Prediction of nonrelapse mortality for patients surviving 100 days after allogeneic hematopoietic stem cell transplantation

BACKGROUND: Patients who survive 100 days after allogeneic hematopoietic stem cell transplantation (alloHSCT) are at risk for chronic graft-versus-host disease and other potentially fatal complications. As the symptoms overlap and the differential diagnosis is difficult, the goal of this study was to verify whether basic laboratory evaluation performed on day +100 may allow identification of patients who are at high risk for nonrelapse mortality (NRM), independent of the underlying complications. PATIENTS AND METHODS: We analyzed 255 patients, mean age 29 years (range, 10-56 years), who remained alive and disease-free on day +100 after myeloablative alloHSCT from an HLA-identical sibling (n=177) or a matched unrelated volunteer (n=78), performed in a single institution between 1992 and 2003. RESULTS: Upon univariate analysis, the following laboratory parameters were associated with increased incidence of NRM: peripheral blood neutrophils<1.5x10(9)/L, platelets<100x10(9)/L, hemoglobin<11 g/dL, total protein<60 g/L, elevated plasma aspartate aminotransferase, elevated alkaline phosphatase, and elevated bilirubin. Upon multivariate analysis, only decreased protein (hazard ratio [HR]=6.97 [3.3-14.7], P<.0001) and elevated bilirubin (HR=3.52 [1.91-6.48], P<.0001) independently influenced the risk for NRM. The cumulative incidence of NRM equaled 6% if none of the above factors was present; 10% for hyperbilirubinemia alone; 22% for hypoproteinemia alone; and 70% for hyperbilirubinemia and hypoproteinemia, both present. CONCLUSIONS: A simple laboratory evaluation is highly predictive of the risk for NRM in patients surviving 100 days after alloHSCT. The prognosis is particularly poor for patients with hypoproteinemia and hyperbilirubinemia. These abnormalities may reflect impaired liver and intestine functions due to various posttransplantation complications.     

存活十年以上同种原位心脏移植三例

目的总结同种原位心脏移植后患者获得长期存活的临床治疗经验和体会。方法为2例扩张性心肌病和1例慢性克山病患者施行心脏移植，术前患者的肺动脉压力为42-53mmHg（5．60-7．07kPa），肺血管阻力为5．6-7．0wood。供、受者体重相差10％～15％，HLA配型有3个抗原相同。供心采用含钾温血经冠状静脉窦连续逆行灌注。2例采用标准法心脏移植，1例采用全心法心脏移植，心房及大血管均采用外翻缝合法。术后应用环孢素A、硫唑嘌呤及皮质类固醇激素预防排斥反应。结果3例患者术后存活时间分别为13年10个月、12年及10年3个月，患者心功能NYHA分级为Ⅰ级，均恢复正常生活和工作。3例术后分别发生6、3、1次排斥反应，经治疗逆转。心电图检查显示，例1、例2有2个P波，例3为正常窦性心律。超声心动图显示，例1、例2有左、右心房增大，三尖瓣轻度返流，例3各心腔大小正常，无二尖瓣、三尖瓣返流。3例术后经449次冠状动脉造影，均未发现异常。结论选择合适的供、受者，保护好供心，采取恰当的术式和吻合技术，合理应用免疫抑制剂以及预防心脏移植物血管病，是关系心脏移植患者长期存活的重要因素。     

Predictors of survival in patients bridged to transplantation with the thoratec VAD device: a single-center retrospective study on more than 100 patients.

