A Rare Case of Methemoglobinemia after Ifosfamide Infusion in a 3-Year-Old Patient Treated for T-ALL.

Methemoglobinemia is a potentially life-threatening, rare condition in which the oxygen-carrying capacity of hemoglobin is diminished. We present the case of a 3-year-old boy treated for T-cell acute lymphoblastic leukemia (T-ALL) who developed methemoglobinemia (MetHb 57.1%) as a side effect of ifosfamide administration. Due to his critical condition, the patient was transferred to the intensive care unit (ICU). The therapy included methylene blue administration, an exchange transfusion, catecholamine infusion, and steroids. Improving the general condition allowed for continuing chemotherapy without ifosfamide and completion of the HR2 block. Vigilance for methemoglobinemia as a very rare side effect should be widespread when using ifosfamide in the treatment protocols.

The influence of different intensity of treatment on hormonal markers of gonadal function in acute lymphoblastic leukemia survivors.

Anti-cancer treatment in children can deteriorate gonadal function and affect future fertility. We analyzed the hormonal markers of gonadal function in adolescent leukemia survivors, treated in childhood with different levels of aggressiveness. We analyzed hormone levels in 69 adolescents and young adults, leukemia survivors stratified into standard (SR), intermediate (IR), and high (HR) risk groups, and in 80 healthy controls (38 men) at a similar age. We assessed follicular stimulating hormone (FSH), luteinizing hormone (LH), and inhibin B in the whole group, testosterone in males, and E2 and anti-Müllerian hormone (AMH) in females. Males classified into HR group presented, in comparison to control, higher levels of FSH, LH, lower inhibin B, and normal testosterone, whereas in SR and IR group, the hormonal values were comparable to the control. In females, in all risk groups, the levels of FSH, LH, E2, and inhibin B were comparable with the control, but the mean AMH levels were slightly lowered. We did not observe the effect of prophylactic cranial irradiation (12 or 18 Gy) or the time of treatment (before vs. during puberty) on hormone levels. In females, a positive correlation was found between the time interval after the end of treatment and AMH levels. Male leukemia survivors having undergone more intensive chemotherapy show the symptoms of disturbed spermatogenesis and need to be followed-up in the future. Women, irrespective of the risk group, can develop the signs of preterm ovarian insufficiency. They should be informed about the impact of the treatment on gonadal function.

The repeatability and reproducibility of gingival thickness measurement with an ultrasonic device.

BACKGROUND: Successful periodontal and implant surgery as well as orthodontic treatment often depends on gingival and mucosal thickness. So far there has been no generally accepted protocol of measuring the thickness of gingiva by non-invasive methods. OBJECTIVES: The aim of the study was to evaluate the repeatability and reproducibility (%R&R) of the 20 MHz A-Scan ultrasonic device in measuring gingival thickness (GT) in the mucogingival complex. MATERIAL AND METHODS: A 2-stage study utilizing non-invasive ultrasonic methods was conducted. In the 1st stage, 3 operators got calibrated by measuring previously established GT in porcine cadaver jaws. In the 2nd stage, 1 periodontally healthy subject was recruited in the study. Three operators performed the measurements of GT in maxillary left central and lateral incisors and canines, using the 20 MHz A-Scan ultrasonic device with a probe of 1.7 mm in diameter. The thickness was measured in 4 standardized points located in the free gingiva (FGT), supracrestal gingiva (SGT), crestal gingiva (CGT) and the mucosa (MGT). RESULTS: The analysis of variance (ANOVA) method was used to quantify %R&R. The repeatability and reproducibility of the measurements was 8.4%. Interobserver reproducibility varied from 0.8% to 13.4%. The average intraobserver coefficient of variation (CV) was 6.6% (1.9-13.6%). The median of the reproducibility of all measurements was 8.1 %. Nevertheless, the median of CV was variable to the observer, i.e. 5.4%, 6.5%, 6.4%. CONCLUSIONS: The obtained results in %R&R prove the good recognition of methodology as well as the usefulness of the device. Non-invasive ultrasonic biometer GT measurements are crucial in periodontology as well as in other fields of dentistry.

Influence of Iron Overload on Immunosuppressive Therapy in Children with Severe Aplastic Anemia.

