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1.
Eduardo Edelman Saul Juan Pablo Alderuccio Isildinha M. Reis Wei Zhao Sunil G. Iyer Gregor Rodriguez Amrita Desai Jennifer R. Chapman David T. Tse Arnold M. Markoe Derek M. Isrow Izidore S. Lossos 《American journal of hematology》2023,98(1):148-158
Comprehensive information on clinical features and long-term outcomes of primary conjunctival extranodal marginal zone lymphoma (PCEMZL) is scarce. We present a large single-institution retrospective study of 72 patients. The median age was 64 years, and 63.9% were female. Stage I was present in 87.5%. Radiation therapy (RT) alone was the most common treatment (70.8%). Complete response (CR) was 87.5%, and 100% in RT-treated patients. With a median follow-up of 6.7 years, relapse/progression and death occurred in 19.4% each, with one relapse within the RT field. The 10-year progression-free survival (PFS) and overall survival (OS) were 68.4% (95% CI 52.8%–79.8%) and 89.4% (95% CI 77.4%–95.2%), respectively. The 10-year rate for time to progression from diagnosis was 22.5% (95% CI 11.6%–35.7%). The 10-year PFS and OS of MALT-IPI 0 versus 1–2 were 83.3% versus 51.3%, (p = .022) and 97.6% versus 76.6%, (p = .0052), respectively. The following characteristics were associated with shorter survival: age > 60 years (PFS: HR = 2.93, 95% CI 1.08–7.95; p = .035, OS: HR = 9.07, 95% CI 1.17–70.26; p = .035) and MALT-IPI 1–2 (PFS: HR = 2.67, 95% CI 1.12–6.31; p = .027, OS: HR = 6.64, 95% CI 1.45–30.37; p = .015). CR following frontline therapy was associated with longer PFS (HR = 0.13, 95% CI 0.04–0.45; p = .001), but not OS. Using the Fine and Gray regression model with death without relapse/progression as a competing risk, RT and CR after frontline therapy were associated with lower risk of relapse (SHR = 0.34, 95% CI 0.12–0.96 p = .041 and SHR = 0.11, 95% CI 0.03–0.36; p < .001, respectively). Patients with PCEMZL treated with frontline RT exhibit excellent long-term survival, and the MALT-IPI score appropriately identifies patients at risk for treatment failure. 相似文献
2.
Arnon Nagler Myriam Labopin Bhagirathbhai Dholaria Jürgen Finke Arne Brecht Urs Schanz Riitta Niittyvuopio Andreas Neubauer Martin Bornhäuser Stella Santarone Dietrich Beelen Avichai Shimoni Wolf Rösler Sebastian Giebel Bipin N. Savani Mohamad Mohty 《British journal of haematology》2019,186(5):767-776
Although second allogeneic haematopoietic cell transplantation (allo-HCT2) is a therapeutic option for patients relapsing after first HCT (allo-HCT1), there is limited data on allo-HCT2 in patients with acute lymphoblastic leukaemia (ALL). We retrospectively studied 245 patients receiving allo-HCT2 as a salvage treatment for relapse following allo-HCT1 between the 2000 and 2017. The median age at allo-HCT2 was 34·6 years (range: 18–74). One hundred and one patients (41%) received sibling donor and 144 (59%) unrelated donor allo-HCT2. Acute graft-versus-host disease (GVHD) grade II–IV and III–IV occurred in 33% and 17% of the patients, respectively. The incidence of 2-year total and extensive chronic GVHD was 38% and 19%, respectively. The 2- and 5-year cumulative incidence of non-relapse mortality, relapse incidence, leukaemia-free survival, overall survival and GVHD-free, relapse-free survival (GRFS) were 24% and 26%, 56% and 62%, 20% and 12%, 30% and 14% and 12% & 7%, respectively. In multivariate analysis, factors associated with overall survival were age, time from allo-HCT1 to relapse, conditioning for allo-HCT1, Karnofsky score at allo-HCT2 and donor type for allo-HCT2. In conclusion, outcomes of allo-HCT2 in ALL patients were poor, with only 14% overall survival and 7% GRFS at 5 years with very high relapse incidence. 相似文献
3.
