Secondary neuroendocrine tumor after allogeneic bone marrow transplantation

Here we report a case of aggressive neuroendocrine tumor (NET), which is an extremely rare secondary solid tumor that occurs after allogeneic hematopoietic cell transplantation (allo‐HSCT). A patient with chronic active Epstein–Barr virus infection received allo‐HSCT from an HLA‐DR two allele‐mismatched unrelated donor. Four years later, he developed NET with multiple metastases. He received thoraco‐abdominal irradiation as a conditioning regimen, and developed repeated episodes of intestinal graft‐versus‐host disease, for which he received long‐term immunosuppressive therapy. Although these factors may be potential contributing factors to the development of secondary NET, the exact pathogenesis remains unclear.     

EBV‐positive low‐grade marginal zone lymphoma in the breast with massive amyloid deposition arising in a heart transplant patient: A report of an unusual case

According to the 2008 World Health Organization classification, low‐grade lymphomas arising in transplant recipients are not considered as specific types of PTLD. Most such cases are not associated with EBV infections, although rare reports of post‐transplant marginal zone lymphoma have been described. We describe the case of an 18‐yr‐old female with history of heart transplant who developed a breast mass, but was otherwise completely asymptomatic. Surgical excision of the mass and histopathologic examination showed a low‐grade B‐cell lymphoma most consistent with marginal zone lymphoma with massive amyloid deposition; furthermore, numerous tumor cells were positive for EBV by in situ hybridization for EBV‐encoded RNA. The patient was treated with reduction in immunosuppression, and no additional lesions developed. This case describes an atypical presentation of post‐transplant low‐grade B‐cell lymphoma, unusual in its location, histopathologic features, and association with EBV, thereby adding to the rare previous accounts of such an entity, suggesting the need to include post‐transplant marginal zone lymphomas in the current classification of PTLD, and helping in determining the optimal treatment modalities for such tumors.     

Epstein–Barr virus‐associated smooth muscle tumors in children following solid organ transplantation: A review

EBV‐SMT are a rare entity following organ transplantation. Given the rarity of the tumor, there is no standard approach to diagnosis and treatment. A literature search identified 28 reported cases of EBV‐SMT in addition to our own experience with one case. The aim of this review is to summarize the existing data regarding pathogenesis, diagnosis, and treatment.     

Proven Epstein–Barr encephalitis with negative EBV‐DNA load in cerebrospinal fluid after allogeneic hematopoietic stem cell transplantation in a child with acute lymphoblastic leukemia

We report a case of EBV encephalitis in a seven‐yr‐old child with Ph+ ALL. Two months after an allogeneic HSCT from his HLA mismatched mother, the patient showed an altered sensorium, generalized seizures, and a left hemiparesis. Brain MRI demonstrated multiple lesions highly suggestive for viral encephalitis. Blood and CSF PCR analyses were negative for the most common viruses involved in immunocompromised patients including EBV. A cerebral biopsy was performed, which showed intense gliosis and perivascular lymphocytic cuffing. PCR analysis performed on brain tissue was positive only for the EBV genome, while extensive investigations for other viral infections were negative. The patient's neurological symptoms rapidly worsened and he died two months later. This case report suggests that in patients presenting neurological and radiological signs of encephalitis after an HSCT, an EBV involvement should be considered, even in the absence of CSF and blood PCR virus detection.     

A case of Epstein–Barr virus–associated pulmonary leiomyosarcoma arising five yr after a pediatric renal transplant