Children with severe aplastic anemia (AA) require multiple transfusions of the red blood cells during the immunosuppressive therapy. This leads to iron overload and manifests as elevated levels of ferritin in blood. The aim of this study was a retrospective analysis of the influence of the elevated serum ferritin on the overall survival, event-free survival, the risk of relapse, and response to treatment in children with AA during immunosuppressive therapy. We analyzed 38 children with AA (19 girls, 19 boys, aged 2-17 years) treated according to the obligatory protocol for AA in Poland. The response rate was assessed on days 84, 112, and 360. Patients were divided into three groups: group I consisted of children with ferritin below 285 ng/mL (6 children), group II with ferritin between 286 and 1,000 ng/mL (13 children), and group III ferritin>1,000 ng/mL (19 children). Kaplan-Meier plot was used to estimate the overall survival and event-free survival. We found the overall survival did not differ between the three groups. Event-free survival was significantly shorter (p=0.03) in patients with ferritin levels>1,000 ng/mL compared with the groups with ferritin bellow 1,000 ng/mL. The time to relapse was significantly shorter in group III than in the other two groups (p=0.02). We also found the differences in the treatment response at day 84 (p=0.03) and day 112 (p<0.0001) of immunosuppressive therapy. These findings confirm a negative influence of iron overload in children with AA on the effect of treatment and the risk of relapse.

Anti-müllerian hormone as a sensitive marker of ovarian function in young cancer survivors.

We evaluated ovarian function by measuring the levels of anti-Müllerian hormone (AMH), estradiol, and gonadotropins in 83 young women treated for cancer during childhood and adolescence, and classified according to post-treatment gonadal toxicity versus 38 healthy females. Results. The mean AMH values were lower in the entire cohort independently of the risk group as compared to the control, whereas FSH was elevated only in the high risk group. The lowest AMH values were noted in patients after bone marrow transplantation (BMT) and those treated for Hodgkin lymphoma (HL). Nineteen patients (22.9%) had elevated FSH. They all had low AMH values. Lowered AMH values (but with normal FSH and LH) were observed in 43 patients (51.8%). There was no effect of age at the time of treatment (before puberty, during or after puberty) on AMH levels. Conclusion. Our results show the utility of AMH measurement as a sensitive marker of a reduced ovarian reserve in young cancer survivors. Patients after BMT and patients treated for HL, independently of age at treatment (prepuberty or puberty), are at the highest risk of gonadal damage and early menopause.

Proteasome chymotrypsin-like activity in plasma as a useful marker for children with acute lymphoblastic leukemia.

BACKGROUND: The proteasome chymotrypsin-like (Cht-L) activity was determined in plasma of children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in correlation to baseline leukocytosis, immunophenotype, LDH at the time of diagnosis and after remission induction. PROCEDURE: The activity was assayed using the fluorogenic peptide substrate in the presence of an artificial activator sodium dodecyl sulfate (SDS) in the plasma of healthy donors (n=25), acute lymphoblastic leukemia, ALL (n=95) and AML (n=17) patients. RESULTS: As compared to healthy subjects, the plasma proteasome ChT-L activity was significantly increased (p=0.001) in ALL patients prior to treatment, especially in those with T-ALL immunophenotype and with high LDH activity. Similarly, in AML patients the plasma proteasome ChT-L activity was elevated (p=0.001). Following remission-inducing chemotherapy, the activity of the ChT-L proteasome was significantly reduced both in ALL and AML patients. CONCLUSION: Plasma proteasome ChT-L activity may serve as an additional marker in monitoring anticancer therapy.

[Characteristics of extracranial malignant germ cell tumours in two age groups of children (0-10 and 10-18 years). Multicentre experiences]. / Charakterystyka pozaczaszkowych zltosliwych guzów germinalnych u dzieci w dwóch grupach wiekowych 0-10 lat i 11-18 lat. Badania wieloosrodkowe.

