Pearson marrow pancreas syndrome in patients suspected to have Diamond-Blackfan anemia.

Pearson marrow pancreas syndrome (PS) is a multisystem disorder caused by mitochondrial DNA (mtDNA) deletions. Diamond-Blackfan anemia (DBA) is a congenital hypoproliferative anemia in which mutations in ribosomal protein genes and GATA1 have been implicated. Both syndromes share several features including early onset of severe anemia, variable nonhematologic manifestations, sporadic genetic occurrence, and occasional spontaneous hematologic improvement. Because of the overlapping features and relative rarity of PS, we hypothesized that some patients in whom the leading clinical diagnosis is DBA actually have PS. Here, we evaluated patient DNA samples submitted for DBA genetic studies and found that 8 (4.6%) of 173 genetically uncharacterized patients contained large mtDNA deletions. Only 2 (25%) of the patients had been diagnosed with PS on clinical grounds subsequent to sample submission. We conclude that PS can be overlooked, and that mtDNA deletion testing should be performed in the diagnostic evaluation of patients with congenital anemia.

[Treatment results of children with neuroblastoma: report of Polish Pediatric Solid Tumor Group]. / Wyniki leczenia dzieci ze zwojakiem zarodkowym wspólczulnym: wstepny raport Polskiej Pediatrycznej Grupy Guzów Litych.

Approximately 60 children aged 0-18 years are diagnosed of NBL each year in Poland. About 60% of all patients suffering from NBL have a chance for durable cure. Unfortunately the prognosis for patients within the high-risk group accounting for more than 50% of all NBL patients remains poor despite the introduction of more intensive chemotherapy regimens with radical surgery procedures and megachemotherapy with subsequent stem cell transplantation. Only one third of patients in this group can be cured. To improve the treatment results of the high-risk patient group and to decrease the rate of therapy related side effects current European treatment protocols have been introduced systematically in Poland. In February 2009 information about 389 patients (age 0.1-16.5 years) diagnosed between 2001 and 2008 were obtained. Results of therapy of 319 patients who started treatment from 2001 to 2007 were analyzed. Between 104 infants and 215 children over 1 year of age, stage 4 of disease was found in 25% and 54.5%, respectively. In this period additionally to European treatment protocols, two another protocols were used. Satisfactory treatment results were obtained in 104 infants (5-year event free survival /EFS/=82.6%), irrespective of the type of treatment protocol. Over 5-year EFS for children over 1 year of age in 1, 2 and 3 stage of disease was: 100%, 86.3% and 64.5%, respectively. On the contrary, 107 patients with 4 stage of disease achieved the 5-year EFS of 27% only. Treatment results obtained in patients treated according to the European HR-NBL-1/ESIOP protocol were better than for patients treated according to other treatment protocols (5-year EFS: 31.1% and 16.4%, respectively), but difference between these groups was not significant. Between 2001 and 2007 data reporting increased to 81% from 19% noted earlier. Unfortunately, results of treatment for children over 1 year of age remain still unsatisfactory. That is why there is a need of improvement of modern, unified treatment realization as well as better data reporting. For realization of these aims adequate financial support is essential.

[Application of long term subcutaneously implanted access into the central veins system of "PORT" type in the Clinic of Pediatry, Pediatric Hematology and Oncology in Zabrze--15 year own observations]. / Zastosowanie dlugoterminowego, implantowanego podskórnie akcesu do ukladu zyl centralnych typu "PORT" w Klinice Pediatrii, Hematologii i Onkologii Dzieciecej w Zabrzu--15 lat obserwacji wlasnych.

