HLA-D compatibility between parent and child: increased occurrence in severe combined immunodeficiency and other hematopoietic diseases.

Weak or weak intermediate reactions in one-way mixed lymphocyte culture (MLC) were seen between a patient and at least one parent in the families of 6 of 15 patients with severe combined immunodeficiency disease, 3 of 4 patients with Fanconi's anemia, and 3 of 7 patients with congenital neutropenia (CN). In control family material, weak MLC reactions were seen in 1.4 per cent (4 of 285) of individual parent-child and child-parent combinations or in 2.1 per cent (3 of 143) of the total number of parent-child pairs. The increase in frequency of weak MLC reactions seen in the familes of patients with severe combined immunodeficiency disease and Fanconi's anemia occurred most frequently between mother and patient. This finding could be relevant to the pathogenesis of these diseases. In children with CN, the disease seems to be associated with the HLA antigen B12; in addition, two of the patients with CN appear to be homozygous for HLA-D. Because of the relatively frequent compatibility seen in MLC reactions between parents and children with severe combined immunodeficiency disease, Fanconi's anemia, and CN, it is suggested that those parents could be potential donors for bone marrow transplantation.     

造血干细胞移植治疗再生障碍性贫血(附视频)

再生障碍性贫血(简称再障)是一种获得性骨髓造血功能衰竭症。免疫抑制治疗或异基因造血干细胞移植是治愈重型再障的必要手段,对于年龄≤40岁的重型再障患者应首选HLA相合的同胞供者骨髓移植。30年来,随着移植技术的发展,重型再障患者的预后获得明显改善。本文就造血干细胞移植治疗再障的适应证及相关进展做一简要评述。     

Double bone marrow transplantation for severe aplastic anemia after orthotopic liver transplantation: implications for clinical management and immune tolerance

A 2-year-old boy underwent liver transplantation for fulminant hepatic failure of unknown cause. Four months later the child developed severe aplastic anemia. Allogeneic bone marrow transplantation (BMT) was performed using marrow from his 14-month-old HLA-identical sister. Severe aplastic anemia recurred 2.5 months later. After reconditioning a second BMT was performed using the same donor. Tapering of immunosuppression 2 years after BMT led to biopsy-confirmed rejection of the liver. Therapy with high-dose corticosteroids and an increase in cyclosporine A medication readily reversed rejection and a low-dose immunosuppression reflected by cyclosporine trough levels less than 50 ng/ml has been maintained since. Eight years later the boy is in excellent health with both bone marrow and liver functioning perfectly. In summary, this case demonstrates that even recurrent severe aplastic anemia after OLT can be cured by BMT, and that a transplanted liver can tolerate a double conditioning regimen without problems. Tolerance towards the liver through BMT did not develop.     

Bone marrow transplantation. Overview and personal results]

Main indications for allogeneic bone marrow transplantation are severe aplastic anemia, severe combined immunodeficiency, acute leukemia and chronic myeloid leukemia. In standard risk situations survival rates are 50 to 80%. The probability of disease-free survival after bone marrow transplantation is depending on the stage of disease. If possible bone marrow transplantation should be performed early, not in advanced disease when conventional measures failed. Main problems are therapy-related organ toxicity, rejection, graft-versus-host disease and a long lasting risk of infection. Usually histocompatible relatives of the patients are selected as marrow donors. Bone marrow transplantation using unrelated donors is under investigation. Autologous transplantations with cryopreserved marrow are performed in acute leukemia, malignant lymphomas and some solid tumors, but prospective studies comparing transplantation and conventional therapeutic procedures are still missing.     

Allogeneic bone marrow transplantation in aplastic anemia--report of 25 cases.

Bone marrow transplantation using an HLA-MLC-identical sibling is the most valuable treatment of severe aplastic anemia.2,6,7 Between November 1973 and March 1977, 25 consecutive patients have been treated by marrow transplantation in our unit. Nine patients are alive with complete hematologic restoration between 3 months and 3 years. The high mortality can be largely accounted for by marrow graft rejection (14 patients). Despite the small number of patients, we have tried to identify prognostic factors associated with marrow graft rejection. They are mainly the existence of anti-HLA antibodies, the sex difference, and the normal PHA and MLC response before grafting. After the graft, the disappearance of anti-HLA antibodies has a good prognostic value. The appearance of autolymphocytotoxins seems to correlate strongly either with rejection or graft-versus-host disease.     

