year TRM was lower in valganciclovir group (9.7% ± 0.2% vs. 26.2% ± 0.3%, p = 0.026), result a superior 2-year overall survival (OS; 88.1% ± 5.2% vs. 64.4% ± 5.5%, p = 0.005) and leukemia-free survival (LFS; 82.0% ± 5.9% vs. 58.9% ± 5.6%, p = 0.009). Valganciclovir might decrease CMV viremia recurrence and led to better long-term outcome than foscarnet in adult AL patients developed CMV viremia post-HCT. Considering the inherent biases of retrospective study, well-designed trials are warranted to validate our conclusion.
Assuntos
Antivirais , Infecções por Citomegalovirus , Citomegalovirus , Foscarnet , Transplante de Células-Tronco Hematopoéticas , Transplante Homólogo , Valganciclovir , Viremia , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Citomegalovirus/etiologia , Valganciclovir/uso terapêutico , Masculino , Feminino , Viremia/tratamento farmacológico , Adulto , Antivirais/uso terapêutico , Foscarnet/uso terapêutico , Pessoa de Meia-Idade , Citomegalovirus/efeitos dos fármacos , Estudos Retrospectivos , Adulto Jovem , Idoso , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/mortalidade , Resultado do Tratamento , Leucemia/terapia , Leucemia/complicações , Leucemia/mortalidadeRESUMO
OBJECTIVE: To explore the impact of prior-to-transplantation induction therapy (IT) on patient outcome after allogeneic hematopoietic stem-cell transplantation (Allo-HSCT) for higher-risk myelodysplastic syndromes (MDS). METHODS: A total of 49 consecutive patients underwent Allo-HSCT for MDS between November 2002 and December 2012. Twenty-six lower-risk MDS cases received supportive therapy (ST). And 17/23 cases of higher-risk MDS received IT prior to transplantation while another 6 only with ST. Their survival, relapse rate and incidence of transplantation-related mortality (TRM) were retrospectively analyzed according to International Prognostic Scoring System (IPSS) scores and marrow blast count. RESULTS: The 5-year cumulative overall survival (OS), disease-free survival (DFS), relapse rate and incidence of transplantation related mortality (TRM) were 59.9%, 59.2%, 10.5% and 31.8% during a median follow-up period of 24.4 (6.2-72.0) months. The OS and DFS of higher-risk group with IT, ST and lower-risk group were different (72.1% vs 16.7% vs 68.1%, P = 0.028; 72.1% vs 16.7% vs 67.9%, P = 0.030). And the OS and DFS of higher-risk group with IT were similar to those of lower-risk group (P = 0.526,0.504) . For the higher-risk group, the patients on IT had improved survival than those on ST in terms of OS and DFS (both P = 0.020). Moreover, the OS and DFS of remission group were higher than non-remission group in patients on IT (both 100% vs 46.7%, P = 0.049). The number of marrow blasts significantly decreased after IT (P = 0.010) without increased TRM (28.9% vs 33.6%, P = 0.612). CONCLUSION: Induction therapy prior to Allo-HSCT for MDS may reduce clone burden and improve the outcomes of higher-risk MDS without increased TRM.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Transplante Homólogo , Adulto JovemRESUMO
OBJECTIVE: To evaluate the efficacy and prognostic factors of autologous hematopoietic stem cell transplantation (ASCT) in multiple myeloma (MM) patients. METHODS: Retrospective analysis was performed in 27 MM patients undergoing ASCT at our hospital from May 2004 to August 2011. After comparing with 28 patients achieving very good partial response (VGPR) or better outcome and not undergoing ASCT, the impact on the extent of response, progression-free survival (PFS) and overall survival (OS) as well as related prognostic factors of MM patients were analyzed. RESULTS: All patients successfully underwent hematopoietic reconstruction without transplantation-related mortality. The complete remission (CR) rate of ASCT group increased from 25.9% (7/27) at pre-ASCT to 70.4% (19/27) at post-ASCT (P < 0.01). The estimated 5-year rate of progression-free survival was 56.2% (median not reached) in the ASCT group and 24.9% (median 29 months) in the non-ASCT group (P < 0.05). The 5-year probability of overall survival was 52.2% (median not reached) in the ASCT group and 33.1% (median 60 months) in the non-ASCT group (P > 0.05). Univariate analysis in ASCT group demonstrated that maintenance/consolidation therapy was associated with PFS (P = 0.010) and OS (P = 0.008).Patients on induction therapy containing bortezomib and early ASCT maintenance therapy all survived without disease progression until final follow-up (P = 0.010). CONCLUSIONS: ASCT can further increase the CR rate, prolong PFS and probably OS. The incorporation of novel agents into induction, consolidation and maintenance phases has optimized the anti-myeloma activity of ASCT and may be important for improved long-term outcomes.