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1.
Nicholas J. Gloude Sonata Jodele Ashley Teusink-Cross Michael Grimley Stella M. Davies Adam Lane Kasiani C. Myers 《Biology of blood and marrow transplantation》2018,24(1):91-95
Veno-occlusive disease (VOD) is a serious complication of hematopoietic stem cell transplant (HSCT), with high mortality in severe cases and until recently very limited therapeutic options consisting largely of supportive care. Defibrotide was recently approved in the United States for the treatment of severe VOD in patients with renal or pulmonary dysfunction after HSCT. Our group previously published on the use of high-dose methylprednisolone (500?mg/m2 per dose every 12 hours for 6 doses) in patients with VOD, showing good success. A small subset of these individuals were also treated with defibrotide, but additional studies using the combination of high-dose methylprednisolone and defibrotide for the treatment of VOD are lacking. We present a single-institution retrospective chart review of 15 HSCT patients with VOD treated with the combination of high-dose methylprednisolone and defibrotide. VOD developed at a median of 17 days post-HSCT, and combination therapy was initiated within 1 day of VOD diagnosis. Twelve of 15 patients (80%) had multiorgan failure. Our single-center experience using both high-dose methylprednisolone and defibrotide showed a day +100 survival rate of 73% and an overall VOD complete resolution rate of 66.7%, higher than the rates reported in the recent literature using defibrotide alone (40% to 50% day +100 overall survival). These data suggest that the combination of high-dose steroids and defibrotide may be superior to defibrotide alone and warrant further investigation. 相似文献
2.
Studies investigating the effect of prophylactic drugs on hepatic veno-occlusive disease (VOD) development are rare in children that have undergone allogeneic hematopoietic stem cell transplantation (HSCT). This study examined risk factors for VOD, the effect of prophylactic low-dose heparin or lipo-prostaglandin E1 (lipo-PGE1) and the survival rate at day +100 in children undergoing allogeneic HSCT. Eighty five children underwent HSCT between June 1997 and September 2004. Patients were diagnosed and classified as having mild, moderate or severe VOD according to Seattle clinical criteria. Among 85 patients, 25 (29%) developed VOD. VOD occurred more frequently in patients receiving busulfan-based conditioning (24/65, 37%) than in those receiving TBI-based (1/10, 10%) or other (0/10, 0%) regimens (p<0.05). The incidence of VOD was lower in patients with non-malignant disease compared to those with malignant disease (p<0.05). Survival at day +100 for non-VOD patients was better than that for VOD patients (92% vs. 76%, p<0.05). No patients receiving prophylactic heparin or lipo-PGE1 were found to develop severe VOD, whereas 5 of 35 patients not receiving such prophylaxis developed severe VOD. Given severe VOD is associated with a high mortality rate, this study indicates that prophylactic heparin or lipo-PGE1 may decrease mortality in children undergoing HSCT. 相似文献
3.
Adrien Picod Agnès Bonnin Giorgia Battipaglia Federica Giannotti Annalisa Ruggeri Eolia Brissot Florent Malard Clémence Médiavilla Ramdane Belhocine Anne Vekhoff Mor Sény Gueye Simona Lapusan Rosa Adaeva Françoise Isnard Ollivier Legrand Minh-Tam Baylatry Anne-Christine Joly Myriam Labopin Mohamad Mohty 《Biology of blood and marrow transplantation》2018,24(7):1471-1475
Sinusoidal obstruction syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a serious complication after hematopoietic stem cell transplantation (HSCT). SOS/VOD usually occurs within 3 weeks of HSCT, but the 2016 European Society for Blood and Marrow Transplantation diagnosis criteria have been revised to include late forms. Prophylactic use of defibrotide is recommended in the pediatric setting, but its value remains uncertain in the adult population. We report here a single-center series of 63 adult patients considered at high risk for SOS/VOD who received defibrotide prophylaxis in combination with ursodeoxycholic acid between May 2012 and August 2016. The median duration of defibrotide therapy was 23 days. Bleeding occurred in 14 patients (21.5%). Defibrotide prophylaxis was discontinued in 7 patients (10.8%): 4 cases (6.3%) due to bleeding and 3 cases (4.6%) because of the need for antithrombotic therapy. Overall, SOS/VOD occurred in 4 cases (6.3%) within 21 days after HSCT (days 13 and 14) in 2 cases and late-onset SOS/VOD (days 57 and 58) in the other 2 cases. SOS/VOD was moderate in 1 case, very severe in 3 cases, with 2 deaths related to SOS/VOD. Cumulative incidence of grades II to IV acute graft-versus-host disease and transplant-associated thrombotic microangiopathy were 22.2% and 3.2%, respectively. With a median follow-up of 31 months (range, 10.7 to 60.3), the rates of 2-year overall survival, progression-free survival, incidence of relapse, and nonrelapse mortality were 56.5%, 49%, 28.7%, and 22.3%, respectively. In our experience defibrotide prophylaxis is associated with a low incidence of SOS/VOD after allogeneic HSCT in a high-risk adult population with an acceptable safety profile. 相似文献
4.
