Maintenance Phase Of Chemotherapy Research Articles

Acute Appendicitis in Children with Hematological Malignancies: The Need for Early Diagnosis and Prompt Treatment—A Single-Center Case Series

Abstract Introduction Appendicitis in patients with hematological malignancies presents with vague symptoms, thus requiring a high degree of suspicion for early diagnosis and treatment to prevent complications. Objectives The aim of this article was to describe the demographic, clinicoradiological, operative findings, and outcomes in patients with acute appendicitis with underlying hematological malignancies. Materials and Methods A retrospective review of pediatric patients with hematological malignancy who developed acute appendicitis was conducted. Medical records of patients were reviewed for patient demographics, disease status, signs, and symptoms at the time of diagnosis of acute appendicitis, and outcome. The laboratory, radiological, and histological findings were retrieved from the hospital records. Results Six (2.4%) patients developed acute appendicitis over the past 8 years among a total of 254 patients treated for hematological malignancies in the unit. Five patients had underlying acute lymphoblastic leukemia (ALL) and one had acute myeloid leukemia (AML). Of the five patients, three were in postremission consolidation, one each in the delayed intensification and maintenance phase of chemotherapy. The child with AML was on induction chemotherapy for the first relapse at the time of diagnosis. Fever and abdominal pain were the common presenting symptoms. Diagnosis was made on ultrasound abdomen in five patients, and one patient was diagnosed on computed tomography. All patients underwent open appendectomy. Two patients had evidence of appendiceal perforation. Three patients had neutropenia at the time of developing appendicitis and underwent appendectomy regardless of the absolute neutrophil count (ANC). Five patients recovered well, and chemotherapy was restarted within 2 weeks of appendectomy. One patient developed a superficial surgical site infection. and one patient with relapsed AML expired due to refractory septic shock. Conclusion Acute appendicitis in patients with hematological malignancies can present with subtle signs and symptoms. Appendectomy can be safely performed irrespective of the ANC.

Mee's Lines in the Maintenance Phase of Chemotherapy in T-Lymphoblastic Leukemia.

Mee's Lines in the Maintenance Phase of Chemotherapy in T-Lymphoblastic Leukemia.

Evaluation of FTO polymorphism in 6-mercaptopurine related intolerance in children with acute lymphoblastic leukemia.

Thiopurine drugs like 6-Mercaptopurine (6MP) are the cornerstone of maintenance therapy in acute lymphoblastic leukemia (ALL). A recently described variant in alpha-ketoglutarate dependent dioxygenase (FTO) gene has been reported to play an important role in thiopurine induced myelosuppression. In this study, we genotyped a coding variant (p.Ala134Thr, rs79206939) and an intronic variant (rs16952570) of FTO in 174 Indian children (age ≤ 12years) with ALL on maintenance phase of chemotherapy and examined correlation with the risk of thiopurine induced myelosuppression and hepatic toxicity. The prevalence of FTO-rs16952570 polymorphism was 18.4% (32/174) with 142 (82%) cases having TT genotype, 26 (15%) cases with TC genotype and 6 (3.4%) cases having CC genotype. FTO-rs79206939 was absent and non-polymorphic in our study group. The mean dose of 6-MP during 36weeks of maintenance of TT, TC and CC carriers of FTO-rs16952570 was 53.7, 53.6 and 54.1mg/m2/day. Number of patients tolerating starting dose of 60mg/m2/day was significantly higher in CC (50%) than TT/TC (14%) genotype carrying cases (p = 0.014). However, no statistical significance was observed for total leukocyte count (TLC), absolute neutrophil count (ANC) as well as for platelets counts in patients harboring FTO-rs16952570 TT/TC/CC genotype at 4, 8, 12, 24 and 36weeks after start of thiopurine therapy. Further, no significant correlation was noted between number of weeks of chemotherapy interruptions or episodes of febrile neutropenia and no evidence of hepatotoxicity was found with the genotype studied. Polymorphism in FTO-rs16952570 did not show any correlation with thiopurine related toxicity in ALL patients.

