Glomerular vasculopathy after unrelated cord blood transplantation

A 1-year-old boy with hemophagocytic lymphohistiocytosis exhibited proteinuria 1 month after unrelated cord blood cell transplantation, which persisted without hematuria. Laboratory study showed an increase of factor VIII-related antigen and total plasminogen activator inhibitor, suggesting endothelial injury. Histological examination of autopsy materials showed increased mesangial matrices and double-contoured basement membranes, and ultrastructurally, swelling of the endothelial cells and widening of the subendothelial space with mesangial interposition. Thrombosis was not observed at any of the sites. This case may be vasculopathy distinct from thrombotic microangiopathy (TMA) or a variant form of TMA following blood stem cell transplantation (BSCT). This vasculopathy should be considered in the differential diagnosis of proteinuria in the early stages after BSCT.     

Serial transplantation resulting in tolerance to an unrelated cord blood graft

Unrelated cord blood (UCB) hematopoietic stem cells were serially transplanted into two human leukocyte antigen (HLA)-identical siblings with T cell, B cell, natural killer cell severe combined immunodeficiency. Brother A received a 4/6-matched, HLA DRbeta1-identical but class I-disparate UCB graft after myeloablative dosages of busulfan, melphalan, and antithymocyte globulin. He experienced complete donor chimerism, severe acute gastrointestinal graft-versus-host disease (GVHD), and limited chronic skin GVHD that resolved with treatment. Two years later, brother B received unfractionated marrow from brother A after reduced-intensity conditioning with cyclophosphamide and antithymocyte globulin. Brother B experienced mixed-donor (i.e. original UCB) chimerism and no histologically documented GVHD. Both brothers are clinically well; brother A is in a fully immunologically reconstituted state. The uneventful course and progressive increase in donor chimerism after the second transplantation indicates that hematopoietic cells derived from the older brother's marrow engrafted without causing GVHD, suggesting that acquired tolerance to disparate unrelated HLA antigens was achieved.     

Endothelial cell chimerism associated with graft rejection after human lung transplantation

Endotheliitis is a major sign of graft rejection. Recipient-derived endothelial cells found in two series of liver and kidney transplants were related to graft rejection. Here, we assessed the presence and the number of chimeric endothelial cells in lung transplants, and their relation with graft rejection. In six males grafted with female lungs out of 193 lung transplantations, endothelial chimerism was studied by combined XY-fluorescent in situ hybridization with CD31 and CD45 immunostainings and blood group antigens. On samples graded according to the revised working formulation for lung allograft rejection, we found chimeric macrophages (73.1 to 87.2%) in all cases and chimeric endothelial cells (1.3 to 2.1%) in four patients. Another method using ABO blood group also showed endothelial cells positive for recipient-type blood group antigens in three patients. By both methods, presence of chimeric endothelial cells was related to pathological signs of acute rejection (P<0.05).     

Nephrotic syndrome after allogeneic peripheral blood stem cell transplantation

Nephrotic syndrome has been rarely reported after hematopoietic stem cell transplantation. We report a patient who developed nephrotic syndrome after allogeneic peripheral blood stem cell transplantation for acute myelogenous leukemia. Renal biopsy was performed and immunofluorescence and light microscopy were compatible with minimal change disease. The patient was treated with cyclophosphamide and prednisolone. Complete remission was achieved after three months. Previous reported cases are discussed.     

双份无关脐血移植治疗高危白血病并长期无病存活二例报告

目的　探讨双份非血缘关系脐血移植 (UCBT)治疗高危白血病的疗效。方法　对 2例高危白血病患者进行了HLA配型不合的双份UCBT。预处理方案为 :在全身照射 (TBI +CY)方案基础上加用抗胸腺细胞球蛋白 (ATG)。移植物抗宿主病 (GVHD)预防方案为 :采用环孢素A(CsA)、甲泼尼龙 (MP)和霉酚酸酯 (MMF)。结果　 2例患者中性粒细胞数恢复至≥ 0 .5× 10 9/L的时间分别为 :移植后 2 1和 2 2d ;血小板数≥ 2 0× 10 9/L的时间分别为 :5 1和 2 8d。植活后DNA分析显示 ,仅有1份脐血植入 ,另 1份被排斥。无严重移植物抗宿主病发生。 2例分别长期无病存活超过 34和 30个月。结论　双份脐血干细胞移植 ,可用于无骨髓供者而需异基因移植治疗的患者。     