INTRODUCTION: Long term disease treatment in children is a very special medical problem due to a necessity of maintaining an efficient venous access for many months and even years. Vascular ports applied in those children improved the conditions of treatment and a quality of life, additionally, made the job of personnel taking care of them easier. MATERIAL AND METHODS: The study presents own experience in long-term venous access into the central veins system, so called vascular ports, gathered for 15 years of using them in children with hemato-oncogical diseases. The analysis of 309 of implanted vascular ports was done taking into consideration the maintenance and complications. Ports were implanted in 300 children with oncological diseases. The received results are presented in numbers and percentage. RESULTS: Mean time of port insertion has decreased in comparison to earlier studies by 35 days and now is 722 days, median 658 days, however, minimal and maximal time of port insertion has changed respectively 7 and 2099 days. The total time of port insertion in this period was 232 536 days. The observation showed 31 (10.03%) cases of complications, out of which the most common were set infection (16 - 5.18%), catheter occlusion by a clot (7 - 2.27%) and "spontaneous" catheter move out of vessel lumen (3 - 0.97%), migration of a torn-off catheter into the right heart ventricle (2 - 0.65%). CONCLUSIONS: 1. Application of vascular ports enabled a long-term and intensive chemotherapy in children with oncological and hematological diseases. 2. Application of vascular ports bears a minor risk of complications, the most dangerous observed complication was a replacement of a torn-off catheter into the right heart ventricle.

Decreased numbers of CD4+ T lymphocytes in peripheral blood after treatment of childhood acute lymphoblastic leukemia.

Treatment-related immunosuppression in patients with acute lymphoblastic leukemia (ALL) is associated with increased susceptibility to infectious diseases, also after the treatment. The aim of the present study was the detailed evaluation of T lymphocyte subsets in peripheral blood in children after treatment of ALL. All children were treated according to the BFM 90 protocol. The patients were divided into 5 groups of 30 children in each, depending on the time from cessation of the ALL treatment. A control group consisted of 30 healthy children subjected to elective "1-day" surgery. The children's age ranged from 6 to 18 years. The examinations were performed in FACScan flow cytometer with the use of wide set of monoclonal antibodies: CD3, CD4, CD8, TCRalphabeta, TCRgammadelta, CD19, CD25, CD45RA, CD45RO, CD69, HLA-DR, CD16 and CD56, which particularly allowed detailed analysis of T lymphocytes. The results showed that most parameters in children 1 year after ALL treatment completion were similar to healthy children. However, we observed persistently low CD4+ T cell numbers, both CD45RA+ as well as CD45RO+ subsets as compared to the control group. This might reflect decreased regenerative potential of immunological system in children 1 year after ALL treatment.

Skin involvement in highly malignant non-Hodgkin lymphomas of childhood and adolescence.

OBJECTIVE: The aim of this study was to demonstrate the clinical spectrum of highly malignant cutaneous non-Hodgkin lymphoma (NHL) in children and to define the outcome among these patients. MATERIAL AND METHODS: A retrospective analysis of children with NHL treated at Polish oncology centers was carried out in order to determine patients with skin involvement. Thirteen subjects with primary and 4 with secondary cutaneous NHL were studied. The diagnosis of NHL was based on histological and immunohistochemical examination of skin biopsy. RESULTS: Nine of 13 cases of primary cutaneous NHL presented as a tumors. Other manifestations were as follows: hard infiltration, edema of subcutaneous tissue, maculopapular lesions, and generalized erythroderma. The mean time between the first cutaneous symptoms and diagnosis of NHL was 5.6 +/- 3.3 months. Secondary cutaneous lesions during the course of NHL were described as maculopapular or nodular eruption. In addition, 2 subjects had generalized ichthyosis. Among patients with primary cutaneous NHL, 11 (84.6%) subjects are still alive without any signs of the disease. Two children (15.4%) died. In patients with secondary skin involvement during the course of NHL only one child is still alive with a residual tumor mass in the mediastinum. The estimated 5-year overall survival for primary cutaneous NHL was significantly better than for individuals with secondary cutaneous NHL (p = 0.02). CONCLUSIONS: Primary cutaneous NHL has a relatively favorable prognosis. On the other hand, cutaneous metastases of extracutaneous NHL seem to be a poor prognostic factor.

[Thyroid function after external irradiation of the neck in patients with Hodgkin's disease--long-term observation]. / Czynnosc tarczycy po radioterapii okolicy szyi u pacjentów z choroba Hodgkina--dlugoletnia obserwacja.