Susceptibility to thiopurine toxicity by TPMT and NUDT15 variants in Colombian children with acute lymphoblastic leukemia

Objective: This study aimed to correlate the genetic profile of the NUDT15 and TPMT genes with the side effects of the treatment of pediatric patients with acute lymphoid leukemia who were undergoing maintenance therapy at a tertiary care hospital in 2017. Methods: This was an analytical, longitudinal, observational study in which the genotypes of the genes of interest were determined by PCR allelic discrimination with TaqMan® probes in patients receiving chemotherapy during the maintenance phase in the Pediatric Hematology and Oncology Unit in 2017. Sociodemographic and clinical data corresponding to the first six months of their maintenance chemotherapy were collected, and the correlation between the genotypes obtained and the development of side effects during the maintenance phase of chemotherapy in these patients was evaluated. Results: Seventy pediatric patients were included in the study. Genetic analyses were carried out of these for NUDT15 and TPMT (rs1800462 and rs1800460) on 68 patients, while for the rs1142345 polymorphism, typing was achieved in 42 patients. 4/68 patients were heterozygous for NUDT15, and the same number of patients were heterozygous for rs1800462 and rs1142345, while for rs1800460, 6 heterozygous patients were identified. No statistically significant association was identified between the genetic variants and the outcomes of interest. Conclusion: Studies with a larger population size are needed and the evaluation of other genetic variants that may influence the development of side effects during maintenance chemotherapy.

Methotrexate-Induced Leukocytoclastic Vasculitis

Erythematous tender cutaneous lesions developed in a 10-year-old child of acute leukemia receiving oral methotrexate and 6-mercaptopurine during maintenance phase of chemotherapy. She was also found to have coagulopathy and transaminitis. Differential clinical diagnosis included infectious processes, pyoderma gangrenosum, connective tissue disorders like rheumatoid neutrophilic dermatitis, and drug-induced side effects. Oral methotrexate was withheld following which the lesions subsided. Skin biopsy revealed a diagnosis of leukocytoclastic vasculitis. Cutaneous vasculitis is a rare side effect of methotrexate and its possibility should be considered in any patient who develops skin lesions while being receiving chemotherapy.

Evaluation of the effectiveness and safety of N-Chromosome Royal Jelly on the number of peripheral white blood cells in patients with acute lymphoblastic leukemia

Objectives: This study to investigate the immune response blood cells following N-Chromosome RJ administration in patients with childhood ALL.
 Methods: This single center before and after 12-weeks clinical trial was done in Ali-Asghar Children Hospital on twenty-six patients diagnosed with ALL during maintenance phase of chemotherapy. After collecting their demographics, patients received a starter dose of 2-gram processed new natural N-chromosome RJ before breakfast and were followed up each 2 weeks, counting their peripheral WBC, ANC and ALC by a blood cell count and differential analysis.
 Results: A total of Twenty-six patients were enrolled in this study (16 males and 10 females). Mean Peripheral WBC count of total patients were raised significantly after administering N-RJ Being 2510 ±1192 cells per cubic millimeter at the beginning and then raised to 4549±1500 cells per cubic millimeter at the end of trial. (P<0.005) None of patients suffered from any adverse reaction during the trial.
 There was a positive statistical relationship between total peripheral WBC, ANC and ALC count and N-Chromosome Royal jelly increased dosage, Being more prominent at the beginning of trial (p<0.001) and the last two weeks of follow-ups. (p<0.0005)
 Conclusion: This study has successfully demonstrated that N-chromosome RJ can be a promising immune- enhancing supplement in patients diagnosed with acute lymphoblastic leukemia in their complete remission and maintenance therapy time. In addition, it is a natural alternative for drugs like G-CSF, but without those long-term adverse effects, we can see in G-CSF drugs.

