Isolated Extramedullary Relapse in the Gastrointestinal Mucosa of a Patient with T cell Lymphoblastic Lymphoma

An unusual case of extramedullary relapse in a known case of T cell lymphoblastic lymphoma is presented here. The patient is a 24-year-old girl diagnosed with T cell lymphoblastic lymphoma in June 2020. The patient th showed extramedullary relapse in the gastrointestinal mucosa without bone marrow recurrence whilst on the 6 month of BFM (Berlin Frankfurt Munster) -90 maintenance. Isolated gastrointestinal infiltrate is unusual at presentation or relapse of T cell lymphoblastic lymphoma. While on BFM-90 maintenance, she presented with multiple vomiting and abdominal pain episodes. Upper gastrointestinal scopy revealed multiple gastric ulcers, with morphology and immune-phenotyping identical to her initial T cell lymphoblastic lymphoma. We could not find evidence of leukaemic activity in the blood, cerebrospinal fluid or bone marrow. Several types of leukemic infiltrates have been recognised at post-mortem examination; the fact that makes our case is unique is T cell lymphoblastic lymphoma presenting as an isolated malignant ulcer, which to the best of our knowledge, has not been reported. We conclude that relapsed T cell lymphoblastic lymphoma may present with gastrointestinal infiltration. Further investigations are warranted to establish the same

Implications of undernutrition in children with acute lymphoblastic leukaemia during induction therapy – experience from a developing country

@#Introduction: Undernutrition is an important prognostic factor in children with acute lymphoblastic leukaemia (ALL) and higher incidences of mortality are reported during induction remission in severely undernourished children. This study was conducted to assess the prevalence and implications of malnutrition among ALL children during induction therapy. Methods: All children ≤18 years diagnosed and treated for ALL at our institution, between June 2010 to July 2016 were included in this retrospective cohort study. Nutrition was assessed by body mass index-forage z-scores calculated using World Health Organization’s Anthro (<5 years) and Anthro-Plus Software (≥5 years). Children with a z-score of <-2 standard deviation (SD) were classified as undernourished. All events and outcomes were compared between undernourished and adequately nourished children. Results: A total of 72 children were included in this study. Nineteen (26.4%) were undernourished at the time of diagnosis. Twenty-eight (38.8%) children had significant weight loss. Sixty-seven of them attained remissions by the end of induction chemotherapy. Five children who died had significant weight loss. Children with significant weight loss during induction phase had a higher risk of developing complications such as febrile neutropenia, pneumonia, mucositis, and drug interruptions. Those with a deteriorating nutritional status had a higher chance of poor treatment outcome (p=0.05, CI=95%). Conclusion: It is important to assess and monitor the nutrition status of children and timely nutritional intervention is essential. A simple, cost effective nutritional intervention that will decrease morbidity and mortality associated with the disease must be devised.

The Role of FLT3-ITD and CCAAT-Enhancer-Binding Protein α Mutations on Prognosis of Acute Lymphoblastic Leukaemia in Turkish Patients

ABSTRACT Background: Acute lymphoblastic leukaemia (ALL) is the most common malignancy in childhood. Although some prognostic factors have been defined to date, the estimation of prognosis is currently not perfect. Previous studies had shown an association of FLT3 with poor prognosis and CCAAT-enhancer-binding protein α (CEBPA) mutation with the development of acute myeloid leukaemia (AML). Here, we aimed to evaluate the prognostic value of FLT3-ITD and CEBPA mutations in ALL. Methods: Sixty-one patients with ALL were included in the study. The patients were divided into three risk groups according to BFM risk classification. All of the patients were examined for FLT3-ITD mutations and 45 of them for CEBPA mutations. Mutation positive and negative patients were compared in terms of their risk groups, translocations and cell lineage. The clinical courses of the patients were appraised. Results: FLT3-ITD mutation was detected in 3 of the 61 patients, and CEBPA mutations were detected in 11 of the 45 patients. The incidence of established prognostic indicators including BFM risk classification, t(9; 22); BCR-ABL, t(1; 19); E2A-PBX1, t(12; 21); TEL-AML1, t(4; 11); MLL-AF4 were similar between FLT3-ITD and CEBPA positive and negative patients. A patient with an FLT3-ITD mutation was very susceptible to pancytopenia after maintenance treatment and two other patients with FLT3-ITD mutations were more prone to febrile neutropenia. Conclusion: Our results suggested that CEBPA or FLT3-ITD mutations might not be related to ALL prognosis in the sampled Turkish patients. However, FLT3-ITD mutation might have an influence on the response of bone marrow to chemotherapy.

