Autologous and Allogeneic Stem-Cell Transplantation for Transformed Follicular Lymphoma: A Report of the Canadian Blood and Marrow Transplant Group.


Purpose To determine whether autologous (auto) or allogeneic (allo) stem-cell transplantation (SCT) improves outcome in patients with transformed follicular lymphoma compared with rituximab-containing chemotherapy alone.

Patients and Methods This was a multicenter cohort study of patients with follicular lymphoma and subsequent biopsy-proven aggressive histology transformation. Patient, treatment, and outcome data were collected from each transplantation center and combined for analysis. A separate control group was composed of patients with transformation treated with rituximab-containing chemotherapy but not SCT. The primary end point was overall survival (OS) after transformation.

Results One hundred seventy-two patients were identified: 22 (13%) treated with alloSCT, 97 (56%) with autoSCT, and 53 (31%) with rituximab-containing chemotherapy. Five-year OS after transformation was 46% for patients treated with alloSCT, 65% with autoSCT, and 61% with rituximab-containing chemotherapy (P = .24). Five-year progression-free survival (PFS) after transformation was 46% for those treated with alloSCT, 55% with autoSCT, and 40% with rituximab-containing chemotherapy (P = .12). In multivariate analysis, patients treated with autoSCT had improved OS compared with those who received rituximab-containing chemotherapy (hazard ratio [HR], 0.13; 95% CI, 0.05 to 0.34; P < .001). On the other hand, there was no OS difference between those treated with alloSCT and rituximab-containing chemotherapy (HR, 0.44; 95% CI, 0.16 to 1.24; P = .12). OS and PFS after SCT were similar between those treated with autoSCT and alloSCT. Five-year transplantation-related mortality was 23% for those treated with alloSCT and 5% for autoSCT.

Conclusion Patients undergoing autoSCT had better outcomes than those treated with rituximab-containing chemotherapy alone. AlloSCT did not improve outcome compared with rituximab-containing chemotherapy and was associated with clinically significant toxicity.

Source: JCO



Maintenance Chemotherapy for Advanced Non–Small-Cell Lung Cancer: New Life for an Old Idea.


Although well established for the treatment of certain hematologic malignancies, maintenance therapy has only recently become a treatment paradigm for advanced non–small-cell lung cancer. Maintenance therapy, which is designed to prolong a clinically favorable state after completion of a predefined number of induction chemotherapy cycles, has two principal paradigms. Continuation maintenance therapy entails the ongoing administration of a component of the initial chemotherapy regimen, generally the nonplatinum cytotoxic drug or a molecular targeted agent. With switch maintenance (also known as sequential therapy), a new and potentially non–cross-resistant agent is introduced immediately on completion of first-line chemotherapy. Potential rationales for maintenance therapy include increased exposure to effective therapies, decreasing chemotherapy resistance, optimizing efficacy of chemotherapeutic agents, antiangiogenic effects, and altering antitumor immunity. To date, switch maintenance therapy strategies with pemetrexed and erlotinib have demonstrated improved overall survival, resulting in US Food and Drug Administration approval for this indication. Recently, continuation maintenance with pemetrexed was found to prolong overall survival as well. Factors predicting benefit from maintenance chemotherapy include the degree of response to first-line therapy, performance status, the likelihood of receiving further therapy at the time of progression, and tumor histology and molecular characteristics. Several aspects of maintenance therapy have raised considerable debate in the thoracic oncology community, including clinical trial end points, the prevalence of second-line chemotherapy administration, the role of treatment-free intervals, quality of life, economic considerations, and whether progression-free survival is a worthy therapeutic goal in this disease setting.

Source: JCO


Oral Antibiotics for Fever in Low-Risk Neutropenic Patients With Cancer: A Double-Blind, Randomized, Multicenter Trial Comparing Single Daily Moxifloxacin With Twice Daily Ciprofloxacin Plus Amoxicillin/Clavulanic Acid Combination Therapy—EORTC Infectious Diseases Group Trial XV.


