The Development of a National Paediatric Psycho-Oncology Service.

Aims To investigate the psychological care provided to children and young adolescents with cancer and their families within the National Children's Cancer Service (NCCS), Ireland, in respect of the national and international standards of care. Methods A retrospective audit of 316 referrals made over 32 months by the NCCS to the psychology service in malignant haematology and oncology was performed. Results The audit revealed that out of 316 patients, a yearly average of 189 (50%) of urgently referred patients received psychological support within the NCCS between January 2013 and August 2016. Furthermore only 20 (22%) undergoing haematopoietic stem cell transplantation (HSCT), 14 (22%) referred to the paediatric palliative care team, and 84 (62%) of teenage patients received psychological input during this timeframe. Conclusion The audit revealed that the current psychology service provision is failing to meet the international standards of care. Due to the data provided by this audit, in conjunction with a clinical risk assessment of the service, funds for the post of principal psychologist have been secured. Further psychology posts (HSCT, late-effects and neuropsychology), and development of the psycho-oncology model of care are required to ensure equality of access and evidence-based psychological care for all children with cancer.

Burkitt Lymphoma/Leukaemia in Children & Young Adolescents.

Aims Burkitt Lymphoma (BL) accounts for approximately 40% of childhood non-Hodgkin Lymphoma (NHL) in the developed world. Survival rates have improved dramatically in recent years, a success attributed to better use of poly-chemotherapy and targeted immunotherapy. Nevertheless, relapse is unpredictable and carries a dismal prognosis. We report on event-free survival (EFS) and overall survival (OS) rates in the Republic of Ireland (ROI) during 2000-2017, and evaluate novel predictors of outcome. Methods Data was collected by retrospective review of patient medical records. Results Thirty-three patients were identified (twenty-five [76%] males, eight [24%] females), fourteen [42%] having stage III disease at presentation. Six [18%] had stage IV disease. Five [15%] had refractory disease; one salvaged with allogeneic stem cell transplantation. Of the four [12%] who died; two [50%] had weights >99th centile, one [25%] >90th centile. One died during induction from refractory lactic acidosis, one from early relapse. Discussion EFS and OS was 85% and 89% respectively; in keeping with the best international standards. Obesity appears to be a poor predictor of outcome in our cohort.

Post-transplant lymphoproliferative disorder in paediatric patients: the Irish perspective-a single centre experience.

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is a serious complication of both solid organ and haematopoietic stem cell transplantation in children. Its incidence has increased over the last decade as a result of more potent immunosuppressive regimens. Many treatments have been explored however optimal therapy remains controversial. AIMS: We report on the diagnosis, treatment and outcome of ten patients who were diagnosed with PTLD in Our Lady's Hospital for Sick Children in Dublin between 2004 and 2015 inclusive. METHODS: Data were collected by retrospective review of patient medical records. RESULTS: 9 out of ten of our patients are alive and disease free following treatment for PTLD with rituximab alone or in combination with chemotherapy. CONCLUSION: The outcome of paediatric patients treated for PTLD at our institution is at least comparable to published international series and supports the use of rituximab ± low dose chemotherapy in the treatment of this malignancy.

Child and adolescent Down syndrome-associated leukaemia: the Irish experience.

BACKGROUND: Down syndrome (DS), the most common syndromic chromosomal abnormality is associated with a unique susceptibility to develop both acute myeloid (ML) and lymphoblastic leukaemia (ALL). These leukaemias differ from the non-DS-related types of leukaemia and are thought to be distinct biological entities. AIMS: To perform a retrospective review of our experience of treating DS-related leukaemia at Our Lady's Children's Hospital. METHODS: Data were extracted from a database established in 2000 to prospectively gather data on DS-associated leukaemias and their outcomes following polychemotherapy. Kaplan-Meier survival curves were constructed. RESULTS: Nineteen patients with DS-ML were treated and 19 with DS-ALL. Sixteen (84%) patients with DS-ML are alive and in complete remission with a median follow-up of 7 years. All deaths in this cohort were due to treatment-related mortality (TRM). Of the DS-ALL patients, 12 (63%) remain alive with a median follow-up of 3.6 years. TRM accounted for five of the six deaths. One death was due to leukaemic relapse. CONCLUSION: High cure rates are seen in DS-ML using contemporary polychemotherapy protocols, however, there is significant TRM in this cohort. DS-ALL does not have the same high cure rate as non-DS-ALL (>90%) and again this is mainly due to an excess of TRM.

Utility of bronchoalveolar lavage in the diagnosis of pulmonary infection in children with haematological malignancies.