Role of MRI in the Detection and Monitoring of Lower Limb Osteonecrosis after Chemotherapy in Pediatric Patients with Acute Lymphoblastic Leukaemia

Background:Magnetic resonance imaging (MRI) is the technique that demonstrated the highest sensitivity and specificity in the early diagnosis of osteonecrosis. It allows detecting initial typical signal intensity alterations of the bone marrow when other examinations showed nonspecific findings or even no alterations at all. The aim of this study is to assess the role of magnetic resonance imaging in detection and monitoring osteonecrotic lesions in pediatric patient with acute lymphoblastic leukemia after chemotherapy.Materials and Methods: This prospective study was performed on 30 pediatric patients ranged from 4 to 18 years with acute lymphoblastic leukemia on chemotherapy or after 3months from ending chemotherapy with symptoms suspicious for osteonecrosis (i.e., articular pain). All patients were explained about the procedure to be done. MRI study of whole lower limbs was done for all patients.Results:In the present study all patients were symptomatic. 24\30 patients (80%) had hip pain, 25\30 patients (83.3%) had knee pain and 8\30 patients (26.7%) had limping. We reported that knee pain was the most common complaint representing 83.3% of patients. 11\30 patients (36.7%) had no MRI findings. 19\30 patients (63.3%) had different positive findings; 4 patients (13.3%) had non -articular osteonecrosis (ON) only with no joint involvement (bone infarction), 2 patients (6.7%) had avascular necrosis of femoral head epiphysis without bone infarction and 13 patients (43.3%) had combined bone infarction and avascular necrosis with Joint involvement. Follow up by MRI was done for all patients (30 patients), 27 patients showed no change in MRI findings, one patient progressed from avascular necrosis of the femoral headepiphysis without deformity to avascular necrosis of the femoral head epiphysis with deformity. The other two patient showed regressive course.Conclusion:We concluded that MRI study is mandatory for early detection and monitoring of lower limb osteonecrosis in pediatric patients with acute lymphoblastic leukemia under or after chemotherapy.The radiologist and clinician must do MRI lower limbs routinely and follow up MRI after 4-6 months to first MRI due to some patients had regressive or progressive findings

A rare case of blood stream infection due to Candida ciferii in an immuno-compromised patient

Invasive infections related to yeast are increasingly observed in immune-compromised patients in hospitals.Fungal infections have increased morbidity and mortality and prolonged hospital stay which can lead to rise in medical care costs. Non-albicans Candida species have been increasingly found as causative agents in human infections with important therapeutic implications. We present a case of a 37-year-old, female patient, known case of B cell Acute Lymphoblastic Leukaemia admitted in a tertiary care hospital in central India for supportive care and chemotherapy. Patient was responding well to chemotherapy. On post induction day 20, she complained of high-grade fever with abdominal pain.Two sets of blood culture were sent to Microbiology Diagnostic Laboratory for diagnosis. She was started on Injection Magnex Forte (Cefoperazone-Sulbactum) empirically.The Gram stain of positive blood culture showed Gram positive budding yeast like cells in all four bottles.The organism was identified as C. ciferrii on Vitek 2 with 95% identification.Antibiotic susceptibility testing showed sensitive to Amphotericin B MIC ?0.25 and voriconazole MIC ?0.12. It was resistant to fluconazole MIC ?64 ?g/ml.

Study of fingerprints in children under 15 years of age with acute lymphoblastic leukaemia

Background: Acute Lymphoblastic leukaemia is a malignant condition resulting due to continuous clonally proliferation of progenitors of lymphoid cells. The objective is to identify the association between dermatoglyphics and acute lymphoblastic leukaemia and to assess the value of dermatoglyphics as a screening tool.Methods: A case-control study was conducted on a total of around 60 subjects below the age of 15, out of which 30 children were already diagnosed and suffering from Acute Lymphoblastic Leukaemia and the other 30 were age and sex matched controls. Fingerprints of 30 affected children were taken through an ink-pad method in both hands, analyzed and compared with controls. Information regarding any significant familial history was obtained.Results: The study suggested with an increased rate of incidence among children of age group 3-4 years and with a male preponderance (63.3%).The findings were found to be statistically significant with an association between whorls and loops among cases and controls with higher frequency of whorls in cases and loops in controls (p value < 0.05), whereas association between whorls, arches and loops, arches was not significant. In quantitative analysis, most of the cases (n=12, 39.6%) had a PII in the range of 16-20 whereas most of the controls (n=22, 72.6%) had it in the range of 11-15, with significant overlapping.Conclusions: The findings are suggestive of association of fingerprint pattern with the patients suffering from Acute Lymphoblastic Leukaemia and therefore they might help in early diagnosis of the condition in high risk children and thus can be helpful as a screening tool.