Measurable residual disease,conditioning regimen intensity,and age predict outcome of allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first remission: A registry analysis of 2292 patients by the Acute Leukemia Working Party European Society of Blood and Marrow Transplantation
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Maria H. Gilleece Myriam Labopin Ibrahim Yakoub‐Agha Liisa Volin Gerard Socié Per Ljungman Anne Huynh Eric Deconinck Depei Wu Jean Henri Bourhis Jean Yves Cahn Emmanuelle Polge Mohamad Mohty Bipin N. Savani Arnon Nagler 《American journal of hematology》2018,93(9):1142-1152
Patients with acute myeloid leukemia (AML) in morphological first complete remission (CR1) pre‐allogeneic hematopoietic cell transplantation (HCT) may have measurable residual disease (MRD) by molecular and immunophenotyping criteria. We assessed interactions of MRD status with HCT conditioning regimen intensity in patients aged <50 years (y) or ≥50y. This was a retrospective study by the European Society for Blood and Marrow Transplantation registry. Patients were >18y with AML CR1 MRD NEG/POS and recipients of HCT in 2000‐2015. Conditioning regimens were myeloablative (MAC), reduced intensity (RIC) or non‐myeloablative (NMA). Outcomes included leukemia free survival (LFS), overall survival (OS), relapse incidence (RI), non‐relapse mortality (NRM), chronic graft‐vs‐host (cGVHD), and GVHD‐free and relapse‐free survival (GRFS). The 2292 eligible patients were categorized into four paired groups: <50y MRD POS MAC (N = 240) vs RIC/NMA (N = 58); <50y MRD NEG MAC (N = 665) vs RIC/NMA (N = 195); ≥50y MRD POS MAC (N = 126) vs RIC/NMA (N = 230), and ≥50y MRD NEG MAC (N = 223) vs RIC/NMA (N = 555). In multivariate analysis RIC/NMA was only inferior to MAC for patients in the <50y MRD POS group, with worse RI (HR 1.71) and LFS (HR 1.554). Patients <50Y MRD NEG had less cGVHD after RIC/NMA HCT (HR 0.714). GRFS was not significantly affected by conditioning intensity in any group. Patients aged <50y with AML CR1 MRD POS status should preferentially be offered MAC allo‐HCT. Prospective studies are needed to address whether patients with AML CR1 MRD NEG may be spared the toxicity of MAC regimens. New approaches are needed for ≥50y AML CR1 MRD POS. 相似文献
4.
Fateeha Furqan Kwang W. Ahn Yue Chen Manmeet Kaur Syed A. Abutalib Nausheen Ahmed Sairah Ahmed Mohamed A. Kharfan-Dabaja Johnathan Friedberg Tara Gregory LaQuisa Hill Cole Sterling Stephan K. Barta Mazyar Shadman Miguel-Angel Perales Jasmine Zain Alex F. Herrera Craig Sauter Mehdi Hamadani 《British journal of haematology》2023,200(1):54-63
The prognosis of relapsed/refractory (R/R) anaplastic large cell lymphoma (ALCL) is poor. Large studies evaluating outcomes of allogeneic haematopoietic cell transplantation (allo-HCT) in systemic R/R ALCL are not available. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we evaluated outcomes of 182 adults (aged ≥18 years) with R/R ALCL undergoing allo-HCT between 2008 and 2019. Non-relapse mortality (NRM), disease relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) were modelled using Cox proportional hazards models. The median (range) follow-up of survivors was 62 (3–148) months. The 1-year NRM was 18%. The 5-year REL, PFS and OS were 32%, 41% and 56% respectively. On multivariable regression analysis African American race (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.6–4.8; p < 0.001) and refractory disease at allo-HCT (HR 3.2, 95% CI 1.6–6.2; p < 0.001) were predictive of inferior OS. Similarly, African-American race (HR 2.1, 95% CI 1.3–3.4; p = 0.003), other minority race (HR 2.5, 95% CI 1.2–5.3; p = 0.02) and refractory disease (HR 2.2, 95% CI 1.2–4.3; p = 0.01) were predictive of inferior PFS. These data, demonstrate that allo-HCT can result in durable disease control in a sizable proportion of patients with R/R ALCL. Refractory disease and racial minority status predicted inferior allo-HCT outcomes. Whether the inferior outcomes of racial minorities with R/R ALCL after allo-HCT are driven by differences in disease biology or disparities in post allo-HCT care, or both, requires further investigation. 相似文献
5.
Wenli Zhang Ruirui Gui Yingling Zu Binglei Zhang Zhen Li Yanli Zhang Xianjing Wang Shuli Guo Xinrong Zhan Yuewen Fu Yongping Song Jian Zhou 《British journal of haematology》2023,200(2):210-221
Anti-thymocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy)-based regimens are widely used for graft-versus-host disease (GVHD) prophylaxis in haploidentical haematopoietic stem cell transplantation (haplo-HSCT). To improve the effectiveness of GVHD prophylaxis in haploidentical peripheral blood stem cell transplantation (haplo-PBSCT), we conducted a multicentre, randomized clinical trial to determine the efficacy of reduced-dose PTCy (40 mg/kg/d on days 3 and 4) combined with low-dose post-transplant ATG (2.5 mg/kg on day 8)-based GVHD prophylaxis (reduced-dose PTCy/ATG) with fludarabine–busulfan–cytarabine (FBA) conditioning for patients with haematological malignancies. From 2018 to 2022, 122 patients from four institutions were randomly assigned 1:1 to either a reduced-dose PTCy/ATG or a standard-dose ATG group (‘Beijing Protocol’, ATG: 10 mg/kg). All patients achieved myeloid engraftment. Cumulative incidences of grade II–IV (11.5% vs 39.3%, p = 0.001) and grade III–IV (6.6% vs 24.6%, p = 0.014) acute GVHD at day 100 were significantly reduced in the reduced-dose PTCy/ATG group. Furthermore, two-year overall survival, disease-free survival and GVHD-free/relapse-free survival were significantly improved in the reduced-dose PTCy/ATG group (75.4% vs 54.1%, p = 0.021; 72.7% vs 55.0%, p = 0.044; 61.3% vs 42.3%, p = 0.022 respectively). Our results demonstrate that the addition of low-dose ATG to reduced-dose PTCy with FBA conditioning is a promising strategy in haplo-PBSCT. 相似文献
6.