PB1686 USE OF FLOW CYTOMETRY AND IMMUNOHISTOCHEMISTRY TO RULE OUT CNS RELAPSE OF ACUTE LYMPHOBLASTIC LEUKEMIA

Background: Increased cerebrospinal fluid (CSF) cellularity in an otherwise asymptomatic patient with acute lymphoblastic leukemia (ALL) may indicate CNS disease. Aims: To describe how flow cytometry and immunohistochemistry helped in ruling out suspicion of CNS relapse because of unexpected CSF findings in a child with acute lymphoblastic leukemia in CR during maintenance phase of chemotherapy. Methods: Examination of cytospin CSF samples with flow cytometry, fluorescent in vitro hybridization (FISH) for centromeres of chromosomes 7 and 8 on 200 cells and immunohistochemistry for CD10 and terminal deoxynucleotidyl transferase (TdT). Results: A 15-year old girl was diagnosed in 2005 with B common ALL with hyperdiploidy including trisomy 8, and no CNS involvement. She was treated according to a modified New York II protocol with good prednisone response and negative flow cytomerty minimal residual disease (MRD) on day 33, and prophylactic cranial radiation of 1200 cGy. She went on with maintenance treatment consisting of 6-mercaptopurine 300 mg/m2/d d0-3, cyclophosphamide 1200 mg/m2 d4, vincristine 1.5 mg/m2 d11, 18, 25, prednisonse 180 mg/m2/d d18-25, methotrexate 200 mg/m2 over 4 h d25, daunorubicin 20 mg/m2 d40, 41, cytosine arabinoside 100 mg/m2, thioguanine 40 mg/m2/dose 6 doses d42-44, methotrexate IT d60/0. Days 0 and 60 CSF findings were normal. However, on day 0 of the subsequent cycle, increased ceullarity was found incidentally. CSF cell number was 45/μL and increased up to 130/μL despite additional methotrexate IT injections. Examination of cytospin preparations showed 75% lymphocytes and 25% monocytes/macrophages. Morphological discrimination between lymphoblasts and mature lymphocytes was difficult. Protein level in CSF was mildly increased up to 71 mg/dL and glucose level in CSF was normal. The patient was free of symptoms and the neuroimaging was normal. Immunohistochemistry on cytospin preparation showed no TdT expression on lymphocytes. Flow cytometry of CSF using the initial immunophenotype showed normal lymphocytes and monocytes and no leukemic blasts. FISH on a cytospin preparation to detect trisomy 8, which was present at diagnosis, and using as an internal negative control chromosome 7 ploidy, was normal with two signals for chromosomes 8 and 7, respectively. Those results in addition to increasing cellularity despite intrathecal chemotherapy and progressive enrichment of CSF in monocytes and uneventful clinical course and undetactable MRD in bone marrow, led to the conclusion that high CSF high cellularity was of reactive nature. CSF cellularity returned to normal within 2 weeks. The patient completed maintenance treatment and remains in persistent complete first remission for 10 years. Summary/Conclusion: Incidental high CSF cellularity arousing suspicion of CNS relapse may be misleading. Sensitive methods of immunophenotyping and genotyping at the cellular level provide confidence in diagnosing reactive CSF pleocytosis secondary to previous intrathecal chemotherapy and avoid unnecessary treatment plan modifications.

Monitoring of cytomegalovirus infection in non-transplant pediatric acute lymphoblastic leukemia patients during chemotherapy.

Cytomegalovirus (CMV) infection is a significant cause of morbidity and mortality in the posttransplant setting; however, it is increasingly recognized in pediatric leukemia during chemotherapy. This study assessed the prevalence and associated factors of CMV infection in pediatric non-transplant leukemia patients.This was a cross-sectional study of 50 pediatric acute lymphoblastic leukemia (ALL) patients receiving chemotherapy at Ramathibodi Hospital from December 2015 to December 2016. CMV viral load quantified by DNA polymerase chain reaction (PCR) was monitored in different phases of chemotherapy: enrolment, post-induction, post-consolidation, post-intensification, and maintenance.One hundred forty one blood tests were evaluated from 50 patients. Overall prevalence of CMV DNAemia (≥20 copies/mL) and high-level CMV DNAemia (≥1000 copies/mL) was 52% (26 of 50) and 16.0% (8 of 50), respectively. All patients with high-level CMV DNAemia were in the maintenance phase of chemotherapy. One patient had CMV retinitis, while the rest had no end-organ CMV diseases. Increased lymphocyte count was significantly associated with protection from high-level CMV DNAemia (odds ratio 0.997, P = .02). Receiver operating characteristic curve identified a cut-off value of 798 cells/mm3 of absolute lymphocyte count (ALC) as a discriminator for the presence of high-level CMV DNAemia (area under the curve 0.756, 95% CI 0.645–0.867, P = .001) with 88.9% sensitivity and 50.4% specificity.CMV infection predominantly occurred during maintenance chemotherapy. Low ALC was significantly associated with high-level CMV DNAemia. CMV infection surveillance by quantitative CMV DNA PCR during maintenance chemotherapy in patients with ALC <800 cells/mm3 may be considered.