Nephrotic syndrome after stem cell transplantation

Nephrotic syndrome occurs rarely after bone marrow transplantation. We describe three patients with myeloid malignancy who developed nephrotic syndrome from 5, 22 and 25 months after allogeneic stem cell transplantation (SCT), confirmed by electron microscopy as membranous glomerulonephritis in two and minimal change glomerulonephritis in one. Proteinuria was initially severe in all and clinically distinct from prior graft-vs.-host disease in two patients. While all responded initially to prednisolone and cyclosporine therapy, two recipients with high-risk leukemia developed late solid organ and bone marrow relapse of their disease, which ultimately proved fatal. The third patient remains alive and disease-free with minimal proteinuria off immunosuppressive therapy. Hence, the onset of de novo high-grade proteinuria after allogeneic SCT should prompt renal histological confirmation, and a trial of immunosuppressive therapy after other causes of nephritic syndrome have been excluded.     

Early occurrence of nephrotic syndrome associated with cord blood stem cell transplantation

Nephrotic syndrome (NS) associated with hematopoietic stem cell transplantation (HSCT) is usually related to chronic graft-versus-host disease (GVHD) and invariably occurs later than 100 days after transplantation. Here, we report the case of a 6-year-old boy who presented with NS only 61 days after cord blood stem cell transplantation (CBSCT). At 4 years old he was diagnosed with acute lymphoblastic leukemia and underwent bone marrow transplantation. Six months later, a recurrence was noted in the thymus, which required CBSCT at the age of 6. Acute GVHD and hemophagocytic syndrome occurred on day +13 and day +15, respectively, and were successfully treated with tacrolimus and a steroid. After tacrolimus was switched from intravenous infusion to oral administration, NS occurred on day +61. Complete remission was achieved in 3 weeks by resuming steroid treatment. Dry erythema with pigmentation and elevation of Th2 cytokine level suggest that NS in this case was also related to chronic GVHD. To our knowledge, this is the earliest occurrence of NS after HSCT. Hematologists and nephrologists should be aware that this condition may occur even in early periods after HSCT.     

Effects of different serum-levels of ATG after unrelated donor umbilical cord blood transplantation

We determined total rabbit-IgG (r-ATG) levels in serum samples before (day 0) and after (day 11 and day 25) unrelated donor umbilical cord blood transplantation (UCBT). Most patients (27/41) suffered from a haematological malignancy. There were 25 children and 16 adults. All patients received rabbit anti-thymocyte globulin (ATG) at a total dose of 6 or 8mg/kg as part of the conditioning. No correlation between the dose of ATG and serum r-ATG levels post UCBT was found. The cumulative incidence of acute GVHD grades III-IV in patients given the 6 and 8mg/kg ATG dose was 15% and 13% (ns), respectively. Patients with r-ATG≤40μg/mL 11days after UCBT (n=19) had a higher incidence of grades III-IV acute GVHD (32% vs. 0%, p<0.01), higher TRM (69% vs. 7%, p=0.005), less relapse (17% vs. 82%, p<0.01) but similar relapse-free survival (RFS) (10% vs. 18%, p=0.4) compared to those with r-ATG>40μg/mL (n=17). Low serum-levels of r-ATG early after transplantation seem to be a strong predictor for acute GVHD grades III-IV, TRM and a low incidence of relapse in patients treated with thymoglobulin before unrelated donor UCBT.     