Narendranath Epperla Ang Li Brent Logan Caitrin Fretham Saurabh Chhabra Mahmoud Aljurf Lynette Chee Edward Copelan César O. Freytes Peiman Hematti Hillard M. Lazarus Mark Litzow Taiga Nishihori Richard F. Olsson Tim Prestidge Wael Saber Baldeep Wirk Jean A. Yared Alison Loren Marcelo Pasquini 《British journal of haematology》2020,189(6):1171-1181
Transplant-associated thrombotic microangiopathy (TA-TMA) is a complication of allogeneic transplantation (allo-HCT). The incidence and risk factors associated with TA-TMA are not well known. A retrospective analysis from the Center for International Blood and Marrow Transplant Research (CIBMTR) was conducted including patients receiving allo-HCT between 2008 and 2016, with the primary objective of evaluating the incidence of TA-TMA. Secondary objectives included identification of risk factors associated with TA-TMA, and the impact of TA-TMA on overall survival and the need for renal replacement therapy (RRT). Among 23,665 allo-HCT recipients, the 3-year cumulative incidence of TA-TMA was 3%. Variables independently-associated with increased incidence of TA-TMA included female sex, prior autologous transplant, primary disease (acute lymphoblastic leukaemia and severe aplastic anaemia), donor type (mismatched or unrelated donor), conditioning intensity (myeloablative), GVHD prophylaxis (sirolimus + calcineurin inhibitor), pre-transplant kidney dysfunction and acute GVHD (time-varying effect). TA-TMA was associated with higher mortality (HR = 3·1, 95% Confidence Interval [CI] = 2·8–16·3) and RRT requirement (HR = 7·1, 95% CI = 5·7–311·6). This study provides epidemiologic data on TA-TMA and its impact on transplant outcomes. Increased awareness of the risk factors will enable providers to be vigilant of this uncommon but serious transplant complication. The results will also provide benchmarking for future study designs and comparisons. 相似文献
7.
Controversy remains regarding the transplant outcomes of human leukocyte antigen-identical related bone marrow transplantation
(BMT) and peripheral blood stem cell transplantation (PBSCT) for the treatment of patients with hematological malignancies.
To provide an estimate of the effect of BMT and PBSCT on clinical outcomes in patients with hematological malignancies, we
conducted a meta-analysis based on time-to-event data from 17 randomized controlled trials. PubMed, EMBASE, and Cochrane Central
Register of Controlled Trials (CENTRAL), from 1972 through July 2010, and conference proceedings through July 2009 and reference
lists, without any language restriction, of randomized trials that compared the transplant outcomes after BMT and PBSCT in
patients with hematological malignancies were searched for details. Two independent reviewers extracted the data. The outcomes
examined were engraftment, graft-versus-host disease (GVHD), relapse, transplant-related mortality (TRM), leukemia-free-survival
(LFS), and overall survival (OS). Compared to PBSCT, BMT had lower neutrophil (HR, 2.08; 95% CI, 1.80 to 2.42; p < 0.00001) and platelet (HR, 2.77; 95% CI, 1.78 to 4.30; p < 0.00001) engraftment. BMT was associated with a significant decrease in the development of grades II–IV (HR, 0.75; 95%
CI, 0.63 to 0.90; p = 0.002) and III–IV (HR, 0.63; 95% CI, 0.47 to 0.84; p = 0.001) acute GVHD as well as overall (HR, 0.70; 95% CI, 0.59 to 0.83; p < 0.0001) and extensive (HR, 0.60; 95% CI, 0.39 to 0.91; p = 0.002) chronic GVHD. BMT was associated with a higher incidence of relapse (HR, 1.91; 95% CI, 1.34 to 2.74; p = 0.0004). Comparable TRM (1.08; 95% CI, 0.56 to 2.10; p = 0.81), LFS (HR, 1.04; 95% CI, 0.83 to 1.30; p = 0.73), and OS (HR, 1.06; 95% CI, 0.81 to 1.39; p = 0.65) were demonstrated for both treatments. An inverse linear relationship was observed between the acute GVHD difference
(PBSCT minus BMT) and the outcome of OS (p = 0.016). Our meta-analysis suggest that BMT leads to slower hematological recovery, increasing rates of relapse, and a lower
risk of GVHD, but no significant difference in LFS and OS. A lower incidence of acute GVHD is associated with a superior OS. 相似文献
8.