《Biology of blood and marrow transplantation》2013,19(3):500-503
Veno-occlusive disease (VOD) of the liver is a well-recognized serious complication of hematopoietic stem cell transplantation (HSCT), with few successful treatment modalities available for severe disease. Some reports have demonstrated success in adults with the use of high-dose steroid therapy, but experience in the pediatric population is lacking. We retrospectively reviewed HSCT patients treated at our institution since 2003 and identified 15 (2.4%) who developed VOD. Of these, nine (60%) were treated with intravenous high-dose methylprednisolone (500 mg/m2 per dose every 12 hours for six doses). Steroid therapy was initiated at or before first ultrasound evidence of reversal of portal venous flow and before meeting criteria for initiation of defibrotide therapy. Four patients were also treated with defibrotide starting 2 to 5 days after initiation of steroids. Eight of nine patients (88%) with VOD were diagnosed with multiorgan failure. Response to high-dose steroid therapy as defined by decrease in bilirubin by 50% in 10 days from therapy initiation was noted in six of nine patients (67%), occurring within 3 to 6 days of steroid therapy. Two patients died from multiorgan failure due to VOD. Seven survivors of VOD recovered at the median 6 days (range, 5 to 38) from VOD diagnosis. Overall, VOD survival as a group was 78%; however, survival among responders was 100%. No serious toxicities related to high-dose steroid therapy were observed. We conclude that high-dose steroid therapy if initiated early may reverse VOD of the liver in pediatric HSCT patients, abrogating the need for defibrotide therapy with its associated toxicities and regulatory difficulties. 相似文献
5.
《Biology of blood and marrow transplantation》2020,26(3):546-552
We compared the incidence of refractory thrombocytopenia (RT) and platelet transfusion requirements (PTR) in 35 children who developed veno-occlusive disease (VOD) with 35 matched control subjects who underwent hematopoietic stem cell transplant but did not develop VOD. RT developed in 100% of the VOD patients, at a median of 8 days before VOD diagnosis, as compared with 71.5% of the control group. VOD patients required more platelet transfusions than control subjects (median PTR, 6.9 mL/kg [range, .57 to 17.59] versus 3.57 mL/kg [range, 0 to 14.63], respectively) with a statistically significant difference (P < .0001). The number of days with platelet requirements was significantly higher for VOD patients as compared with control subjects (median 68% versus 39%, P =< .0001). The PTR peaked at ~12 mL/kg/day, 2 days before VOD diagnosis, whereas the PTR in the control population was 5 mL/kg/day. The positive predictive value of developing VOD was 88.9% (95% confidence interval, 66.5% to 97%) in patients who were given >7 mL/kg/day of platelets during the at-risk period of days +3 to +13 after transplant. For patients who received >8 mL/kg/day of platelets, the positive predictive value of developing VOD was 86.7% (95% confidence interval, 61.2% to 96.4%). There was no difference in the PTR in patients with mild to moderate VOD as compared with severe VOD; however, the PTR was higher in patients whose VOD did not resolve. The median daily PTR after the diagnosis of VOD in 17 patients who got defibrotide as compared with those who did not get defibrotide was 6.04 mL/kg and 5.72 mL/kg, respectively, but the difference was not statistically significant (P = .56). On univariate and multivariate analysis use of intravenous immunoglobulin was significantly associated with VOD (P = .0088) but was not significantly associated with fatal VOD. In conclusion, RT occurs in 100% of patients at a median of 8 days before VOD diagnosis. VOD should be suspected in any patient with RT after the exclusion of other causes of consumptive thrombocytopenia, especially if they require >7 mL/kg/day of platelets. 相似文献
6.