BACKGROUND: Fibre-optic bronchoscopy with bronchoalveolar lavage (BAL) is a safe procedure and is associated with low morbidity and mortality in immunocompromised children. Although many studies have highlighted the advantages of positive BAL results in the diagnosis of pulmonary infections, there have been few reports examining the impact of a negative BAL result on clinical management in immunocompromised children on empiric broad-spectrum antimicrobial therapy. AIM: The aim of this study was to evaluate BAL in the diagnosis of pulmonary infections in children with haematological malignancies who develop pneumonia unresponsive to empiric antimicrobial therapy, and also to determine whether a negative BAL result contributed to the clinical management of these patients. MATERIALS AND METHODS: A retrospective review of 44 BAL procedures performed in 33 children with haematological malignancy diagnosed and treated at Our Lady's Children Hospital, Crumlin, Dublin 12, Ireland, over a 10-year period was carried out. RESULTS: We identified a pathogen causing pneumonia in 24 of 44 BAL procedures (54.5 %). The BAL procedure resulted in modification of antimicrobial treatment after 20 of 24 procedures with positive results (83.3 %) in 16 of 20 patients (80 %). Management was changed after 8 of 20 procedures with negative results (40 %) in 8 of 18 patients (44.4 %). The procedure was well tolerated in all patients. CONCLUSIONS: Our study supports the use of bronchoscopy with BAL as a diagnostic intervention in this patient population. We consider BAL a safe procedure from which both positive and negative results contribute to the patient's clinical management.

In search of Pinkel's children: unravelling the biological heterogeneity of childhood acute lymphoblastic leukaemia by genotype and treatment molecular response.

BACKGROUND: Acute lymphoblastic leukaemia (ALL), the commonest childhood malignancy has seen remarkable progress since the 1960s with cure rates now approaching 85%. To achieve this patients undergo intensive treatment that usually takes 2.5-3.5 years involving on average 15 different chemotherapeutic drugs. In 1971, Donald Pinkel reported Total Therapy-Protocol V that used 5 drugs and cranial radiation therapy over a similar time period. Today, one half of these patients (Pinkel's children) remain alive and free of leukaemia. AIM: The aim of this study was to evaluate the impact post-induction minimal residual disease (MRD) levels had on survival and its relationship with the more established clinical and biological prognostic predictors of outcome in the hope of identifying a subgroup of patients that are at very low risk of failure. METHODS: A retrospective review of 250 Irish children with ALL was carried out. MRD status after 28 days of induction chemotherapy and other known predictors of outcome were correlated with 5 year event-free survival (EFS). RESULTS: MRD status was the strongest predictor of outcome with 5 year EFS rates greater that 90% seen in those patients with low-risk MRD and this was associated with TEL/AML1 rearrangement, high hyperdiploidy (HH) karyotype and female gender. CONCLUSION: Both MRD and karyotype are powerful determinants of outcome in childhood ALL. Therefore, it is reasonable to conclude that the majority of children cured by Pinkel et al. in the late 1960s were most likely composed of low-risk MRD, TEL/AML1 and HH patients.

Paediatric umbilical cord blood transplantation.

Umbilical cord blood is being used increasingly as a source of haematopoietic stem cells for transplantation because of rapid availability, and the unavailability of a HLA matched adult donor for some patients. This study reports the characteristics and outcomes of 15 patients who have undergone umbilical cord blood transplantation (UCBT) in Ireland between 1998 and 2009. The median total nucleated cell and CD34+ doses post-processing were 6.5 x 107cells/kg and 1.8 x 105 cells/kg, respectively. Median neutrophil recovery time was 30 days (range, 14-44). Median platelet recovery time was 46.5 days (range, 35-148). 33.3% of patients developed acute cutaneous graft-versus-host disease (GVHD) grade I-II. Three patients died of transplant-related toxicity and two died of leukaemic relapse. We conclude that, with a satisfactory stem cell dose, UCBT offers a high chance of engraftment with acceptable toxicity, and should be regarded as a favourable option in selected patients when satisfactory bone marrow or peripheral blood stem cell donors are not available.

Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study.

We report on the outcome of children with advanced primary myelodysplastic syndrome (MDS) transplanted from an HLA-matched sibling (MSD) or an unrelated donor (UD) following a preparative regimen with busulfan, cyclophosphamide and melphalan. Ninety-seven patients with refractory anemia with excess blasts (RAEB, n=53), RAEB in transformation (RAEB-T, n=29) and myelodysplasia-related acute myeloid leukemia (MDR-AML, n=15) enrolled in the European Working Group of MDS in Childhood (EWOG-MDS) 98 study and given hematopoietic stem cell transplantation (HSCT) were analyzed. Median age at HSCT was 11.1 years (range 1.4-19.0). Thirty-nine children were transplanted from an MSD, whereas 58 were given the allograft from a UD (n=57) or alternative family donor (n=1). Stem cell source was bone marrow (n=69) or peripheral blood (n=28). With a median follow-up of 3.9 years (range 0.1-10.9), the 5-year probability of overall survival is 63%, while the 5-year cumulative incidence of transplantation-related mortality (TRM) and relapse is 21% each. Age at HSCT greater than 12 years, interval between diagnosis and HSCT longer than 4 months, and occurrence of acute or extensive chronic graft-versus-host disease were associated with increased TRM. The risk of relapse increased with more advanced disease. This study indicates that HSCT following a myeloablative preparative regimen offers a high probability of survival for children with advanced MDS.