Yasmina Chouik Olivier Chazouillères Claire Francoz Eleonora De Martin Olivier Guillaud Armand Abergel Mario Altieri Louise Barbier Camille Besch Filomena Conti Christophe Corpechot Sébastien Dharancy François Durand Christophe Duvoux Jean Gugenheim Jean Hardwigsen Marie-Noëlle Hilleret Pauline Houssel-Debry Nassim Kamar Delphine Maucort-Boulch Anne Minello Martine Neau-Cransac Georges-Philippe Pageaux Sylvie Radenne Olivier Roux Faouzi Saliba Olivier Serée Didier Samuel Claire Vanlemmens Marie-Lorraine Woehl-Jaegle Vincent Leroy Jean-Charles Duclos-Vallée Jérôme Dumortier 《Liver international》2023,43(5):1068-1079
Background & Aims
Autoimmune hepatitis (AIH) is a rare indication for liver transplantation (LT). The aims of this study were to evaluate long-term survival after LT for AIH and prognostic factors, especially the impact of recurrent AIH (rAIH).Methods
A multicentre retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted. Early deaths and retransplantations (≤6 months) were excluded.Results
The study population consisted of 301 patients transplanted from 1987 to 2018. Median age at LT was 43 years (IQR, 29.4–53.8). Median follow-up was 87.0 months (IQR, 43.5–168.0). Seventy-four patients (24.6%) developed rAIH. Graft survival was 91%, 79%, 65% at 1, 10 and 20 years respectively. Patient survival was 94%, 84% and 74% at 1, 10 and 20 years respectively. From multivariate Cox regression, factors significantly associated with poorer patient survival were patient age ≥58 years (HR = 2.9; 95% CI, 1.4–6.2; p = 0.005) and occurrence of an infectious episode within the first year after LT (HR = 2.5; 95% CI, 1.2–5.1; p = 0.018). Risk factors for impaired graft survival were: occurrence of rAIH (HR = 2.7; 95% CI, 1.5–5.0; p = 0.001), chronic rejection (HR = 2.9; 95% CI, 1.4–6.1; p = 0.005), biliary (HR = 2.0; 95% CI, 1.2–3.4; p = 0.009), vascular (HR = 1.8; 95% CI, 1.0–3.1; p = 0.044) and early septic (HR = 2.1; 95% CI, 1.2–3.5; p = 0.006) complications.Conclusion
Our results confirm that survival after LT for AIH is excellent. Disease recurrence and chronic rejection reduce graft survival. The occurrence of an infectious complication during the first year post-LT identifies at-risk patients for graft loss and death. 相似文献9.
Sairah Ahmed Nilanjan Ghosh Kwang W. Ahn Manoj Khanal Carlos Litovich Alberto Mussetti Saurabh Chhabra Mitchell Cairo Matthew Mei Basem William Sunita Nathan Nelli Bejanyan Richard F. Olsson Parastoo B. Dahi Marjolein van der Poel Amir Steinberg Jennifer Kanakry Jan Cerny Umar Farooq Sachiko Seo Mohamed A. Kharfan-Dabaja Anna Sureda Timothy S. Fenske Mehdi Hamadani 《British journal of haematology》2020,190(4):573-582
Reduced-intensity conditioning (RIC) allogeneic haematopoietic cell transplantation (allo-HCT) is a curative option for select relapsed/refractory Hodgkin lymphoma (HL) patients; however, there are sparse data to support superiority of any particular conditioning regimen. We analyzed 492 adult patients undergoing human leucocyte antigen (HLA)-matched sibling or unrelated donor allo-HCT for HL between 2008 and 2016, utilizing RIC with either fludarabine/busulfan (Flu/Bu), fludarabine/melphalan (Flu/Mel140) or fludarabine/cyclophosphamide (Flu/Cy). Multivariable regression analysis was performed using a significance level of <0·01. There were no significant differences between regimens in risk for non-relapse mortality (NRM) (P = 0·54), relapse/progression (P = 0·02) or progression-free survival (PFS) (P = 0·14). Flu/Cy conditioning was associated with decreased risk of mortality in the first 11 months after allo-HCT (HR = 0·28; 95% CI = 0·10–0·73; P = 0·009), but beyond 11 months post allo-HCT it was associated with a significantly higher risk of mortality, (HR = 2·46; 95% CI = 0·1.32–4·61; P = 0·005). Four-year adjusted overall survival (OS) was similar across regimens at 62% for Flu/Bu, 59% for Flu/Mel140 and 55% for Flu/Cy (P = 0·64), respectively. These data confirm the choice of RIC for allo-HCT in HL does not influence risk of relapse, NRM or PFS. Although no OS benefit was seen between Flu/Bu and Flu/Mel 140; Flu/Cy was associated with a significantly higher risk of mortality beyond 11 months from allo-HCT (possibly due to late NRM events). 相似文献
10.
