Publications by authors named "Mary Taj"

27 Publications

  • Page 1 of 1

Risk of thyroid disorders in adult and childhood Hodgkin lymphoma survivors 40 years after treatment.

Leuk Lymphoma 2021 Nov 5:1-11. Epub 2021 Nov 5.

Department of Epidemiology, The Institute of Cancer Research, London, UK.

Thyroid abnormalities are well reported following childhood treatment for Hodgkin Lymphoma (HL). Limited information exists for adult patients and after modern treatments. We analyzed risks of thyroid disorders in 237 female participants treated at the Royal Marsden Hospital 1970-2015. Multivariable analyses of risk according to treatment and time-related factors, survival analyses, and Cox regression modeling were undertaken. Overall, 33.8% of patients reported thyroid disorders (hypothyroidism 30.0% and thyroid nodules 6.8%). Cumulative prevalence was 42.9% by 40 years follow-up. Risks were greatest after supradiaphragmatic radiotherapy (RR = 5.0,  < 0.001), and increasing dose (RR = 1.03/Gy,  < 0.001). There was no association with a chemotherapy agent. Risks of thyroid disease were as raised following adult as childhood treatment. There was no trend in risk by decade of supradiaphragmatic radiotherapy treatment. Risks of thyroid disease after supradiaphragmatic radiotherapy are as great after adult as childhood treatment and persist after more recent treatment periods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2021.1999445DOI Listing
November 2021

Genomic abnormalities of TP53 define distinct risk groups of paediatric B-cell non-Hodgkin lymphoma.

Leukemia 2021 Oct 21. Epub 2021 Oct 21.

School of Health & Life Sciences, Teesside University, Middlesbrough, UK.

Children with B-cell non-Hodgkin lymphoma (B-NHL) have an excellent chance of survival, however, current clinical risk stratification places as many as half of patients in a high-risk group receiving very intensive chemo-immunotherapy. TP53 alterations are associated with adverse outcome in many malignancies; however, whilst common in paediatric B-NHL, their utility as a risk classifier is unknown. We evaluated the clinical significance of TP53 abnormalities (mutations, deletion and/or copy number neutral loss of heterozygosity) in a large UK paediatric B-NHL cohort and determined their impact on survival. TP53 abnormalities were present in 54.7% of cases and were independently associated with a significantly inferior survival compared to those without a TP53 abnormality (PFS 70.0% vs 100%, p < 0.001, OS 78.0% vs 100%, p = 0.002). Moreover, amongst patients clinically defined as high-risk (stage III with high LDH or stage IV), those without a TP53 abnormality have superior survival compared to those with TP53 abnormalities (PFS 100% vs 55.6%, p = 0.005, OS 100% vs 66.7%, p = 0.019). Biallelic TP53 abnormalities were either maintained from the presentation or acquired at progression in all paired diagnosis/progression Burkitt lymphoma cases. TP53 abnormalities thus define clinical risk groups within paediatric B-NHL and offer a novel molecular risk stratifier, allowing more personalised treatment protocols.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-021-01444-6DOI Listing
October 2021

Prognostic value of Oncogenetic mutations in pediatric T Acute Lymphoblastic Leukemia: a comparison of UKALL2003 and FRALLE2000T protocols.

Leukemia 2022 Jan 28;36(1):263-266. Epub 2021 Jun 28.

Laboratory of Onco-Hematology, AP-HP Hôpital Necker-Enfants Malades, Université de Paris and Institut Necker-Enfants Malades, Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-021-01334-xDOI Listing
January 2022

Treatment and Outcome Analysis of 639 Relapsed Non-Hodgkin Lymphomas in Children and Adolescents and Resulting Treatment Recommendations.

Cancers (Basel) 2021 Apr 25;13(9). Epub 2021 Apr 25.

Department of Pediatric Hematology, Oncology and BMT, University Hospital Muenster, 48149 Münster, Germany.