UNLABELLED: In order to assess if any differences exist in children germ cell tumours depending on age, we compared some features of germ cell tumours in two age groups:younger than 10 and between 11 and 18 years. MATERIAL AND METHODS: Data of 146 patients with germ cell tumours treated in 15 Polish paediatric oncology departments between 1995 and 2005 were evaluated. They were divided into two groups: 76 children 0-10 years old (group I) and 70 patients 11-18 years old (group II). Tumour morphology, sex of patients, primary tumour and metastases localization, disease stage, biochemical markers, treatment response, disease relapse and long survival were analyzed. Every patient was treated according to the TGM 95 protocol. RESULTS: In group 1, 67 tumours were assessed histologically. 64%t tumours had homogenous structure with yolk sac tumour in predominance and 36% were mixed. Yolk sac tumour (YST) or teratoma as components of mixed tumours were the most commonly found. In older group 64 tumours were examined, 41% were homogenous, and seminoma/dysgerminoma predominated. In 59% mixed tumours the most common components were YST embryonal carcinoma and teratoma. The most common primary site in group I was the sacrococcygeal region while in group II - the gonads. Disseminated disease was recognized mostly in older children. Among two evaluated serum markers, AFP was increased mostly in younger patients (76% vs 44%), and 3HCG in older group (40% vs 9%). Treatment response was comparable in both groups. Two relapses were observed in each group. Poor outcome was noted in 17/140 analyzed patients: 9 (12%) in group I and 8 (11%) in group II. In 12 of patients with poor outcome the cause of death was progression and in 5 of them - treatment complications. CONCLUSIONS: 1. Germ cell tumours in younger and older children differ in histology, primary localization and serum level of biochemical markers. 2. In older patients germ cell tumours are recognized more frequently in advanced clinical stages. 3. Treatment response was comparable in both groups. 4. There is a need to analyze the intensity of chemotherapy to precise the adequate risk groups according to primary treatment response.

[Anti-mullerian hormone in young women after chemotherapy and infradiaphragmatic radiotherapy for childhood cancer]. / Stezenie hormonu anty-mullerowskiego u mlodych kobiet po chemioterapii i radioterapii pól podprzeponowych z powodu choroby nowotworowej.

INTRODUCTION: Composed anticancer treatment leads to different late effects, such as ovarian failure, causing infertility or premature menopause. AIM OF THE STUDY: was to analyse ovarian function, particularly anti-mullerian hormone levels, in young females after anticancer treatment. PATIENTS AND METHODS: We analysed FSH, LH, estradiol and anti-mullerian hormone (AMH) levels on days 3-5 of a menstrual cycle in thirty three cancer survivors in mean age 19.1+/-4.7 years treated in age 12.0+/-5.6 years for Hodgkin Lymphoma (HL) (n=16), nephroblastoma (n=7), soft tissue sarcoma (n=4), germinal tumor (n=3), neuroblastoma (n=2), histiocytosis (n=1). Infradiaphragmatic radiotherapy was needed in 16 patients (10 treated for HL). Results were compared with healthy girls of the same age. RESULTS: The mean values of FSH, LH, E2 and AMH did not differ in all survivors comparing to controls. Patients treated for HL with chemo- and radiotherapy presented higher FSH levels than controls (8.53+/-3.25 vs. 5.8+/-2.03 mIU/ml; p=0.045). Mean AMH levels were lower in all patients that received radiotherapy for the infradiaphragmatic region (17.19+/-14.84 pmol/l) than in controls (29.40+/-13.2 pmol/l; p=0.037). Particular analysis of all cases showed higher (>2 SD) FSH levels in 8 patients: 5 patients treated for HL with radiotherapy and higher total doses of procarbazine, nitrogen mustard and vinblastine; 2 patients treated for soft tissue sarcoma and one patient for Wilms tumor (all received radiotherapy). Lowered AMH levels were found in 8 patients treated with chemo- and radiotherapy (4 - for HL, 2 - for Wilms tumor and 2 - for soft tissue sarcoma). CONCLUSION: Composed anticancer treatment, especially radiotherapy, leads to ovarian failure. Decreased AMH values at young adulthood suggest a lower ovarian reserve. All causes and first symptoms of ovary damage should be known to the doctors who take care of the patients after anticancer treatment.

[Gonadal and thyroid function after treatment for Hodgkin's lymphoma in adolescents]. / Ocena wybranych funkcji endokrynnych po leczeniu ziarnicy zlosliwej.