Post‐transplantation cyclophosphamide versus conventional graft‐versus‐host disease prophylaxis in mismatched unrelated donor haematopoietic cell transplantation
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Rohtesh S. Mehta Rima M. Saliba Julianne Chen Gabriela Rondon Aimee E. Hammerstrom Amin Alousi Muzaffar Qazilbash Qaiser Bashir Sairah Ahmed Uday Popat Chitra Hosing Issa Khouri Elizabeth J. Shpall Richard E. Champlin Stefan O. Ciurea 《British journal of haematology》2016,173(3):444-455
Post‐transplantation cyclophosphamide (PTCy) is an effective strategy to prevent graft‐versus‐host disease (GVHD) after haploidentical haematopoietic cell transplantation (HCT). We determined the efficacy of PTCy‐based GVHD prophylaxis in human leucocyte antigen (HLA)‐mismatched unrelated donor (MMUD) HCT. We analysed 113 adult patients with high‐risk haematological malignancies who underwent one‐antigen MMUD transplantation between 2009 and 2013. Of these, 41 patients received PTCy, tacrolimus and mycophenolate mofetil (MMF) for GVHD prophylaxis; 72 patients received conventional prophylaxis with anti‐thymocyte globulin, tacrolimus and methotrexate. Graft source was primarily bone marrow (83% PTCy vs. 63% conventional group). Incidence of grade II–IV (37% vs. 36%, P = 0·8) and grade III–IV (17% vs. 12%, P = 0·5) acute GVHD was similar at day 100. However, the incidence of grade II‐IV acute GVHD by day 30 was significantly lower in the PTCy group (0% vs. 15%, P = 0·01). Median time to neutrophil (18 days vs. 12 days, P < 0·001) and platelet (25·5 days vs. 18 days, P = 0·05) engraftment was prolonged in PTCy group. Rates of graft failure, chronic GVHD, 2‐year non‐relapse mortality, relapse, progression‐free survival or overall survival were similar. Our results demonstrate that PTCy, tacrolimus and MMF for GVHD prophylaxis is safe and produced similar results as conventional prophylaxis in patients with one antigen HLA‐MMUD HCT. 相似文献
11.
《British journal of haematology》2017,176(3):431-439
This study analysed the outcome of 267 patients with relapse/refractory acute myeloid leukaemia (AML ) who received sequential chemotherapy including fludarabine, cytarabine and amsacrine followed by reduced‐intensity conditioning (RIC ) and allogeneic haematopoietic stem cell transplantation (HSCT ). The transplants in 77 patients were from matched sibling donors (MSD s) and those in 190 patients were from matched unrelated donors. Most patients (94·3%) were given anti‐T‐cell antibodies. The incidence of acute graft‐versus‐host disease (GVHD ) of grades II ‒IV was 32·1% and that of chronic GVHD was 30·2%. The 3‐year probability of non‐relapse mortality (NRM ) was 25·9%, that of relapse was 48·5%, that of GVHD ‐free and relapse‐free survival (GRFS ) was 17·8% and that of leukaemia‐free survival (LFS ) was 25·6%. In multivariate analysis, unrelated donor recipients more frequently had acute GVHD of grades II ‒IV [hazard ratio (HR ) = 1·98, P = 0·017] and suffered less relapses (HR = 0·62, P = 0·01) than MSD recipients. Treatment with anti‐T‐cell antibodies reduced NRM (HR = 0·35, P = 0·01) and improved survival (HR = 0·49, P = 0·01), GRFS (HR = 0·37, P = 0·0004) and LFS (HR = 0·46, P = 0·005). Thus, sequential chemotherapy followed by RIC HSCT and use of anti‐T‐cell antibodies seems promising in patients with refractory AML . 相似文献
12.
Frédéric Baron Myriam Labopin Annalisa Ruggeri Jorge Sierra Stephen Robinson Hélène Labussière-Wallet Michael Potter Josep-Maria Ribera Eric Deconinck Alessandro Rambaldi Pierre-Simon Rohrlich Thierry de Revel Eliane Gluckman Arnon Nagler Mohamad Mohty 《American journal of hematology》2020,95(9):1057-1065
The impact of measurable residual disease (MRD) on cord blood transplantation (CBT) outcomes has remained debated. To address this issue, we assessed the impact of measurable MRD at CBT on outcomes in large cohort of patients with acute leukemia. Inclusion criteria included adult patients with acute myeloid (AML) or acute lymphoblastic leukemia (ALL), CBT as first allo-HCT in first or second complete remission (CR) at transplantation, and known MRD status at the time of CBT. Data from 506 patients were included in the analysis. Among them, 317 patients had AML and 189 had ALL. Positive MRD was reported in 169 (33%) patients while the remaining 337 patients were MRD negative at CBT. At 2 years, relapse incidence was 18% in patients with MRD negativity vs 33% in those with MRD positivity at transplantation (P < .001). Two-year leukemia-free survival (LFS) and overall survival (OS) were 57% and 60%, respectively, in MRD negative patients, vs 38% (P < .001) and 48% (P = .004), respectively, in those with MRD positivity. There was no interaction between the impact of MRD on OS and LFS and diagnosis (ie, ALL vs AML), single or double CBT, and reduced-intensity or myeloablative conditioning. On multivariate analysis, MRD positivity was associated with a higher risk of relapse (HR = 1.8, P = .003), comparable non-relapse mortality (P = .44), worse LFS (HR = 1.4, P = .008) and a trend towards worse OS (HR = 1.3, P = .065). In conclusion, these data suggest that novel strategies that are aiming to achieve MRD negativity at CBT are needed for leukemic patients with positive MRD pre-CBT. 相似文献
13.