Comparison of efficacy of hepatitis B vaccination during induction versus maintenance phase of chemotherapy in acute lymphoblastic leukemia: A nonrandomized clinical trial

Background: Acute lymphoblastic leukemia (ALL) patients are susceptible to hepatitis B infection due to profound immunosuppression and repeated transfusions. However, the comparative effectiveness of hepatitis B vaccination in different phases of chemotherapy has not been studied. Aim: In this comparative interventional study (CTRI/2017/08/009402), vaccination in the induction phase (IP) was compared to that in the maintenance phase (MP). Materials and Methods: The participating ALL patients in both groups (29 per group) were vaccinated with double the dose of hepatitis B vaccine at 0, 1, and 2 months. The proportion of patients with seroprotective anti-hepatitis B surface titers (>10 IU/ml) was compared between the two groups after each dose. Results: The seroprotection rates between both the phases were similar following the first (relative risk [RR] = 4, confidence interval [CI]: 0.47–33.65) and third (RR = 1.4, CI: 0.73-2.84) doses of vaccination, whereas following the second dose of vaccination, the seroprotection rate in IP was significantly higher than that of MP (RR = 1.9, CI: 1.07–3.35). Conclusion: This study concluded that a 0, 1, and 2 schedule of hepatitis B vaccination has similar efficacy in both the IP and the MP of chemotherapy in ALL patients. As the IP has a higher trend of seroprotection rates compared to MP, vaccination in IP followed by revaccination postchemotherapy may be preferred in countries with a high prevalence of hepatitis B infection.

The Effect of Soy Nut Compared to Cowpea Nut on Body Weight, Blood Cells, Inflammatory Markers and Chemotherapy Complications in Children with Acute Lymphoblastic Leukemia: A Randomized Controlled Clinical Trial

No previous studies were found to examine the effect of soy as a whole food on patients with leukemia. The present randomized controlled clinical trial studied the effect of soy nut on children with B-cell acute lymphoblastic leukemia (ALL) who were in the maintenance phase of chemotherapy. The eligible patients were randomized to receive 30 g/day soy or cowpea nut powder for 12 weeks. Dietary intake, physical activity, anthropometric measurements, complete blood count, serum albumin, serum highly sensitive C-reactive protein (hs-CRP), and Tumor necrosis factor alpha (TNF-α) as well as chemotherapy side effects were assessed at the start and the end of the study. In total 29 and 27 children completed the study (aged 6.34 ± 2.44 and 5.85 ± 2.35 years) in soy and cowpea nut groups, respectively. The total energy and protein intake, and physical activity as well as body weight, body mass index, number of red blood cells, hemoglobin and hematocrit levels, and fatigue were significantly improved in the soy nut group compared to patients who consumed cowpea nut (P < 0.05). Soy nut intake might improve the nutritional status, anemia, and fatigue in children with ALL. Studies targeting blood cell fractions and disease recurrence are highly recommended.

SALIVARY SECRETORY IMMUNOGLOBULIN A LEVEL OF CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA IN MAINTENANCE PHASE

Objective: The objective of this research is to investigate the differences in salivary secretory immunoglobulin A (sIgA) levels between children with gingivitis who have acute lymphoblastic leukemia (ALL) and are in the maintenance phase of chemotherapy and the levels in healthy children with gingivitis.Methods: This study used cross-sectional and laboratory observation methods with 19 ALL children and 19 healthy children who all had mild gingivitis. Two mL of saliva were collected and stored at −200°C. Then, salivary sIgA levels were measured using the ELISA method.Results: The results indicate an insignificant difference (p&gt;0.05) in salivary sIgA levels between the ALL children in the maintenance phase with the level of 21.38 (7.23–107.26) and 37.26 (11.24–135.63) for the healthy children.Conclusion: There is no significant difference in salivary sIgA levels between the ALL children in the maintenance phase and the healthy children.

