Clinical Characteristics and Treatment Outcomes of Myeloid Sarcoma in Children: The Experience of the Polish Pediatric Leukemia and Lymphoma Study Group.

Introduction: Myeloid sarcoma (MS) is an extramedullary malignant tumor composed of immature myeloid cells. It occurs in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myeloid leukemia (CML). MS may coincide with disease diagnosis or precede bone marrow involvement by months or even years; it can also represent the extramedullary manifestation of a relapse (1, 2). Aim: The aim of this study is to describe clinical characteristics of children diagnosed with MS in Poland as well as to analyze diagnostic methods, treatment, and outcomes including overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS). The study also attempted to identify factors determining treatment outcomes. Patients: The study group comprised 43 patients (F=18, M=25) aged 0-18 years (median age, 10.0 years; mean age, 8.8 years) diagnosed with MS based on tumor biopsy and immunohistochemistry or identification of underlying bone marrow disease and extramedullary tumor according to imaging findings. Methods: The clinical data and diagnostic and therapeutic methods used in the study group were analyzed. A statistical analysis of the treatment outcomes was conducted with STATISTICA v. 13 (StatSoft, Inc., Tulsa, OK, USA) and analysis of survival curves was conducted with MedCalc 11.5.1 (MedCalc Software, Ostend, Belgium). Statistical significance was considered at p<0.05. Results: In the study group, MS was most frequently accompanied by AML. The most common site of involvement was skin, followed by orbital region. Skin manifestation of MS was more common in the age group <10 years. The most frequent genetic abnormality was the t(8;21)(q22;q22) translocation. The 5-year OS probability (pOS), 5-year RFS probability (pRFS), and 5-year EFS probability (pEFS) were 0.67 ± 0.08, 0.79 ± 0.07, and 0.65 ± 0.08, respectively. In patients with isolated MS and those with concurrent bone marrow involvement by AML/MDS, pOS values were 0.56 ± 0.12 and 0.84 ± 0.09 (p=0.0251), respectively, and pEFS values were 0.56 ± 0.12 and 0.82 ± 0.08 (p=0.0247), respectively. In patients with and without the t(8;21)(q22;q22) translocation, pEFS values were 0.90 ± 0.09 and 0.51 ± 0.14 (p=0.0490), respectively. Conclusions: MS is a disease with a highly variable clinical course. Worse treatment outcomes were observed in patients with isolated MS compared to those with concurrent bone marrow involvement by AML/MDS. Patients with the t(8;21)(q22;q22) translocation were found to have significantly higher pEFS. MS location, age group, chemotherapy regimen, surgery, and/or radiotherapy did not have a significant influence on treatment outcomes. Further exploration of prognostic factors in children with MS is indicated.

[Analysis of an abnormal coagulation profile in children qualified for adenoidectomy/tonsilectomy]. / Ocena zaburzen krzepniecia u dzieci zakwalifikowanych do adeno/tonsilektomii.

INTRODUCTION: The routine pre-operative evaluation of children undergoing elective tonsillectomy and/or adenoidectomy includes coagulation screening tests. THE PURPOSE OF THE STUDY: detection of coagulation defects in children with planned tonsillectomy and/or adenoidectomy. MATERIAL AND METHODS: In our study we examined 68 children with abnormal coagulation profile, age 1-17 (average 7.5), 43 male and 25 female. All children underwent coagulation tests (APTT, PT, INR, D-dimer, fibrynogen). In case of twice indicated coagulopathy we diagnosed the levels of the coagulation protein factors. RESULTS: After second verification 15/68 (22%) patients presented prolonged APTT and/or PT. The most common disorder was isolated prolongation of APTT--47/53 (89%), 3/53 (5.5%) had prolonged PT and 3/53 (5.5%) had both disorders in the same time. After vitamin K admission in 19/53 (36%) coagulation tests returned to normal. 13/53 (24%) patients had the factor XII deficiency, 1 patient had a low activity of von Willebrand factor and temporary deficient of factor VIII. In one case we found temporary deficiency of factors VIII and IX and one boy had isolated, temporary deficiency of factor IX. Rest of patients 21/53 (40%), in which the activity of coagulation factors were normal, underwent surgery despite prolonged APTT without any bleeding during or after surgery. CONCLUSIONS: The coagulation disorders in analized group of children were unstable or inessential, but in a group of 3/68 (4%) nondiagnosed disorders of coagulation tests, may due to heavy bleeding during or after surgery.