Perfil neuropsicológico y efectos de la rehabilitación cognitiva en la leucemia linfoblástica aguda: a propósito de un caso / Neuropsychological profile and cognitive rehabilitation training effects on acute lymphoblastic leukaemia: a case study

La Leucemia Linfoblástica Aguda (LLA) infantil es el cáncer pediátrico más frecuente. Actualmente cuenta con un alto porcentaje de supervivencia, pero dichos pacientes presentan secuelas cognitivas secundarias a la enfermedad debidas, principalmente, al tratamiento médico recibido para evitar la recidiva del cáncer. Por lo tanto, resulta necesaria la implementación de programas de rehabilitación cognitiva específicos para este tipo de población. Es por ello que el objetivo del presente estudio fue describir los déficits cognitivos en un varón de 17 años que fue diagnosticado con LLA a los 9 años. Tras la valoración neuropsicológica inicial se desarrolló un programa de rehabilitación cognitiva intensivo durante dos años consecutivos. Realizamos un estudio pre-post en el que administramos el Conners Continuous Performance Test (CPT-II) y la Escala de Inteligencia de Wechsler para niños (WISC-IV). Los resultados, antes de la intervención, mostraron que el paciente manifestaba una menor velocidad de procesamiento y dificultades de atención sostenida y alternante, comprensión verbal y razonamiento perceptivo. Además, también presentó un número considerable de errores perseverativos, signo de dificultades de flexibilidad cognitiva y control inhibitorio. Dichos déficits mejoraron notablemente tras el programa de rehabilitación cognitiva. En conclusión, nuestro estudio pone de manifiesto la necesidad de aplicar programas de rehabilitación cognitiva tempranos para paliar las secuelas cognitivas derivadas de la LLA y de su tratamiento médico, así como mejorar la calidad de vida del paciente, ya que las mejoras cognitivas redundarán en su rendimiento académico y en su funcionamiento cotidiano.

Childhood Acute Lymphoblastic Leukemia (ALL) is the most common pediatric cancer. It currently has a high survival rate, but these patients have cognitive sequelae secondary to the disease, mainly due to the medical treatment received to prevent cancer recurrence. Therefore, it is necessary to implement specific cognitive rehabilitation programs for this type of population. Hence, the main objective of this study was to describe cognitive deficits in a 17-year-old male who was diagnosed with ALL when he was 9 years old. After the initial neuropsychological evaluation, an intensive cognitive rehabilitation program was developed during two consecutive years. We conducted a pre-post study in which we administered the Conners Continuous Performance Test (CPT-II) and the Wechsler Intelligence Scale for Children (WISC-IV). Results, before the intervention, showed that the patient presented a lower processing speed and difficulties of sustained and alternating attention, verbal comprehension and perceptive reasoning; in addition to a large number of perseverative errors, sign of self-monitoring difficulties and inhibitory control. These deficits improved markedly after a program of cognitive rehabilitation. In conclusion, our study highlights the need to apply early cognitive rehabilitation programs to alleviate the cognitive sequelae derived from ALL and its medical treatment. In addition, any improvement in their cognitive capabilities will have a positive impact in their academic performance and quality of life.

Clofarabine: a next-generation deoxyadenosine analogue

Acute lymphoblastic leukaemia (ALL) is the most common of the paediatric leukaemias. It is estimated that the use of modern combination chemotherapy results in long-term remission in nearly 80% of children diagnosed with ALL. Despite therapy advances, approximately 20% of children with ALL, experience leukaemia relapse. Clofarabine (2-chloro-2’-fluoro-2’-deoxy-9-?-D-arabinofuranosyladenine) is a second-generation nucleoside analogue and is structurally related to fludarabine and cladribine which are widely used in the treatment of lymphoproliferative disorders. Clofarabine exhibits greater affinity to deoxycytidine kinase (dCyd kinase) and prolonged retention in leukaemic blasts compared to fludarabine and cladribine. Clofarabine inhibits both DNA polymerases and ribonucleotide reductase (RNR). This results in impaired DNA synthesis through inhibition of DNA elongation as well as depletion of deoxyribonucleotides. Accumulation of clofarabine triphosphate, in the blasts of patients with refractory leukemia has been demonstrated. Prolonged intracellular half-life of 24 hours for clofarabine triphosphate. Clofarabine is indicated for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens.