BACKGROUND: Careful patient selection markedly influences the outcome of patients who undergo mechanical circulatory support. Therefore, we tried to evaluate predictors of survival after implantation of the Thoratec ventricular assist device (VAD). METHODS: Between October 1992 and January 2000, 104 patients (86 men, 18 women, aged 11 to 69 years) received the Thoratec VAD as a bridge to transplant. A total of 51 patients required left ventricular support (LVAD), 50 patients required biventricular support (BVAD), and 3 patients required total artificial heart implantation. We performed univariate analysis of 25 parameters with regard to their effect on survival and then applied a multivariate analysis to evaluate those factors that turned out to be marginally significant. We performed all analysis for the total collective as well as for the LVAD and BVAD sub-group. RESULTS: The BVAD patients tended to have worse outcomes than did LVAD patients. We found no significant predictors of survival in either sub-group. In the total collective, however, we found the following pre-implant conditions were independent risk factors for survival after VAD implantation: patient age > 60 years (odds ratio [OR] 3.87, confidence interval [CI] 1.39 to 10.76), pre-implant ventilation (OR, 6.76; CI 2.42 to 18.84), and increased pre-implant total bilirubin (OR, 1.42; CL, 1.19 to 1.69). CONCLUSIONS: Transplant candidates on inotropic support should be considered for bridging to transplant as soon as bilirubin values start to increase or before respiratory function deteriorates and ventilation becomes necessary. In elderly patients, careful patient selection, particularly considering potential risk factors, might favorably affect their outcomes.     

Clinical study of patients with renal carcinoma surviving for more than 10 years after nephrectomy.

Of 207 patients with renal carcinoma we studied 50 who survived for more than 10 years after nephrectomy. These 50 patients were younger than the others at the time of operation and included more females. They had lower stage and lower grade tumours. Recurrence was detected in 18/50 patients and 6 died from cancer. Recurrence developed approximately 10 years after nephrectomy. Eleven patients with recurrences had metastases to a single organ and 9 received multidisciplinary treatment, mainly surgery and radiotherapy. The survival rate 10 years after nephrectomy was lower in patients with recurrences than in those without recurrent tumours and there was a significant decrease in the survival rate 17 years after nephrectomy. Although the patients had low grade and low stage tumours 10 years after nephrectomy, careful follow-up is recommended in such cases as it is possible that they may have dormant tumours.     

One hundred days or more bridged on a ventricular assist device and effects on outcomes following heart transplantation

BACKGROUND: Successful bridging to transplantation (BTT) with ventricular assist devices (VAD) is an alternative to mitigate the effects of end-stage heart failure on organ function while awaiting a heart. The effects of long-term VAD BTT on patient outcomes following transplantation are poorly studied. METHODS: A retrospective chart review identified 145 patients BTT with a VAD between November of 1996 and June of 2005 at the Cleveland Clinic. Patients were divided into two groups and outcomes were compared: group 1 was supported for <100 days (median=44 days) and group 2 was supported for > or =100 days (median=161 days). RESULTS: Patients in group 1 were less likely to be blood type O (33% vs 68%, p<0.0001). BTT <100 days trended towards independently predicting improved survival by multivariate proportional hazards analysis (risk ratio=0.75, 95% CI=0.52-1.08, p=0.12), largely due to reduced in-hospital mortality in this group (2% vs 11%, p=0.055); however, no significant difference with respect to long-term survival was observed by Kaplan-Meier analysis (p=0.14). Furthermore, causes of death differed between groups: group 1 more commonly died of coronary artery vasculopathy (26% vs 0%, p=0.022) and group 2 more commonly died of sepsis (60% vs 26%, p=0.026). Ultimately, 21% of all group 2 patients died from sepsis (compared to 7% of group 1 patients, p=0.018). CONCLUSIONS: This study suggests that prolonged BTT with a VAD is a viable treatment strategy but may lead to significantly more post-transplant deaths from sepsis and higher in-hospital mortality. These data may inform management of this high-risk patient population.     

Prognostic factors in patients surviving for more than 1 or 5 years after removal of metastatic brain tumors.

Favorable and unfavorable prognostic factors were identified in 28 patients surviving for more than 1 year after surgery for metastatic brain tumor and 18 patients surviving for more than 5 years. A high incidence of favorable factors, including neurological grade and location of the brain lesion, indicated significance in the prognosis. A low incidence of favorable factors, including tumor-free interval and presence or absence of extracranial tumor, indicated little significance to the prognosis.     