Purpose This double-blind, multicenter trial compared the efficacy and safety of a single daily oral dose of moxifloxacin with oral combination therapy in low-risk febrile neutropenic patients with cancer.

Patients and Methods Inclusion criteria were cancer, febrile neutropenia, low risk of complications as predicted by a Multinational Association for Supportive Care in Cancer (MASCC) score > 20, ability to swallow, and ≤ one single intravenous dose of empiric antibiotic therapy before study drug treatment initiation. Early discharge was encouraged when a set of predefined criteria was met. Patients received either moxifloxacin (400 mg once daily) monotherapy or oral ciprofloxacin (750 mg twice daily) plus amoxicillin/clavulanic acid (1,000 mg twice daily). The trial was designed to show equivalence of the two drug regimens in terms of therapy success, defined as defervescence and improvement in clinical status during study drug treatment (< 10% difference).

Results Among the 333 patients evaluated in an intention-to-treat analysis, therapy success was observed in 80% of the patients administered moxifloxacin and in 82% of the patients administered combination therapy (95% CI for the difference, −10% to 8%, consistent with equivalence). Minor differences in tolerability, safety, and reasons for failure were observed. More than 50% of the patients in the two arms were discharged on protocol therapy, with 5% readmissions among those in either arm. Survival was similar (99%) in both arms.

Conclusion Monotherapy with once daily oral moxifloxacin is efficacious and safe in low-risk febrile neutropenic patients identified with the help of the MASCC scoring system, discharged early, and observed as outpatients.


Source: JCO

Breast Cancer Follow-Up and Management After Primary Treatment: American Society of Clinical Oncology Clinical Practice Guideline Update.


Purpose To provide recommendations on the follow-up and management of patients with breast cancer who have completed primary therapy with curative intent.

Methods To update the 2006 guideline of the American Society of Clinical Oncology (ASCO), a systematic review of the literature published from March 2006 through March 2012 was completed using MEDLINE and the Cochrane Collaboration Library. An Update Committee reviewed the evidence to determine whether the recommendations were in need of updating.

Results There were 14 new publications that met inclusion criteria: nine systematic reviews (three included meta-analyses) and five randomized controlled trials. After its review and analysis of the evidence, the Update Committee concluded that no revisions to the existing ASCO recommendations were warranted.

Recommendations Regular history, physical examination, and mammography are recommended for breast cancer follow-up. Physical examinations should be performed every 3 to 6 months for the first 3 years, every 6 to 12 months for years 4 and 5, and annually thereafter. For women who have undergone breast-conserving surgery, a post-treatment mammogram should be obtained 1 year after the initial mammogram and at least 6 months after completion of radiation therapy. Thereafter, unless otherwise indicated, a yearly mammographic evaluation should be performed. The use of complete blood counts, chemistry panels, bone scans, chest radiographs, liver ultrasounds, pelvic ultrasounds, computed tomography scans, [18F]fluorodeoxyglucose–positron emission tomography scans, magnetic resonance imaging, and/or tumor markers (carcinoembryonic antigen, CA 15-3, and CA 27.29) is not recommended for routine follow-up in an otherwise asymptomatic patient with no specific findings on clinical examination.

Source: JCO

New Syndrome of Paraganglioma and Somatostatinoma Associated With Polycythemia .


Purpose The occurrence of ≥ two distinct types of tumors, one of them paraganglioma (PGL), is unusual in an individual patient, except in hereditary cancer syndromes.

Patients and Methods Four unrelated patients were investigated, with thorough clinical evaluation. Plasma and tissue catecholamines and metanephrines were measured by high-performance liquid chromatography. Anatomic and functional imaging were performed for tumor visualization. Germline and tumor tissue DNA were analyzed for hypoxia-inducible factor 2 alpha (HIF2A) mutations. The prolyl hydroxylation and stability of the mutant HIF2α protein, transcriptional activity of mutant HIF2A, and expression of hypoxia-related genes were also investigated. Immunohistochemical staining for HIF1/2α was performed on formalin-fixed, paraffin-embedded tumor tissue.