Low spontaneous apoptosis index at diagnosis predicts a high-risk phenotype in paediatric acute lymphoblastic leukaemia

Background & objectives: Significance of apoptosis as a prognostic marker is less well studied in paediatric acute lymphoblastic leukaemia (ALL) cases. Hence, a prospective study, involving 30 paediatric ALL cases, was done to assess the clinical relevance of in vivo apoptosis. Methods: Peripheral blood mononuclear cells from all patients were subjected to annexin V/propidium iodide staining to detect the degree of apoptosis [apoptotic index (AI)] at day 0 and day 35 post-induction chemotherapy. In addition, Bax and Bcl2 apoptotic protein expressions were studied at day 0 and their relative fluorescence mean intensity (RFMI) ratios were calculated. Results: Mean age of patients was 5.1 years. Of the 30 cases, 21 (70%) were at standard-risk, five (17%) at intermediate and four (13%) at high risk. Majority (83%) were B-ALL. Day 8 absolute blast count was >1000/?l in seven (23%) and <1000/?l in 23 of 30 (77%) cases. Day 35 marrow was M1 in 23 (92%) and M2 in two of 25 (8%) cases. AI at day 0 and day 35 ranged from 0.9 to16.6 per cent and 1.4 to 62.8 per cent with a mean of 5.90 and 19.64 per cent, respectively. The Bax/Bcl2 ratio ranged from 0.2 to 3.5 with a mean of 0.83. The ratio was predominantly anti-apoptotic, i.e. <1 (77%). A significant association was noted between low AI at day 0 and high total leucocyte count (P=0.02), T-cell phenotype (P=0.043) and high-risk as per NCI category (P=0.025). Significant increase (>30%) in day 35 AI was seen in only six cases. Interpretation & conclusions: Our study showed that low AI at day 0 was associated with a high-risk clinical phenotype in paediatric ALL. However, studies on larger group, especially with longer follow up or study of relapse cases, will help draw conclusions regarding apoptosis assessment in paediatric ALL.

La leucemia linfoblástica aguda y modelos animales alternativos para su estudio en Colombia / Alternative animal models for acute lymphoblastic leukaemia studies in Colombia

Resumen El pez cebra es un modelo establecido para el estudio del desarrollo en vertebrados y es especialmente útil para la investigación del proceso de hematopoyesis y las enfermedades asociadas a esta. Los linajes principales, los genes y los procesos de desarrollo con los seres humanos son conservados. En los últimos años, el pez cebra se ha utilizado cada vez más como un modelo para estudiar enfermedades hematopoyéticas humanas, incluyendo la leucemia linfoblástica aguda. Esta revisión evidencia la importancia del estudio de esta enfermedad en Colombia debido a las diferencias de la etiología que presenta este tipo de leucemia en comparación con otros países. Además, describe la aplicación del pez cebra como una herramienta alternativa para investigaciones preclínicas de la leucemia linfoblástica aguda. Este modelo es asequible, facilita la experimentación, su manipulación es relativamente simple y tiene gran versatilidad para estudios moleculares y genéticos del cáncer y está disponible en Colombia.

Abstract The zebrafish is an established model for the study of vertebrate development, and it is specially useful for the research into haematopoiesis and diseases associated with this process. Major lineages, genes, and developmental processes are conserved between zebrafish and humans. Thus it has been increasingly used as a model for a number of haematopoietic human diseases, such as acute lymphoblastic leukaemia. This review highlights the importance of the study of this disease in Colombia, because of the differences in its aetiology compared to other countries. It also describes the application of the zebrafish as an alternative tool for pre-clinical research of acute lymphoblastic leukaemia. This model is affordable, facilitates experimentation and handling, and is extremely versatile for molecular and genetic studies into cancer, and it is now available in Colombia.

Relapse of B-cell acute lymphoblastic leukaemia presenting as right aural polyp with facial and mandibular nerves palsy

A patient presenting with an ear polyp is a common finding in otorhinolaryngology practice. The common causes include chronic otitis media and cholesteatoma. We report an adult female patient with a history of acute leukaemia presenting with chronic otitis media symptoms and right ear polyp. She was subsequently diagnosed as relapse of B-cell acute lymphoblastic leukaemia based on histopathological examination. The presentation may be similar to an inflammatory pathology of the middle ear, making it misleading.