Despite poor survival, controversies remain in the treatment for refractory or relapsed pediatric non-Hodgkin lymphoma (r/r NHL). The current project aimed to collect international experience on the re-induction treatment of r/r NHL, hematopoietic stem cell transplantation (HSCT), risk factors associated with outcome, and to suggest treatment recommendations. Inclusion criteria were (i) refractory disease, disease progression or relapse of any NHL subtype except anaplastic large cell lymphoma, (ii) age < 18 years at initial diagnosis, (iii) diagnosis in/after January 2000. Data from 639 eligible patients were evaluable. The eight-year probability of overall survival was 34 ± 2% with highly significant differences according to NHL subtypes: 28 ± 3% for 254 Burkitt lymphoma/leukemia, 50 ± 6% for 98 diffuse large B-cell lymphomas, 57 ± 8% for 41 primary mediastinal large B-cell lymphomas, 27 ± 3% for 177 T-lymphoblastic lymphomas, 52 ± 10% for 34 precursor-B-cell lymphoblastic lymphomas and 30 ± 9% for 35 patients with rare NHL subtypes. Subtype-specific factors associated with survival and treatment recommendations are suggested. There were no survivors without HSCT, except in few very small subgroups. Conclusions: There is an urgent need to further improve survival in r/r NHL. The current study provides the largest real-world series, which underlines the role of HSCT and suggests treatment recommendations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13092075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123268PMC
April 2021

Primary post-transplant lymphoproliferative disorder of the central nervous system: characteristics, management and outcome in 25 paediatric patients.

Br J Haematol 2021 06 25;193(6):1178-1184. Epub 2021 Mar 25.

Department of Pediatric Hematology and Oncology, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.

Primary central nervous system (CNS) post-transplant lymphoproliferative disorder (PTLD) in childhood is rare. Twenty-five patients were retrieved from nine European Intergroup for Childhood Non-Hodgkin's Lymphoma and/or international Berlin-Frankfurt-Münster Study Group members. Types of allografts included kidney (n = 11), liver (n = 4), heart (n = 5), bowel (n = 1) and haematopoietic stem cells (n = 4). Eighteen were male, 16 ≥ 10 years old, 21 had monomorphic disease and 24 solid intracranial tumour masses. Four-year event-free and overall survival rates were 50% ± 10% and 74% ± 9% respectively. This report represents the largest paediatric series of CNS PTLD reported to date, showing favourable survival odds following systemic and intrathecal chemotherapy and rituximab administration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.17398DOI Listing
June 2021

Utility of 18F-FDG-PET/CT in lymphoblastic lymphoma.

Leuk Lymphoma 2021 04 4;62(4):1010-1012. Epub 2020 Dec 4.

Department of Clinical Haematology, University College London Hospitals NHS Foundation Trust, London, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2020.1855346DOI Listing
April 2021

Infection Prevention and Control Measures at the Children Hospital Lahore: A My Child Matters Collaborative Project.

JCO Glob Oncol 2020 10;6:1540-1545

Department of Pediatric Cardiology, The Children's Hospital and Institute of Child Health, Lahore, Pakistan.

Purpose: Infection prevention among children with cancer is a major challenge at Children Hospital Lahore (CHL), a public health care facility in Pakistan with 1,000 new pediatric cancer admissions annually. The objective has been to reduce infections through collaboration between CHL and the St Jude Children's Hospital Global Infectious Disease program via a grant by the Sanofi Espoir foundation through the My Child Matters program. The aim of the current study was to describe the effect of the collaborative improvement strategy on existing infection prevention and control (IPC) standards at CHL.

Materials And Methods: Our work was a prospective before-and-after study to improve IPC standards. We compared the WHO Hand Hygiene Self-Assessment Framework and four modules of the St Jude modified Infection Control Assessment Tool (ICAT) scores over a 3-year period. Our strategy included creating a multidisciplinary team of pediatric oncologists, infectious disease physicians, nurses, a microbiologist, and a data manager; engaging in monthly online IPC mentoring sessions with St Jude Children's Hospital Global Infectious Disease program and My Child Matters mentors; performing daily inpatient health care-associated infection surveillance rounds; and performing regular hand hygiene training and compliance audits.