ACQUIRED β−THALASSEMIA IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

Thalassemias are heterogeneous group of genetic disorders. β-thalassemia is existed due to impaired production of beta globins chains, which leads to a relative excess of alpha globin chains. The abnormalities of haemoglobin synthesis are usually inherited but may also arise as a secondary manifestation of another disease, most commonly haematological neoplasia. This article presenting two cases of acquired β-thalassemia in children with ALL focusing on the diagnosis and the possible relationship between the two haematological diseases. The first case is a four (4) year old boy with ALL-L1 type at maintenance phase of chemotherapy, he suffered from anaemia with Hb 8.0 g/dL, WBC 22,600/mm3 and platelets count of 200,000/mm3, peripheral blood smear revealed anisocytosis, polychromes, hypochromia, basophilic stippling, and normoblastocytes. The result of Hb electrophoresis of Hb A of 54.9%, Hb F of 29.4%, Hb E of 13.4% and Hb A2 of 2.3%. The patient was diagnosed as ALL-L1 type and β-thalassemia. The second case, is a 13 year old girl with remission ALL-L1 type after chemotherapy, she suffered from anaemia with Hb 6.7 g/dL, WBC 12,400/mm3, platelet count was 200,000/mm3, and peripheral blood smear obtained anisocytosis, hypochromia, normoblastocytes, myelocytes and basophilic stippling. The result of Hb electrophoresis are: Hb F 0.41%, Hb A1c 0.78%, Hb A2 2.95% with the conclusion of a β-thalassemia trait, this patient was diagnosed with ALL-L1 type remission + β-thalassemia trait. The case reviewers assume that acquired β-thalassemia which happened in those patients were the altered expression of globin chain which mechanism for this syndrome might be the acquisition of a mutation that affects RNA or proteins involved in β-globin gene regulation and resulting the reduction of the (α/β)-globin biosynthetic ratios, or/and associated with chemotherapy-inducement.

PHA-Induced Peripheral Blood Cytogenetics and Molecular Analysis: a Valid Diagnostic and Follow-up Modality for Acute Promyelocytic Leukemia Patients Treated with ATRA and/or Arsenic Tri-oxide.

Acute promyelocytic leukemia (APML) is characterized by the reciprocal translocation t(15;17) (q22;q12) resulting in the PML-RARα fusion gene. A dual diagnostic and follow up approach was applied including cytogenetic demonstration of the t(15;17) translocation and detection of PML-RARα chimeric transcripts by molecular means. Conventional cytogenetics involving bone marrow is beset with high probability of poor metaphase index and was substituted with phytohemagglutinin (PHA)-induced peripheral blood culture based cytogenetic analysis as a diagnostic and follow up modality in APML patients of Kashmir (North India). Both qualitative (RT-PCR) and quantitative (Q-PCR) tests were simultaneously carried out to authenticate the modified cytogenetics. Patient samples were subjected to the said techniques to establish their baseline as well as follow-up status. Initial cytogenetics revealed 30 patients (81%) positive for t(15;17) whereas 7 (19%) had either cryptic translocation or were negative for t(15;17). Two cases had chromosome 16q deletion and no hallmark translocation t(15;17). Q-PCR status for PML-RARα was found to be positive for all patients. All the APML patients were reassessed at the end of consolidation phase and during maintenance phase of chemotherapy where 6 patients had molecular relapse, wherein 4 also demonstrated cytogenetic relapse. It was found that PHA-induced peripheral blood cytogenetics along with molecular analysis could prove a reliable modality in the diagnosis and assessment of follow up response of APML patients.