Indications for admission, treatment and improved outcome of paediatric haematology/oncology patients admitted to a tertiary paediatric ICU.

BACKGROUND: Overall survival in paediatric cancer has improved significantly over the past 20 years. Treatment strategies have been intensified, and supportive care has made substantial advances. Historically, paediatric oncology patients admitted to an intensive care unit (ICU) have had extremely poor outcomes. METHODS: We conducted a retrospective cohort study over a 3-year period in a single centre to evaluate the outcomes for this particularly vulnerable group of patients admitted to a paediatric ICU. RESULTS: Fifty-five patients were admitted a total of 66 times to the ICU during the study period. The mortality rate of this group was 23% compared with an overall ICU mortality rate of 5%. 11/15 patients who died had an underlying haematological malignancy. Twenty-eight percent of children with organism-identified sepsis died. CONCLUSIONS: While mortality rates for paediatric oncology patients admitted to a ICU have improved, they are still substantial. Those with a haematological malignancy or admitted with sepsis are most at risk.

Cytomegalovirus infection in paediatric haemopoietic stem cell transplantation.

A retrospective audit of CMV infection was undertaken to determine prevalence and outcome in the national paediatric Haemopoietic Stem Cell Transplant (HSCT) unit, with particular reference to surveillance and treatment. All patients undergoing HSCT (125 allogeneic, 50 autologous) from January 1994 to December 2004 were included. Nine underwent a second transplant for graft failure or disease recurrence. Of 134 allogeneic transplants performed, 62 were unrelated. Shell vial cultures of throat swabs and urine, and blood samples for pp65 antigenemia +/- PCR were tested weekly for a mean of 147 days post transplant. CMV negative blood products and filters were used in all. 11 rec+/donor-, 12rec-/donor+ and 10rec+/donor+ transplants were performed. All received prophylactic acyclovir, IVIG was prescribed for all but CMV -/- transplants. Initial detection of CMV was urine in 5 cases, four of whom developed antigenemia. Of ten patients who developed antigenemia, nine were treated with ganciclovir +/- foscarnet and two of these patients developed CMV pneumonitis and died. The current policy of strict surveillance, matching donor and recipient CMV status, use of CMV negative blood products and filters and pre-emptive therapy appears to be effective in controlling CMV disease/infection in the peritransplant period.

The dental management of five paediatric patients with a history of acute intermittent porphyria.

BACKGROUND: Acute Intermittent Porphyria (AIP) is a rare autosomal dominant metabolic disorder resulting from partial deficiency of porphobobilinogen deaminase, the third enzyme of the haem synthetic pathway. Patients with AIP may be vulnerable to acute neurovisceral attacks if exposed to certain drugs, including some drugs used in dental practice. CASE REPORTS: This article outlines the dental management of 5 children with a diagnosis of latent AIP or a family history of AIP. The local analgesic agent used in all cases was bupivacaine or levobupivacaine. Nitrous oxide and oxygen inhalation sedation was used in 2 cases and general anaesthesia, using propofol, isoflurane with nitrous oxide and oxygen, was used in another case. The dental treatment undertaken included restorations, endodontics and extractions. CONCLUSION: Dental treatment using bupivacaine or levobupivacaine as local analgesic agents was successfully and safely provided for 5 children with a diagnosis of latent AIP or a family history of AIP.

Breaking bad news--parents' experience of learning that their child has leukaemia.

This study aimed to seek parents' experiences of how they learned their child had leukaemia and therefore identify ways of improving this process. To achieve this task a questionnaire was designed to ask parents about specific elements of the initial interview and give them opportunity to add their thoughts and feelings on the subject. All children with a diagnosis of leukaemia over an eighteen-year period were identified and parents of those children still alive were invited to partake in the study. 49 out of 50 families agreed to participate of which 35 (72%) returned completed questionnaires. The majority 29 (83%) expressed overall satisfaction. Their replies confirmed some findings of previous studies, and also offered some new insights. Examples of new findings or expansion on previous findings include observations on the presence of young children at the initial interview; the importance of the language used in conveying the diagnosis and prognostic information, and a preference for actuarial terms when discussing prognosis. Telling parents their child has leukaemia is a challenging and important task. The experience of parents gives us valuable insights into our own communication skills and highlights areas of possible improvement in this difficult area.