Results Patients were found to have polycythemia, multiple PGLs, and duodenal somatostatinomas by imaging or biochemistry with somatic gain-of-function HIF2Amutations. Each patient carried an identical unique mutation in both types of tumors but not in germline DNA. The HIF2A mutations in these patients were clustered adjacent to an oxygen-sensing proline residue, affecting HIF2α interaction with the prolyl hydroxylase domain 2–containing protein, decreasing the hydroxylation of HIF2α, and reducing HIF2α affinity for the von Hippel–Lindau protein and its degradation. An increase in the half-life of HIF2α was associated with upregulation of the hypoxia-related genes EPOVEGFAGLUT1, and END1 in tumors.

Conclusion Our findings indicate the existence of a new syndrome with multiple PGLs and somatostatinomas associated with polycythemia. This new syndrome results from somatic gain-of-function HIF2A mutations, which cause an upregulation of hypoxia-related genes, including EPO and genes important in cancer biology.


Source: JCO


Sequential Phase I and II Trials of Stereotactic Body Radiotherapy for Locally Advanced Hepatocellular Carcinoma.


Purpose To describe outcomes of prospective trials of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC).

Patients and Methods Two trials of SBRT for patients with active HCC unsuitable for standard locoregional therapies were conducted from 2004 to 2010. All patients had Child-Turcotte-Pugh class A disease, with at least 700 mL of non-HCC liver. The SBRT dose range was 24 to 54 Gy in six fractions. Primary end points were toxicity and local control at 1 year (LC1y), defined as no progressive disease (PD) of irradiated HCC by RECIST (Response Evaluation Criteria in Solid Tumors).

Results A total of 102 patients were evaluable (Trial 1, 2004 to 2007: n = 50; Trial 2, 2007 to 2010: n = 52). Underlying liver disease was hepatitis B in 38% of patients, hepatitis C in 38%, alcohol related in 25%, other in 14%, and none in 7%. Fifty-two percent received prior therapies (no prior sorafenib). TNM stage was III in 66%, and 61% had multiple lesions. Median gross tumor volume was 117.0 mL (range, 1.3 to 1,913.4 mL). Tumor vascular thrombosis (TVT) was present in 55%, and extrahepatic disease was present in 12%. LC1y was 87% (95% CI, 78% to 93%). SBRT dose (hazard ratio [HR] = 0.96; P = .02) and being in Trial 2 (HR = 0.38; P = .03) were associated with LC1y on univariate analysis. Toxicity ≥ grade 3 was seen in 30% of patients. In seven patients (two with TVT PD), death was possibly related to treatment (1.1 to 7.7 months after SBRT). Median overall survival was 17.0 months (95% CI, 10.4 to 21.3 months), for which only TVT (HR = 2.47; P = .01) and being in Trial 2 (HR = 0.49; P = .01) were significant on multivariate analysis.

Conclusion These results provide strong rationale for studying SBRT for HCC in a randomized trial.

Source: JCO


Steroids control paradoxical worsening ofMycobacterium ulcerans infection following initiation of antibiotic therapy.

A 19-year-old man with a 3-month history of a non-healing ulcer of the right knee and indurated oedema involving the entire lower leg (Box 1) presented after not responding to multiple courses of antibiotics. A punch biopsy showed necrosis of the dermis and subcutaneous tissues, and extensive infiltration with extracellular acid-fast bacilli on auramine–rhodamine staining. Polymerase chain reaction (PCR) testing for the IS2404 insertion sequence of Mycobacterium ulcerans was positive,1 andM. ulcerans was isolated from culture at 6 weeks. The patient reported holidaying on the Bellarine Peninsula, an endemic area for M. ulcerans, 6 months before the development of the lesion. Surgical intervention was deferred due to the extensive area involved and World Health Organization guidelines suggesting antibiotics as first-line treatment for extensive oedematous disease.2

He commenced oral daily rifampicin (600 mg) and moxifloxacin (400 mg) and, within a week, noted a marked decrease in exudate and improvement in the painful oedematous disease of the lower leg. Therapy was well tolerated and the ulcer remained stable with only one small area of new skin loss lateral to the primary lesion.