PURPOSE: Complete treatment for Hodgkin's lymphoma (HL) may disturb functioning of different organs leading to deteriorated quality of future life. Endocrine complications are one of the most common and may be the result of radiotherapy of neck, mediastinal and infradiaphragmatic regions, as well as chemotherapy, especially with alkylating agents. The aim of our study was to analyse gonadal and thyroid disturbances in young adults after the treatment for HL in childhood. MATERIAL AND METHOD: In 36 adolescents and young adults (19 males; mean age 20.5+/-3.1) 5.9+/-3.4 years after treatment for HL, we have examined the thyroid function (TSH, thyroxine-T4, tri-iodothyronine-T3, ultrasound) as well as gonadal function in males: FSH, LH, testosterone, inhibin B and in females: FSH,LH, estradiol, inhibin B and anti-müllerian hormone (AMH). Radiotherapy of supradiaphragmatic region was used in 34/36 patients and for infradiaphragmatic region in 17 patients (7 males). Chemotherapy was composed of B-DOPA and MVPP protocols. RESULTS: 1. Signs of subclinical hypothyroidism (elevated TSH) were found in three survivors (irradiated on upper mediastinum). Ultrasonic abnormalities (simple nodules) were found in three patients after mantle radiotherapy. 2. In males the mean values of FSH were higher than in healthy boys (16.0 mIU/ml+/-13.0 vs 3.9 mIU/ml+/-2.0) p=0.0004, inhibin B- lower (50.1 ng/L +/- 43.5 vs.68.1 ng/L +/- 77.2) p = 0.0001, and testicular volume lower (17,3 ml+/-3.8 vs 18.5 ml+/-4.8) p = 0.05. The mean values of LH and testosterone were normal. Inhibin B<2SD and FSH>2SD in 6/19 males, LH>2SD in 4 cases (irradiated infradiaphragmatically) were found. 3. In females, we observed higher FSH values (8.53 mIU/ml+/-3.25 vs 5.8 mIU/ml+/-2.03) p=0.045; lower AMH (17.19 pmol/L+/-14.84 vs 29.40 pmol/L+/-13.2) p=0.05 and tendency to lower inhibin B (31.47 ng/L+/-18.83 vs 47.9 ng/L+/-26.39) p=0.08 than in control group. LH and estradiol concentrations did not differ in between groups. FSH>2SD, inhibin B and AMH<2SD were found in 5 girls (infradiaphragmatic irradiations in 4 cases). CONCLUSIONS: Our observations show the possibility of different endocrine disturbances after combined treatment for HL, especially gonadal function disturbances. Considering these long-term complications, further follow-up is needed, even in the absence of clinical symptoms.

[Ovarian function in young women after anticancer treatment in childhood]. / Czynnosc jajników u mlodych kobiet po zlozonym leczeniu przeciwnowotworowym w dziecinstwie.

AIM: We investigated pituitary-ovarian function in young women after treatment for different cancers in prepubertal and pubertal periods, with or without radiotherapy of infradiaphragmatic areas. PATIENTS AND METHODS: We analyzed the values of follicle-stimulating hormone (FSH) luteinizing hormone (LH), estradiol (E2), inhibin B and anti-müllerian hormone (AMH) in the group of 28 young women aged 18.6 +/- 4.7 years, who had been treated for Hodgkin's Lymphoma HL (n=16), nephroblastoma (n=7), soft tissue sarcoma (n=4), neuroblastoma (n=1). Abdominal irradiation was given in fifteen survivors. Control group was composed of ten healthy women at similar age. RESULTS: In the whole group the mean levels of FSH, LH and E2 did not differ from the control group, but in the subgroup irradiated infradiaphragmatically FSH concentration was higher than in the control group (8.06+/-3.28 vs 5.8+/-2.03 mIU/ml) p=0.042, particularly after HL treatment (8.53+/-3.25 mIU/ml), p=0.045. Mean AMH levels were significantly lower in the whole analyzed group than in the control one (22.8+/-16.3 vs 29.4+/-13.2 pmol/l) p=0.036, particularly in the subgroup irradiated for abdomen (17.2+/-14.9 pmol/l) p=0.025. Inhibin B was also lower in the whole group, (27.98+/-17.8 ng/l vs 47.9+/-26.4 ng/l) p=0.035, and in the subgroup with non-irradiated abdomen 25.9+/-14.1 ng/l, p=0.01. We did not observe the influence of age at treatment (prepubertal vs pubertal period) on the values of analyzed hormones. We found a correlation between AMH and inhibin B. CONCLUSIONS: In young women after anti-cancer treatment, with normal menstrual cycles, the signs of ovarian dysfunction and diminished ovarian reserve are observed. This situation can lead to a shorter period of fertility. Those women should be informed about their reproductive potential.