Analysis of 58 patients surviving more than ten years after operative treatment of gastric cancer

We evaluated 58 patients who were still alive more than ten years after operative treatment of gastric cancer. We reexamined their histologic specimens and compared them with those of matched paired controls of the same sex and age who had died of gastric cancer. Forty-two patients consented to a follow-up study. The age of the patients did not affect survival. For patients with gastric cancer, those with distal cancer or an ulcer simulating cancer had had a better prognosis. Forty percent of the patients had had an early gastric cancer. Only two patients had had lymph node metastases in regional lymph nodes, and macroscopic tumor growth through the serosa had been recorded in only four cases. In 23 cases, a distal resection had proved successful. No significant correlation between intestinal or diffuse types of cancer and prognosis was observed. One recurrence after ten years was found; in one case, there was a new cancer in the gastric remnant. In addition, biopsy specimens from two patients showed grave dysplasia. We suggest that throughout their lives annual follow-up examinations be performed in patients who have undergone radical operations for gastric cancer.     

Comparative group study between patients surviving five or more years after portacaval shunt procedure and those surviving less than one year.

The classic criteria utilizing preoperative clinical evaluations and laboratory tests for predicting risk and long-term survival in cirrhotic patients under-going portacaval shunting still appear to be the most useful. Analysis of the factors that could be determinant in separating patients who are going to survive a portacaval shunt for five or more years from the short-term survivors revealed the former group had a lesser incidence of preoperative encephalopathy, ascites, malnutrition, and hypoalbuminemia. None of the intraoperative factors were found to be decisive. However, the prompt and uncomplicated postshunt recovery was an accurate prediction for long-term survival. This could be explained by the assumption that these patients had a better hepatic functional reserve at the time of portal-systemic shunting. The early appearance in the postoperative period, of fluid retention, azotemia, oliguria, inability to eat, and the early appearance of the symptoms of portal encephalopathy were premonitory of short-term survival. Return to alcohol ingestion was also associated with short-term survival. The hepatorenal syndrome was usually the cause of death in the short-term survivors whereas nonhepatic disease was the cause of demise in the long-term survivors. The operative mortality for all patients undergoing portacaval shunting during an eight year period was 10.7 per cent. Of the patients who left the hospital alive, 16.1 per cent died within the subsequent twelve months, 53 per cent survived from thirteen to fifty-nine months after their operation, and 19.6 per cent survived sixty or more months.     

Baboons undergoing orthotopic concordant cardiac xenotransplantation surviving more than 300 days: effect of immunosuppressive regimen

OBJECTIVE: We reviewed long-term survival among hosts in 3 consecutive series of a rhesus monkey-baboon orthotopic cardiac xenotransplantation model with reference to host immune response, including the effectiveness in preventing rejection and limiting toxicity concerning infection, to evaluate specific immunosuppressive regimens for long-term outcomes. METHODS: Six juvenile baboons surviving more than 300 days after transplantation were reviewed. Regimen A consisted of splenectomy, FK506, methotrexate, and antilymphocyte globulin. Regimen B consisted of pretransplantation and chronic maintenance with cyclosporine A (INN: ciclosporin), methotrexate, and antithymocyte globulin. Regimen C was the same as regimen B plus pretransplantation total lymphoid irradiation and intraoperative donor bone marrow cell infusion. Rejections were detected by means of echocardiography. RESULTS: Long-term survivors in 3 groups were followed for a range of 332 to 515 days (mean, 436 days). Rejection frequency in regimens A, B, and C was 0.35, 0.58, and 0.18 per month, and rescue therapy days were 23 (4.8%), 123 (9.5%), and 20 (2.4%), respectively (P <.0001). Infection frequency was 0.58, 0.56, and 0.19 per month, and therapy days were 192 (38.2%), 164 (12.6%), and 7 (0.9%), respectively (P <.0001). Concerning the host immune response, interleukin 2-activated T cells of all groups during rejection-free periods showed lower numbers compared with those of control animals (P <.0005), and regimen C was the lowest among 3 groups (P <.01). The production of xenoantibody was sufficiently attenuated in all groups. CONCLUSION: Regimen C leads to long-term survival with fewer rejection and infection episodes by means of suppression of the interleukin 2 pathway and xenoantibody production.     