Severe asymptomatic hypophosphataemia in a child with T-acute lymphoblastic leukaemia

Hypophosphataemia is a metabolic disorder that is commonly encountered in critically ill patients.Phosphate has many roles in physiological functions, thus the depletion of serum phosphate could leadto impairment in multiple organ systems, which include the respiratory, cardiovascular, neurologicaland muscular systems and haematological and metabolic functions. Hypophosphataemia is defined asplasma phosphate level below 0.80 mmol per litre (mmol/L) and can be further divided into subgroupsof mild (plasma phosphate of 0.66 to 0.79 mmol/L), moderate (plasma phosphate of 0.32 to 0.65mmol/L) and severe (plasma phosphate of less than 0.32 mmol/L). The causes of hypophosphataemiainclude inadequate phosphate intake, decreased intestinal absorption, gastrointestinal or renal phosphateloss, and redistribution of phosphate into cells. Symptomatic hypophosphataemia associated withhaematological malignancies has been reported infrequently. We report here a case of asymptomaticsevere hypophosphataemia in a child with acute T-cell lymphoblastic leukaemia.A 14-year-old Chinese boy was diagnosed to have acute T cell lymphoblastic leukaemia (ALL).His serum biochemistry results were normal except inorganic phosphate and lactate dehydrogenaselevels. The serum inorganic phosphate level was 0.1mmol/L and the level was low on repeatedanalysis. The child had no symptoms related to low phosphate levels. The possible causes of lowphosphate were ruled out and urine Tmp/GFR was normal. Chemotherapy regime was started andthe serum phosphate levels started to increase. Hypophosphataemia in leukaemia was attributed toshift of phosphorus into leukemic cells and excessive cellular phosphate consumption by rapidlyproliferating cells. Several reports of symptomatic hypophosphataemia in myelogenous andlymphoblastic leukaemia in adults have been reported. To our knowledge this is the first case ofsevere asymptomatic hypophosphataemia in a child with ALL.

Factores pronósticos de remisión en pacientes con leucemia linfoblástica aguda posterior a primer recaída / Prognostic factors of remission in patients with acute lymphoblastic leukemia after a first relapse

Objetivos: Identificar aquellos factores que impactan en la respuesta terapéutica para alcanzar una segunda remisión (2 RC) en pacientes con leucemia aguda linfobl´stica (LAL) en recaída. Métodos: Estudio observacional y analítico anidado en una cohorte retrospectiva de adultos (>18 años) portadores de LAL que fueron atendidos durante 2008-2014 y que interrumpieron el protocolo HGMLAL07 al detectarse recaída e iniciaron otro esquema. Resultados: Se estudiaron 69 pacientes y el 62,3% (n = 43) correspondía a hombres. La media de edad fue de 29 años. Los regímenes terapéuticos empleados fueron: alta intensidad (55,1%) [Hyper-CVAD (n = 34), IDA-Flag (n = 1), mitoxantrona-DARAC (n = 3) ], moderada intensidad (4,3%) [Esquemas de reinducción (n = 3) ] y tratamiento paliativo de baja intensidad con soporte transfusional (40,6%, n = 28). Solo 19 pacientes (27,5%) integraron una 2 RC. La media de supervivencia fue 120 (2- 575) días y el 29% sobrevivió al año de seguimiento. El uso de un segundo régimen intensivo o moderado no brindó ventaja sobre el esquema conservador (prueba log-Rank, p = 0,812). Ninguna variable demostró valor pronóstico sobre la supervivencia a 1 año. La duración de la primera RC (OR 6,78, p = 0,005, 95% IC: 1,7532-26,2803) y recibir un primer tratamiento intensivo (OR 0,22, p = 0,018, 95% IC: 0,0661-0,7813) fueron variables pronósticas de falla terapéutica para alcanzar la 2 RC. Conclusiones: Poseer una primera RC < 1 año fue un factor de riesgo importante para no integrar una 2 RC. No se identificaron factores pronósticos de supervivencia ni superioridad de alguno de los esquemas de rescate empleados.