Results: Baseline needs assessment showed health care-associated infections identified by positive blood cultures as 8.7 infections per 1,000 patient-days. Deficient hand hygiene supplies, health education measures, and bed sharing of neutropenic patients were identified as major challenges. Our hand hygiene facility level, per WHO scores, increased from Inadequate to Intermediate/Consolidation by the end of the 3-year implementation (122 352 WHO Hand Hygiene Self-Assessment Framework scores). The sink:bed and hand sanitizer:bed ratios improved to 1:6 and 1:1, respectively. The ICAT general infection control module increased by 40% (45 78 ICAT scores) and hygiene compliance improved by 20%.

Conclusion: Implementing a collaborative improvement strategy improved IPC standards in our center, which can be easily replicated in other pediatric oncology centers in lower- and middle-income countries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/GO.20.00403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605375PMC
October 2020

Rare non-Hodgkin lymphoma of childhood and adolescence: A consensus diagnostic and therapeutic approach to pediatric-type follicular lymphoma, marginal zone lymphoma, and nonanaplastic peripheral T-cell lymphoma.

Pediatr Blood Cancer 2020 08 26;67(8):e28416. Epub 2020 May 26.

Department of Pediatric Hematology and Oncology, The Queen Silvia's Hospital for Children and Adolescents, University of Gothenburg, Gothenburg, Sweden.

Pediatric-type follicular (PTFL), marginal zone (MZL), and peripheral T-cell lymphoma (PTCL) account each for <2% of childhood non-Hodgkin lymphoma. We present clinical and histopathological features of PTFL, MZL, and few subtypes of PTCL and provide treatment recommendations. For localized PTFL and MZL, watchful waiting after complete resection is the therapy of choice. For PTCL, therapy is subtype-dependent and ranges from a block-like anaplastic large cell lymphoma (ALCL)-derived and, alternatively, leukemia-derived therapy in PTCL not otherwise specified and subcutaneous panniculitis-like T-cell lymphoma to a block-like mature B-NHL-derived or, preferentially, ALCL-derived treatment followed by hematopoietic stem cell transplantation in first remission in hepatosplenic and angioimmunoblastic T-cell lymphoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.28416DOI Listing
August 2020

High-dose etoposide and cyclophosphamide in adults and children with primary refractory and multiply relapsed acute leukaemias: The Royal Marsden experience.

Leuk Res 2019 10 13;85:106217. Epub 2019 Aug 13.

Paediatric Haemato-Oncology Department, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, United Kingdom; Division of Clinical Studies, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, United Kingdom. Electronic address:

Introduction: For patients with primary refractory and relapsed acute leukaemias allogeneic stem cell transplantation is the only hope for cure, but morphological remission is not always achieved after standard salvage regimens. Here we review the experience with high-dose etoposide and cyclophosphamide (HD-Et/Cy) in relapsed/refractory acute leukaemias at the Royal Marsden Hospital.

Patients And Methods: Twenty-three patients (15 adults, 8 children) with refractory/relapsed acute myeloblastic (n = 18; 78%), lymphoblastic (n = 4; 17%) or biphenotypic (n = 1; 4%) leukaemia who had failed to respond to at least one previous line of chemotherapy received HD-Et/Cy at our institution between 2006 and 2015.

Results: Overall response rate was 21.7% (95%CI 4.0-40.0). Median overall survival was 14.8 months (95%CI 9.1-49.1). Eight (35%) patients (7 AML, 1 biphenotypic leukaemia) proceeded to allogeneic transplant after one cycle of HD-Et/Cy: four of them (50%; 3 adults, 1 child) in complete remission and another four children (50%) with aplastic bone marrow with scattered blasts. Among the transplant recipients, three with AML (38%), ie. one adult (responder) and two children with aplastic bone marrow with scattered blasts, became long-term survivors 9.8, 4.4 and 2.5 years post-HD-Et/Cy, respectively. Toxicity profile was comparable to similar regimens with no treatment-related deaths. The most common grade 3-4 toxicity was febrile neutropenia (96%).