Wilms' tumor gene 1 (WT1) expression in childhood acute lymphoblastic leukemia: a wide range of WT1 expression levels, its impact on prognosis and minimal residual disease monitoring.

Wilms' tumor gene 1 (WT1) is overexpressed in the majority (70-90%) of acute leukemias and has been identified as an independent adverse prognostic factor, a convenient minimal residual disease (MRD) marker and potential therapeutic target in acute leukemia. We examined WT1 expression patterns in childhood acute lymphoblastic leukemia (ALL), where its clinical implication remains unclear. Using a real-time quantitative PCR designed according to Europe Against Cancer Program recommendations, we evaluated WT1 expression in 125 consecutively enrolled patients with childhood ALL (106 BCP-ALL, 19 T-ALL) and compared it with physiologic WT1 expression in normal and regenerating bone marrow (BM). In childhood B-cell precursor (BCP)-ALL, we detected a wide range of WT1 levels (5 logs) with a median WT1 expression close to that of normal BM. WT1 expression in childhood T-ALL was significantly higher than in BCP-ALL (P<0.001). Patients with MLL-AF4 translocation showed high WT1 overexpression (P<0.01) compared to patients with other or no chromosomal aberrations. Older children (> or =10 years) expressed higher WT1 levels than children under 10 years of age (P<0.001), while there was no difference in WT1 expression in patients with peripheral blood leukocyte count (WBC) > or =50 x 10(9)/l and lower. Analysis of relapsed cases (14/125) indicated that an abnormal increase or decrease in WT1 expression was associated with a significantly increased risk of relapse (P=0.0006), and this prognostic impact of WT1 was independent of other main risk factors (P=0.0012). In summary, our study suggests that WT1 expression in childhood ALL is very variable and much lower than in AML or adult ALL. WT1, thus, will not be a useful marker for MRD detection in childhood ALL, however, it does represent a potential independent risk factor in childhood ALL. Interestingly, a proportion of childhood ALL patients express WT1 at levels below the normal physiological BM WT1 expression, and this reduced WT1 expression appears to be associated with a higher risk of relapse.

Outcome of bone marrow transplantation in acquired and inherited aplastic anaemia in the Republic of Ireland.

BACKGROUND: Severe Aplastic Anaemia (SAA) and Fanconi Anaemia (FA) are rare haematological disorders characterised by pancytopenia and bone marrow hypoplasia. AIMS: We performed a retrospective study of all patients who underwent BMT for SAA and FA at St James's Hospital, Dublin, and at OLHSC, Crumlin, between 1985 and 2002. METHODS: The medical records of 63 patients, 50 with acquired SAA and 13 with FA, were reviewed. RESULTS: The median age at the time of transplant was 14 years (range 3-43 years). The actuarial survival (OS) (n = 63) was 76% at 17 years. The transplant related mortality (TRM) was 22% (n = 14). The most common cause of death was infection (46%). The survival was significantly better in patients receiving their transplant after 1995 (p = 0.002). Outcome was superior in those receiving less than 20 red cell transfusions prior to transplant: OS 91% (< 20 Units) versus 62% (> or = 20 Units). CONCLUSIONS: These national results are comparable to those of published international series and support the use of BMT in the treatment of SAA and FA. The known adverse effect of prior transfusion was confirmed.

Management of a large bronchial haemangioma in an infant.

Haemangiomas are the most common soft tissue tumor of infancy. Despite the benign and trivial nature of most cutaneous haemangiomas, airway haemangiomas are rare but potentially life threatening. We report the case of a 9-week-old infant with a left main stem bronchial haemangioma. This was successfully treated with the oral corticosteroids. We discuss the current available treatments for haemangiomas and highlight that treatment should be specific to each individual case.

Potentiation of vincristine toxicity by itraconazole in children with lymphoid malignancies.

UNLABELLED: Eight consecutive paediatric patients with acute lymphoblastic leukaemia (ALL) (n = 7) and T-cell non-Hodgkin's lymphoma (NHL) (n = 1) presenting within a 5-wk interval were started on a standard induction protocol which included weekly treatment with vincristine for 4 wk. Itraconazole was commenced as antifungal prophylaxis, 1-21 d after the first injection of vincristine. Within 2 to 4 wk, enhanced vincristine neurotoxicity was noted in all patients, abdominal cramps and constipation occurred most frequently, and one patient developed a bowel perforation associated with paralytic ileus. Hyponatraemia associated with SIADH was observed in three patients and four patients developed seizures. An additional patient with B cell NHL developed seizures 5 d after an injection of vincristine. Recovery was complete in all patients and ranged from 2 d to 15 wk. CONCLUSION: The extent and consistency of adverse effects documented in this study support the recommendation that concurrent administration of vincristine and itraconazole should be avoided.