[Changes in concentrations of circulating insulin-like growth factors I and II and binding proteins BP-2 and BP-3 in children treated for acute lymphoblastic leukaemia]. / Zmiany w stezeniach insulinopodobnych czynników wzrostu IGF-1 i IGF-2 i bialek wiazacych BP-2 i BP-3 w czasie leczenia ostrej bialaczki limfoblastycznej.

UNLABELLED: We determined serum levels of insulin-like growth factors (IGF-1, IGF-2) and binding proteins (IGFBP-2 and IGFBP-3) at diagnosis (I), during (II) and after therapy (III) in 28 children treated for ALL. RESULTS: 1) Serum absolute levels of IGF-1, IGF-2, IGFBP-3 rose and IGFBP-2 - decreased during analysis. 2) Mean values of IGF-1 SDS were similar at diagnosis, during and after treatment (-1.78+/-0.9 vs. -1.86+/-1.36 vs. -1.8+/-0.83). IGF-2 SDS rose from 0.06+/-1.45 (I) to 0.64+/-1.4 (II) and to 0.83+/- 2.01 (III) and IGFBP-3 SDS increased from -0.23+/-2.23 (I) to 0.92+/-1.95 (II) and to 1.76+/-2.43 (III). IGFBP-2 SDS were elevated at diagnosis, during and after treatment 11.94+/-9.42 (I) and 10.58+/-7.37 (II) and to 7.90+/-7.20 (III). 3) We observed positive correlations between: a) IGF-1 and IGFBP-3 at diagnosis (r=0.58 p=0.0001), during (r=0.69 p=0.0001) and after treatment (r=0.79 p=0.00001), b) IGF-1 and IGF-2 at diagnosis (r=0.57 p=0.00001) and after the end of therapy (r=0.48 p=0.01) c) IGF-2 and IGFBP-3 at diagnosis (r=0.7 p=0.0004) and after treatment (r=0.64 p=0.003) and d) negative correlation between IGF-1 and IGFBP-2 - at diagnosis (r=0.38 p=0.02) and after treatment (r=0.43 p=0.02). CONCLUSIONS: Decreased serum IGF-1 and elevated IGFBP-2 were observed at diagnosis and during treatment for ALL suggesting that especially IGFBP-2 may be related to the proliferation of lymphoblasts.

[The assessment of plasma levels of insulin-like growth factor (IGF-I) and binding protein (IGFBP-3) during the maintenance therapy and after remissionof acute lymphoblastic leukemia (ALL)]. / Ocena wartosci insulinopodobnego czynnika wzrostu (IGF-I) i bialka wiazacego (IGFBP-3) w czasie leczenia podtrzymujacego remisje i po zakonczeniu leczenia ostrej bialaczki limfoblastycznej (ALL).

INTRODUCTION: Antineoplastic therapy may cause metabolic disturbances, which result in e.g. abnormal growth rate. The aim of the study was the assessment of IGF-1 and IGFBP-3 plasma concentrations in children after intensive therapy of ALL completed according to age, weight, height and therapy protocols (Methotrexate dose, Central Nervous System - CNS prophylaxis). MATERIALS AND METHODS: 63 children (43 boys) were involved in this study with mean age 10.95+/-4.73 years after ALL therapy according to BFM protocols. 35 patients were in maintenance therapy and 28 completely finished the therapy. 20 children had cranial irradiation as CNS prophylaxis (12 Gy). We assessed plasma levels of IGF-1 and IGFBP-3 in radioimmunoassay method and the obtained results were related to mean age values (SDScore). RESULTS: 1. A) IGF-1 mean plasma levels in children (n=30) before puberty (Tanner I) was 151.48+/-75.75 ng/ml and was lower than compared to value in the puberty group (n=16, Tanner II-IV) - 222.06+/-96.61 ng/ml p=0.000008. After puberty (Tanner V) IGF-1 was 332.03+/-75.66 ng/ml. b) IGFBP-3 was highest after puberty (3837.4 ng/ml +/-598.49); before puberty it was 2899.68+/-656.57 ng/ml, and in puberty it was 3593.14+/-598,49 ng/ml. 2. IGF-1 SDS values were lower than mean age values. 3. IGFBP-3 SDS were insignificantly higher than mean age values. 4. There were no differences between IGF-1 SDS and IGFBP-3 SDS according to gender, prior CNS prophylaxis, methotrexate dose and phase of maintenance therapy and completed therapy. 5. IGF-1 and IGFBP-3 correlated to each other and to body mass index, height but IGF-1 SDS and IGFBP-3 SDS was independent on age, CNS prophylaxis, BMI SDS and height SDS. CONCLUSIONS: 1. IGF-1 and IGFBP-3 values are dependent on puberty degree, body mass index and height. 2. IGF-1 SDS are lower and IGFBP-3 values higher, independent on gender, therapy protocol and CNS prophylaxis (12 Gy).