《Biology of blood and marrow transplantation》2020,26(11):2089-2097
Hepatic veno-occlusive disease or sinusoidal obstruction syndrome (VOD/SOS) is a threatening complication after both autologous and allogeneic hematopoietic stem cell transplantation (HSCT), with high mortality rates despite early medical treatment, including the use of defibrotide (DF). We retrospectively analyzed 185 unmanipulated haploidentical (haplo-) HSCT with post-transplantation cyclophosphamide as graft-versus-host disease prophylaxis performed consecutively between 2011 and June 2019 in a single center. Seventeen patients (9.2%) were diagnosed with VOD/SOS. Based on revised European Society for Blood and Marrow Transplantation severity criteria, the VOD/SOS cases were classified as mild in 2 patients (11.7%), moderate in 2 (11.7%), severe in 2 (11.7%), and very severe in 11 (64.9%). Thirteen patients (76%) were treated with DF, including all patients with severe or very severe VOD/SOS, except 1 patient with CNS hemorrhage. Sixteen patients (94%) were alive at day +100 after HSCT. Seven patients (41%) with very severe VOD/SOS were treated with transjugular intrahepatic portosystemic shunt (TIPS) owing to rapid clinical or analytical deterioration or refractory hepatorenal syndrome despite medical treatment, including DF. TIPS insertion was performed at a median time since VOD/SOS diagnosis of 4 days (range, 1 to 28 days) without technical complications in any case. The median hepatic venous pressure gradient before and after TIPS treatment was 24 mmHg (range, 14 to 29 mmHg) and 7 mmHg (range, 2 to 11 mmHg), respectively, with a median drop of 16 mmHg (range, 9 to 19 mmHg). Following TIPS insertion, all patients showed clinical improvement with hepatomegaly, ascites, and renal failure resolution, and all showed analytical improvement with reduced alanine aminotransferase (ALT), creatinine, and international normalized ratio values, except for patient 2, whose indication for TIPS was refractory hepatorenal syndrome with a normal ALT level. The 6 patients who had initiated DF before TIPS insertion completed 21 days of treatment. All patients met the criteria for complete remission (CR) at a median of 8 days after TIPS insertion (range, 2 to 82 days). The 100-day overall survival was 100%. For patients with rapid progressive VOD/SOS, early TIPS insertion allowed completion of DF therapy. The use of TIPS together with DF resulted in CR and no associated complications with no VOD/SOS-associated mortality despite high severity. In our experience, timely and individualized use of TIPS significantly improves outcomes of very severe VOD/SOS after haplo-HSCT. Therefore, TIPS should be promptly considered in rapidly progressive cases. 相似文献
7.
Ryotaro Nakamura Minoo Battiwalla Scott Solomon Dean Follmann Sakti Chakrabarti Karoll Cortez Nancy Hensel Richard Childs A John Barrett 《Biology of blood and marrow transplantation》2004,10(1):49-57
Numerous clinical studies link cytomegalovirus (CMV) infection with incomplete posttransplantation T-cell recovery. We hypothesized that the inability of transplant recipients to handle CMV reactivation might correlate with a defective graft-versus-leukemia response and increased posttransplantation morbidity. Between May 1995 and August 2001, 82 patients who were CMV seropositive and survived the first 100 days after transplantation were identified for a day 100 landmark analysis of the effect of CMV reactivation patterns on eventual transplantation outcome. All patients underwent a myeloablative HLA-identical sibling donor T cell-depleted stem cell transplantation with scheduled donor T-cell add-back on day 45. Median follow-up was 1032 days. Forty-two patients who had either no reactivation or only 1 positive test with quick clearance were designated as a CMV immune competent group. Forty patients designated as CMV immune deficient (ID) had at least 2 positive tests. Apart from younger age (33 versus 38 years; P =.05) in the ID group, the 2 groups were balanced for clinical characteristics. In multivariate analysis, ID patients had a significantly higher incidence of leukemia relapse (58% versus 21%; P =.03) and worse disease-free survival (31% versus 66%; P =.04). There was no significant difference in week 1 to 14 posttransplantation lymphocyte counts between the 2 groups. In 67 patients tested 3 to 6 months after transplantation, a proliferative response to CMV antigen (stimulation index > or =2) occurred in 27 of 36 immune competent patients compared with 15 of 31 ID patients (P =.006). These results show that recurrent CMV reactivation in the first 100 days after transplantation predicts for reduced disease-free survival and increased leukemic relapse beyond 100 days and correlates with inferior proliferative responses to CMV. The higher relapse rate may reflect poor immune reconstitution in ID patients or an adverse effect of prolonged antiviral treatment. 相似文献
8.
Anna Nordlander Jonas Mattsson Olle Ringdén Katarina Leblanc Britt Gustafsson Per Ljungman Petter Svenberg Johan Svennilson Mats Remberger 《Biology of blood and marrow transplantation》2004,10(3):195-203
To determine the graft-versus-leukemia effect after hematopoietic stem cell transplantation (HSCT), we studied 199 patients with acute lymphoblastic leukemia who underwent transplantation at Huddinge University Hospital between 1981 and 2001. Seventy-four patients were in first complete remission (CR1), and 125 were in later stages of the disease. Most patients had an HLA-identical sibling donor. Conditioning consisted mainly of total body irradiation and cyclophosphamide, and graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. Acute GVHD developed in 143 patients and chronic GVHD in 67. The 5-year probability of relapse and relapse-free survival (RFS) were 32% and 49%, respectively, in patients in CR1, as compared with 53% and 33% in those with more advanced disease. In the multivariate risk factor analysis of relapse, we found that the absence of chronic GVHD (P<.001), absence of herpes simplex virus infection after HSCT (P=.003), combination prophylaxis with methotrexate and cyclosporine (P=.01), and >6 weeks from the diagnosis to CR (P=.025) were independent risk factors for relapse after HSCT. Factors associated with a better relapse-free survival were chronic GVHD (P<.001), ABO blood group mismatch (P=.006), younger patient age (P=.01), and an HLA-matched donor (P=.01). The association between herpes simplex virus infection and a low frequency of relapse is a new observation and may indicate that viral antigens play a role in the induction of an antileukemic effect. 相似文献
9.