《Hematology/oncology and stem cell therapy》2020,13(1):32-39
Objective/BackgroundCytomegalovirus (CMV) infection and disease are common infectious complications after allogeneic hematopoietic cell transplantation (alloHCT). Major histocompatibility complex (MHC) class I chain-related gene A (MICA) is a ligand of the natural killer (NKG2D) receptor on immune effector cells that helps mediate NK cell alloreactivity. We hypothesized that MICA polymorphisms may influence CMV infection and disease incidence after alloHCT.MethodsWe conducted a retrospective analysis of 423 adults at the Cleveland Clinic with hematologic malignancies treated with a matched related or unrelated donor alloHCT. CMV cases analyzed included a compositive of instances of viral copy replication above detection limits as well as any biopsy-proven tissue invasive disease episodes. Genotypes at the MICA-129 position have been categorized as weak (valine/valine; V/V), intermediate (methionine/valine; M/V), or strong (methionine/methionine; M/M) receptor affinity.ResultsIn multivariable analysis, V/V donor MICA-129 genotype was associated with CMV infection and disease (hazard ratio [HR] = 1.40; 95% confidence interval [CI], 1.00–1.96; p = .05), but not MICA mismatch (HR = 1.38; 95% CI, 0.83–2.29; p = .22). There was no association of acute or chronic GVHD with MICA donor–recipient mismatch (HR = 1.05; 95% 95% CI, 0.66–1.68; p = .83 and HR = 0.94; 95% CI, 0.51–1.76; p = .85, respectively) or V/V donor MICA-129 genotypes (HR = 1.02; 95% CI, 0.79–1.31; p = .89 and HR = 0.89; 95% CI, 0.65–1.22; p = .47, respectively).ConclusionThese findings suggest that the donor MICA-129 V/V genotype with weak NKG2D receptor binding affinity is associated with an increased risk of CMV infection and disease after alloHCT. 相似文献
14.
Ting Huang Lanping Xu Xiaohui Zhang Yingjun Chang Xiaodong Mo Yuqian Sun Xiaojun Huang Yu Wang 《British journal of haematology》2023,200(4):494-505
Acute myeloid leukaemia (AML) patients with tumour protein p53 (TP53) mutations are often resistant to chemotherapy and have worse clinical outcomes than patients without TP53 mutations. In this study, we compared clinical outcomes of patients with AML with and without TP53 mutations who underwent haploidentical haematopoietic stem cell transplantation (haplo-HSCT). For the TP53-mutation group and TP53 wild-type group, the 2-year cumulative incidence of relapse (CIR) was (39.0% vs. 21.2% respectively, p = 0.088), the 2-year non-relapse mortality (NRM) rate was (3.2% vs. 8.4% respectively, p = 0.370), the 2-year leukaemia-free survival (LFS) was (57.7% vs. 71.3% respectively, p = 0.205), the 2-year overall survival (OS) rate was (69.9% vs. 81.3% respectively, p = 0.317), the 100-day cumulative incidence of Grade II–IV acute graft-versus-host disease (GvHD) was (6.5% vs. 20.7% respectively, p = 0.074), the 2-year cumulative incidence of chronic GvHD was (52.3% vs. 53.1% respectively, p = 0.493) and the 2-year GvHD-free/relapse-free survival (GRFS) was (57.7% vs. 69.6% respectively, p = 0.347). Our data showed that there were no significant differences in 2-year clinical outcomes between the two groups. Multivariable analysis showed TP53 mutations had no significant impact on CIR, NRM, OS, GvHD, LFS or GRFS. Our findings suggest that patients with AML with TP53 mutations may at least partially benefit from haplo-HSCT. Haplo-HSCT might be the recommended treatment for such patients. 相似文献
15.