[Results of immunosupressive therapy in children with severe aplastic anaemia. Report of the Polish Paediatric Haematology Group]. / Wyniki leczenia ciezkiej postaci anemii aplastycznej u dzieci. Raport Polskiej pediatrycznej grupy do spraw nienowotworowych chorób ukladu krwiotwórczego.

INTRODUCTION: Bone marrow transplantation from HLA identical family donors is the treatment of choice for children with severe aplastic anaemia (SAA). When there is no donor available, combined immunosuppressive therapy is given. AIM: evaluation of results of immunosupressive therapy in children with severe aplastic anaemia. MATERIAL AND METHODS: SAA was diagnosed in 105 children (42 girls, 73 boys), aged 2-18 years, in the eleven haematological centres in Poland, between 1993-2007. All patients received the Severe Aplastic Anaemia Working Party of the EBMT protocol which included: antilymphocyte globulin or antithymocyte globulin, cyclosporin A, prednisolone. Granulocyto- or granulocytomacrophagic-cell stimulation factor was additionally administered during deep neutropenia. Haematological response was evaluated on day 84 or 112 and 180 of the therapy. RESULTS: complete remission occurred in 53 patients (51.5%), partial remission in 27 (24.7%), no response was obtained in 25 children (23.8%) on day 180, of the therapy. Period of observation was from 12 months to 12.5 years. During this time relapse occurred in 10 patients (9.5%). We observed 22 deaths: 8 early, during the first 3 months of IS and 14 after the first 3 months of immunosuppresive therapy (IS). At present 70 children (66.6%) are in first remission with lasts from 12 months to 12.5 years. The survival at 12.5-years is 78.6%. During the 12.5 years of follow-up we had two cases with a late clonal complication (PNH and MDS). Transformation to acute nonlymphoblastic leukaemia was observed in two of our patients. CONCLUSIONS: 1. Immunosuppresive therapy (IS) in children with SAA, without bone marrow family donors, is more effective after introduction of combined IS (12.5 years survival in this study was 80% for children with very severe aplastic anaemia (v SAA). 2. In our studies among the children followed up after IS therapy, there were: 1 case of periodic nocturnal haemoglobinuria (PNH), 1 case of myelodysplastic syndrome (MDS) and 2 cases of myeloid leukaemia (probability of incidence was 3.8%).

[Plasma proteasome 20S activity in children treated for acute lymphoblastic leukaemia]. / Ocena aktywnosci proteasomu 20S w osoczu u dzieci z ostra bialaczka limfoblastyczna. Doniesienie wstepne.

UNLABELLED: THE AIM of our study was: to determine the proteasome 20S activity in plasma of patients treated for acute lymphoblastic leukaemia. METHODS: Plasma proteasome activity was measured in children (n=16) at two points: at diagnosis and on the 33rd day using the spectrophotometric method with peptidic substrate and selective proteasome activator 0.03% SDS. RESULTS: 1. At diagnosis we observed high activity of the proteasome 20S in comparison to control (p<0.005). After haematological remission the proteasome 20S activity lowered by about 50% (p<0.05). 3. We did not find the influence of immunophenotype, initial leucocytosis, LDH activity and hepatosplenomegaly on initial proteasome values. CONCLUSIONS: Dynamic changes of the proteasome 20S activity confirm its participation in cancerogenic process. Proteasome 20S activity may be an effective indicator in the monitoring of anticancer treatment.

[Results of immunosuppressive therapy in children with severe aplastic anaemia. Report by the Polish Paediatric Leukaemia and Lymphoma Study Group]. / Efekty leczenia immunosupresyjnego ciezkiej postaci anemii aplastycznej u dzieci. Raport polskiej pediatrycznej grupy ds. leczenia bialaczek i chloniaków.