Lindsey E. Roeker Haesook T. Kim Brett Glotzbecker Prashant Nageshwar Sarah Nikiforow John Koreth Philippe Armand Corey Cutler Edwin P. Alyea Joseph H. Antin Paul G. Richardson Robert J. Soiffer Vincent T. Ho 《Biology of blood and marrow transplantation》2019,25(1):137-144
Hepatic veno-occlusive disease (VOD), or sinusoidal obstruction syndrome (SOS), is a serious complication of hematopoietic stem cell transplantation (HSCT) with mortality in its severe form exceeding 80%. Although the incidence of VOD/SOS has fallen with contemporary transplantation practices, the increasing use of inotuzumab, the return of gemtuzumab, and the popularity of pharmacokinetic-guided high-dose busulfan may impact incidence. Early intervention with defibrotide improves survival, but prompt diagnosis can be difficult. We aimed to identify clinical parameters that could aid in early detection of VOD/SOS in a large, retrospective, cohort study. Of the 1823 adult patients who underwent myeloablative HSCT between 1996 and 2015 in our center, 205 (11%) developed VOD/SOS, with a median onset of day +14. We compared parameters in the 7 days preceding VOD/SOS onset for cases to 447 randomly selected control subjects in an analogous time frame to determine those with predictive value. Between 7 days before and the day of diagnosis, VOD/SOS patients had higher serum creatinine levels and were more likely to develop acute kidney injury (61% versus 33%, P < .0001), more commonly experienced refractoriness to platelet transfusion (48% versus 24%, P < .0001), and had higher trough serum tacrolimus levels (7 days before VOD/SOS onset: median 8.8 versus 7.3, P?=?.0002; day of onset: median 9.3 versus 7.2, P < .0001) compared with control subjects. Acute renal dysfunction, platelet refractoriness, and elevated or abnormal tacrolimus levels are dynamic clinical markers that should alert clinicians to the development of VOD/SOS before the presence of classical diagnostic criteria. Using these clinical features to recognize VOD/SOS earlier in its clinical course could promote earlier treatment and lead to improved outcomes of this potentially serious complication. 相似文献
10.
Maura Faraci Alice Bertaina Roberto Luksch Elisabetta Calore Edoardo Lanino Francesco Saglio Arcangelo Prete Mariacristina Menconi Giusy De Simone Veronica Tintori Simone Cesaro Stella Santarone Maria Grazia Orofino Franco Locatelli Marco Zecca 《Biology of blood and marrow transplantation》2019,25(2):313-320
Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD), is a potentially life-threatening complication that may develop after hematopoietic stem cell transplantation (HSCT). The aims of this retrospective multicenter study were to evaluate the incidence of SOS/VOD in a large cohort of children transplanted in centers across Italy by applying the new European Society for Blood and Marrow Transplantation (EBMT) criteria and to analyze the risk factors underlying this complication. We retrospectively reviewed data of pediatric HSCTs performed in 13 AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica)-affiliated centers between January 2000 and April 2016. The new pediatric EBMT criteria were retrospectively applied for diagnoses of SOS/VOD and severity grading. Among 5072 transplants considered at risk for SOS/VOD during the study period, 103 children (2%) developed SOS/VOD, and the grade was severe or very severe in all patients. The median time of SOS/VOD occurrence was 17 days after HSCT (range, 1 to 104). Sixty-nine patients (67%) were treated with defibrotide for a median time of 16 days (range, 4 to 104). In multivariable analysis age < 2 years, use of busulfan during the conditioning regimen, female gender, and hemophagocytic lymphohistiocytosis were risk factors statistically associated with the development of SOS/VOD. The overall mortality directly related to SOS/VOD was 15.5%. Overall survival at 1 year was worse in patients with SOS/VOD (P?=?.0033), and this difference disappeared 5 years after HSCT. Nonrelapse mortality was significantly higher 1 and 5 years after transplantation in patients who developed SOS/VOD (P < .001). Based on the application of new EBMT criteria, the overall incidence of SOS/VOD recorded in this large Italian pediatric retrospective study was 2%. Nonrelapse mortality was significantly higher in patients who developed SOS/VOD. Identifying the risk factors associated with SOS/VOD can lead to more effective early treatment strategies of this potentially fatal HSCT complication in childhood. 相似文献
11.