Aims: To identify those factors that affect therapeutic response to achieve a second remission (2 RC) in patients with acute lymphoblastic leukaemia (ALL) in relapse. Methods: Observational, descriptive and analytical study nested in a retrospective cohort of adults (> 18 years-old) ALL carriers treated during the period from 2008 to 2014 that disrupted the HGMLAL07 protocol when relapse was detected and began another therapeutic scheme. Results: The study included 69 patients, of whom 62.3% (n = 43) were males, and the mean age was 29 years-old. The therapeutic regimens used were: high intensity (55.1%) [Hyper-CVAD (n = 34), IDA-Flag (n = 1), mitoxantrone-DARAC (n = 3) ], moderate intensity (4.3%) [Re-induction schemes (n = 3) ], and palliative treatment of low intensity with transfusion support (40.6%, n = 28).Only 19 patients (27.5%) achieved a 2 RC. The median overall survival was 120 (2-575) days, 29% of patients were alive at one year. Using a high or moderate intensity regime as the rescue scheme gave no advantage over the conservative one (log-rank test, P = .812). None of the variables showed prognostic value of survival at one year. The duration of the first RC (OR 6.78, P = .005, 95% CI; 1.75 -26.28) and receiving high intensity treatment (OR 0.22, P = 018, 95% CI: 0.06 -0.78) were predictors of treatment failure to achieve 2 RC. Conclusions: To achieve a first RC < 1 year was an important risk factor for not achieving a 2 RC. No prognostic factors for survival were identified. None of the schemes used for rescue showed superiority.

Risk factors for traumatic lumbar punctures in children with acute lymphoblastic leukaemia / 实用医学杂志

Objective To investigate the risk factors for traumatic lumbar punctures in children with acute lymphoblastic leukaemia. Methods 132 children with acute lymphoblastic leukemia totally received 2634 lumbar punctures. The basic data on age, sex, body mass index (BMI), platelet count, interval between two punctures, and presence or absence of ultrasound-guided procedure were collected and analyzed. The risk factors for traumatic lumbar puncture were identified by logistic regression. Results The risk for traumatic lumbar puncture was higher in children younger than 1 year, and it was relatively lower in those aged 1 to 10 years. The risk for traumatic lumbar puncture was slightly higher in children with a BMI index of more than 95. The longer the interval between two punctures, the lower the risk. If lumbar puncture was guided under ultrasound or radiographic images, the risk was much smaller. Conclusions Age of younger than 1 year, BMI index of more than 95, shorter interval between two punctures, and direct puncture can increase the risk for traumatic lumbar puncture.

Unusual fungal sepsis of Alternaria alternata in acute lymphoblastic leukaemia in an adult patient.

We report a case of unusual fungal sepsis of Alternaria alternata in a patient of acute lymphoblastic leukaemia in 62‑year‑old male who presented with complaints of ‘off and on’ fever with decreased oral intake. On evaluation, haemogram showed low platelet count and 68% blast cells in peripheral blood. On flow cytometry of peripheral blood, the gated blasts (approximately 55%) highly express CD45, CD10, CD19, CD22 and condition was diagnosed as acute lymphoblastic leukaemia. He was started on standard induction treatment along with supportive therapies. During the course of treatment, two sets of paired blood cultures were sent 48 h apart. All of blood cultures were done on Bac‑T alert 3D system. All of them yielded fungus. The fungus was then grown on Sabouraud’s Dextrose agar media. It was identified as A. alternata. The patient condition worsened and later had cardiac arrest in ICU and could not be revived.

Double Philadelphia chromosome-positive B acute lymphoblastic leukaemia in an elderly patient

A rare case of double Philadelphia chromosome-positive B Acute lymphoblastic Leukaemia (B-ALL) is reported here. A 60-year-old lady presented with one month history of fever, submandibular lymphadenopathy, loss of appetite and weight loss. Physical examination revealed multiple palpable cervical lymph nodes. Blood film showed leucocytosis with 72% blasts. Bone marrow assessment confirmed a diagnosis of B-ALL with presence of double Philadelphia (Ph) chromosomes. As she was very ill, she was initially treated with an attenuated regimen of induction chemotherapy consisting of rituximab, cyclophosphamide, vincristine and prednisolone (R-CVP) along with intrathecal chemotherapy comprising methotrexate, cytarabine and hydrocortisone. Bone marrow examination post-induction chemotherapy showed >5% blasts. She was subsequently re-induced with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) along with intrathecal chemotherapy, following which she went into complete remission. Consolidation chemotherapy consisting of methotrexate, methylprednisolone, cytarabine, intrathecal chemotherapy and imatinib was subsequently administered followed by maintenance chemotherapy consisting of vincristine, prednisolone and imatinib (IDEAMOP). She developed spontaneous bruises and relapsed four months into her maintenance chemotherapy with 90% blasts in the bone marrow which was treated with fludarabine, cytarabine and granulocyte colony stimulating factor (FLAG). Unfortunately she developed neutropenic sepsis which was complicated by invasive lung aspergillosis. Bone marrow examination post-FLAG showed 80% blasts. Despite aggressive antifungal therapy, her lung infection worsened and she finally succumbed to her illness 13 months after the initial diagnosis. We highlight a rare case of elderly B-ALL with double Ph chromosomes which carries a poor prognosis despite aggressive treatment for the disease and its complications.