ω-3 fatty acids as an adjuvant therapy ameliorates methotrexate-induced hepatotoxicity in children and adolescents with acute lymphoblastic leukemia: A randomized placebo-controlled study

ObjectivesMethotrexate (MTX)-induced hepatotoxicity is a significant clinical problem that may affect overall prognosis and disease outcome. Oxidative stress is a key player in its pathogenesis. The aim of this study was to investigate the role of ω-3 fatty acids as an adjuvant therapy in children and adolescents with acute lymphoblastic leukemia (ALL) during the maintenance phase of chemotherapy and the effect of ω-3 on MTX-induced hepatotoxicity. MethodsThis randomized, double-blind, placebo-controlled trial included 70 patients with ALL who were in the maintenance phase. The participants were divided into two groups: group A received oral MTX and ω-3 fatty acids (1000 mg/d) and group B (received MTX and placebo). Both groups were followed-up for 6 mo with assessment of liver enzymes, total antioxidant capacity (TAC), uric acid, malondialdhyde, superoxide dismutase (SOD), and glutathione peroxidase. The trial was registered at ClinicalTrials.gov (NCT02373579). ResultsBaseline clinical and laboratory parameters were consistent between the two groups (P > 0.05). After 6 mo, liver enzymes and malondialdhyde increased, whereas TAC, uric acid, SOD, and glutathione peroxidase decreased in group B (MTX and placebo) compared with baseline levels or with group A ALL patients receiving ω-3 fatty acids (P < 0.001). The addition of ω-3 to MTX maintained normal liver function and oxidant–antioxidant levels among group A patients at the end of treatment compared with pretherapy levels (P > 0.05). No adverse reactions due to ω-3 supplementation were reported. ALT was inversely correlated to TAC and SOD in the MTX group. ConclusionsThe study determined that ω-3 fatty acids ameliorated MTX-induced hepatotoxicity and could be safely used during the maintenance phase of ALL.

Pulmonary function of children with acute leukemia in maintenance phase of chemotherapy

ObjectiveThe aim of this study was to assess the pulmonary function of children with acute leukemia. MethodsCross-sectional observational analytical study that enrolled 34 children divided into groups A (17 with acute leukemia in the maintenance phase of chemotherapy) and B (17 healthy children). The groups were matched for sex, age and height. Spirometry was measured using a spirometer Microloop Viasys® in accordance with American Thoracic Society and European Respiratory Society guidelines. Maximal respiratory pressures were measured with an MVD300 digital manometer (Globalmed®). Maximal inspiratory pressures and maximal expiratory pressures were measured from residual volume and total lung capacity, respectively. ResultsGroup A showed a significant decrease in maximal inspiratory pressures when compared to group B. No significant difference was found between the spirometric values of the two groups, nor was there any difference between maximal inspiratory pressure and maximal expiratory pressure values in group A compared to the lower limit values proposed as reference. ConclusionChildren with acute leukemia, myeloid or lymphoid, during the maintenance phase of chemotherapy exhibited unchanged spirometric variables and maximal expiratory pressure; However, there was a decrease in inspiratory muscle strength.

Pulmonary function of children with acute leukemia in maintenance phase of chemotherapy

OBJECTIVE: The aim of this study was to assess the pulmonary function of children with acute leukemia.METHODS: Cross-sectional observational analytical study that enrolled 34 children divided into groups A (17 with acute leukemia in the maintenance phase of chemotherapy) and B (17 healthy children). The groups were matched for sex, age and height. Spirometry was measured using a spirometer Microloop Viasys(r) in accordance with American Thoracic Society and European Respiratory Society guidelines. Maximal respiratory pressures were measured with an MVD300 digital manometer (Globalmed(r)). Maximal inspiratory pressures and maximal expiratory pressures were measured from residual volume and total lung capacity, respectively.RESULTS: Group A showed a significant decrease in maximal inspiratory pressures when compared to group B. No significant difference was found between the spirometric values of the two groups, nor was there any difference between maximal inspiratory pressure and maximal expiratory pressure values in group A compared to the lower limit values proposed as reference.CONCLUSION: Children with acute leukemia, myeloid or lymphoid, during the maintenance phase of chemotherapy exhibited unchanged spirometric variables and maximal expiratory pressure; However, there was a decrease in inspiratory muscle strength.