John E Levine Joseph P Uberti Lois Ayash Christopher Reynolds James L m Ferrara Samuel M Silver Thomas Braun Gregory Yanik Raymond Hutchinson Voravit Ratanatharathorn 《Biology of blood and marrow transplantation》2003,9(3):189-197
Reduced conditioning intensity has extended the option of allogeneic hematopoietic stem cell transplantation to patients who cannot tolerate fully myeloablative regimens. However, relapse and graft-versus-host disease (GVHD) continue to be major causes of morbidity and mortality. We prospectively tested whether a moderate reduction of the intensity of the preparative regimen would lead to significant reduction in regimen-related toxicity without compromising tumor control in a cohort of 44 patients ineligible for conventional hematopoietic stem cell transplantation. Patients were conditioned with fludarabine, busulfan, mycophenolate, and total lymphoid irradiation. Tacrolimus and methotrexate were given as prophylaxis for GVHD. Donors were 5 of 6 or 6 of 6 matched family members. The median age was 61 years. Eleven patients had comorbid conditions that precluded conventional myeloablative transplantation. Fatal regimen-related organ toxicity occurred in 3 patients. The cumulative incidence of grade 2 to 4 or grade 3 to 4 acute GVHD by day 100 was 38% (95% confidence interval [CI] = 25%, 55%) and 20% (95% CI = 10%, 39%), respectively, with a median time to onset of 66 days. For the entire cohort, 1-year overall survival, disease-free survival, and relapse rates were 54% (95% CI = 41%, 71%), 47% (95% CI = 35%, 65%), and 37% (95% CI = 19%, 51%), respectively. Outcomes differed based on stage of disease at time of transplantation, advanced (n = 19) versus nonadvanced (n = 25). Median survival times were 138 days and 685 days for subjects with advanced and nonadvanced disease, respectively (P =.005). After adjusting for age and comorbidity, disease stage continued to be significantly associated with overall survival (P =.005). In conclusion, a moderate reduction in conditioning dose intensity resulted in delayed onset of acute GVHD (compared with historical controls). A reduction in conditioning intensity is associated with poor survival for patients with advanced-stage disease, highlighting the importance of the conditioning regimen for tumor control. 相似文献
12.
背景:异基因外周血造血干细胞移植成为造血干细胞移植的主要方式,近年来HLA单倍体相合造血干细胞移植因供者来源广泛在临床应用较多,急性移植物抗宿主病仍是影响移植成功率的主要因素。
目的:观察亲缘HLA单倍体相合与全相合异基因外周血造血干细胞移植后急性移植物抗宿主病的发生特点,探讨降低急性移植物抗宿主病发生率的方法及单倍体造血干细胞移植应用于临床的意义。
方法:行异基因外周血造血干细胞移植的患者52例,其中HLA全相合组31例,单倍体组21例。HLA单倍体组采用改良马利兰/环磷酰胺+兔抗人胸腺T细胞免疫球蛋白预处理方案,HLA全相合组采用改良马利兰/环磷酰胺预处理方案。移植物抗宿主病的预防采用短程甲氨蝶呤+环孢素A+吗替麦考酚酯的方案。
结果与结论:52例患者均获得完全持久干细胞植入。其中,急性移植物抗宿主病发病率为48%(25/52),Ⅲ-Ⅳ度急性移植物抗宿主病发病率为23%(12/52);全相合组及单倍体组急性移植物抗宿主病累积发病率分别为39%(12/31)和62%(13/21)(P > 0.05);全相合组及单倍体组Ⅲ-Ⅳ度急性移植物抗宿主病累积发病率分别为10%(3/31)和43%(9/21)(P < 0.05);发生于移植后+30 d、+31 d-+60 d、+61 d-+100 d的急性移植物抗宿主病类型分布差异无显著性意义(P > 0.05);发生在移植后+30 d内的急性移植物抗宿主病发生率高于移植后 +31 d-+60 d和+61 d-+100 d;发生急性移植物抗宿主病组和无急性移植物抗宿主病组复发率、2年无病生存率差异无显著性意义(P > 0.05),全相合组与单倍体组相比复发率差异无显著性意义(P > 0.05),2年无病生存率前者高于后者(P < 0.05)。说明采用上述移植方案,单倍体组安全性与疗效接近全相合组;在缺乏HLA相合供者时,单倍体造血干细胞移植是治疗恶性血液病的重要方法。中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接: 相似文献
13.