Increased soluble HLA-DRB1 in B-cell acute lymphoblastic leukaemia

Soluble HLA (sHLA) are potential tumour markers released in order to counter immune surveillance. sHLA-class II is less known especially in acute lymphoblastic leukaemia (ALL). This study aimed to investigate soluble, surface and allelic expression of HLA Class II (sHLA-DR) in B-cell ALL patients and compare with soluble expression in normal individuals. A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to measure soluble HLA-DRB1 in plasma. Flow cytometric analysis was performed to determine median fluorescence intensity in HLA-DR surface expression. HLA-DNA typing by polymerase chain reaction, sequence specific oligonucleotides, PCRSSO was performed to determine HLA-DRB1 type in ALL samples. Results showed sHLA-DRB1 (mean+SEM) was significantly increased (p=0.001) in plasma of ALL patients (0.260±0.057 μg/mL; n=30) compared to healthy controls (0.051±0.007μg/mL; n=31) of Malay ethnicity. However, these levels did not correlate with percentage or median fluorescence intensity of HLA-DR expressed on leukemia blasts (CD19+CD34+/-CD45loHLA-DR+) or in the normal B cell population (CD19+CD34- CD45hiHLA-DR+) of patients. No significant difference was observed in gender (male/female) or age (paediatric/adult). Only a trend in reduced sHLA was observed in patients carrying HLA-DR04. These results have to be validated with a larger number of samples.

Acute Lymphoblastic Leukaemia in Pregnancy: A Case Report.

Background: Acute Lymphoblastic leukaemia (ALL) is a malignant disorder which originates in a single B–or T-lymphocytes progenitor as a result of somatic mutation. ALL represents about 15% of all malignancies in 1-15 year olds, 5% in 15-19 year olds, and <10% of malignancy in >20 year olds. This condition is rare in pregnancy and when it occurs, its management and the use of chemotherapy during pregnancy, poses a significant risk to both the mother and fetus. Aim: To underscore the difficult dilemma physicians are faced with in the management of ALL in pregnancy. Study Design: Case study. Place of Study: Obstetrics & Gynaecology Department of the Federal Medical Centre, Bida, Nigeria. Methods: A review of the index case was conducted at the Obstetrics & Gynaecology Department of the Federal Medical Centre, Bida-a tertiary health care facility in Nigeria. This review took into cognizance the patient’s demographic bio-data, case history, methods of diagnosis and various supportive measures. A comprehensive analysis and account of events during this period were also reviewed. Results: This case identifies a 26-year old gravida 2, para 1+0, a full term housewife and secondary school leaver, a Muslim background from a tribe of the Nupe part of Niger State. She was on a routine antenatal visit to Obstetrics Unit, when patient was noticed to have purpuric lesions. She was subsequently referred to our unit (Haematology Department) at a gestational age of 22 weeks 4 days along with florid features of bleeding diathesis. A complete blood count, cytochemical, Immunophenotyping and molecular analysis done classified patient as having a Ph Negative, pre B acute lymphoblastic leukaemia in pregnancy. Patient was then offered some supportive measures though inadequate due to the absence of aphaeretic machine in the centre. Patient had early uneventful spontaneous vaginal delivery of a live baby (birth weight; 2.6kg) at 30 weeks gestation thereby making administration of chemotherapy much less worrisome. Meanwhile, mother and baby remain clinically stable while being followed up on the aftermath of remission induction of combination chemotherapy. Conclusion: Supportive management for ALL patients with anaemia and thrombocytopaenia is a necessary pre-induction workup step, and as in this case, would allow room for fetal growth and lung maturity; when the fetus would be mature enough to cope with extra-uterine life but also without endangering the health of the mother. This patient however, had early spontaneous vaginal delivery precluding the anticipated risk of fetal exposure to cytotoxic agents.

Interleukin-5, interleukin-6, interleukin-8 and tumour necrosis factor-alpha levels obtained within 24-h of admission do not predict high-risk infection in children with febrile neutropenia.