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Prognóstico , Estudos Retrospectivos , Transplante Autólogo , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the efficacy and safety of dose-reduced decitabine for the lower risk myelodysplastic syndrome (MDS) patients with transfusion dependent. METHODS: Twenty-five cases of lower risk (low or intermediate-1 risk in IPSS risk group) MDS patients with transfusion dependence from November 2009 to September 2012 were treated by dose-reduced decitabine (20 mg/m(2) intravenously once daily for 3 days). And their efficacy, side effects, quality-of-life and survival rate were evaluated. RESULTS: Among them, the responses included complete remission (CR, n = 3, 12%), transfusion independence (n = 4, 16%), hematologic improvement (HI, n = 8, 32%) and stable disease (SD, n = 2, 8%). And the overall response rate (ORR) was 68% (17/25) . Among 11 cases available for cytogenetic evaluation, 1 achieved partial cytogenetic remission (PRc). IV grade hematologic toxicity rate was 48% (12/25) and III-IV grade infection rate 20% (5/25). No severe hematologic toxicity was observed. After treatment, the Karnofsky performance score (KPS) increased from 47 ± 16 to 66 ± 22 (P = 0.001); more patients were reclassified as WPSS ≤ 1 (44%vs 16%, P = 0.031) or MDACC score ≤ 7 (64% vs 8%, P = 0.022). The median follow-up time was 467(14-881) d. The 100 and 600-day expected survive rates of low and intermediate -1 risk in IPSS risk group were 100% versus 95.2% and 100% versus 90.5%. CONCLUSIONS: Dose-reduced decitabine is well-tolerated and effective in transfusion dependent MDS patients in IPSS-lower risk. There is a low rate of severe hematologic toxicity and early mortality. It may prolong their survival time.
Assuntos
Azacitidina/análogos & derivados , Síndromes Mielodisplásicas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Azacitidina/administração & dosagem , Azacitidina/uso terapêutico , Transfusão de Sangue , Decitabina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Prognóstico , Resultado do Tratamento , Adulto JovemRESUMO
Background: Chimeric antigen receptor T cell (CAR-T) therapy is an effective salvage treatment in relapsed or refractory(r/r) diffuse large B-cell lymphoma (DLBCL), but the impact of hepatitis B virus (HBV) infection has not been studied. Methods and results: Here, 51 patients with r/r DLBCL receiving CAR-T therapy were enrolled and analyzed at the First Affiliated Hospital of Soochow University. The overall response rate and the complete remission rate (CR) of CAR-T therapy were 74.5% and 39.2%, respectively. With a median follow-up of 21.1 months after CAR-T, the probabilities of overall survival (OS) and progression-free survival (PFS) at 36 months were 43.4% and 28.7%, respectively. These patients were divided into three cohorts including chronic HBV infection group (n=6), resolved HBV infection group (n=25) and non-HBV infection group (n=20). Bone marrow involvement was significantly higher in the HBV infection group(P<0.001), other basic characteristics before CAR-T therapy were comparable. Subgroup analysis showed that HBV infection status did not affect the efficacy of CAR-T therapy in CR rate, OS or PFS, and there was no significant difference in CAR-T related toxicities between three cohorts. Only one cirrhosis patient with chronic HBV infection experienced HBV reactivation. Conclusions: CAR-T therapy was effective and can be used safely in r/r DLBCL with HBV infection under proper monitoring and antiviral prophylaxis.