Four weeks later, there was a rapid deterioration in clinical condition, with fevers, sweats, anorexia and a recurrence of lower limb oedema and pain. Significant skin breakdown occurred around the ulcer and distally on the leg, with copious serous exudate (Box 2). Full blood examination showed a neutrophilia (neutrophil count, 14.9 × 109/L [reference interval, 1.9–8.0 × 109/L]) and a raised C-reactive protein level (69.8 mg/L [reference interval, < 3 mg/L]). Prednisolone 50 mg daily and

intravenous piperacillin–tazobactam 4.5 g three times daily was commenced. An ultrasound of the limb showed extensive liquefaction of the subcutaneous fat, and swabs were PCR-positive for M. ulcerans but culture-negative following prolonged incubation.

Within 12 hours of commencing prednisolone therapy (combined with broad-spectrum antibiotics), the patient became afebrile, with neutrophil and C-reactive protein levels within reference intervals on full blood examination and an improvement in ulcer appearance. He was discharged on a 25 mg maintenance dose of prednisolone while continuing rifampicin and moxifloxacin. Increasing areas of skin loss and exudate developed when prednisolone was decreased to 12.5 mg daily, and thus he underwent a limited debridement of the lateral knee and negative-pressure wound therapy (VAC GranuFoam dressing, KCI Medical), followed by successful split skin grafting. Heat therapy (Bair Hugger, 3M Arizant Healthcare) was used to maintain skin temperature at 39°C.

Prednisolone was continued for 2 weeks postoperatively (15 mg daily) and then stopped without further deterioration in the patient’s condition. The patient completed a 3-month course of antimycobacterial antibiotics, at which time there was no sign of ongoing infection. Two skin sites subsequently discharged a small amount of culture-negative material but, at 12 months, there was no evidence of microbiological relapse.

Mycobacterium ulcerans infection is a geographically restricted infection often referred to by its local name as Daintree, Buruli or Bairnsdale ulcer (BU). The disease occurs in sub-Saharan Africa and within discrete regions of Australia, predominantly coastal Victoria and northern Queensland. Significant diagnostic delays, which place patients at risk of more extensive disease, are common. A recent review identified a mean duration of 42 days of symptoms before diagnosis (range, 2–270 days).3 These delays often occur when patients present outside endemic areas, a factor affected by the long incubation period of 4–7 months.4

BU is characterised by slowly progressive skin lesions with local necrosis, destruction of lipocytes and surprisingly little systemic inflammation. This unusual pattern of infection is the result of its unique virulence factor mycolactone, an immunomodulatory toxin that induces necrosis of host tissues and can limit initiation of immune responses and the recruitment of inflammatory cells.5 Following the increased use of antibiotics in BU, there have been descriptions of worsening clinical condition after an initial response to therapy.6 Such deteriorations (referred to as paradoxical reactions) are most common in patients with extensive disease and can take a variety of forms including increased ulcer size, ulceration of previously non-ulcerative papules or the development of new lesions not detectable before antibiotics.7 It is particularly important that paradoxical reactions are not misinterpreted as antibiotic failure, as the vast majority of lesions will resolve without a change in antibiotic regimen.

Paradoxical reactions may be the result of antibiotic-induced suppression of mycolactone synthesis, leading to decreased mycolactone concentrations and thus a reversal of macrophage and neutrophil dysfunction with renewed immune surveillance and response.7 There are many parallels to the paradoxical reactions described with Mycobacterium tuberculosis in HIV co-infected patients who initiate antiretroviral therapy. In that setting, the reaction likely represents an increased inflammatory response secondary to antiretroviral-induced immune reconstitution. As with M. tuberculosis,paradoxical reactions to BU commonly occur 4–8 weeks after therapy commences.7

In our case, the deterioration 4 weeks into therapy at the time that mycobacterial cultures became sterile indicates that this was not a failure of antibiotics but an unmasked immune phenomenon. Although our patient did receive a short course of intravenous antibiotics at the time of initiation of steroid therapy, the rapidity of his response and lack of identification of a new bacterial pathogen suggests that the steroid therapy itself was responsible for his improvement. This is supported by the fact that his condition deteriorated when his prednisolone dose was weaned.