Conclusions: HD-Et/Cy can salvage patients with refractory/relapsed AML who remain candidates for allogeneic stem cell transplantation after failure of standard salvage regimens and do not have access to clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.leukres.2019.106217DOI Listing
October 2019

Preliminary experience on the use of PET/CT in the management of pediatric post-transplant lymphoproliferative disorder.

Pediatr Blood Cancer 2017 Dec 14;64(12). Epub 2017 Jun 14.

Pediatric Oncology, The Royal Marsden Hospital, Sutton, UK.

Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication following prolonged immunosuppression. Contrary to other lymphomas, there is no standardized imaging approach to assess PTLD either at staging or for response to therapy. Positron emission tomography/computed tomography (PET/CT) is an imaging modality that has proven to be useful in lymphoma. However, there is still limited data concerning its use in pediatric PTLD. Our study evaluates the use of PET/CT in pediatric PTLD at our institution.

Methods: To assess the role of PET/CT in pediatric PTLD, we reviewed the pediatric patients with PTLD who had undergone PET/CT at our institution between 2000 and 2016.

Results: Nine patients were identified. Six had PET/CT at diagnosis. All lesions seen on CT were identified with PET/CT. Fourteen PET/CTs were done during treatment. Eight PET/CTs were negative, including three where CT showed areas of uncertain significance. In these cases, PET/CT helped us to stop treatment and the patients remain in remission after a long follow-up (mean 74.3 months; range 12.4-180.9 months). PET/CT revealed additional disease in two cases, therefore treatment was intensified. Six biopsies and close follow-up was done to confirm PET/CT results. In one case, PET/CT did not identify central nervous system involvement demonstrated on magnetic resonance imaging.

Conclusion: PET/CT may have an important role in the staging and follow-up of pediatric PTLD. In our cohort, PET/CT was helpful in staging and assessing treatment response and in clarifying equivocal findings on other imaging modalities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.26685DOI Listing
December 2017

Comparison of Presentation and Outcome in 100 Pediatric Hodgkin Lymphoma Patients Treated at Children Hospital, Lahore, Pakistan and Royal Marsden Hospital, UK.

J Coll Physicians Surg Pak 2016 Nov;26(11):904-907

Department of Paediatrics, Lahore General Hospital and PGMI, Lahore, Pakistan.

Objective: To compare differences in demographics and outcomes in childhood Hodgkin lymphoma (HL) presenting at the Children's Hospital Lahore (CHL), and Royal Marsden Hospital (RMH), UK.

Study Design: An observational comparative study.

Place And Duration Of Study: From January 2011 to February 2012 at CH, Lahore and from October 2008 to February 2012 at RMH, UK.

Methodology: Consecutive HL patients (50 from each hospital) were inducted. Data regarding age, gender, staging, histopathology and outcome were analysed. Clinical and pathological staging done according to Ann-Arbor and World Health Organization classification. Treatment duration was 6-8 months. They were followed for 6 months post-treatment. Frequencies of variables were noted and compared. Chi-square test was used for determining significance.

Results: Patients from Children's Hospital, Lahore were younger (mean 7.9 years) with male predominance (n=42, 84%). Histopathology showed Mixed Cellularity (MC) in 32 (64%), Nodular Sclerosis (NS) in 5 (10%), Lymphocyte Rich in 4 (8%) and lymphocyte depleted in 1 (2%), nodular lymphocyte predominant (NLP) in 1 (2%) each. Majority presented in stage IV (n=25,50%), or stage III (n=20,40%). Constitutional B symptoms were present in 37 (74%). Bone marrow involvement observed in 23 (46%). Remission was achieved in 42 (84%) patients; 2 (4%) relapsed, 4 (8%) expired and 2 (4%) left against medical advice. In contrast, RMH patients were older (mean 11.8 years.) and 30 (60%) were males. NS (n=40,80%) and NLP (n=6,12%) types were predominant. Two (4%) patients were in stage I, 27 (54%) in stage II, 12 (24%) in stage III and 9 (18%) presented in stage IV. Fourteen (28%) had B-symptoms. None had bone marrow disease. Event free survival was 46 (92%). Four (8%) patients relapsed. Three responded to second line therapy and one relapsed postautologous transplant.