INTRODUCTION: The modern therapy of Hodgkin's disease (HD): chemotherapy (CT) or/and radiotherapy (RT) gives a chance of a long time survival but it brings a possibility of early and late complications including thyroid gland function disorders (post-radiotherapy thyroiditis, thyroid hypofunction, Graves disease, thyroid nodules, thyroid cancer). AIM: Evaluation of thyroid gland function in patients with total HD remission status from 6 to 16 years after the treatment. MATERIAL AND METHODS: The study included 29 patients suffering from HD (9 women, 20 men, mean age 22.8 years), treated with CT (cycles MVPP and B-DOPA) and with RT (cervical region; 18-40 Gy) in their childhood. The patients were examined by palpation, ultrasound, fine-needle aspiration biopsy. The thyroid gland on the average 6 (1st examination) and 16 years (2nd examination) after the treatment as well as thyroid hormones (TSH, fT3, fT4), thyroglobulin (Tg) and anti-thyroid antibodies in blood serum were estimated. The results were analyzed statistically; the percentage of abnormal results of estimated hormones with reference range was calculated. RESULTS: There were no abnormalities in thyroid palpation examination in any patient. The mean thyroid volume in ultrasound in 2nd examination cor-responded to 66.3% of healthy individuals thyroid volume. In 8 patients thyroid nodules were found, in one thyroid papillary carcinoma was diagnosed. In one patient (3.4%) the features of subclinical thyroid hypofunction and in 17.2% the increased level of Tg in blood serum with normal thyroid hormone levels were found. In two patients (6.8%) the raised titre of a-TG and a-TPO was observed. CONCLUSIONS: 1. In majority of patients with HD after RT in cervical region in long term remission period the normal thyroid function was observed. 2. Due to thyroid cancer hazard even many years after radiotherapy regular morphological thyroid evaluation is necessary.

Clinical features and treatment outcomes of peripheral T-cell lymphoma in children. A current data report from Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG).

PURPOSE: Peripheral T-cell lymphomas (PTCL) are lymphoproliferative disorders derived from post-thymic cells, that occur extremely rarely in children. The optimal treatment of pediatric PTCL remains still unclear. PATIENTS AND METHODS: Ten children with PTCL from 3 up to 18 years of age registered by the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) were retrospectively analyzed. All patients were treated with different regimens including protocols: for lymphoblastic lymphoma in 7 cases, for anaplastic large cell lymphoma in 1, CHOP in 1. Five of the 10 patients with PTCL were classified as stage II; 4 as stage III and 1 as stage IV due to extralymphatic organs (bone marrow) involvement. Four histological subtypes of PTCL were recognized: extranodal NK/T-cell lymphoma, nasal type (ENTNT), peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), subcutaneous panniculitis-like T-cell lymphoma (SPL), Sezary syndrome (SS). After first-line therapy 9 patients initially achieved complete remission, 4 relapsed, 5 died. One patient achieved remission spontaneously. Three children (1 with stage IV and 2 in relapse) underwent high-dose chemotherapy with allogeneic bone marrow stem cell transplantation and all of them are alive and in CR. RESULTS: The cumulative probability of 5-year overall survival (OS) for our whole group was 63.9% (95%CI: 35.2-88.2%) with a median follow-up time of 48.4 months (range 24-90+ months). The 5-year event free survival (EFS) was 81%. PTCLs are a heterogeneous and rare group of childhood NHLs. CONCLUSIONS: According to our experience the standard chemotherapy for precursor lymphomas seems to be a beneficial treatment option for children with PTCL. Allogeneic stem cell transplantation may improve the outcome in selected patients.

[Tumor lysis syndrome in the course of acute lymphoblastic leukemia as the consequence of prednisone monotherapy]. / Zespól lizy guza w przebiegu ostrej bialaczki limfoblastycznej spowodowany monoterapia prednizonem.