Unrelated donor marrow transplantation between 1977 and 1987 at four centers in the United Kingdom

Retrospectively we analyzed the histocompatibility data and clinical results of bone marrow transplantation in 51 patients who received marrow from unrelated donors (UD) from 1977 to 1987 at one of four UK BMT centers. We compared the results with those obtained in 51 transplants carried out at the same centers using HLA-identical (ID) sibling donors. Of the UD/recipient pairs 32 (63%) were serologically identical for HLA A, B, and DR antigens, and 37% showed varying degrees of mismatch. UD-BMT primary diagnoses were: severe aplastic anemia or Fanconi's anemia (n = 17), acute leukemia (n = 11), chronic myeloid leukemia (n = 21), and other conditions (n = 2). T cell depletion of the graft was associated with a significant improvement in survival in both UD and ID-BMT. Graft failure was more common in recipients of UD than of ID transplants (13 [25%] vs. 5 [10%] P = 0.05) but there was no significant difference in the frequency of acute or chronic graft-versus-host disease. Actuarial survival was superior for recipients of ID transplants (UD vs. ID: 49% vs. 78%, respectively, at 3 months; 32% vs. 63% at one year). Reduced survival for recipients of UD-BMT was confirmed in case control regression analysis (relative risk 3.0, P = 0.01). Nevertheless in patients whose only alternative is a partially mismatched family donor we think that UD-BMT is justified.     

Hepatic resection and transplantation for primary carcinoid tumors of the liver

OBJECTIVE: To discuss the diagnosis and management of primary carcinoid tumors of the liver in light of our experience and a literature review. SUMMARY BACKGROUND DATA: Carcinoid tumors of the liver are rare and pose a diagnostic and management dilemma. This series is the largest reported and the only one to include liver transplantation as a treatment option. METHODS: Between March 1994 and May 2002, we treated 8 patients (4 male, 4 female) with primary hepatic carcinoid tumors. Carcinoid syndrome complicated only 1 of the cases. Treatment was by liver resection in 6 patients and orthotopic liver transplantation in 2. RESULTS: The diagnosis was confirmed histologically with light microscopy and immunohistochemistry in the absence of an alternative primary site. Six patients remain alive and disease free after follow-up of more than 3 years: 39, 43, 45, 50, 50, and 95 months. Two patients are recently postoperative. CONCLUSIONS: Active exclusion of an extrahepatic primary site is essential for the diagnosis of primary carcinoid of the liver. The mainstay of treatment should be liver resection, although liver transplantation may be considered in patients with widespread hepatic involvement. A radical surgical approach is warranted as this disease carries a better prognosis than for other primary hepatic tumors and for secondary hepatic carcinoids.     

Early Evidence of Bone Marrow Dysfunction in Children with Indeterminate Fulminant Hepatic Failure Who Ultimately Develop Aplastic Anemia

In children, aplastic anemia (AA) is a common complication associated with fulminant hepatic failure (FHF). The objective of this study was to determine whether specific pretransplantation clinical and laboratory characteristics can be used to distinguish between patients with FHF who are at higher risk of developing AA. We performed a retrospective case-control study to evaluate the clinical and laboratory characteristics of those patients who presented with evidence of FHF and eventually developed aplastic anemia. We identified nine patients with AA, and all had the indeterminate form of FHF and underwent liver transplantation (LTx). The AA patients were compared with a control group of 47 patients with indeterminate FHF that underwent transplantation and did not develop AA. We found that males were over-represented in the group of patients that developed AA (p = 0.01). Furthermore, during the pretransplant period, the AA group had a significantly lower white count (p = 0.005), absolute lymphocyte count (p = 0.004), and platelet count (p = 0.019) when compared with controls. We conclude that evidence of early bone marrow dysfunction is apparent before liver transplantation and the development of AA in a subset of patients with the indeterminate form of FHF.     