It has been shown in animal models that corticosteroids do not adversely affect the outcome of antibiotic therapy in BU,8 and Friedman and colleagues reported a marked improvement in the appearance of lesions when steroids were used for paradoxical reactions in this setting.9Established dosing guidelines are available for the management of paradoxical reactions to M. tuberculosis (most popularly, 1 mg/kg/day until improvement, followed by a 2-week wean),10 yet the degree of applicability of these guidelines to BU management is unknown.

As treatment evolves from a purely surgical approach to an adjunctive or primary antibiotic focus, optimal management remains controversial. In patients with extensive and oedematous disease, pre-emptive steroid therapy may have a role in preventing paradoxical deteriorations, although to date there is no randomised evidence to support its use in this way.

  • Mycobacterium ulcerans should be considered in patients who present with non-healing chronic ulcers or atypical cellulitis that do not respond to standard treatment.
  • It is common for M. ulcerans infections to worsen following the initiation of antibiotics; these paradoxical reactions are likely due to an enhanced immune response directed at dead and dying bacteria and do not reflect a failure of antibiotic therapy.
  • Antibiotics should be continued unchanged when a paradoxical reaction occurs.
  • Steroids may play a role in diminishing skin loss and systemic symptoms associated with paradoxical reactions.

Source: MJA





Angiostrongylus meningoencephalitis: survival from minimally conscious state to rehabilitation.

The nematode Angiostrongylus cantonensis has spread down the eastern coast of Australia over recent decades. A healthy 21-year-old man developed life-threatening eosinophilic meningoencephalitis following ingestion of a slug in Sydney. We describe the first case of this severity in which the patient survived.

Clinical record

A 21-year-old man presented with a 3-day history of insomnia and paraesthesia affecting his lower limbs bilaterally. He had no associated headache, meningism or fever. He was previously well with no significant medical history.

On admission, he had begun to develop progressive weakness of his lower limbs associated with pain and dysaesthesia. A full blood count showed a total white cell count of 10.6 × 109/L (reference interval [RI], 4.0–11.0 × 109/L) with mild eosinophilia (0.5 × 109/L [RI, < 0.4 × 109/L]). Magnetic resonance imaging (MRI) scans of his brain and spine showed no abnormality. His cerebrospinal fluid (CSF) was acellular, with normal glucose and protein levels.

A provisional diagnosis of Guillain–Barré syndrome was made and the patient was treated with a 5-day course of intravenous immunoglobulin. Over 1 week he developed evidence of autonomic instability with urinary retention, fluctuating sinus tachycardia and hypertension, and a paralytic ileus. By the second week of hospitalisation he had developed hallucinations and a fluctuating level of consciousness.

A repeat CSF sample revealed a raised protein level of 1.20 g/L (RI, 0.15–0.45 g/L), a low glucose level of 2.3 mmol/L (RI, 2.5–5.6 mmol/L), with 2 × 109/L red cells (RI, < 5 × 109/L), 406 × 109/L mononuclear cells (RI, < 5 × 109/L), and 30 × 109/L polymorphs (RI, nil). The opening pressure was elevated at 31 cm H2O (RI, 6–20 cm H2O). He was commenced on empirical antibiotic and antiviral treatment, with intravenous hydrocortisone (100 mg four times daily) to cover the possibility of a steroid-responsive encephalopathy. An electroencephalogram was consistent with generalised encephalopathy without focal epileptiform activity. CSF bacterial cultures, cryptococcal antigen testing and polymerase chain reaction testing for herpes simplex virus and enterovirus were negative. HIV serological testing was negative. The patient’s condition continued to deteriorate, with a declining level of consciousness, progressive quadriparesis and respiratory failure necessitating endotracheal intubation and mechanical ventilation on Day 12 after admission.