Conclusion: Significant differences were observed in age at presentation, stage, histopathology and extent of bone marrow involvement between the groups. Of interest is the bone marrow involvement in stage IV patients in Pakistan. Delayed diagnosis account for advanced stage but difference in pathological subtype needs further study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/2474DOI Listing
November 2016

Use of volumetric-modulated arc therapy for treatment of Hodgkin lymphoma.

Med Dosim 2013 7;38(4):372-5. Epub 2013 Jun 7.

Joint Department of Physics, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK. Electronic address:

To evaluate volumetric-modulated arc therapy (VMAT) for treatment of Hodgkin lymphoma (HL) in patients where conventional radiotherapy was not deliverable. A planning computed tomography (CT) scan was acquired for a twelve-year-old boy with Stage IIIB nodular sclerosing HL postchemotherapy with positive positron emission tomography scan. VMAT was used for Phase 1 (19.8Gy in 11 fractions) and Phase 2 (10.8Gy in 6 fractions) treatment plans. Single anticlockwise arc plans were constructed using SmartArc (Philips Radiation Oncology Systems, Fitchburg, WI) with control points spaced at 4°. The inverse-planning objectives were to uniformly irradiate the planning target volume (PTV) with the prescription dose while keeping the volume of lung receiving greater than 20Gy (V20Gy) to less than 30% and minimize the dose to the other adjacent organs at risk (OAR). Pretreatment verification was conducted and the treatment delivery was on an MLCi Synergy linear accelerator (Elekta Ltd, Crawley, UK). The planning results were retrospectively confirmed in a further 4 patients using a single PTV with a prescribed dose of 19.8Gy in 11 fractions. Acceptable dose coverage and homogeneity were achieved for both Phase 1 and 2 plans while keeping the lung V20Gy at 22.5% for the composite plan. The beam-on times for Phase 1 and Phase 2 plans were 109 and 200 seconds, respectively, and the total monitor units were 337.2MU and 292.5MU, respectively. The percentage of measured dose points within 3% and 3mm for Phase 1 and Phase 2 were 92% and 98%, respectively. Both plans were delivered successfully. The retrospective planning study showed that VMAT improved PTV dose uniformity and reduced the irradiated volume of heart and lung, although the volume of lung irradiated to low doses increased. Two-phased VMAT offers an attractive option for large volume sites, such as HL, giving a high level of target coverage and significant OAR sparing together with efficient delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.meddos.2013.04.004DOI Listing
August 2014

Outcome of childhood relapsed or refractory mature B-cell non-Hodgkin lymphoma and acute lymphoblastic leukemia.

Leuk Lymphoma 2012 Oct 23;53(10):1882-8. Epub 2012 Apr 23.

Department of Paediatric Haemato-Oncology, Royal Marsden Hospital NHS Foundation Trust, Sutton, Surrey, UK.

Patients with childhood relapsed and refractory mature B-cell non-Hodgkin lymphoma (B-NHL) and acute lymphoblastic leukemia (B-ALL) are rare and have a dismal prognosis. The previous UK national analysis of 26 children over a 7-year period prior to 1996 had highlighted the poor outcome, with only three survivors. This 10-year multicenter study evaluated recent data, since 2000. Of 33 children, nine survived (27.3%), with a median follow-up of 4.3 years. On exclusion of six children treated with palliative intent, the survival was one-third (nine of 27; 33.3%). All patients with primary refractory disease (n = 7) and all except one with early relapse (n = 11) died. Administration of four doses of 375 mg/m(2) of rituximab was associated with a longer survival (p = 0.006). Response to reinduction (p < 0.001) and autologous hematopoietic stem cell transplant (auto-HSCT) (p = 0.003) were significant on multivariate analysis. Patients with a time to relapse of at least 6 months are potentially curable and must be offered intensive treatment with salvage chemotherapy, rituximab and auto-HSCT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/10428194.2012.677534DOI Listing
October 2012

Symptomatic severe hypertriglyceridaemia with asparaginase therapy in acute lymphoblastic leukaemia (ALL) and lymphoblastic lymphoma: is rechallenging safe?