Hemostatic complications in bone marrow transplantation: a retrospective analysis of 447 patients

BACKGROUND: Hemostatic complications are not uncommon after bone marrow transplantation (BMT). However, little is known about the frequency, localization, determinants, and outcome of hemostatic events in autologous and allogeneic BMT. METHODS: Four hundred forty-seven patients (364 allogeneic, 83 autologous transplants) were evaluated retrospectively for the presence of hemostatic complications (bleeding, thrombosis, hepatic veno-occlusive disease [VOD], microangiopathic hemolytic anemia) from the start of conditioning therapy until June 2000. RESULTS: A total of 83.2% of the patients presented with at least one hemostatic complication during the investigational period. Most bleeding episodes occurred within the first 4 weeks after transplantation and were relatively mild. However, 27.1% of the patients hemorrhaged severely, generally doubling the overall mortality of the BMT recipients. Fatal gastrointestinal or intracerebral hemorrhages contributed to 1.1% of the events. Bleeding was strongly associated with prolonged thrombocytopenia and graft-versus-host disease (GVHD). Hemorrhagic cystitis may additionally have been triggered by the preceding conditioning regimens containing cyclophosphamide. Thromboembolic events occurred most frequently in allogeneic transplant recipients, for whom the incidence was 14.6%. Chronic GVHD and treatment with steroids were the major determining factors. The incidence of hepatic VOD in 4.7% of the allogeneic transplant recipients was associated with a high fatality rate. Busulfan conditioning increased the VOD risk 2.6-fold. Moderate or severe microangiopathic hemolytic anemia was associated with GVHD and occurred in 14.6% of the allogeneic transplant recipients, leading to an increased overall mortality. CONCLUSION: Hemostatic disturbances, commonly found in the course of transplantation, are associated with a high transplantation risk and closely related to thrombocytopenia and immunologic complications.     

Bone marrow transplantation--present status.

In the short space of the last 10 years, marrow transplantation has become a reasonable treatment option for persons with severe aplastic anemia. It has not as yet convincingly established itself in the treatment of leukemia and other malignancies but shows promise with new approaches. Many of the immunologic problems generic to bone marrow transplantation have been identified, and solutions are actively being pursued in the clinic and at the laboratory bench. As solutions to some of the present-day obstacles to the full therapeutic potential of bone marrow transplantation are met, we should see, in the next 10 years, a wider application of this therapy to various hematologic and malignant disorders.     

Variables predicting bacterial and fungal infections after allogeneic marrow engraftment

Sixty-seven consecutive patients with aplastic anemia or leukemia who had been treated by allogeneic marrow transplantation and had survived for more than 1 month were surveyed in order to determine the incidence of nonviral infections occurring from 1 month to 3 years after transplantation. Twenty-eight of the 67 patients had one or more infections during this period. Around 20% suffered from pulmonary infections and 20% were classified as having a systemic infection. Ten patients died of bacterial or fungal infection, of whom 6 had graft-versus-host disease. In multivariate analyses acute graft-versus-host disease (P less than 0.0009), splenectomy (P less than 0.02), cytomegalovirus infection (P less than 0.05), and a low marrow cell dose (P less than 0.07) were correlated with nonviral infections.     

Partial resection of the spleen and spleno-renal shunt in the treatment of portal hypertension with splenomegaly and hypersplenism

Some of serious hepatic diseases with cirrhosis may be complicated by portal hypertension, splenomegaly and hypersplenism. Splenomegaly inhibits regenerative processes of the liver, and also intensifies sequestration of the cellular components of blood up to hypersplenism. Cytopenia caused by hypersplenism is aggravated by negative hepatic influence on bone marrow activity-hemathopoesis, and also by recurrent bleeding from oesophageal varices, and from the other site of gastrointestinal tract. This circle of pathologic conditions may be interrupted only by liver transplantation, until which patients are jeopardized by acute bleeding and chronic anemia. Partial resection of the spleen and splenorenal shunt may correct portal hypertension and hypersplenism, prevent gastrointestinal bleeding, and alleviate hepatic regenerative processes inhibition. In this study, 51 patients with partial resection of the spleen and splenorenal shunt, were analyzed.     

肝移植术后并发急性溶血性贫血一例

目的报道1例ABO血型不同肝移植术后并发急性溶血性贫血的治疗经验。方法 2010年9月对1例肝癌复发患者行肝癌射频消融联合同种异体背驮式肝移植术,供、受者ABO血型分别为O型及A型。术后第10天发生急性溶血性贫血,血常规示血红蛋白下降至56 g/L,骨髓穿刺检查提示各系增生活跃,粒红比0.52∶1,给予免疫抑制剂及输注O型洗涤红细胞治疗。结果患者一般情况好转,血红蛋白上升,术后第34天上升至111 g/L。随访12个月,患者血红蛋白维持在正常范围。结论对于ABO血型不同但血型相合的肝移植术后并发急性溶血性贫血,免疫抑制剂及输注供体血型的洗涤红细胞可有效缓解溶血,提高肝移植成功率。     

Role of liver transplantation in cancer therapy.