Surgical treatment of intrahepatic cholangiocarcinoma: four patients surviving more than five years.

BACKGROUND. To find the rational surgical strategy for the treatment of intrahepatic cholangiocarcinoma (ICC), clinical features of ICC were studied in 20 patients who underwent hepatic resection in the National Cancer Center Hospital from 1980 to 1990. METHODS. According to the morphologic pattern, we classified the ICCs into two subcategories, mass-forming and infiltrating, which correlated with their biologic behavior. RESULTS. Of 10 patients who underwent hepatectomy for mass-forming ICC, three survived more than 5 years without recurrence. The 1-, 3-, and 5-year survival rates were 59.3%, 44.4%, and 44.4%, respectively. Of 10 patients who underwent hepatectomy for infiltrating ICC, one survived more than 5 years without recurrence. The 1-, 3-, and 5-year survival rates were 72.0%, 27.0%, and 27.0%, respectively. The pathologic findings and recurrences indicated that the salient feature of the mass-forming type was its tendency for intrahepatic metastasis especially near a main lesion, and of the infiltrating type was the infiltrative spread via Glisson's capsule and hilar lymph nodal metastasis. CONCLUSIONS. An anatomic and extensive liver resection should be performed for mass-forming ICC, whereas a hepatectomy with excision of the extrahepatic bile duct and hilar lymph nodal dissection is recommended for infiltrating ICC.     

损伤超过12小时后股动脉的重建及其疗效

目的探讨损伤超过12h后股动脉的重建方法和疗效。方法1997年10月～2000年2月采用自体静脉移植修复股动脉及小腿内、外侧筋膜室彻底切开减压治疗11例股动脉损伤超过12h的患者,术后重点防治肾功能衰竭。结果11例患者获2～7年随访,均保存了肢体。但有不同程度的肢体功能障碍,5例屈趾肌腱挛缩引发足趾屈曲畸形,术后1年内行肌腱松解术,外观及症状改善。6例踝部肌力差、步态不稳者行踝关节融合术,步态明显改善。结论对于股动脉损伤时间不超过18h、无肾功能衰竭及明显中毒表现且伤肢肌肉无大部分坏死和感染的患者,仍可争取修复血管,术后需密切观察。     

Long-term survival after the diagnosis of malignant glioma: a series of 22 patients surviving more than 4 years after diagnosis.

Long-term survival after the diagnosis of malignant glioma is uncommon but not rare. To define better the population of patients who have extended survival with this disease, we reviewed the records of 22 of our patients who survived more than 4 years after the biopsy-proven diagnosis of anaplastic astrocytoma, malignant mixed glioma, or glioblastoma multiforme. Surprisingly, 21 of the 22 patients are still alive and being actively followed by the authors. The long-term survivors were typically young and with minimal or no functional impairment at the time of diagnosis. Survivals ranged from 4.2 to 15.8 years. The quality of survival was generally good, with the surviving patients having a mean Karnofsky Performance Score of 76. Three-quarters of the patients had no enhancement or mass effect on their most recent computed tomography scans. A review of the available literature, together with our own series, suggests that death from recurrent disease is unusual in glioma patients who survive more than 4 or 5 years.     

Late rejection episodes more than 1 year after pediatric heart transplantation: risk factors and outcomes.