Progress computed tomography (CT) brain imaging results remained normal. His peripheral eosinophil count had risen, later peaking at 1.9 × 109/L on Day 24. A third lumbar puncture was performed. His CSF protein remained elevated at 0.71g/L, CSF red cell count was 216 × 109/L and CSF white cell count was 504 × 109/L. Specific staining for eosinophils was performed, showing 37% of the leukocytes to be eosinophils (RI, < 10%,Box 1).

By this stage it had emerged that the patient had eaten a slug from a Sydney garden, as a dare, 7 days before presentation. An enzyme immunoassay for Angiostrongylus IgG performed on the CSF was positive. A progress MRI scan, performed on Day 26 after admission, revealed multiple foci of hyperintensity in the cerebral hemispheres, brainstem and cerebellum as well as within the spinal cord (Box 2). Several of the lesions showed restricted diffusion and some showed contrast enhancement. Pial enhancement was seen within the posterior fossa and over the spinal cord.

Treatment with high-dose corticosteroids was continued but the patient’s condition continued to decline. An unresponsive state developed, with flaccid tone in all four limbs and the loss of brainstem reflexes. Given the severity of the patient’s condition, a trial of albendazole 400 mg twice daily was given, with continued corticosteroid cover (dexamethasone 4 mg intravenously four times daily) and he remained on this treatment for 1 month. There was no change in his condition and he remained supported by mechanical ventilation via a tracheostomy in a minimally conscious state for 8 months.

During this time, there was much discussion between the patient’s family and treating doctors about his prognosis and probable outcome. Treatment was continued on the basis of his age and the uncertainty of the natural history of this rare disease. His clinical course was complicated by hydrocephalus requiring a ventriculoperitoneal shunt, recurrent episodes of ventilator-associated pneumonia, and seizures that were difficult to control despite multiple antiepileptic drugs. After 13 months, there was a very slow improvement in his level of consciousness, such that a slow weaning of respiratory support could be attempted. He could successfully maintain his own ventilation during the day (though with an ataxic respiratory pattern), but remained dependent on nocturnal mechanical ventilation.

The patient was discharged to the ward from intensive care in the 15th month of admission, where he continued to make slow but definite progress. There was gradual recovery of some distal power in his upper and lower limbs and he developed the ability to communicate with head movements. He was discharged to a rehabilitation facility 22 months after admission, where there has been ongoing gradual improvement. He now has antigravity power in his limbs and is capable of more complex non-verbal communication.


Angiostrongylus cantonensis, also known as the rat lungworm, is the most common cause of eosinophilic meningitis globally. This condition generally follows a benign, self-limited course.1 Rarely, the parasite causes meningoencephalitis, which should be considered a related but distinct clinical entity with a dramatically poorer prognosis. The mortality rate has been reported at 79%2 and, of patients who become comatose, at least 90% do not survive.3

A. cantonensis is endemic in South-East Asia and the Pacific region, and has spread down the eastern coast of Australia over the past 50 years.4 In Australia, it has been observed that cases tend to be particularly severe. This reflects the higher total larval load ingested from terrestrial hosts, which feed on rat faecal pellets harbouring thousands of larvae. In comparison, aquatic snails, which commonly cause the disease in South-East Asia, generally carry a smaller larval load.5,6 The first reported human case acquired in Sydney occurred in 2001,7 in the remarkably similar circumstances of a young man accepting a dare to eat a slug, highlighting the importance of specific questioning in the patient’s history. Our patient’s case is only the second reported case acquired in Sydney and, internationally, our patient is the first with the disease of this severity to have survived.