Suzuki K, Urushihara N, Fukumoto K, Watanabe K, Wada N, Takaba E. A case of Epstein–Barr virus–associated pulmonary leiomyosarcoma arising five yr after a pediatric renal transplant. Pediatr Transplantation 2011: 15: E145–E148. © 2010 John Wiley & Sons A/S. Abstract: EBV‐associated SMTs in immuno‐compromised patients have recently been reported. We report on a case of EBV‐associated pulmonary leiomyosarcoma arising five yr after renal transplantation. The patient was an eight‐yr‐old girl, who received a living related kidney transplant from her mother. She had had bilateral giant Wilm’s tumors as an infant and underwent bilateral nephrectomy at one and two yr of age. At the age of seven, she suffered from bronchitis several times, and a year later, two nodules were detected in her left lung by X‐ray and computed tomography. We suspected a recurrence of Wilm’s tumor and performed surgical resection. The pathological finding was SMT with moderate mitosis and no evidence of Wilm’s tumor. The fact that the tumors were positive for EBER suggested an association with the EBV. Six months later, there was a recurrence in her left lung. Surgical resection was performed, and immunosuppressive agents were reduced. Two yr after the second operation, she is well with no recurrence. We report the first case of EBV‐associated pulmonary leiomyosarcoma in a pediatric patient after renal transplantation owing to a malignant tumor.     

Successful treatment of a classic Hodgkin lymphoma‐type post‐transplant lymphoproliferative disorder with tailored chemotherapy and Epstein–Barr virus‐specific cytotoxic T lymphocytes in a pediatric heart transplant recipient

CHL type is the least common major form of EBV‐related PTLD but rarely occurs in pediatric recipients; development of CHL subsequent to other PTLD subtypes in the same transplant recipient is even more unusual. Because of its rarity, indications on the best treatment strategy are limited. Patients have been mostly treated with standard HL chemotherapy/radiotherapy, and prognosis seems more favorable than other monomorphic PTLDs. Herein, we describe a pediatric case of EBV‐associated, stage IV‐B, CHL arising in a heart allograft recipient eight yr after diagnosis of B‐cell polymorphic PTLD. The patient was successfully treated with adjusted‐dose HL chemotherapy and autologous EBV‐specific CTL, without discontinuation of maintenance immunosuppression. At two yr from therapy completion, the patient is in CR with stable organ function. With this strategy, it may be possible to reproduce the good prognostic data reported for CHL‐type PTLD, with decreased risk of organ toxicity or rejection.     

Transient seizure‐related MRI abnormalities in a child with primary Epstein–Barr virus infection

We describe the case of a 6‐year‐old girl with typical infectious mononucleosis syndrome complicated by clustered right hemiconvulsions and disturbed consciousness. Diffusion‐weighted magnetic resonance imaging on admission demonstrated reduced diffusion in the left temporo‐posterior cortex and pulvinar of the ipsilateral thalamus. Her neurological symptoms resolved completely by the next day, with complete disappearance of abnormal signal intensities on magnetic resonance imaging (MRI). Elevated cerebrospinal fluid interleukin (IL)‐6 with normal IL‐10 might indicate a neuroprotective role of IL‐6 rather than injury. We concluded that the MRI abnormalities could have been due to the seizure activity itself rather than Epstein–Barr virus‐associated encephalitis. The recognition of transient seizure‐related MRI abnormalities may help in the diagnostic approach to MRI changes in suspected encephalopathy.     

Successful treatment of a patient with tumor necrosis factor receptor‐associated periodic syndrome using a half‐dose of etanercept

TNF receptor‐associated periodic syndrome (TRAPS) is caused by mutations of TNFRSF1A gene and characterized by recurrent febrile episodes of prolonged duration and initial good response to steroids. Etanercept, a TNF blocker, has been used as a putative molecular‐targeted agent for TRAPS, with some patients showing limited efficacy. Here, we report a patient with TRAPS who recovered from steroid dependency by etanercept and kept remission with a reduced dose of etanercept. The pathophysiology of TRAPS still remains to be elucidated and several hypotheses have been proposed. In the most recent hypothesis, the concerted action of wild‐type and mutant TNF receptors plays an important role in provoking enhanced inflammation in TRAPS. The excellent response to etanercept in our patient suggested that there is heterogeneity in TRAPS patients in terms of the contribution of normal TNF signaling to autoinflammation.     