Authors present the case of 15-year-old girl with diagnosed pre T-acute lymphoblastic leukaemia with hyperleukocytosis--at admission 213 x 10(9)/l. At clinical evaluation a major peripheral and abdominal lymphadenopathy, mediastinal mass, hepatosplenomegaly were revealed. After administration of prednisone for two times--11.4 mg/m2/24 h--the features of tumour lysis syndrome rapidly increased. Hyperphosphatemia, hyperkalemia and hyperuricemia resulted in acute renal failure. Renal replacement therapy was introduced with simultaneous application of cytoreduction phase therapy and induction of remission according to New York protocol. Total number of performed hemodialysis sessions was 12. Obtained haematological remission in 8th week of treatment is still present. Renal function remains normal. Remission supportive treatment has been continued according to above-mentioned protocol.

[Leukapheresis in children with chronic myeloid leukemia and pulmonary leukostasis]. / Leukafereza u dzieci chorych na przewlekla bialaczke szpikowa z objawami leukostazy plucnej.

We present two patients with chronic myeloid leukemia and hyperleukocytosis above 350 x 10(9)/l causing the symptoms of pulmonary leukostasis. Therapeutic leukapheresis procedures with concomitant chemotherapy were initiated within 12 hours from the diagnosis. After the therapy commencement the general condition of the patients systematically improved and leukocytosis gradually decreased from the second day of treatment with disappearance of pulmonary leukostasis symptoms. Thanks to application of such treatment procedures during the cytoreductive period, severe complications related to leukostasis could be prevented.

[Acute lymphoblastic leukemia in a 3-week-old neonate]. / Ostra bialaczka limfoblastyczna u 3-tygodniowego noworodka.

We present a case of 3-week-old infant, in whom we established the diagnosis of congenital acute lymphoblastic leukemia (ALL), characterized by the immunophenotype of the most immature B-cell precursors (pro-B-ALL) and chromosomal translocation t(4;11) associated with the rearrangement of MLL and AF4 genes. The clinical course of this leukemia deserves particular attention, because it was different from classical presentation: diagnosis--not immediately after birth--but at the age of 3 weeks, no signs of hemorrhagic diathesis, lack of nodular skin infiltrates, and no central nervous system involvement. Exchange blood transfusions performed during the remission induction treatment saved the child from life-threatening symptoms of leukostasis at the initial stage of leukemia. Despite successful remission induction in bone marrow, the infant relapsed during the fifth month of treatment. After subsequent chemotherapy course the child died owing to fatal infectious complications. Despite enormous progress in treatment of childhood ALL, this type of leukemia in infants below 6 months of age, and particularly in cases of congenital leukemia is still associated with a very poor prognosis.

[Progress in the treatment of non-Hodgkin's lymphoma (NHL) in children. The report of Polish Pediatric Leukaemia/lymphoma Study Group (PPLLSG)]. / Postep w leczeniu nieziarniczych chloniaków zlosliwych (NHL) u dzieci. Raport Polskiej Pediatrycznej Grupy ds. Leczenia Bialaczek i Chloniaków u Dzieci (PPGLBC).

Treatment results of non-Hodgkin lymphoma (NHL) in children has been shown in this study. From 1979 to 2003 children were registered with the diagnosis of NHL in oncology centers of Polish Pediatric Leukaemia/Lymphoma Study Group, a group of 397 patients with NHL B, 222 pts with NHL T and 54 pts with anaplastic large cell lymphoma (ALCL). The pts with NHL T have been treated according to BFM-90 protocol. The predominant primary site of disease was mediastinum (59.3%). Complete remission (CR) was achieved by 87%. EFS for all NHL T pts was 65% and 56% for pts with extensive tumours and 73% for pts with tumours < 10 cm. Patients with NHL B were treated according to the adopted LMB-89 protocol. The majority were Burkitts type and presented abdominal location (50%). 80% with disseminated disease. CR was achieved by 89% patients, but 94% with LDH < 500 IU/L and 73% with LDH > 500 IU. The median time of follow up was 53 months. EFS was 73% for all patients. The patients with ALCL were treated according to several protocols. Peripheral nodes were the most often primary location (40%), than mediastinum (24%) and abdomen (21%). EFS for all pts was 63%. Despite great progress in the therapy of NHL in children during 20 years of observation, the results are not satisfactory in disseminated stages. It is necessary to look for new prognostic markers which make it possible to improve classification of patients. Major surgery in advanced stages is not recommended since it delays chemotherapy and fails to improve overall survival. Early detection of neoplasm is one of the most important efforts to improve therapy success.