Nephrotic syndrome associated with hemophagocytic syndrome

Hemophagocytic syndrome (HPS) is defined by bone marrow and organ infiltration by activated, nonmalignant macrophages, which phagocytose blood cells. The clinical spectrum of HPS is broad, but renal involvement has rarely been investigated. We report a previously unknown renal manifestation of HPS: nephrotic syndrome. This multicentric retrospective study included patients fulfilling the following criteria: (i) no history of nephropathy; (ii) HPS diagnosis with histologic evidence of hemophagocytosis; (iii) occurrence of nephrotic syndrome during HPS; and (iv) available renal histology. Using the same criteria, we also searched the literature for additional cases. We identified nine patients retrospectively and found two additional cases in the literature (five males and six females, whose mean age was 34 +/- 27 years). Black African patients predominated (63.6%). HPS was due to lymphoma (six cases), infectious disease (three cases), and autoimmune disease (one case), and was primary in one patient. Acute renal failure was associated with nephrotic syndrome in 10/11 cases. Renal histology showed acute tubular necrosis associated with collapsing glomerulopathy in five patients (all Africans with negative human immunodeficiency virus serology), minimal change glomerulopathy in four, and thrombotic-microangiopathy with abnormal podocytes in two. Death occurred in seven cases. Nephrotic syndrome should be included among the renal complications of HPS with acute renal failure. We postulate that abnormal T-cell activation and/or high pro-inflammatory cytokine levels during HPS might cause podocyte injuries, especially among African patients with a susceptible genetic background.     

无关供者脐带血和骨髓移植治疗不同亚型急性白血病的疗效

除同胞供者骨髓移植之外,无关供者脐带血移植（cordbloodtransplantation,CBT）与无关供者骨髓移植（bonemallowtrans—plantation,BMT）也是治疗成年急性白血病患者的重要方法。急性白血病分为急性淋巴细胞白血病（ALL）和急性髓细胞白血病（AML）两类。既往比较CBT和BMT治疗效果的研究由于受样本量的限制,未比较两种方法分别对AML与ALL的疗效。最近,13本脐带血库和骨髓库对CBT和BMT治疗急性白血病的结果进行分析,弥补了这个不足。     

Nephrotic syndrome in a child after umbilical-cord-blood transplantation

We report a 12-year-old girl who developed nephrotic syndrome 6 months after umbilical-cord-blood transplantation (UCBT) for acute lymphoblastic leukemia (L2). In addition to nephrotic syndrome, she also showed autoimmune hemolytic anemia, thrombocytopenia and gastrointestinal symptoms. Since these symptoms were manifested during the course of tapering immunosuppressive agents, a diagnosis of chronic graft-versus-host disease (GVHD) was made. Findings from a kidney biopsy were compatible with minimal-change disease (MCD), and focal glomerular capillary thrombosis and mild tubular damage were also noted. She was treated with methylprednisolone pulse therapy followed by oral prednisolone. Proteinuria disappeared in 14 days. Gastrointestinal symptoms, anemia and thrombocytopenia were also corrected. This is a case report of nephrotic syndrome as a manifestation of chronic GVHD developed after stem-cell transplantation. A review of the cases reported in the literature is also made.This case was presented at the 3rd Japan-Korea Pediatric Nephrology Seminar held in Tokyo, Japan, on 28 May 2005.     

Circumocular exanthema associated with chronic rejection after kidney transplantation

A 43-year-old man had severe circumocular exanthema associated with chronic rejection 10 years after receiving a kidney transplant to treat end-stage renal failure. After the renal allograft was extracted, the exanthema diminished rapidly without any treatment. Donor-reactive immune cells seem to have cross-reacted with unknown pathogens on the skin and contributed to inflammation.     

Relationship between CMV and graft rejection after heart transplantation

Abstract  This study, which included 153 heart transplant patients, was designed to determine whether the cytomegalovirus (CMV) status of both donor and recipient may influence graft rejection. The follow-up was 1 year and they all received the same triple-drug immunosup-pressive regimen with induction (antilymphocyte serum). There was no difference in the total rejection rate, but an increase in repeated rejection rate was shown in transplant recipients with hearts from CMV seropositive donors ( P < 0.05). These data strongly suggest the impact of CMV in enhancement but not in induction of rejection. To prevent iterative rejection in the CMV seropositive donor group, antiviral therapy could be proposed during enhancement of antirejection therapy.     