The value of 18F‐FDG PET in pediatric patients with post‐transplant lymphoproliferative disorder at initial diagnosis

PTLD is a serious complication of both solid organ and BMT. This study assessed whether ¹⁸F‐FDG PET, when added to CT scan, had additional value in the initial evaluation of PTLD in pediatric patients and whether PET/CT at baseline can reliably guide biopsy. This retrospective study evaluated 34 consecutive pediatric patients (14 female), aged 3.5–17.0 yr (mean age: 9.9 yr, s.d.: 4.9 yr), who had undergone ¹⁸F‐FDG PET/CT from May 2007 to December 2014 at initial diagnosis of PTLD following heart (n = 13), lung (n = 8), kidney (n = 4), liver (n = 3), liver and bowel (n = 3), and bone marrow (n = 3) transplantation. PTLD was diagnosed histopathologically in 33 patients and was based on clinical findings, elevated EBV, and imaging and follow‐up results in one patient. On lesion‐based analysis, ¹⁸F‐FDG PET showed more lesions than conventional CT scan (168 vs. 134), but CT revealed 22 lesions negative on PET. On per patient analysis, PET detected more lesions in 13 patients, CT identified more abnormalities in seven, and both showed the same number of lesions in 14. Adding ¹⁸F‐FDG PET to CT scans upstaged the disease in seven patients (20.5%). A combination of ¹⁸F‐FDG PET and CT was also useful in guiding biopsy, being positive in 36 of 39 samples (92.3%). These findings indicated that ¹⁸F‐FDG PET and CT are complementary at initial staging of pediatric PTLD and that ¹⁸F‐FDG PET/CT scanning can guide biopsies.     

Selective expansion of donor‐derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome

IPEX syndrome is a rare and fatal disorder caused by absence of regulatory T cells (Tregs) due to congenital mutations in the Forkhead box protein 3 gene. Here, we report a patient with IPEX syndrome treated with RIC followed by allogeneic BMT from an HLA‐matched sibling donor. We could achieve engraftment and regimen‐related toxicity was well tolerated. Although the patient was in mixed chimera and the ratio of donor cells in whole peripheral blood remained relatively low, selective and sustained expansion of Tregs determined as CD4+CD25+Foxp3+ cells was observed. Improvement in clinical symptoms was correlated with expansion of donor‐derived Tregs and disappearance of anti‐villin autoantibody, which was involved in the pathogenesis of gastrointestinal symptoms in IPEX syndrome. This clinical observation suggests that donor‐derived Tregs have selective growth advantage in patients with IPEX syndrome even in mixed chimera after allogeneic BMT and contribute to the control of clinical symptoms caused by the defect of Tregs.     

KIR–HLA receptor‐ligand mismatch associated with a graft‐versus‐tumor effect in haploidentical stem cell transplantation for pediatric metastatic solid tumors

Killer immunoglobulin‐like receptors (KIRs) on natural killer cells (NKs) recognize groups of human leukocyte antigen (HLA) class I alleles. Cells without an inhibitory HLA ligand may trigger NK activation. Reduced risk of relapse has been reported in malignant hematologic diseases after haploidentical transplantation when HLA ligands against the inhibitory KIRs present in the donor were absent in the recipient. We performed haploidentical transplant in three children with refractory solid tumors. Our results showed that beneficial antitumor effects could be observed in the presence of inhibitory KIR–HLA mismatch. These preliminary results suggest a possible association between disease control and NK cell alloreactivity. Pediatr Blood Cancer 2009;53:120–124. © 2009 Wiley‐Liss, Inc.     

Central venous catheter‐related blood stream infection with pyomyositis due to Stenotrophomonas maltophilia after allogeneic bone marrow transplantation in a patient with aplastic anemia

Stenotrophomonas maltophilia causes pneumonia and CVC‐CRBSI in HSCT. However, there are few reports of pyomyositis due to S. maltophilia. We report a patient with CRBSI and pyomyositis due to S. maltophilia after allogeneic HSCT who was successfully treated by removing the CVC and antibiotics without surgical drainage. Removing the CVC and the combined antibiotics without preventing the neutrophil engraftment could avoid surgical drainage in pyomyositis due to S. maltophilia when detected in an early stage.