Hemorrhagic cystitis associated with urinary excretion of adenovirus type 11 following allogeneic bone marrow transplantation

We studied a total of 50 recipients who had received allogeneic bone marrow transplantation (BMT) and evaluated both the presence of hemorrhagic cystitis (HC) and the urinary excretion of adenovirus. Twelve recipients developed HC and eight of these 12 patients excreted adenovirus type 11 at the onset of cystitis. Urine for virus isolation was attempted 30, 60 and 100 days after BMT. Among 137 specimens examined, eight were positive for adenovirus type 11. Of these eight samples, six were collected during HC; while in the 129 samples which were negative for adenovirus, only three specimens was collected during HC. Female patients, seropositivity for the antibody to adenovirus prior to BMT and acute graft-versus-host disease (grade 2-4) showed a significant impact on the risk of adenovirus HC. It may be said that adenovirus type 11 is one of the causative agents of HC in BMT recipients.     

Hemorrhagic cystitis associated with adenovirus infection in bone marrow transplantation

A retrospective study of bone marrow transplant recipients shedding adenovirus type 11 in the urine was carried out to determine the association between viral shedding and hemorrhagic cystitis in this population. Weekly urine virology surveillance cultures were obtained during the first 100 days following transplantation. Adenovirus type 11 was cultured from five of 502 bone marrow transplant recipients from 1977 through 1984. In four of these five patients there was associated hemorrhagic cystitis. This contrasts with an overall incidence of hemorrhagic cystitis of 20% in this bone marrow transplant population. A case of hemorrhagic cystitis occurred in a patient following bone marrow transplantation. Recognition of a viral origin of hemorrhagic cystitis may explain the occurrence of late hemorrhagic cystitis in patients despite interventions designed to prevent cyclophosphamide-induced hemorrhagic cystitis. Hemorrhagic cystitis may be the presenting sign of a lethal adenoviral infection.     

粒细胞-巨噬细胞集落刺激因子膀胱灌注治疗骨髓移植术后出血性膀胱炎的疗效观察

目的：评估粒细胞-巨噬细胞集落刺激因子(GM-CSF)治疗单倍体骨髓移植术后并发Ⅲ～Ⅳ级出血性膀胱炎的临床效果。方法：对7例出血性膀胱炎患者应用GM-CSF进行膀胱灌注300μg／d，连用5天。结果：7例患者中有6例完全缓解，1例无效，获得完全缓解的中位时间为11．3d(范围5～16d)。结论：膀胱灌注GM-CSF治疗骨髓移植术后出血性膀胱炎有效，未见不良反应发生。     

Successful hyperbaric oxygen treatment of life-threatening hemorrhagic cystitis after allogeneic bone marrow transplantation

Hemorrhagic cystitis (HC) is a major cause of morbidity after allogeneic bone marrow transplantation (BMT). Many therapies have been investigated to prevent or treat HC, but effective treatment for HC is still limited. While the efficacy of hyperbaric oxygen therapy has been established for HC due to chemotherapy and/or radiation therapy, its role in HC occurring after allogeneic BMT has yet to be defined. We report two cases of life-threatening late-onset HC after allogeneic BMT in children, which resolved after treatment with hyperbaric oxygen.     

Immunotherapy after bone marrow transplantation.

Residual disease after bone marrow transplantation (BMT) can either cause relapse or persist in a balanced state in which immune mechanisms keep control over malignant cell proliferation. After allogeneic BMT the latter mechanism [summarized as graft-versus-leukemia (GVL)] is probably supported by cellular (e.g. T lymphocytes, natural killer cells) and humoral (e.g. cytokines) effectors and often linked to clinical manifestations of GVHD. Preclinical and clinical studies are now emerging in which cytokines, such as interleukin-2 or interferons, are given after BMT to support cellular immune function particularly in situations in which GVL does not occur. We summarize here results from both pre-clinical and clinical studies that are relevant to the design of protocols seeking to improve elimination of residual malignant disease in BMT patients by modulation of the immune system.     