[The influence of age, gender and modifications of therapeutic protocols on physical development of children and adolescents after completion of therapy for acute lymphoblastic leukemia]. / Wplyw wieku, plci oraz modyfikacji protokolów leczniczych na rozwój fizyczny dzieci i mlodziezy po zakonczonym leczeniu ostrej bialaczki limfoblastycznej.

UNLABELLED: THE AIM of the study was the longitudinal assessment of physical development of children treated for acute lymphoblastic leukemia (ALL) in the past. A total group of 76 children (51 girls), from whom 63 get ill before puberty, were included in the study. Therapy was managed according to BFM protocols in which central nervous system (CNS) prophylaxis was used in 27 children in dose 12 Gy, methotrexate in dose 5 g/m(2) was used in 63 children and 1g/m(2) in 13 children. Height and body mass index expressed as standard deviation score (SDS) in the time of diagnosis (H1 SDS, BMI1 SDS), after intensive therapy (H2 SDS, BMI2 SDS) and after 1.7+/-3.13 years from therapy (H3 SDS, BMI3 SDS) were assessed. RESULTS: 1. BMI2 SDS values increased in relation to BMI1 SDS (p=0.0000001) and BMI3 SDS values insignificantly decreased, but they were higher than at the time of diagnosis. 2. We affirmed increase of BMI2 SDS in the group of boys directly after the treatment (p=0.00006) and later decrease (p=0.04), so there were no differences between BMI1 SDS and BMI3 SDS. 3. The increase of BMI2 SDS in comparison with BMI1 SDS (p=0.007) was kept until the treatment completed in the group of girls (p=0.05 between BMI1 SDS and BMI3 SDS). 4. The increase and next decrease of BMI SDS values was observed among children who get ill before puberty. But we noticed intermittent increase of BMI SDS in the puberty children at the time of diagnosis. 5. We affirmed increase of BMI SDS after the treatment completed in the group of children treated with only cytostatics. The increase of BMI SDS (p=0.02) and next decrease of BMI3 SDS (p=0.007) was noticed in the group with CNS prophylaxis, there were no differences between BMI1 SDS and BMI3 SDS. 6. We observed increase of BMI2 SDS and BMI3 SDS in comparison with BMI1 SDS (p=0.00001 and p=0.0004) in the group treated with 5 g/m(2) methotrexate. BMI3 SDS values were decreased in comparison with BMI2 SDS (p=0.01) and BMI1 SDS (p=0.006) in the group treated with 1 g/m(2) methotrexate. 7. There were no significant changes in the growth rate during the treatment and after therapy. CONCLUSIONS: 1. ALL treatment contributes to the increase of body mass, which is kept until therapy completed, especially in the group of girls. 2. Growth rate including children with CNS prophylaxis does not submit significantly disturbances.

[Renal function and size after complex treatment of Wilms' tumour]. / Czynnosc i wymiary nerki po kompleksowym leczeniu guza Wilmsa.

The aim of our study was to measure renal function and growth in survivors of unilateral Wilms' tumour in 21 children and young adults (7 female). The mean age was 12.6 +/- 4.8 years, mean follow-up time was 7.01 +/- 4.25 years: seven of the group received irradiation (35 Gy). Blood pressure was normal in all patients. Three of them had elevated cystatin C and clearance of cystatin C below referenced normal value. The others had normal renal function tests (cystatin C, creatinine and cystatin clearance, B2 microglobulin, microalbuminuria, osmolality). Compared to the control we found higher cystatin C values in children treated before the age 3 years old (p=0.03) and in children treated more than 5 years before (p=0.03), and lower cystatin clearance in group treated before the age 3 years old (p=0,03). No difference between the irradiated and non-irradiated group was found. We observed a greater increase in volume (155.9% +/- 33.4) than in length (127.9% +/- 6.3). The highest rise of renal volume was in children treated more than 5 years before (174.6% +/- 22.3). In conclusion, our data suggest that after combined treatment for Wilms' tumour compensatory renal hypertrophy and a tendency progressive renal dysfunction takes place.