非血缘脐血移植治疗高危急性白血病的临床研究

目的探讨非血缘脐血移植(UCBT)治疗儿童和成人高危急性白血病的效果。方法对高危急性白血病10例患者进行脐血移植,儿童3例,成人7例,中位年龄29岁(11~41岁)。6例接受单份脐血移植,4例接受双份脐血移植。采用清髓性不含抗胸腺细胞球蛋白(ATG)预处理方案。在白消安(Bu)加环磷酰胺(Cy)基础上加用阿糖胞苷(Ara-C)、氟达拉滨(Flu)或全身照射(TBI)。移植物抗宿主病(GVHD)预防采用环孢素及吗替麦考酚酯。结果 8例(80%)患者获得成功植入,白细胞植入中位时间为19 d(14~25 d),血小板植入中位时间为40 d(33~60 d)。3例患者发生急性GVHD,无1例发生慢性GVHD。中位随访时间为24个月(1~29个月),7例患者无病存活。2年总体存活率及无病存活率均为66.7%。结论 UCBT治疗高危急性白血病是可行的,对于无HLA相合同胞供者的高危患者,UCBT可作为首选,其GVHD发生率低、复发率低,有可能使急性白血病患者长期生存。     

Perioperative blood pressure control,delayed graft function,and acute rejection after renal transplantation

BACKGROUND: Blood pressure (BP) control immediately after renal transplantation is poorly understood, with patients experiencing both high and low BP levels. Donor kidneys lack the ability to autoregulate their blood flow, meaning high pressures are directly translated to the graft endothelium, whereas reduced perfusion may augment ischemic injury. We hypothesize that early BP control may therefore influence the early alloimmune response. METHODS: A total of 276 patients undergoing primary cadaveric renal transplantation who received cyclosporine-based therapy were followed; standard transplant variables were identified. BP was serially recorded before, during, and after reperfusion until 50 hr after surgery. Variables predicting acute rejection and delayed graft function were identified using Cox and logistic regression models. RESULTS: The mean (SD) BP after surgery was 161(19) mm Hg systolic and 73(12) mm Hg diastolic. Forty-two percent had perioperative hypertension defined by conventional parameters. Increasing postoperative systolic BP, measured as standardized area-under-the-curve, was associated with an increased risk for acute rejection (hazard ratio [per mm Hg]=1.008), independent of other covariables including the preoperative BP level. Diastolic BP was inversely associated with the risk of delayed graft function (odds ratio [per mm Hg]=0.956). CONCLUSIONS: Early hypertension is common after renal transplantation. Early BP control has the potential to influence the risk of allograft rejection and delayed graft function.     

Nephrotic syndrome associated with Kimura disease

Kimura disease presents as benign subcutaneous swelling predominantly around the head and neck region. It has a high incidence of renal involvement. However, the pathogenesis of this association remains elusive. Only 2 pediatric cases and 11 adult cases of Kimura disease with renal involvement have been reported in the literature. In recent years many immunopathogenetic features suggesting an underlying T-cell and related cytokine defect have been noted in Kimura disease. We describe a unique case of an Asian boy who presented with nephrotic syndrome resistant to steroid and cytotoxic therapy, and 5 years later developed cervical lymphadenopathy consistent with Kimura disease. We also review the literature, summarizing the presentation, differential diagnosis, incidence of renal disease, prognosis, immunopathogenetic features, and therapy. Received: 24 June 1999 / Revised: 1 November 1999 / Accepted: 2 November 1999     

Nephrotic syndrome associated with Kimura's disease

Kimura's disease consists of lesions that appear as single or multiple red-brown papules or as subcutaneous nodules with a predilection for the head and neck region. Although it principally affects the skin and soft tissues, there is a high prevalence of associated renal disease. We report a case of nephrotic syndrome associated with Kimura's disease. Our patient is distinctive in that his disease first manifested while residing in the Western hemisphere; the renal disease was characterized as mesangial proliferative glomerulonephritis with renal impairment, and his nephrotic syndrome remitted with standard doses of prednisone.