BACKGROUND: Little is known about late rejection episodes after pediatric heart transplantation. We determined the frequency of late rejection episodes (>1 year) after pediatric heart transplantation, defined risk factors for its occurrence, and evaluated outcome after late rejection. METHODS: We analyzed data from 685 pediatric recipients (<18 years at transplantation) who underwent transplantation between January 1, 1993, and December 31, 1997, at 18 centers in the Pediatric Heart Transplant Study (PHTS). Probability of freedom from late rejection was determined and risk factors for late rejection and for death after late rejection were sought using univariate and multivariate analyses. RESULTS: We followed 431 patients for >1 year (median follow-up, 32.9 months) of whom 106 (24.6%) experienced 1 or more late rejection episodes (total of 178 episodes, 27 with severe hemodynamic compromise). Probability of freedom from first late rejection was 73% at 3 years and 66% at 4 years after transplantation. Risk factors (multivariate analysis) for first late rejection were >1 episode of rejection in the first year (p = 0.009), recipient black race (p = 0.0002), and older age at transplantation (p = 0.0003). Only 4 of 325 (1.2%) children who survived beyond 1 year without late rejection died compared with 26 of 106 (24.6%) with late rejection (p < 0.0001). Nine of these 26 died within 1 month of the first late rejection episode, and 17 died subsequently: 5 of acute rejection, 3 of sudden unexplained deaths, 3 of documented coronary artery disease, and 6 of other causes. Severe hemodynamic compromise with late rejection was identified as a risk factor for death among children with 1 or more episodes of late rejection. CONCLUSIONS: Approximately 25% of pediatric recipients in the PHTS who survived beyond 1 year experienced late rejection episodes. Late rejection is associated with poor survival, especially when associated with hemodynamic compromise. Absence of late rejection episodes is associated with very low risk of death during medium-term follow-up after pediatric heart transplantation. Determining the risk factors for late rejection will help to identify a cohort of patients who may benefit from enhanced rejection surveillance and treatment.     

Outcome of patients listed for heart transplantation after a failed surgical ventricular restoration procedure

Patients with end-stage ischemic cardiomyopathy (IHD) and left ventricular (LV) dilatation are increasingly treated by means of surgical ventricular restoration (SVR). In some patients, SVR can delay heart transplantation (HTX). We retrospectively analyzed our experience, trying to ascertain whether HTX after a failed SVR (fSVR) carried a greater mortality risk. Since 1985, we performed 742 HTX. Since June 1999, 133 IHD patients were listed for HTX. We assigned them to 3 groups: (A) not a redo (n=54); (B) redo after coronary artery bypass grafting (n=54); and (C) redo after fSVR (n=25). Respectively, 37, 33, and 12 patients underwent HTX with in-hospital mortality after HTX of 4/37 (10.8%), 12/33 (36.4%), and 2/12 (16.7%). Mortality on the list was 9/54 (16.7%), 11/54 (20.4%), and 7/25 (28.0%) respectively. Removal from the list occurred in 4, 5, and 2 patients, and 4, 5, and 4 patients are still awaiting HTX, respectively. In group C, the mean time from SVR to HTX list was 45.6+/-43.3 months, and list mortality occurred after 5.83+/-5.81 months. In-hospital mortality in both patients of group C was due to the occurrence of multisystem organ failure; 10/12 were extubated after 19.3+/-9.6 hours and discharged from the intensive care unit after 3.9+/-1.6 days. The recorded complications were: 3 acute renal failure, 1 pericardial effusion, and 2 episodes of acute rejection. Since only 5/25 patients with fSVR had undergone SVR at our institution, we cannot establish which patients were really eligible for HTX at the time of SVR. Our experience showed that patients listed for HTX displayed a high list mortality, but that HTX after a failed SVR did not seem to have a poorer outcome than HTX after previous conventional CABG.     

Analysis of survivors more than 10 years after heart transplantation in the cyclosporine era: Stanford experience.

BACKGROUND: Truly long term survival post heart transplantation has become increasingly frequent over the past two decades. METHODS: We analyzed multiple clinical outcomes in the cohort of 140 patients in the Stanford database who underwent heart transplantation after the introduction of cyclosporine-based immunosuppression in 1980 and survived >10 years after transplantation. RESULTS: We found generally excellent functional status in these patients, but a high incidence of hypertension, renal dysfunction, and graft CAD as well as malignancy. CONCLUSION: With continued improvement in post-transplant survival rates, providing complex care for such long-term recipients as these will assume increasing clinical importance in the everyday practice of transplant medicine and these data highlight the problems to be anticipated.