Prognostic factors for early severe pulmonary complications after hematopoietic stem cell transplantation. 总被引:5,自引:0,他引:5
V T Ho E Weller S J Lee E P Alyea J H Antin R J Soiffer 《Biology of blood and marrow transplantation》2001,7(4):223-229
Pulmonary complications are a significant cause of early mortality (before day 100) after bone marrow transplantation (BMT). To identify factors associated with development of early post-BMT severe pulmonary complications (SPCs), we conducted a retrospective review of the medical records of 339 consecutive patients who underwent hematopoietic stem cell transplantation for hematologic disorders and identified pulmonary complications that occurred before day 60 posttransplantation. SPCs, defined as (1) diagnosis of diffuse alveolar hemorrhage, (2) need for mechanical ventilation, or (3) death from respiratory failure, occurred in 48 (24%) of 199 patients receiving allogeneic transplants and 4 (2.9%) of 140 patients receiving autologous transplants (P < .001). Multiple clinical variables were analyzed to determine their influence on the development of SPCs in allogeneic marrow recipients. The method of graft-versus-host disease (GVHD) prophylaxis was the single most important factor affecting SPC incidence. Of patients who received cyclosporine/methotrexate (CYA/MTX) as GVHD prophylaxis, 33% experienced SPCs compared with 8% of those receiving T-cell depletion (TCD) alone (P < .0001). Multivariate analysis confirmed that TCD was associated with a lower risk of SPCs (relative risk [RR], 0.18; P = .0006). In addition to GVHD prophylaxis, a reduced pretransplantation FEV1 (forced expiratory volume in 1 second) (< or = 80% of predicted) was associated with an increased risk for SPCs (odds ratio, 4.4; P = .0025). Grades 2 to 4 acute GVHD, tobacco use, age > or = 50 years, sex, unrelated donor, cytomegalovirus serologic status, disease status at transplantation, pretransplantation carbon monoxide diffusing capacity, and total body irradiation were not associated with development of SPCs. We conclude that autologous BMT is associated with a significantly lower incidence of SPCs compared with allogeneic BMT and that for allogeneic BMT, GVHD prophylaxis using TCD is associated with a significantly lower risk for SPCs compared with prophylaxis using CYA/MTX. Patients with pretransplantation FEV1 of < or = 80% appear to have a higher risk for SPCs. 相似文献
14.
Mutsumi Nishida Kaoru Kahata Eiko Hayase Akio Shigematsu Megumi Sato Yusuke Kudo Satomi Omotehara Takahito Iwai Junichi Sugita Hitoshi Shibuya Chikara Shimizu Takanori Teshima 《Biology of blood and marrow transplantation》2018,24(9):1896-1900
Sinusoidal obstruction syndrome (SOS)/hepatic veno-occlusive disease (VOD) is a well-documented complication after hematopoietic stem cell transplantation (HSCT). Transabdominal ultrasonography (US) enables the visualization of blood flow abnormalities and is therefore useful for the diagnosis of SOS/VOD. We herein prospectively evaluated accuracy of a novel US diagnostic scoring system of SOS/VOD based on US findings. We carried out US in 106 patients on day 14 and when SOS/VOD was suspected after allogeneic HSCT. Among 106 patients, 10 patients (9.4%) were diagnosed as SOS/VOD by Baltimore or Seattle criteria. According to univariate analysis of 17 US findings (US-17 screening), we established a novel scoring system (HokUS-10) consisting of 10 parameters, such as gallbladder wall thickening, ascites, and blood flow signal in the paraumbilical vein. The sensitivity and specificity were 100% and 95.8%, respectively. Diagnostic performance of the HokUS-10 was significantly better than US-17 screening. In 4 of 10 patients US detection of SOS/VOD preceded to clinical diagnosis. The HokUS-10 scoring system is useful in the diagnosis of SOS/VOD; however, our results should be validated in other cohorts. 相似文献
15.
Nicolaus Kr?ger Jose A Perez-Simon Han Myint Hans Klingemann Avichai Shimoni Arnon Nagler Rodrigo Martino Adrian Alegre Jose F Tomas Rainer Schwerdtfeger Michael Kiehl Axel Fauser Herbert Gottfried Sayer Angel Leon J?rg Beyer Tatjana Zabelina Francis Ayuk Jesus F San Miguel Ronald Brand Axel Rolf Zander 《Biology of blood and marrow transplantation》2004,10(10):698-708
We evaluated prognostic factors of melphalan/fludarabine-based dose-reduced allografts in patients with multiple myeloma. From 1998 to 2002, 120 patients with multiple myeloma were treated with melphalan/fludarabine followed by allogeneic stem cell transplantation. The cumulative risk at 1 year for treatment-related mortality (TRM) was 18% (95% confidence interval [CI], 12%-28%). In a multivariate analysis, relapse after prior high-dose chemotherapy was the most significant risk factor for TRM (hazard ratio [HR], 2.80; 95% CI, 1.16-6.74; P =.02), relapse (HR, 4.14; 95% CI, 2.04-8.38; P <.001), event-free survival (HR, 3.11; 95% CI, 1.77-5.46; P <.001), and overall survival (HR, 2.69; 95% CI, 1.35-5.35; P =.005). In addition, relapse was also significantly diminished by chronic graft-versus-host disease (GVHD) in a time-dependent Cox model (HR, 0.37; 95% CI, 0.16-0.87; P =.02). At transplantation, 8% of the patients were in complete remission, whereas 27% had progressive disease. After allografting, 49% achieved complete remission, and 38% achieved partial remission. In a subgroup of patients with chemosensitivity at transplantation and no relapse after prior high-dose chemotherapy who underwent transplantation with peripheral blood stem cells (n = 46), the cumulative risk of TRM at 1 year was only 8% (95% CI, 1%-54%). The 2-year estimated event-free and overall survival was 60% (95% CI, 42%-78%) and 75% (95% CI, 59%-91%), respectively, for related donors (n = 34) and was 81% (95% CI, 59%-100%) and 92% (95% CI, 76%-100%), respectively, for unrelated donors (n = 12). 相似文献
16.