Fifty-four patients underwent total hepatectomy and liver replacement in the presence of a primary liver malignancy. In 13 recipients in whom the hepatic tumors were incidental to some other endstage liver disease, recurrence was not seen and 12 of the 13 patients are alive after 4 months to 15 1/2 years. In contrast, tumors recurred in 3 of every 4 patients who received liver replacement primarily because of hepatic malignancies that could not be resected by conventional techniques of subtotal hepatectomy and who lived for at least 2 months after transplantation. The most encouraging results were in patients with the fibrolamellar hepatocellular carcinomas that grow slowly and metastasize late, but even with this lesion, the recurrence rate was 57%. In future trials, additional effective anticancer therapy will be needed to improve the results of liver transplantation for primary liver malignancy, but what an improved strategy should be has not yet been defined.     

The prevalence, course, and characteristics of chronic anemia after heart and lung transplantation.

A retrospective study of the 99 surviving heart and lung transplant (HLT) recipients at one center showed that 31% had significant anemia (hemoglobin less than 100g/L) six months after transplantation. Chronic anemia persisted in 18% of HLT recipients two years posttransplantation. A similar study of 100 heart transplant recipients showed no unexplained anemic patients. The prevalence of anemia after HLT was unrelated to the original diagnosis, immunosuppression, or acute rejection. All HLT recipients appeared to be unduly sensitive to the myelosuppressive effects of azathioprine. Detailed studies in 16 representative patients showed a normochromic, anisocytotic anemia with normal reticulocyte counts, B12 and folate levels, and haptoglobin levels and appropriate erythropoietin levels--but increased ESRs, low/normal iron levels and low/normal total iron binding capacity, normal or raised ferritin levels, and autoantibodies in 4 (25%). Bone marrow aspirates in 10 patients showed dyshemopoiesis out of proportion to the degree of anemia and colonies of activated lymphoid cells. The cause for this anemia appears to be a combination of anemia of chronic disease and dyshemopoiesis, both of uncertain etiology.     

Liver transplantation for neuroendocrine tumors

Liver transplantation for the treatment of metastatic neuroendocrine tumors (NETs) is radical. Although cure is not impossible, it is improbable. The reported experience with transplantation for NETs is limited to less than 150 cases with widely varying results and few 5-year disease-free survivors. We reviewed our experience with transplantation for patients with NETs. Fourteen symptomatic patients with unresectable NET liver metastases who had failed medical management were listed for transplantation. Two patients listed for transplantation underwent prior right lobectomies. Three patients were listed but did not undergo transplantation: one was lost to follow-up, one died 14 months after listing, and one remains waiting over 4 years. Eleven patients underwent liver transplantation, three with living donor grafts. There were four men (36.4%) and seven women (63.6%) who had a mean age of 51.2 ± 6.3 years. Three patients had distal pancreatectomies and one patient had a Whipple procedure at the time of transplantation. There were six nonfunctioning tumors (54.6%), three carcinoid tumors (27.3%), and two (18.2%) Vipomas. In one patient, with fulminant hepatic failure, the NET was an incidental finding in the explant. The 1- and 5-year survival among transplanted patients is 73% and 36%, respectively, with a mean follow-up of 34 ± 40 months (range 0 to 119 months). Of the three patients surviving more than 5 years, only one was disease free. In carefully selected patients with metastatic NETs, liver transplantation may be an appropriate option. Presented in part at the Fourth Americas Congress of the American Hepato-Pancreatico-Biliary Association, Miami, Florida, February 28, 2003.     