Int J Hematol 2011 Dec 8;94(6):571-5. Epub 2011 Nov 8.

The Royal Marsden Hospital NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, UK.

Severe hyperlipidaemia with asparaginase therapy is rare. We report six cases, four of which developed significant problems with severe hyperlipidaemia during induction therapy for ALL and lymphoblastic lymphoma. The median triglyceride level was 22.3 mmol/L and the median cholesterol level was 12.3 mmol/L. None of the patients showed signs or symptoms of pancreatitis. Three children were re-exposed with Peg asparaginase, and one with Erwinia asparaginase, without recurrence of hyperlipidaemia or other symptoms. These cases highlight the dilemma in managing such rare cases of symptomatic hypertriglyceridaemia secondary to asparaginase and steroid therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12185-011-0966-9DOI Listing
December 2011

Long-term outcome for immune suppression and immune related lymphoproliferative disorder: prospective data from the United Kingdom Children's Leukaemia and Cancer Group registry 1994-2004.

Leuk Lymphoma 2012 May 13;53(5):842-8. Epub 2011 Dec 13.

Royal Marsden Hospital, Sutton, Surrey, UK.

Prospective national registry data on 98 patients were studied to determine the long-term outcome of immune related lymphoproliferative disease (LPD) and define prognostic factors. Seventy-three developed LPD following organ transplant (26 liver, 21 heart, 15 kidney, nine bone marrow [BM], two bowel). Twenty-five had non-transplant related immunosuppression. Age was 1.1-17 years (median 8.6). Fifty-eight patients had lymphomatous, 21 systemic and 17 lymphadenopathic disease. Sixty (73%) were disseminated and 22 (27%) localized. Thirty-three (54%) were monoclonal. Seventy-three (83%) were Epstein-Barr virus (EBV) positive. Median follow-up was 7.6 years. LPD developed earlier after liver and BM as compared to heart or kidney transplant. Five-year overall survival (OS) was 58%. Prognosis was best after liver and kidney transplant (OS >77%). Mortality was higher following heart (2.5 times) and BM transplant (5 times). Adverse prognostic factors were disseminated or lymphomatous disease and lack of reduction of immunosuppression. With appropriate reduction of immunosuppression, rituximab and low-dose chemotherapy, long-term survival is high.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/10428194.2011.634045DOI Listing
May 2012

Developmental origins and impact of BCR-ABL1 fusion and IKZF1 deletions in monozygotic twins with Ph+ acute lymphoblastic leukemia.

Blood 2011 Nov 29;118(20):5559-64. Epub 2011 Sep 29.

Centro Ricerca Tettamanti, Clinica Pediatrica, Universita di Milano-Bicocca, Ospedale San Gerardo, Monza, Italy.

The timing and developmental sequence of events for BCR-ABL1(+) acute lymphoblastic leukemia (ALL), usually associated with IKAROS (IKZF1) deletions, are unknown. We assessed the status of BCR-ABL1 and IKZF1 genes in 2 pairs of monozygotic twins, one pair concordant, the other discordant for Philadelphia chromosome positive (Ph(+)) ALL. The twin pair concordant for ALL shared identical BCR-ABL1 genomic sequence indicative of monoclonal, in utero origin. One twin had IKZF1 deletion and died after transplantation. The other twin had hyperdiploidy, no IKZF1 deletion, and is still in remission 8 years after transplantation. In the twin pair discordant for ALL, neonatal blood spots from both twins harbored the same clonotypic BCR-ABL1 sequence. Low level BCR-ABL1(+) cells were present in the healthy co-twin but lacked the IKZF1 deletion present in the other twin's leukemic cells. The twin with ALL relapsed and died after transplantation. The co-twin remains healthy and leukemia free. These data show that in childhood Ph(+) ALL, BCR-ABL1 gene fusion can be a prenatal and possibly initiating genetic event. In the absence of additional, secondary changes, the leukemic clone remains clinically silent. IKZF1 is a secondary and probable postnatal mutation in these cases, and as a recurrent but alternative copy number change is associated with poor prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2011-07-366542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217357PMC
November 2011

Prognosis of patients with t(8;16)(p11;p13) acute myeloid leukemia.