Vikas Gupta Andrew Daly Jeffrey H Lipton Wanda Hasegawa Kathy Chun Suzanne Kamel-Reid Richard Tsang Qi-long Yi Mark Minden Hans Messner Thomas Kiss 《Biology of blood and marrow transplantation》2005,11(10):764-772
We analyzed the outcomes of 24 consecutive patients aged >or=60 years with poor-prognosis myelodysplastic syndrome or acute myeloid leukemia undergoing transplantation with nonmyeloablative conditioning using fludarabine (125 mg/m2) and low-dose total body irradiation (2 Gy) followed by allogeneic peripheral blood stem cell grafts from HLA-identical sibling donors. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. The median age of the patients was 64 years (range, 60-71 years). In addition to age, 88% of patients had 1 or more adverse biological features of the disease. With a median follow-up of 21 months, 12 patients are alive, 11 of whom are disease free. The probabilities of 2-year overall and progression-free survival were 52% and 44%, respectively. The cumulative probabilities of relapse and of acute and chronic GVHD were 27%, 45%, and 74%, respectively. Nonrelapse mortality at 100 days and 2 years was 8% and 25%, respectively. Of the 15 patients with extensive chronic GVHD, 1 patient relapsed. These data suggest that nonmyeloablative stem cell transplantation is a feasible treatment option in patients aged >or=60 years with poor-prognosis myelodysplastic syndrome or acute myeloid leukemia. The reasonable disease control with nonmyeloablative transplantation in this high-risk group of patients merits further investigation. 相似文献
17.
Gordon Cook Richard E Clark Charles Crawley Stephen Mackinnon Nigel Russell Kirsty Thomson Rachel M Pearce Keiren Towlson David I Marks 《Biology of blood and marrow transplantation》2006,12(3):293-300
The optimal management of patients with initially refractory acute myeloid leukemia is unknown. We analyzed the outcomes of 68 adult patients (median age, 37 years) with acute myeloid leukemia in first complete remission with initially refractory disease who were treated with matched sibling (n=44) or unrelated donor (n=22) stem cell transplantation or who received transplants from other donors (n=2). Thirty-one patients took 2 courses of chemotherapy to achieve first complete remission, a further 31 took 3 courses, and 6 patients took 4 or 5 courses. Ten patients (15%) had adverse cytogenetics. Patients were mainly conditioned with cyclophosphamide and total body irradiation (87%). Four patients (6%) did not engraft by day 28; 2 of these engrafted at 47 and 60 days. Grades II to IV and III/IV acute graft-versus-host disease (GVHD) were seen in 34% and 14% of patients, respectively. Chronic GVHD was seen in 50% of patients. The estimated actuarial disease-free and overall survivals were 34% and 37%, respectively, at 4 years. The performance status of survivors is good; 82% of patients have Karnofsky scores of 90 to 100. On multivariate analysis, overall and disease-free survival were associated with adverse cytogenetics (P=.055 and .023). Approximately one third of patients survived 4 years after allogeneic stem cell transplantation for initially refractory acute myeloid leukemia in first complete remission: relapse and treatment-related mortality were the major causes of treatment failure. Further studies are needed to determine the optimal conditioning regimens and GVHD prophylaxis. 相似文献
18.
Frédéric Baron Brenda M Sandmaier Barry E Storer Michael B Maris Amelia A Langston Thoralf Lange Effie Petersdorf Wolfgang Bethge Richard T Maziarz Peter A McSweeney Michael A Pulsipher James C Wade Thomas R Chauncey Judith A Shizuru Mohamed L Sorror Ann E Woolfrey David G Maloney Rainer Storb 《Biology of blood and marrow transplantation》2007,13(9):1041-1048
We previously reported data from 103 patients with hematologic malignancies (median age 54 years) who received peripheral blood stem cell (PBSC) grafts from HLA-matched unrelated donors after nonmyeloablative conditioning and were given postgrafting immunosuppression consisting of mycophenolate mofetil (MMF; administered from day 0 until day +40 with taper through day +96) and cyclosporine (CSP; given from day -3 to day +100, with taper through day 180) (historical patients). The incidences of grade II-IV acute and extensive chronic graft-versus-host disease (aGVHD, cGVHD) were 52% and 49%, respectively, and the 1-year probabilities of relapse, nonrelapse mortality (NRM), and progression-free survival (PFS) were 26%, 18%, and 56%, respectively. Here, we treated 71 patients with hematologic malignancies (median age 56 years) with unrelated PBSC grafts and investigated whether postgrafting immunosuppression with an extended course of MMF, given at full dosing until day +150 and then tapered through day +180, and a shortened course of CSP, through day +80, would promote tolerance induction and reduce the incidence of GVHD (current patients). We observed 77% grade II-IV aGVHD and 45% extensive cGVHD (P=.03, and P=.43, respectively, in current compared to historical patients). The 1-year probabilities of relapse, NRM, and PFS were 23%, 29%, and 47%, respectively (P=.89, P=.02, and P=.08 compared to the historical patients). We conclude that postgrafting immunosuppression with extended MMF and shortened CSP failed to decrease the incidence of GVHD among unrelated PBSC recipients given nonmyeloablative conditioning. 相似文献
19.