肝移植术后噬血细胞综合征临床分析

目的分析肝移植术后患者发生噬血细胞综合征（hemophagocytic syndrome,HPS）的危险因素及其临床特点、诊断和预后。方法回顾性分析中山大学附属第三医院肝移植中心772例肝移植受者中发生的1例HPS患者的临床资料,并结合已经报道的13例肝移植术后HPS的临床资料进行文献复习。结果患者,男性、45岁,在肝移植术后36d发生持续性高热、全血细胞减少、凝血功能障碍和血清铁蛋白的水平升高。根据临床表现、实验室检查和骨髓活组织检查结果诊断为HPS。给予积极的肾上腺皮质激素冲击、注射粒细胞集落刺激因子和大剂量的免疫球蛋白治疗,因病情凶险,患者于术后54d死于颅内出血和多器官功能衰竭。在14例肝移植术后HPS患者中,临床表现为发热（14／14）、脾肿大（8／14）;实验室检查发现贫血、血小板减少、白细胞减少、肝脏转氨酶升高（9／14）;71％的患者血清铁蛋白水平升高。HPS的发生与病毒感染（8／14）有关。尽管给予积极的抗感染治疗和免疫抑制剂的减量,但仍有9例患者在术后2个月内死亡。结论肝移植术后HPS的发生与病毒尤其是爱泼斯坦一巴尔病毒（Epstein—Barruirus,EBV）和巨细胞病毒（CMV）感染有关。临床上疑似HPS时,应反复进行骨髓涂片检查,有助于早期确诊。尽管早期积极的合理治疗能够一定程度上控制病情,但总体预后极差。     

Ten years survival with excellent outcome after living donor liver transplantation from 70 years old donor for primary hepatic neuroendocrine carcinoma: Case report

BACKGROUNDPrimary hepatic carcinoid tumors (PHCT) are rare entities; they are even rarer than extrahepatic neuroendocrine gastrointestinal tumors with only about 95 cases reported in the literature. An extrahepatic primary tumor must be excluded to confirm the diagnosis of PHCT.CASE PRESENTATIONWe report a case of a 42-year-old male patient with a primary hepatic neuroendocrine carcinoma, who successfully underwent living donor liver transplantation from his 70 years old mother with 10 years follow-up. Both donor and recipient are still alive and in the good health.CONCLUSIONLiving liver donation from elderly donors for the patients with irresectable neuroendocrine liver malignancies can be as safe as deceased donation or liver donation from young donors (age < 50). Living donation from elderly donors might significantly expand the donor pool for patients with liver neuroendocrine tumors (NET) and potentially reduce waiting list mortality. Especially young patients with irresectable NET can benefit from this option. However, case–control studies are needed to verify the advantage of living liver transplantation (LDLT) for the patients with irresectable liver NET and to define selection criteria for these patients.     

Total hepatectomy and liver transplantation for metastatic neuroendocrine tumors of the pancreas – a single center experience with ten patients

Background: Metastatic neuroendocrine pancreatic tumors have a poor prognosis. We have studied retrospectively the efficacy of liver transplantation as ultimate therapy of otherwise untreatable symptomatic neuroendocrine hepatic metastases originating in the pancreas. Methods: We reviewed our experience of liver transplantation (LTx) for hepatic metastases of neuroendocrine pancreatic tumors in ten patients. The indication for liver grafting was seen in cases of irresectable metastases and when patients were suffering from otherwise untreatable tumor-associated symptoms due to massive hormonal release or large intra-abdominal tumor bulk. Results: In four patients, the primary tumors had been removed before LTx, in five patients simultaneously with LTx and in one case 46 months after grafting. There was no operative mortality. After hepatectomy and LTx, all patients had complete relief of symptoms and all preoperatively increased hormonal levels returned to normal. In nine of ten patients, the transplant procedure had the potential for cure, whereas, in one patient, the primary tumor had remained in situ at LTx and was removed 46 months later by an R2-resection. At present, nine patients are alive with a median follow-up of 33 months (range 13.5 months to 117 months). The one patient in whom the primary tumor was removed after transplantation died due to massive intra-abdominal tumor spread 68 months after LTx. Currently, two patients are without evidence of disease, but one of them after re-operation because of lymph-node metastases 8 months after transplantation. The longest disease-free survival is now more than 7 years. In seven of nine patients, tumor recurred between 1.5 months and 48 months after transplantation. Conclusions: Patients with otherwise untreatable symptomatic neuroendocrine hepatic metastases of pancreatic origin may benefit from total hepatectomy and liver transplantation with regard to symptomatic relief and long-term survival, despite frequent recurrence of disease. In some patients, liver transplantation may even offer the chance for cure. Received: 8 January 1999 Accepted: 22 April 1999