Purpose: Biomarkers that can predict the severity of febrile neutropenia (FN) are potential tools for clinical practice. Objective: The objective of this study is to evaluate the reliability of plasma interleukin (IL) levels as indicators of high-risk FN. Materials and Methods: Children with haematological malignancies and FN were enrolled prospectively. A blood sample was obtained within 24-h of admission for estimation of IL-5, IL-6, IL-8 and tumour necrosis factor-alpha (TNF-α) level by the enzyme-linked immunosorbent assay. Patients were stratified into three groups. Group I (low-risk): No focus of infection; Group II: Clinical/radiological focus of infection; Group III: Microbiologically proven infection or FN related mortality. Groups II and III were analysed as high-risk. The cytokines were assessed at three different cut-off levels. Results: A total of 52 episodes of FN in 48 patients were evaluated. The mean age was 6 years (range: 2-13). Primary diagnosis included acute lymphoblastic leukaemia (82%), non-Hodgkin's lymphoma (13%) and acute myeloid leukaemia (5%). Absolute neutrophil count was < 200 cells/μl in half and 200-500 in 23%. Majority were categorised as Group I (69%), followed by Group II (16%) and III (15%). The range of IL-5 was too narrow and similar in the two risk-groups to be of any relevance. The best sensitivity of TNF-α and IL-6 for high-risk group was 78% and 70%, respectively. The highest specificity observed was 35%. The negative predictive value of IL-6, IL-8 and TNF-α exceeded 80%. Conclusion: IL-5, IL-6, IL-8 and TNF-α failed as predictors of clinically localised or microbiologically documented infection in children with chemotherapy induced FN. However, IL-6, IL-8 and TNF-α could be useful in excluding the possibility of high-risk infection.

Leucemia linfoblástica aguda en pacientes portadores de síndrome de Down / Acute lymphoblastic leukemia in children with Down's syndrome

Background: Children with Down's Syndrome (DS) present a higher incidence of Acute Lymphoblastic Leukemia (ALL) with more complications and shorter survival than healthy children. Objective: To describe clinical characteristics, laboratory and treatment results in patients with DS and ALL. Patients and Method: Retrospective analysis of 42 DS and ALL patients treated in three consecutive trials (1992,1996,2002) from the Pediatric National Cancer Program (PINDA). Clinical data, immunophenotype, cytogenetics and treatment results were analyzed. Results: There was no difference by age or gender, no patient presented LLA-T, t (9;22) o t (4;11). Of the 42 patients, 38 patients went into remission, 10 relapsed (26,3 percent, 11 died because of infection, none died from other toxicity. Survival at 5 years was 35 +/- 9 percent (median of follow-up was 50 mo), similar for all protocols (p = 0,61). Conclusion: The group of patients with ALL and DS evaluated was not associated with classic treatment resistance factors. The relapse rate was not increased, if compared with non DS ALL patients; in this group the infections were the determinant factor for a lower survival. These patients can be treated with the current trials but they require a detailed infection care.

Los niños con Síndrome de Down (SD) tienen mayor incidencia de leucemia linfoblástica aguda (LLA) con más complicaciones y menor sobrevida que los niños sin SD. Objetivo: Describir características clínicas, de laboratorio y resultados de tratamiento en niños con SD y LLA. Pacientes y Método: Análisis retrospectivo de 42 pacientes con LLA y SD tratados en 3 protocolos consecutivos (1992, 1996 y 2002) del Programa Nacional de Cáncer Infantil (PINDA). Se analizaron datos clínicos, de laboratorio, inmunofenotipo, citogenética y resultados de tratamiento. Resultados: La distribución por género o grupo etario no mostró diferencias, ningún paciente presentó LLA-T, t (9;22) o t (4;11). De los 38 pacientes que remitieron, 10 recayeron (26,3 por ciento), fallecieron por infección 11/42 (26,2 por ciento). Ninguno falleció por otra toxicidad. La sobrevida libre de eventos global a 5 años fue 35 +/- 9 por ciento (mediana de seguimiento 50 meses), siendo similar en los diferentes protocolos usados (p = 0,61). Conclusión: Los pacientes evaluados con SD y LLA no presentaron factores clásicos de resistencia a tratamiento. No se observó mayor frecuencia de recaída respecto a los pacientes con LLA sin SD y la menor sobrevida en este grupo fue determinada por infecciones. Estos pacientes pueden ser tratados con los protocolos actuales pero requieren un manejo precoz e intensivo de las infecciones.