Recent investigations have sought to identify factors associated with the development of clinically severe angiostrongyliasis. In one study, clinical features including headache, abnormal CSF pressure and abnormal peripheral blood eosinophil count were associated with severe disease.8 An Activation Criteria for Angiostrongyliasis (ACA) scoring system, incorporating these factors, was proposed and validated in a population of Chinese patients, with a score of ≥ 7 predictive of severe disease. If we had used the presenting eosinophil count, our patient would only have had an ACA score maximum of 5, and most likely lower than this if his CSF opening pressure had been recorded at the first lumbar puncture. He would have scored 8 if his peak peripheral eosinophil count and his highest recorded CSF pressure had been used.

A second study investigated factors specifically associated with the development of the encephalitic form of the disease.2 In a cohort of 94 patients with angiostrongyliasis, of whom 14 developed encephalitis, it was found that the clinical factors predictive of encephalitis were temperature > 38°C at presentation, older age and longer duration of headache. Fever at presentation was associated with a remarkable 37-fold risk of encephalitis. Interestingly, other variables such as CSF opening pressure, peripheral or CSF eosinophil counts or paraesthesia were not predictive of encephalitis in this study. Our case indicates that caution should be used when applying the predictive factors reported in these studies, and suggests that peak eosinophil count and delayed CSF pressure results may be more useful when calculating the ACA.

The initial difficulty with diagnosis in this case emphasises the need for clinical suspicion of this condition in the setting of acute-onset neurological symptoms and peripheral eosinophilia in endemic areas, including the eastern coast of Australia. It is essential to seek a history of consuming raw or undercooked food, and specifically any ingestion of molluscs. The case illustrates the importance of repeat CSF examination if the diagnosis is suspected and the initial CSF test results are negative. It also highlights the need to request specific CSF examination to ensure any eosinophils are not mistaken for neutrophils.

The optimal treatment for Angiostrongylus meningoencephalitis remains poorly defined. Corticosteroids are commonly used, with the rationale of dampening the inflammatory reaction to the nematode, and have been shown in a double-blind, placebo-controlled trial to provide symptomatic relief in eosinophilic meningitis.9 However, studies of patients with the encephalitic form of the disease have not found corticosteroids to be effective.3 Anthelmintics are generally not used due to the theoretical possibility of exacerbating cerebral inflammation and damage as a result of larval death in the central nervous system (CNS), and the lack of evidence of their efficacy.9,10 We used albendazole when there was little to lose and, perhaps as expected, it did not lead to any appreciable benefit. In the absence of effective treatment of angiostrongyliasis, it is important in endemic areas that the public understand the small but very serious risks associated with ingestion of uncooked molluscs.

It is known that time spent in a minimally conscious state following traumatic brain injury does not correlate with the chance of functional recovery.11 This observation may extend to patients with diffuse brain injury caused by severe cerebral infection or inflammation. This case shows the potential for the CNS to recover following a severe, generalised insult in a young patient with supportive care. It is important for doctors to appreciate this capacity when wrestling with difficult decisions about continuation of care for critically unwell patients.

Source: MJA

Majority of children readmitted to hospital following transplant.

Nearly two-thirds of children receiving stem cell transplants returned to the hospital within six months for treatment of unexplained fevers, infections or other problems, according to a study performed at Dana-Farber/Children’s Hospital Cancer Center in Boston. Children who received donor cells were twice as likely to be readmitted as children who received their own stem cells.

“No one had ever looked at these data in children,” said Leslie E. Lehmann, MD, clinical director of pediatric stem cell transplantation at Dana-Farber/Children’s Hospital Cancer Center (DF/CHCC). “This is very important information and will allow us to counsel families appropriately, as well as try to devise interventions that reduce the rate of readmissions.”

The study by Lehmann and Harvard Medical School student David Shulman is being presented at the 26th annual meeting of the American Society of Pediatric Hematology Oncology in Miami, April 24-27.