Mobilidade torácica de crianças em tratamento quimioterápico para leucemia agudaMobilidade torácica de crianças em tratamento quimioterápico para leucemia aguda

Introdução: As leucemias representam a neoplasia que mais acometem a população infantil. Objetivo: Comparar a mobilidade torácica entre crianças com leucemia aguda durante a fase de manutenção da quimioterapia e escolares saudáveis. Métodos: Foram avaliadas 34 crianças divididas entre os grupos: A, composto por 17 pacientes com leucemia aguda; e B, formado com 17 saudáveis. A mobilidade torácica foi avaliada por meio da cirtometria torácica nos níveis axilar e xifoide. Foram utilizados os testes “t” de Student não pareado e pareado para comparação dos valores encontrados durante as avaliações. Resultados: As integrantes do grupo com leucemia aguda apresentaram menor mobilidade torácica axilar e xifoideana, quando comparadas ao grupo das saudáveis. No entanto, não houve diferença entre os valores encontrados nesses níveis em cada grupo avaliado. Conclusão: A crianças com leucemia aguda durante o período de manutenção do tratamento quimioterápico apresentam redução da mobilidade torácica.

Effects of pre-existing undernutrition on treatment-related complications and treatment outcomes in children with acute lymphoblastic leukemia: A tertiary care center experience

Background: Our study aimed to assess the influence of undernutrition on treatment tolerance, treatment-related complications, and treatment outcomes in acute lymphoblastic leucomia (ALL) patients during induction and maintenance phase of chemotherapy and subsequent follow-up visits. Materials and Methods: This retrospective, cohort study was conducted between January 2005 and September 2012 in the Departments of Pediatrics and Radiation Oncology in a tertiary care Medical College and Hospital of Eastern India. Using weight-for-age Z scores (WHO), we divided the 159 ALL patients into 4 groups: Group 1 without malnutrition, Group 2 with mild undernutrition, Group 3 with moderate undernutrition, and Group 4 with severe malnutrition. Data regarding blood counts, hematological support, bone marrow remission status and complications during treatment, and follow-up records were analyzed and compared to find out the impact of undernutrition on treatment tolerance and outcomes in different groups. Results: During the intensive phase of chemotherapy treatment, tolerance was assessed by the nadir of absolute neutrophil count and hemoglobin which fell significantly in moderate and severe malnutrition group. Significantly, more packed red blood cell support and platelet transfusions were required by those two groups P < 0.002 and P < 0.001, respectively. The incidence of febrile neutropenia was significantly more in severe malnutrition group (P < 0.001). Ninety-eight (61.63%) patients could not complete chemotherapy within the specified 145-day period of which 23 (76.67%) patients was of severe malnutrition group (P < 0.002). Remission after induction has shown declining trend with more undernutrition. A total of 24 patients relapsed in spite of bone marrow remission which was proportionately more from moderate and severe malnutrition group. During the 5-year follow-up, 20 patients died which was proportionately more in Group 3. Conclusion: Undernutrition adversely affect the final outcome, treatment tolerance, and treatment complications in children with ALL. So, baseline malnutrition should be considered as an important prognostic factor in therapeutic decision of ALL.

Milk Thistle Is Associated with Reductions in Liver Function Tests (LFTs) in Children Undergoing Therapy for Acute Lymphoblastic Leukemia (ALL).