Yves Chalandon Giulia Sbianchi Luuk Gras Linda Koster Jane Apperley Jenny Byrne Urpu Salmenniemi Henrik Sengeloev Mahmoud Aljurf Grzegorz Helbig Francesca Kinsella Goda Choi Péter Reményi John A. Snowden Marie Robin Stig Lenhoff Stephan Mielke Jakob Passweg Annoek E. C. Broers Nicolaus Kröger Zeynep Arzu Yegin Sen Mui Tan Patrick J. Hayden Donal P. McLornan Ibrahim Yakoub-Agha the Chronic Malignancies Working Party of the European Group for Blood Marrow Transplantation 《American journal of hematology》2023,98(1):112-121
Following the introduction of tyrosine kinase inhibitors (TKI), the number of patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) for chronic phase (CP) chronic myeloid leukemia (CML) has dramatically decreased. Imatinib was the first TKI introduced to the clinical arena, predominantly utilized in the first line setting. In cases of insufficient response, resistance, or intolerance, CML patients can subsequently be treated with either a second or third generation TKI. Between 2006 and 2016, we analyzed the impact of the use of 1, 2, or 3 TKI prior to allo-HCT for CP CML in 904 patients. A total of 323-, 371-, and 210 patients had 1, 2, or 3 TKI prior to transplant, respectively; imatinib (n = 778), dasatinib (n = 508), nilotinib (n = 353), bosutinib (n = 12), and ponatinib (n = 44). The majority had imatinib as first TKI (n = 747, 96%). Transplants were performed in CP1, n = 549, CP2, n = 306, and CP3, n = 49. With a median follow-up of 52 months, 5-year OS for the entire population was 64.4% (95% CI 60.9–67.9%), PFS 50% (95% CI 46.3–53.7%), RI 28.7% (95% CI 25.4–32.0%), and NRM 21.3% (95% CI 18.3–24.2%). No difference in OS, PFS, RI, or NRM was evident related to the number of TKI prior to allo-HCT or to the type of TKI (p = ns). Significant factors influencing OS and PFS were > CP1 versus CP1 and Karnofsky performance (KPS) score > 80 versus ≤80, highlighting CP1 patients undergoing allo-HCT have improved survival compared to >CP1 and the importance of careful allo-HCT candidate selection. 相似文献
16.
《Nutrition, metabolism, and cardiovascular diseases : NMCD》2022,32(1):176-185
Background and aimsThis study assesses the influence of demographic, lifestyle, and medication in the association between CRP and mortality in a national sample of adults with diabetes.Methods and resultsCross-sectional study of data from 1999 to 2010 National Health and Nutrition Examination Survey (unweighted n = 3952; Weighted n = 19,064,710). Individuals were categorized as having diabetes if told by a provider they had diabetes, were taking insulin or other diabetes medications, or had a glycosylated hemoglobin A1c (HbA1c) ≥ 6.5%. CRP was classified into four categories: normal (≤0.1 mg/dL); moderate risk (0.11–0.3 mg/dL); high-risk (0.31–1.0 mg/dL); very high-risk (>1.0 mg/dL). Higher risk for mortality was associated with a very high-risk of CRP (HR = 1.88 (95% CI: 1.27–2.78), being a current (HR = 1.49 (95% CI: 1.10–2.01) or former (HR = 1.34 (95% CI: 1.03–1.73) smoker, and taking insulin (HR = 1.60 (95% CI: 1.25–2.05), taking anti-hypertensives (HR = 1.50 (95% CI: 1.22–1.85), and having co-morbidities such as cancer (HR = 1.32 (95% CI: 1.05–1.66) and hepatitis infection (HR = 1.76 (95% CI: 1.07–2.91), while taking Metformin (HR = 0.62 (95% CI: 0.50–0.76) had a lower risk of mortality.ConclusionIn this sample of adults with diabetes, demographic, lifestyle, and medication factors influenced the association between CRP and mortality. Interventions should focus on these factors to reduce mortality in adults with diabetes. 相似文献
17.
Marianne Ifversen Dominik Turkiewicz Hanne V. Marquart Jacek Winiarski Jochen Buechner Karin Mellgren Johan Arvidson Jelena Rascon Lenne-Triin Körgvee Hans O. Madsen Jonas Abrahamsson Bendik Lund Olafur G. Jonsson Carsten Heilmann Mats Heyman Kjeld Schmiegelow Kim Vettenranta 《British journal of haematology》2019,184(6):982-993
The population-based Nordic/Baltic acute lymphoblastic leukaemia (ALL) Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol combined minimal residual disease (MRD)-driven treatment stratification with very intense first line chemotherapy for patients with high risk ALL. Patients with MRD ≥5% at end of induction or ≥10−3 at end of consolidation or following two high risk blocks were eligible for haematopoietic cell transplantation (HCT) in first remission. After at least three high risk blocks a total of 71 children received HCT, of which 46 had MRD ≥5% at end of induction. Ten patients stratified to HCT were not transplanted; 12 received HCT without protocol indication. Among 69 patients with evaluable pre-HCT MRD results, 22 were MRD-positive, one with MRD ≥10−3. After a median follow-up of 5·5 years, the cumulative incidence of relapse was 23·5% (95% confidence interval [CI]: 10·5–47·7) for MRD-positive versus 5·1% (95% CI: 1·3–19·2), P = 0·02) for MRD-negative patients. MRD was the only variable significantly associated with relapse (hazard ratio 9·1, 95% CI: 1·6–51·0, P = 0·012). Non-relapse mortality did not differ between the two groups, resulting in disease-free survival of 85·6% (95% CI: 75·4–97·2) and 67·4% (95% CI: 50·2–90·5), respectively. In conclusion, NOPHO block treatment efficiently reduced residual leukaemia which, combined with modern transplant procedures, provided high survival rates, also among pre-HCT MRD-positive patients. 相似文献
18.