INTRODUCTION: Bone marrow transplantation from HLA identical family donors is the treatment of choice for children with severe aplastic anaemia (SAA). When no donor is available, combined immunosuppressive therapy is given. AIM: Evaluation of results of immunosuppressive therapy in children with severe aplastic anaemia. MATERIAL AND METHODS: SAA was diagnosed in 85 children (31 girls, 54 boys) aged 2-17.5 years in the eleven centres of the Polish Paediatric Leukaemia and Lymphoma Study Group (PPLLSG) in Poland between 1993-2003 years. All patients received protocol of the Severe Aplastic Anaemia Working Party of the Europe Bone Marrow Transplant (EBMT): antilymphocyte globulin or antithymocyte globulin, cyclosporin A, prednisolone and granulocyto- or granulocyto-macrophagic-cell stimulation factor was additionally administered during deep neutropenia. Haematological response was evaluated on day 84, 112 or 180 of the therapy. RESULTS: complete remission occurred in 43 patients (50.5%), partial remission in 22 (25.4%), no response was obtained in 20 children (23.7%) in 180 day of the therapy. Period of observation was from 12 months to 10.5 years. During this time relapse occurred in 6 patients (7%). We observed 16 deaths: 7 early during the first 3 months of immunosuppressive therapy (IS) and 9 after the first 3 months of IS. CONCLUSION: the actual survival at 10-years, after immunosuppressive therapy is 81.2% in our group. Transformation to leukaemia or myelodysplastic syndrome (MDS) was not observed in any of our patients. We observed one case with paroxysmal nocturnal haemoglobinuria (PNH).

[Immunophenotype of lymphoblastic leukaemia in children in relation to clinical symptoms and laboratory tests, preceding its diagnosis]. / Immunofenotyp ostrych bialaczek limfoblastycznych u dzieci a objawy kliniczne i laboratoryjne poprzedzajace rozpoznanie.

The aim of study was to compare the clinical picture and results of laboratory tests according to the acute lymphoblastic leukaemia (ALL) immunophenotype. The observation was carried out on a group of 67 patients treated in the IIIrd Department of Paediatrics and Department of Children Oncology in the Medical Academy of Bialystok from January 1994 to April 2001. This group consists of 4 children with pro-B acute lymphoblastic leukaemia, 52 children with pre-B cell ALL, 1 child with B-cell acute lymphoblastic leukaemia and 9 children with T-cell acute lymphoblastic leukaemia. Haemorrhagic diathesis. splenomegaly, enlargement of peripheral lymph nodes as well as higher values of white blood cells count, blasts count, haemoglobin concentration, haematocrit and LDH activity were observed more frequently in patients with T-cell leukaemia than in others.

[Diagnostic significance of reticulocyte analysis by flow cytometry, in children with acute lymphoblastic leukaemia (ALL) on chemotherapy]. / Znaczenie diagnostyczne oznaczania retikulocytów metoda cytometrii przeplywowej u dzieci chorych na ostra bialaczke limfoblastyczna (ALL) poddanych chemoterapii.

INTRODUCTION: Reticulocytes and their fractions quickly show changes at the time of chemotherapy, therefore they can be an early indicator of changes arising in the erythrocytic line. THE AIM: of the study was an assessment of percentage, absolute number and immature reticulocyte fraction (IFR) by flow cytometry in children with acute lymphoblastic leukaemia (ALL) and comparing them with classical indexes of the erythrocyte line. MATERIAL AND METHODS: The examined group of 14 children from 2 to 16 years with ALL, on remission support treatment (New York II protocol). RESULTS: The group which was treated by thioguanine and cyclophosphamide showed reduction of reticulocytes from mean value 3,1+/-1:1,4 to 2,5+/-1,8. IFR reduction was not significant statistically. In the group treated with vincristine and methotrexate an average percentage of reticulocytes fell from 3.5+/-O.8 to l,5+/-0,4 and IFR did not change significantly. In children who were treated by daunorubicin and cytosine arabinoside an average percentage of reticulocytes reduced from 3.2+/-O,8 to value 2,1+/-1, 7. The immature reticulocyte fraction (IFR) reduced significantly from 22,0+/-6,0 to 12,0+/-8,0 (p<0,03). CONCLUSIONS: The indicators of reticulocytes were reduced after each cycle chemotherapy: this indicates damage in the erythrocyte line. The indicators examined by cytometric method can show changes earlier than classical indicators used in haematology.