Clinical effectiveness of hyperbaric oxygen therapy for BK-virus-associated hemorrhagic cystitis after allogeneic bone marrow transplantation

Late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT) has been associated with BK virus (BKV). Antiviral drugs are of limited efficacy and the optimal treatment for HC has not yet been established. Hyperbaric oxygen (HBO) may benefit these patients. We, therefore, retrospectively evaluated the effectiveness of HBO therapy in 16 patients with HC after allogeneic HSCT. All 16 patients had macroscopic hematuria and BKV infection. Patients received 100% oxygen in a hyperbaric chamber at 2.1 atmospheres for 90?min, 5 days per week, with a median 13 treatments (range, 4-84). Fifteen patients (94%) showed complete resolution of hematuria. Median urinary DNA BKV titers declined after HBO (P<0.05). Patients started on HBO earlier after diagnosis of HC responded sooner (P<0.05). HBO was generally well tolerated and proved to be a reliable option for this difficult to manage condition.     

Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: donor type matters

Hemorrhagic cystitis (HC) remains a common complication of allogeneic blood and marrow transplantation. Previous analyses of risk factors for this complication were performed in heterogeneous populations, with dissimilar diagnosis and conditioning regimens. We postulated that HC is more prevalent in matched unrelated donor (MUD) and unrelated cord blood (UCB) transplantations than in matched related donor (MRD) transplantations. We performed a retrospective study on 105 acute lymphocytic leukemia patients treated with 12 Gy total body irradiation-based regimens and allogeneic transplants (MUD, n = 38; UCB, n = 15; mismatched related, n = 20; MRD, n = 32). HC occurred in 16% of patients receiving MRD transplants, 30% of recipients of mismatched related, and 40% of MUD or UCB transplants (hazard ratio 2.9, 95% CI 1.0-7.9 for the comparison of MRD versus MUD). The excessive rate of HC among MUD and UCB patients became evident after the first 30 days after transplantation. Recipients younger than 26 years had a significantly higher incidence of HC (HR 2.5, 95% CI 1.1-5.8). This donor type and age effect was independent of platelet engraftment, development of graft-versus-host disease (GVHD), source of stem cells, use of anti-thymocyte globulin (ATG) or cyclophosphamide in the regimen, steroid use, or stem cell source. We concluded that HC is more prevalent in MUD and UCB transplantations.     

Adenovirus is a key pathogen in hemorrhagic cystitis associated with bone marrow transplantation.

Late-onset hemorrhagic cystitis (HC) is a well-known complication of bone marrow transplantation (BMT) that is mainly attributed to infection with BK virus (BKV) and adenovirus (AdV). From 1986 through 1998, 282 patients underwent BMT, and 45 of them developed HC. Urine samples tested positive for AdV in 26 patients, of which 22 showed virus type 11. Among patients who underwent allogeneic BMT, logistic regression analysis revealed acute graft-versus-host disease (grade, > or = 2) to be the most significant predictive factor for HC (P < .0001). In addition, a total of 193 urine samples regularly obtained from 26 consecutive patients who underwent allogeneic BMT were examined for BKV, JC virus (JCV), and AdV by means of polymerase chain reaction. Of patients without HC, approximately 30% of the specimens tested positive for BKV (58 samples) and JCV (55 samples), whereas 5 (3%) tested positive for AdV. Of the 3 samples obtained from patients with HC, the numbers of positive results for BKV, JCV, and AdV were 3, 1, and 1, respectively; the numbers of positive results increased to 14 of 17, 9 of 17, and 10 of 17, respectively, when we added another 14 samples obtained from 14 patients with HC (P < .0001, P = .026, and P < .0001, respectively). In conclusion, there was significant correlation between AdV and HC in the patients we studied.     

Administration of human urinary colony stimulating factor after bone marrow transplantation

A phase II study of the use of colony stimulating factor derived from human urine (CSF-HU) was performed after bone marrow transplantation (BMT). Steady and rapid recovery of leukocyte and granulocyte numbers was observed. In most patients who received CSF-HU from day 1, leukocyte numbers started to increase on day 6 and monocytes and granulocytes on day 11. Significant differences in the days to recovery of leukocytes over 1 x 10(9)/l and of granulocytes over 0.5 x 10(9)/l were observed in comparison with non-randomized control patients. In some patients in whom recovery of leukocytes was delayed, CSF also seemed to be effective in increasing leukocyte numbers from 8 days after the start of administration. There was no significant difference in the rate of relapse of leukemia between the two groups. CSF-HU seems very promising as a treatment of patients after BMT by shortening the period of leukopenia or granulocytopenia.     