Zhuoyan Li Myriam Labopin Fabio Ciceri Didier Blaise Johanna Tischer Gerhard Ehninger MT Van Lint Yener Koc Stella Santarone Edouard Forcade Luca Castagna Emmanuelle Polge Audrey Mailhol Annalisa Ruggeri Mohamad Mohty Bipin N. Savani Arnon Nagler 《American journal of hematology》2018,93(6):769-777
Secondary acute myeloid leukemia (sAML) traditionally has inferior outcomes compared to de novo AML. Allogeneic hematopoietic cell transplantation (HCT) is the sole potentially curative therapy. This study analyzes the outcomes for unmanipulated haploidentical HCT (haploHCT) for sAML using the Acute Leukemia Working Party (ALWP) registry of the European Society for Blood and Marrow Transplantation (EBMT). We identified 154 patients with sAML who underwent haploHCT from 2006 to 2016. Median age at HCT was 60 years with time from diagnosis to HCT 5 months. At transplantation, 69 patients were in first CR and 85 had active disease. Fifty‐seven (38.0%) patients underwent myeloablative conditioning and 97 (62.0%) reduced intensity conditioning (RIC) conditioning. Multivariate analysis showed that there was no difference in RI, nonrelapse mortality (NRM), leukemia free survival (LFS), overall survival (OS), or GVHD‐free/relapse free survival (GRFS) for conditioning intensity, age, performance status, or graft source. Active disease was associated with higher RI and inferior LFS, OS, and GRFS compared with patients in CR at time of transplant. T‐cell depletion with anti‐thymoglobulin resulted in higher NRM and inferior LFS, OS, and GRFS compared to post‐transplant cyclophosphamide (PTCy) (HR 2.25, 2.01, 2.16, and 1.73, respectively with P values <.05). Our data shows that haploHCT is a feasible alternative for sAML when matched transplantation is unavailable. 相似文献
19.
Kristian Løvvik Juul-Dam Hans B. Ommen Charlotte G. Nyvold Christiane Walter Helen Vålerhaugen Veli Kairisto Jonas Abrahamsson Sofie J. Alm Kirsi Jahnukainen Birgitte Lausen Dirk Reinhardt Bernward Zeller Nils von Neuhoff Linda Fogelstrand Henrik Hasle 《British journal of haematology》2020,190(2):198-208
20.
Jian Hu Susu Gong Keke Chen Rui Yang Leyuan Wang Kaitai Yang Lin Nie Lang Zou Tao Su Cong Chen Yajing Xu Xianglin He Liangchun Yang Hong Xiao Bin Fu 《British journal of haematology》2023,200(3):329-337
Haploidentical transplantation strategies for patients with transfusion-dependent thalassaemia (TD-TM) remain to be investigated. In this study, 54 paediatric patients with TD-TM were treated with a novel approach using post-transplant cyclophosphamide (PTCy) and low-dose methotrexate (LD-MTX), following a myeloablative regimen. The incidence of neutrophil and platelet engraftment was 96.3% ± 2.6% and 94.4% ± 3.1% respectively. The cumulative incidence of grades II–III acute graft-versus-host disease (GVHD) was 13.8% ± 4.8% at 100 days. At three years, the cumulative incidence of chronic GVHD was 28.5% ± 8.5%. With a median follow-up of 520 days (132–1325 days), the overall survival (OS) and event-free survival (EFS) were 98.1% ± 1.8% and 90.7% ± 3.9% respectively. Compared with the low-dose cyclophosphamide (CTX) conditioning regimen (120 mg/kg), the high-CTX regimen (200 mg/kg) achieved a higher incidence of stable engraftment (100% vs 66.7% ± 15.7%, p = 0.003), a comparable incidence of grades II–III acute GVHD, a lower incidence of chronic GVHD (20.2% ± 8.3% vs 66.6% ± 19.2%, p = 0.011), and better overall survival (100% vs 88.9% ± 10.5%, p = 0.025) as well as EFS (95.6% ± 3.1% vs 66.7% ± 15.7%, p = 0.008). Our results using unmanipulated haploidentical grafts and PTCy with LD-MTX in TD-TM are encouraging. (chictr.org.cn ChiCTR1800017969) 相似文献