《Biology of blood and marrow transplantation》2020,26(12):2245-2251
Cyclosporine (CsA) combined with short-course methotrexate is considered standard-of-care graft-versus-host disease (GVHD) prophylaxis for patients with severe aplastic anemia (AA) who undergo transplantation using cyclophosphamide (Cy) plus anti-thymocyte globulin (ATG) conditioning. However, there is no consensus on optimal post-transplant GVHD prophylaxis for patients undergoing matched related donor (MRD) transplantation using fludarabine (Flu)-based conditioning. We conducted a single-center retrospective analysis of patients with acquired AA (n = 106) undergoing MRD transplantation from July 2007 through January 2019. All patients received Flu-Cy-ATG conditioning and single-agent CsA as GVHD prophylaxis. Median age of the study cohort was 20 years (range, 3 to 52) and male to female ratio was 3.8:1. Median time from diagnosis to transplant was 11.5 months (range, 2.8 to 62). Graft source was bone marrow harvest in 71 (68%), combined bone marrow and peripheral blood stem cells in 34 (31%), and peripheral blood alone in 1 (1%) patient. Cumulative incidence of neutrophil engraftment at day 28 was 93.4% (95% confidence interval [CI], 87.3% to 97.1%) while that of platelet engraftment at day 100 was 90.5% (95% CI, 84% to 96%). Cumulative incidence of primary graft failure at day 28 was 6.6% (95% CI, 4% to 8%) while secondary graft failure occurred at a median of 190 days (range, 90 to 415) at a cumulative incidence of 3.7% (95% CI, 2% to 5%). Cumulative incidence of grade II to IV acute GVHD at day 100 was 3.8% (95% CI, 1.4% to 9.9%), while a 1-year probability of chronic GVHD was calculated as 7.5% (95% CI, 2.6% to 15%). Median follow-up post-transplant was 61 months (range, 6 to 144). Overall survival was 84.9%, disease-free survival was 80.2%, and GVHD-free relapse-free survival was 76.3%. This study indicates that single-agent cyclosporine is a feasible option for GVHD prophylaxis in MRD hematopoietic stem cell transplantation using Flu-Cy-ATG conditioning and is associated with very low rates of acute and chronic GVHD. 相似文献
20.
Cytomegalovirus disease before hematopoietic cell transplantation as a risk for complications after transplantation. 总被引:1,自引:0,他引:1
Bettina C Fries Stanley R Riddell Hyung W Kim Lawrence Corey Christine Dahlgren Ann Woolfrey Michael Boeckh 《Biology of blood and marrow transplantation》2005,11(2):136-148
Cytomegalovirus (CMV) disease in candidates for hematopoietic cell transplantation (HCT) is increasingly observed. Among 22 patients with CMV disease before HCT, the incidence of CMV disease before HCT was significantly higher in patients with severe underlying immune deficiency syndromes compared with patients with hematologic malignancies (P < .001). The lung was the most commonly involved site of infection, followed by the gastrointestinal tract and the retina. Fourteen of 22 patients with CMV disease before HCT responded to treatment and proceeded to HCT; 8 of 22 did not receive an HCT because of fatal CMV disease (n = 2) or other complications (n = 6). Of 14 patients with CMV disease who subsequently underwent HCT, 6 (42%) had CMV disease diagnosed after transplantation despite antiviral prophylaxis or preemptive therapy, and 1 patient had evidence of persistent CMV disease before day 100 after HCT. This proportion was significantly higher than that in patients without CMV disease before HCT during the same time period (day 30, adjusted P = .003; day 100, adjusted P = .02). Thirteen of 14 patients with pretransplantation CMV disease died a median of 36 days after transplantation (range, 19-399 days; adjusted P = .005 compared with CMV-seropositive transplant recipients without a history of pretransplantation CMV disease). In summary, although CMV disease before HCT may be mild and responsive to treatment, it is associated with a high risk of early CMV disease and death after transplantation. 相似文献