[Sudden blindness of 11-year old boy in the course of acute lymphoblastic leukemia]. / Nagle zaniewidzenie u 11-letniego chlopca w przebiegu ostrej bialaczki limfoblastycznej.

PURPOSE: The aim of this study is to present dramatic ocular manifestation of acute lymphoblastic leukemia. MATERIAL AND METHODS: The 11 years old boy was hospitalized due to acute leukemia at the Department and Clinic of Pediatric Hematology, and was referred to ophthalmic examination because of sudden blindness of the right eye. General ophthalmic examination and electrophysiological tests were done. RESULTS: No light perception of right eye, and markedly reduced visual evoked responses were caused by infiltration with great edema in optic nerve and its surrounding of retina. In spite of the fact, that the infiltrations disappeared after general therapy, the vision did not recover at all. CONCLUSIONS: Even intensive treatment may be ineffective in blindness prevention in severe course of acute leukemia.

[Acute endophthalmitis of 15-year old boy in the course of acute lymphoblastic leukemia--part I]. / Ostre zapalenie galki ocznej u 15-letniego chlopca w przebiegu ostrej bialaczki limfoblastycznej--czesc I.

PURPOSE: The aim of this study is to present dramatic ocular manifestation of acute lymphoblastic leukemia. MATERIAL AND METHODS: 15-year old boy was hospitalized due to acute leukemia at the Department and Clinic of Pediatric Hematology and was referred to ophthalmologist because of strong pain and decreased visual acuity of the left eye. General ophthalmic examination and electrophysiology were done. These procedures were repeated after 1, 2, 5 and 11 weeks and also after 6 and 9 months. RESULTS: Acute uveitis with cellular exudation to the vitreous, papilledema, swelling of the macula and green-yellowish infiltration which elevated the temporal part of the retina, were noticed. Swelling of the iris and miosis were observed. After one week of local anti-inflammatory treatment the eye became painless with little deep injection only. Simultaneously causal treatment of basic disease was continued. Control examinations revealed step by step improvement of ocular changes. After 6 months in the place of retinal infiltration choroidoretinal atrophy was seen. The functional deficits in visual field and electrophysiological examinations were found, too. One year later, the patient came again because of recurrence. Involvement of the central nervous system with signs of meningitis occurred. Visual acuity was normal and no infiltration of eyes was found, but there was papilledema in both eyes. CONCLUSIONS: In acute leukemia ocular manifestation may be highly expressed. The patients require local symptomatic and general causal treatment in cooperation of ophthalmologist with hematologist.

[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%).

[Organ-specific fungal infections as a complication of treatment of children with cancer. A single centre observation]. / Grzybice narzadowe--jako powiklanie leczenia dzieci z choroba nowotworowa. Obserwacje wlasne.

Increasing intensity of treatment of childhood malignancies as well as administration of the new generation broad-spectrum antibiotics is associated with increased risk of fungal infections. In this paper, we describe two patients, in whom anti-neoplastic treatment was complicated by systemic fungal infection. Early suspicion and/or detection of fungal infection enables more effective and shorter treatment. Administration of an anti-fungal drug should be considered in every neutropenic patient after chemotherapy and/or with protracted fever. Since the anti-fungal treatment is usually prolonged, this results in significant interruption of the chemotherapy.

ALK-positive diffuse large B-cell lymphoma.