Fiberoptic bronchoscopy for diagnosis of opportunistic pulmonary infections after bone marrow transplantation

As a part of the diagnostic procedure for 16 suspected pulmonary infections in 15 marrow transplant recipients fiberoptic bronchoscopy with bronchoalveolar lavage (BAL), transbronchial lung biopsy (TBB) and brushing were performed. Cytomegalovirus (CMV) was the most common microorganism and CMV pneumonia was diagnosed in 8/16 (50%) episodes of pulmonary disease studied. Pneumonias were diagnosed as caused by Candida or Aspergillus species in 6 episodes and by gram-positive cocci in 2 cases. Adenovirus and Pneumocystis carinii was also isolated in 1 patient each. Three noninfectious diseases (pulmonary oedema, idiopathic pneumonia and pulmonary embolism) were diagnosed by methods other than bronchoscopy. The use of fiberoptic bronchoscopy with BAL and TBB allowed correct identification of 14/18 microorganisms involved. Brushing was less useful. Four patients' pneumonias had a multiple etiology. The bronchoscopy methods used were well tolerated even by patients whose condition was poor.     

Liver disease after bone marrow transplantation.

Liver dysfunction occurs after bone marrow transplantation but the relative importance of graft versus host disease and other factors, such as infection, radiation, and drugs, has not been clearly established. We have studied liver status before and after bone marrow transplantation in 43 consecutive patients and have related this to survival and factors that are recognised to cause liver injury. Minor abnormalities of liver tests occurred in 21% of patients before grafting but this did not influence survival or the development of liver disease after transplantation. During the first 50 days after grafting, 83% of patients had abnormal liver tests which were more severe in patients who subsequently died. Alanine transaminase was significantly higher in non-survivors and appeared to predict survival early after transplantation. Only non-survivors developed clinical signs of liver disease. Severe liver disease was always associated with graft versus host disease and atypia of the small bile ducts was the most useful histological marker of hepatic involvement with this disease. Two of the patients with hepatic graft versus host disease also has hepatic veno-occlusive disease and three fatalities had opportunistic infection of the liver, although, in the latter, death was not due primarily to liver dysfunction. Previous hepatitis and androgen therapy could not be implicated as important causes of hepatic damage but chemotherapy for acute leukaemia and conditioning regimens for bone marrow transplantation appear to be the most important factors in the development of hepatic veno-occlusive disease.     

Obstructive jaundice after bone marrow transplantation.

Jaundice after bone marrow transplantation is usually a consequence of graft versus host disease. Reported is a patient who presented with obstructive jaundice several months after a successful marrow allograft. Despite a benign bone marrow examination, abdominal ultrasound, upper gastrointestinal series, and endoscopic biopsy were utilized to diagnose recurrent leukemia at the pancreatic head and descending duodenum. The entities of graft versus host disease as related to jaundice, and gastrointestinal leukemia, in the presence of a "remission" bone marrow, are reviewed.     

Unilateral papilledema after bone marrow transplantation.

We describe a patient who developed unilateral papilledema after allogeneic BMT. This is a rare manifestation of pseudotumor cerebri, which results from elevated intracranial pressure caused by cyclosporin A. The papilledema usually involves the fundi bilaterally, but unilateral involvement has been described. Congenital anomalies, compression and adhesion of the optic nerve sheath are its causes. In this patient, the right optic fundus was spared although leukemic infiltration was present on this side and high-dose irradiation (72 Gy) was given. Although papilledema is a sensitive marker of elevated intracranial pressure, this sign may be masked by constriction of the optic sheath in patients who suffer from leukemic infiltration of the central nervous system and receive high doses of cranial irradiation.     

Toxoplasmosis with hemophagocytic syndrome after bone marrow transplantation: diagnosis at autopsy

Abstract: Toxoplasmosis is a rare but well recognized opportunistic infection that can occur after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Besides encephalitis, other common presentations of Toxoplasma gondii infection are interstitial pneumonitis and myocarditis. Because of its non‐specific clinical and biological signs and its lethal outcome, toxoplasmosis is often misdiagnosed and only revealed at autopsy. We report a case of a postmortem diagnosis of disseminated toxoplasmosis associated with hemophagocytic syndrome, which underlines the value of necropsy in cases of death after transplantation. We also discuss clinical presentations and risk factors that lead to toxoplasmosis in allo‐HSCT recipients.     

A simple technique for processing of bone marrow for human marrow transplantation

Summary A simple stainless steel device is described for the processing of marrow for intravenous infusion to marrow graft recipients. The device can be cleaned easily and sterilized for re-use.