Background: Milk Thistle (MT), an herbal plant widely used in Europe for treating liver and biliary disorders, is commonly self prescribed for its hepatoprotectant effects. Chemotherapy associated hepatotoxicity is a primary reason for dose reductions or withdrawal of chemotherapy in children with ALL.Purpose: To investigate the toxicity and efficacy of MT supplementation for treatment of hepatotoxicity in children with ALL during 1 maintenance chemotherapy phase.Methods: Children ages 1–21 yrs with ALL and grade 2 or greater hepatic toxicity (defined by elevations in AST, ALT, or total bilirubin (TB), by NCI CTC v2 criteria) were eligible for participation during a maintenance phase of chemotherapy by Childrens Oncology Group or Dana Farber Cancer Institute ALL protocols. Participants were randomized to MT (Siliphos®, Thorne Research, Dover, ID, 5.1mg/kg/day) or placebo orally for 28 days while receiving the prescribed chemotherapy. LFTs were evaluated at baseline, day 28 (end of supplementation) and day 56 (28 days after MT discontinuation). MT stability was assessed at onset and at 21 mos by HPLC with UV detection relative to standard curves and known retention times of authentic silybin A and B reference standards. CCRF-CEM T-cell ALL cell culture studies were conducted with MT and vincristine (V) or L-asparaginase (A).Results: 50 children, ages 1–19 yrs (median = 7) were enrolled. 1 child withdrew consent before treatment was initiated; 2 had insufficient data. No significant differences in age, gender, ethnicity, or treatment protocols were observed between the 2 groups. Adverse effects from MT/placebo were mild: diarrhea (2/3), anorexia (0/1), flatulence (1/0), abdominal pain (2/2), irritability (2/0). No differences between MT/placebo in grade 3/4 toxicities from chemotherapy were seen: heme-infectious (6/17), non-heme (10/6). Mean AST and ALT declined greater from baseline to day 28 with MT but the differences were not significant. A greater decrease in mean AST from baseline to Day 56 was observed with MT (78 to 47) compared to placebo (71 to 67) (p= 0.05). A trend towards a greater reduction in mean ALT from baseline to Day 56 with MT (187 to 122 vs placebo 140 to 139) was also seen (p=.07). More children in the MT group developed greater than a 50% reduction in TB at day 28 as compared to placebo (p = 0.0069). The decline in day 56 TB was greater with MT but the difference was not significant. MT was composed of 49.6% silybin A and 50.4% silybin B, with no change in total content and ratios at 21 mos. In T-cell ALL cell culture studies, no effect was observed on cytotoxicity with A, but MT enhanced V-mediated CEM cell kill.Conclusions: In children with ALL with established liver toxicity, MT supplementation for 28 days in conjunction with hepatotoxic chemotherapy is associated with significant reductions in LFTs compared with placebo. Future study will evaluate the effect of MT in allowing delivery of full doses of chemotherapy and its subsequent impact on leukemia-free survival, along with xenograft studies to determine whether the beneficial antileukemic potentiation of vincristine persists in vivo.

Immunogenicity of a two-dose regime of varicella vaccine in children with cancers.

Live-attenuated varicella vaccine is effective and safe in immunocompetent children. In this study, we assess the immunogenicity and adverse events following varicella vaccination in immunosuppressed cancer children. Varicella-zoster virus (VZV)-seronegative cancer children received two doses of live-attenuated VZV vaccine (Varilrix) in a span of 3 months. Patients with acute lymphoblastic leukaemia (ALL) were in the maintenance phase of chemotherapy, whereas those with solid tumours joined the study around 3-6 months from treatment discontinuation. VZV-specific cellular and humoral immune responses were measured before and after VZV vaccination. The median (range) age of the 17 patients was 4.4 yr (2.0-14.5). Thirteen had ALL, one had myelodysplastic syndrome and three had solid tumours. Following vaccination, the VZV-specific stimulation index (SI) increased from 1.7 (0.9-2.9) to 17.9 (5.9-36.0) (P < 0.001). Similarly, SI to phytohaemagglutinin mitogen increased from 1136 (499-1930) to 1714 (848-2518) (P = 0.028). There were also significant increases in CD4+ cells and CD4:CD8 ratio as well as a reduction in CD16/56+ cells in peripheral blood lymphocytes. Seroconversion rate to VZV was 19% after one dose and increased to 94% after the second dose of VZV vaccine. Serum VZV-specific IgG concentrations also increased significantly following two doses when compared with one dose of VZV vaccine (P = 0.0004). One subject developed possibly vaccine-related chickenpox with self-limiting hepatitis at 5 wk following vaccination. None of the patients developed herpes-zoster at a median (range) follow-up of 27.5 months (24.0-30.0). Non-immune cancer children can be effectively vaccinated against chickenpox at the defined period. However, the safety of chickenpox vaccine in these immunosuppressed children needs to be further studied.