Leuk Lymphoma 2012 Feb 23;53(2):338-41. Epub 2011 Sep 23.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/10428194.2011.614703DOI Listing
February 2012

Clinical profile and outcome of urotheliotropic viral haemorrhagic cystitis following haematopoietic stem cell transplantation: a 7-year tertiary centre analysis.

Hematology 2011 Jul;16(4):213-20

Department of Haematology, Royal Marsden Hospital NHS Foundation Trust, Sutton, Surrey, UK.

Viral haemorrhagic cystitis (HC) is a significant complication after haematopoietic stem cell transplantation (HSCT), with a potential for major morbidity. The aim of this 7-year analysis of 1160 HSCT patients was to evaluate risk factors for the incidence, severity, toxicity of therapy, clinical course, and outcome of this condition. The overall incidence of HC was 5·8%, with most cases occurring after allogeneic HSCT. Unrelated donors (P = 0·001), non-peripheral blood stem cell source (P = 0·005), myeloablative conditioning (P<0·001), use of alemtuzumab in conditioning (P = 0·001), and severe acute graft versus host disease (P<0·001) were independent risk factors for an increased incidence of HC post-allogeneic transplant on multivariate analysis. Severe forms of HC were associated with grades II-IV acute graft versus host disease and a longer duration of haematuria. Contrary to previous studies which were carried out on smaller patient populations, busulphan, cyclophosphamide, anti-thymocyte globulin, and total body irradiation were not found to independently increase the risk of viral HC, unless used in a myeloablative combination. Neither duration of viriuria nor peak viral load in urine influenced the severity of HC on multivariate analysis. Severe HC contributed to the deaths of two patients. Overall survival was not statistically different between patient subgroups with non-severe and severe HC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1179/102453311X13025568941763DOI Listing
July 2011

Early UK experience in the use of clofarabine in the treatment of relapsed and refractory paediatric acute lymphoblastic leukaemia.

Br J Haematol 2011 Aug 21;154(4):482-5. Epub 2011 Jun 21.

Department of Haematology, Birmingham Children's Hospital, Birmingham, UK.

Clofarabine is a second-generation purine nucleoside analogue, which has shown promising activity in relapsed and refractory paediatric acute lymphoblastic leukaemia (ALL). This report summarizes the early United Kingdom experience of clofarabine for the treatment of paediatric ALL in 23 patients, outside of the context of a clinical trial. Our results demonstrated that clofarabine-based chemotherapy regimes were effective and well-tolerated in this heavily pre-treated group, with an overall response rate of 67% when used in combination regimes. Responses were seen in both B and T cell disease and in patients with adverse cytogenetics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1365-2141.2011.08752.xDOI Listing
August 2011

Immunogenicity of pandemic (H1N1) 2009 vaccine in children with cancer in the United Kingdom.

Clin Infect Dis 2010 Dec 10;51(12):e95-104. Epub 2010 Nov 10.

Dept of Child Health, St George's, University of London, London, England.

Background: Children with cancer have an increased susceptibility to influenza infection. The objective of this study was to assess the immunogenicity of pandemic (H1N1) 2009 vaccine in children with cancer.

Methods: Children were recruited from the Royal Marsden Hospital, England, during November 2009. The vaccination schedule consisted of 2 doses of an AS03(B)-adjuvanted vaccine given at days 0 and 21. Serological analysis was performed on blood samples obtained at day 0 and day 42. The primary immunological end point was the seroconversion rate, which was defined as the proportion of subjects with an individual 4-fold increase in hemagglutination inhibition titer and a postvaccination hemagglutination inhibition titer ≥1:32.