A record review of 129 children from 2008 to 2011 revealed that 64 percent had at least one hospital readmission within 180 days of transplant. The source of the donor cells was a key predictor: 79 percent of patients receiving transplants from a related or unrelated donor were readmitted compared to 38 percent who received their own cells (autologous transplant). The mean number of readmissions was 2.4, indicating that for some children, discharge after transplant is just the beginning of a long process characterized by repeated hospital stays.

Fever without a documented source of infection accounted for 39 percent of the readmissions; 24 percent were for infections and 15 percent for gastrointestinal problems.

“Most of the patients went on to be successfully treated and ultimately did very well,” commented Lehmann.

“We hope these findings can eventually lead to identifying a group of low-risk children who could be managed at local hospitals rather than transplant centers, reducing costs and inconvenience to families.”

Lehmann said the goal is to identify which patients could be safely treated without requiring an admission to the hospital.

Source: Dana-Farber/Children’s Hospital Cancer Center


Scientists find mutation driving pediatric brain tumors.

A type of low-grade but sometimes lethal brain tumor in children has been found, in many cases, to contain an unusual mutation that may help to classify, diagnose and guide the treatment of the tumors, report scientists at Dana-Farber Cancer Institute.

The researchers led a study of pediatric low-grade gliomas, samples of which were collected through an international consortium organized by brain tumor specialists at Dana-Farber/Children’s Hospital Cancer Center. Their findings are being published online by the Proceedings of the National Academy of Sciences (PNAS) the week of April 29.

Low-grade gliomas are the most common type of pediatric brain tumors, diagnosed in about 1,000 young patients annually in the United States. There are about 30 distinct types of these tumors, which arise from specialized cells called glia in the brain. Low-grade gliomas are generally slow-growing, said Keith Ligon, MD, PhD, a senior author of the study, but they behave unpredictably and can be life-threatening.

The investigators focused on diffuse low-grade gliomas, so-called because they lack a tumor mass but spread throughout the brain. As a result, diffuse gliomas often recur after surgery and are more likely to evolve into lethal glioblastomas than are non-diffuse low-grade tumors. “Many of these patients do well, but it’s hard to generalize, as the tumors are difficult to diagnose and study because without better tools pathologists can’t name them consistently,” explained Ligon, who in addition to being a researcher is also a neuropathologist. The research was undertaken in hopes of identifying a common genetic alteration that could be used to better define and design treatments for them.

The researchers analyzed DNA from 45 tissue samples collected from seven institutions in collaboration with Rameen Beroukhim, MD, PhD, a Dana-Farber genome biologist and co- senior author of the study. They looked for mutations caused by extra or missing copies of DNA code in the tumor genomes.

One alteration stood out: a gene called MYBL1, a transcription factor important for controlling other genes, was rearranged and missing a part of its genetic message in nearly 30 percent of the diffuse tumors categorized as grade 2 in terms of aggressiveness. The scientists went on to show that the mutated version of MYBL1 can cause tumors in mice. Previously MYBL1 was not known to cause cancer, but a closely related gene, MYB, is one of the oldest “proto-oncogenes” — a normal gene that can become a cancer-causing gene.

“The creation of these truncated genes, reminiscent in structure of the viral oncogene, is a potential driver for this type of tumor,” said Lori Ramkissoon, PhD, co-first author along with Peleg Horowitz, MD, PhD, a neurosurgery resident, both of Dana-Farber. “It gives us something to follow up on and investigate the function of this gene. It may lead to a specific test for diagnosing these tumors, and we will also try to determine whether patients who have this mutation do better or worse than those lacking the mutation.”

The paper’s other authors include investigators and clinicians from Dana-Farber; the Broad Institute; Brigham and Women’s Hospital; Boston Children’s Hospital; Stanford University School of Medicine; Children’s Cancer Hospital, Cairo, Egypt; University of Texas South Western Medical Center, Dallas; Hospital for Sick Children, Toronto; Children’s National Medical Center, Washington; Johns Hopkins University School of Medicine; and the University of Calgary.

Source: Dana-Farber/Children’s Hospital Cancer Center