Anaplastic lymphoma kinase (ALK) positive diffuse large B-cell lymphoma (DLBCL) is a rare subtype of non-Hodgkins lymphoma. Five such cases have been described in children. We present a 9-year-old boy, in whom diagnosis of DLBCL has been established in addition to congenital multiple enchondromatosis. Immunohistopathological evaluation of tumor biopsy established the final diagnosis of ALK + DLBCL. The clathrin gene (CLTC)-ALK fusion underlying aberrant expression of ALK in the present case was demonstrated by interphase fluorescence in situ hybridization (FISH) using break-apart rearrangement probes for ALK and CLTC. The disease in this patient was highly resistant to applied chemotherapy regimens and to radiotherapy. Analysis of the disease course in our patient and review of other cases reported previously show that ALK + DLBCL can be an aggressive malignancy that can be cured with conventional chemotherapy protocols only at stage of localized disease.

[Analysis of microvascular density and the expression of vascular-endothelial growth factor (VEGF) and its membrane receptor Flk-1 in neuroblastoma]. / Analiza gestosci naczyniowej oraz ekspresji sródblonowo-naczyniowego czynnika wzrostu (VEFG) i jego receptora blonowego (FLK-1) w neuroblastoma.

AIM: To assess selected angiogenic markers; microvascular density and the expression of VEGF and Flk-1 in relation to clinical features and morphologic types of neuroblastoma. PATIENTS AND METHODS: Eighty-two children with neuroblastoma were studied. Morphological assessment was performed in paraffin embedded tissues of the primary tumours. Microvessels within tumour tissue were counted on immunohistochemically stained sections using anti CD34 antibody. The expression of VEGF and Flk-1 was estimated semiquantitively in immunohistochemically stained sections with adequate antibodies. The results of angiogenic studies were referred to the clinical data: age, clinical stage, localization and site of the primary tumour, serum LDH and ferritin at diagnosis. The correlation between angiogenic markers and morphological type of neuroblastoma was also evaluated. RESULTS: Microvascular density varies in a wide range (32-325/mm(2)). There was no significant statistical difference between previously untreated and tumours assessed after chemotherapy. Analyzing the correlations between the angiogenic markers and clinical features we found a converse relation between the age and microvascular density. The highest expression of VEGF was found in adrenal tumours in comparison to other localizations. Undifferentiated and poorly differentiated tumours presented a higher expression of VEGF and higher vascular density. Non significant higher expression of VEGF and higher vascular density was noticed in smaller <5 cm tumours. CONCLUSIONS: Correlations were found between the microvascular density and the age, diameter and the localisation of the primary tumour. Expression of VEGF depends on the localisation of the tumour. Neuroblastoma tumours arising in small children and poorly differentiated types of neuroblastoma indicate higher angiogenic activity.

[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).

Carrier frequency of mutation 657del5 in the NBS1 gene in a population of Polish pediatric patients with sporadic lymphoid malignancies.

Nijmegen breakage syndrome (NBS) is a human autosomal recessive disease characterized by genomic instability and enhanced cancer predisposition, in particular to lymphoma and leukemia. Recently, significantly higher frequencies of heterozygous carriers of the Slavic founder NBS1 mutation, 657del5, were found in Russian children with sporadic lymphoid malignancies, and in Polish adults with non-Hodgkin lymphoma (NHL). In addition, the substitution 643C>T (R215W) has also been found in excess among children with acute lymphoblastic leukemia (ALL). In an attempt to asses the contribution of both mutations to the development of sporadic lymphoid malignancies, we analyzed DNA samples from a large group of Polish pediatric patients. The NBS1 mutation 657del5 on one allele was found in 3 of 270 patients with ALL and 2 of 212 children and adolescents with NHL; no carrier was found among 63 patients with Hodgkin lymphoma (HL). No carriers of the variant R215W were detected in any studied group. The relative frequency of the 657del5 mutation was calculated from a total of 6,984 controls matched by place of patient residence, of whom 42 were found to be carriers (frequency = 0.006). In the analyzed population with malignancies, an increased odds ratio for the occurrence of mutation 657del5 was found in comparison with the control Polish population (OR range 1.48-1.85, 95% confidence interval 1.18-2.65). This finding indicates that the frequency of the mutation carriers was indeed increased in patients with ALL and NHL (p < 0.05). Nonetheless, NBS1 gene heterozygosity is not a major risk factor for lymphoid malignancies in childhood and adolescence.