Results: Fifty-four children with a median age of 6.3 years (range, 1.4-16.6 years) were vaccinated and had samples taken for serological analysis. Twenty-four (44.4%) of 54 children demonstrated seroconversion. Seroconversion rates were 33.3% (9 of 27) among children with acute lymphoblastic leukemia, 36.4% (4 of 11) among those with lymphoma or other leukemias, 66.7% (6 of 9) among those with brain tumors, and 71.4% (5 of 7) among those with other solid tumors. Seroconversion occurred in 4 (28.6%) of 14 children receiving acute lymphoblastic leukemia maintenance therapy. Univariate analysis showed significantly higher responses among children with solid tumors, compared with those with hematological malignancies (11 [68.8%] of 16 vs 13 [34.2%] of 38; P = .03), and among those not receiving treatment, compared with those receiving treatment (7 [87.5%] of 8 vs 17 [37.0%] of 46; P = .02). Multivariable analysis showed that age, cancer type, and lymphopenia did not influence seroconversion rates.

Conclusion: These data suggest that this AS03(B)-adjuvanted pandemic (H1N1) 2009 vaccine can induce limited but useful protective immune responses in children with cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1086/657403DOI Listing
December 2010

Efficacy and tolerability of high-dose methotrexate in central nervous system positive or relapsed lymphoproliferative disease following liver transplant in children.

Br J Haematol 2008 Jan;140(2):191-6

Department of Paediatric Oncology, Royal Marsden Hospital, Sutton, Surrey, UK.

Childhood post-transplant lymphoproliferative disease (PTLD) is a heterogeneous condition in which treatment varies, from the reduction of immunosuppression to moderately intensive chemotherapy. While low-dose chemotherapy/rituximab has been found to be effective, moderately intensive chemotherapy is required for patients who relapse, have classic non-Hodgkin lymphoma or have fulminant PTLD. Methotrexate (Mtx) is highly effective in lymphomas and crosses the blood-brain barrier. However, there are no data in the literature regarding its safety in post-liver transplant patients. We describe four cases of high-grade lymphomas (three diffuse large B cell and one T-cell lymphoblastic), post-liver transplant, for which chemotherapy including high-dose Mtx (HDMTX) was the treatment of choice. In total, 20 doses of HDMTX (1-5 g/m(2)) were given. The treatment was well tolerated and all four patients had a good response. One case of central nervous system (CNS) diffuse large B-cell lymphoma was treated with HDMTX alone. We conclude that, in the absence of significant organ damage, HDMTX can safely be given to liver transplant patients, but should only be administered in specialist oncology units. Proof of effectiveness as a single agent in CNS lymphoma needs further studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1365-2141.2007.06896.xDOI Listing
January 2008

Single agent efficacy of rituximab in childhood immunosuppression related lymphoproliferative disease: a United Kingdom Children's Cancer Study Group (UKCCSG) retrospective review.

Leuk Lymphoma 2006 Dec;47(12):2584-9

Royal Marsden Hospital, Sutton, Surrey, UK.

Survival in childhood lymphoproliferative disease (LPD) remains poor, particularly in non-transplant patients. The anti-CD20 antibody rituximab shows promise but data in children is scant. A retrospective study of 22 (aged 11 months to 18 years) children treated with rituximab is presented. Two had primary immunodeficiency, two had prolonged immunosuppression and 18 had post-transplant LPD (eight bone marrow, five liver, four heart, one kidney). Nine patients had multi-organ involvement and 13 single site disease. Seventeen out of 22 had rituximab alone. In 16, a dose of 375 mg/m2 i.v. weekly was used (less in one patient due to renal dysfunction). Twelve patients received four courses and ten patients received one to three courses. Fever was the main side-effect in four. Eight (47%) had single agent response; four complete and four partial. All had other treatment prior to rituximab. Median follow-up was 35 months (range 22 - 47 months). In childhood LPD unresponsive to standard treatment, rituximab showed single agent response and requires further evaluation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428190600908349DOI Listing
December 2006
-->