Total body irradiation is a crucial risk factor for developing secondary carcinomas after allogeneic hematopoietic stem cell transplantation in childhood.

Allogeneic hematopoietic stem cell transplantation (HSCT) has become a standard part of therapy for a variety of malignant and non-malignant disorders. With improved outcomes after HSCT, increasing attention has been drawn to late complications in long-term survivors. The development of secondary malignancies is recognized as one of the most serious complications. We have evaluated data from 426 patients (272 males, 154 females) who underwent allogeneic transplantation at a median age of 7.9 years from 1989 till 2017 and were alive more than one year after transplantation for the occurrence of secondary solid tumors. We have documented the occurrence of secondary solid tumors in 20 patients (4.7%). The median duration of the development of secondary solid cancer from HSCT was 11.7 (range, 5.4-21.5 years). 18 out of 20 patients (90%) had total body irradiation (TBI) 12-14.4 Gy as a part of a conditioning regimen. All but two had transplantation for malignant disease. All patients underwent surgery and/or chemo-radiotherapy. Eighteen are alive, and two died due to the progression of their secondary malignancy. The most frequent solid cancer was thyroid carcinoma (n=9). Cumulative incidence of secondary solid cancer in all groups was 15.2±3.9%, in a group using TBI based regimen 34.7±8.9%, in non-TBI (only chemo) group was 1.5±1.1%. Overall, the cumulative incidence is statistically significantly different between the TBI based and non-TBI (chemo only) group. The incidence and number of complications following allogeneic HSCT in childhood are increasing in time. The early diagnosis of secondary malignancies is one of the key tasks of long-life multidisciplinary post-transplant care.

Blastic plasmacytoid dendritic cell neoplasm: First retrospective study in the Czech Republic.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with aggressive behavior and poor prognosis. We present the first retrospective analysis mapping its incidence and therapeutic outcomes in patients diagnosed and treated from 2000 to 2017 in the Czech Republic. The cohort comprised 14 patients (10 males, 4 females) with a median age at diagnosis of 39 years (range, 5-68 years). Initially, skin involvement was noted in 10 (71%) patients and bone marrow infiltration was present in 9 (64%). The first complete remission was achieved in 6/14 (43%) patients after acute lymphoblastic leukemia/lymphoma induction therapy and in 3/14 (21%) patients after acute myeloid leukemia regimen. Nine patients underwent allogeneic hematopoietic cell transplantation, with two patients achieving the first complete remission only after allogeneic transplantation. Patients undergoing allogeneic hematopoietic cell transplantation had longer overall survival than those treated without transplantation (the median survival over the period 16.4 vs. 8.1 months). Relapse of the disease was a significant predictor of mortality (p=0.05). Over the study period, patients' survival ranged from 3.3 to 44.2 months, with a median overall survival of 13 months. Our results revealed an effectivity of allogeneic hematopoietic cell transplantation on complete remission achievement in refractory/relapsed disease. The study aimed to present the actual data from the Czech Republic and thus contribute to a global understanding of BPDCN.

The use of broad-range bacterial PCR in the diagnosis of infectious diseases: a prospective cohort study.

OBJECTIVES: Broad-range PCR has the potential to detect virtually any bacterial species via amplification and nucleotide sequencing of a DNA region common to all bacteria. We aimed to evaluate its usefulness and clinical relevance when applied to a wide variety of primary sterile materials. METHODS: A prospective study including 1370 samples (75 heart valves, 151 joint tissue samples, 230 joint aspirates, 848 whole blood samples and 66 culture-negative cerebrospinal fluid samples) were studied by using a commercial PCR system for detecting 16S rDNA (Molzym). The PCR results were compared with culture and were considered to provide added diagnostic value only if the PCR approach revealed new pathogens that were missed by culture. RESULTS: The added value of PCR was evident in 173 of 555 PCR-positive samples (0.126; 0.109-0.144 (proportion from all tested samples; 95% confidence interval)), most frequently in examinations of heart valves (0.56; 0.448-0.672) and joint tissue samples (0.219; 0.153-0.284). In contrast, the lowest rate of PCR with added value was noted for blood samples, regardless of the patient cohort they had been drawn from (nononcologic patients from intensive care: 0.065; 0.043-0.087, haematooncologic children: 0.048; 0.027-0.070). Moreover, PCR missed up to 7.1% of blood culture findings (0.071; 0.048-0.095) regarded as clinically relevant, which was the second highest failure rate after joint tissue samples (0.099; 0.052-0.147). CONCLUSIONS: Broad-range PCR substantially increases detection rate of pathogens, especially from heart valves and joint samples. However, a concurrent risk of false-negative PCR results justifies the need for parallel culture.

Monitoring minimal residual disease in children with high-risk relapses of acute lymphoblastic leukemia: prognostic relevance of early and late assessment.

The prognosis for children with high-risk relapsed acute lymphoblastic leukemia (ALL) is poor. Here, we assessed the prognostic importance of response during induction and consolidation treatment prior to hematopoietic stem cell transplantation (HSCT) aiming to evaluate the best time to assess minimal residual disease (MRD) for intervention strategies and in future trials in high-risk ALL relapse patients. Included patients (n=125) were treated uniformly according to the ALL-REZ BFM (Berlin-Frankfurt-Münster) 2002 relapse trial (median follow-up time=4.8 years). Patients with MRD ⩾10(-3) after induction treatment (76/119, 64%) or immediately preceding HSCT (19/71, 27%) had a significantly worse probability of disease-free survival 10 years after relapse treatment begin, with 26% (±6%) or 23% (±7%), respectively, compared with 58% (±8%) or 48% (±7%) for patients with MRD <10(-3). Conventional intensive consolidation treatment reduced MRD to <10(-3) before HSCT in 63% of patients, whereas MRD remained high or increased in the rest of this patient group. Our data support that MRD after induction treatment can be used to quantify the activity of different induction treatment strategies in phase II trials. MRD persistence at ⩾10(-3) before HSCT reflects a disease highly resistant to conventional intensive chemotherapy and requiring prospective controlled investigation of new treatment strategies and drugs.

[Peripartal hemorrhage with a necessity to make a hysterectomy as a life-rescuing operation - case report]. / Peripartální zivot ohrozující krvácení s nutností provedení hysterektomie jako zivot zachranujícího výkonu - kazuistika.

OBJECTIVE: To present a case of peripartal hemorrhage with a necessity to make a hysterectomy. DESIGN: Case Report. SETTING: Department of Obstetrics and Gynecology, Hospital Mladá Boleslav. CASE REPORT: We report a case of 34-year-old secundigravida secundipara in 40th week of pregnancy after caesarean section, when after an iterative caesarean section strong peripartal hemorrhage appeared with a necessity to make an urgent revision of an abdominal cavity. Conservative farmacological methods do not stop the bleeding, so it is necessary to make a hysterectomy as a life-rescuing operation. CONCLUSION: Presenting this case report authors want to refer to the fact, that even in these days of modern medicine it is still necessary to manage the technic of abdominal hysterectomy as a life-rescuing operation and claim necessity of interdisciplinary co-operation, especially in between obstetrician, anesthetist and haematologist.

[Femoral lengthening. A critical review of ten-year results]. / Kritické zpracování prodluzování femuru za posledních deset let.

PURPOSE OF THE STUDY: To evaluate the results of femoral lengthening in the patients treated from 2000 to 2009 in whom complete radiographic data were available and the lengthening procedure involved mainly the use of a Mephisto fixator. MATERIAL AND METHODS: A total of 28 femoral lengthening procedures were carried out in 26 patients,16 girls and 10 boys. The external fixator Mephisto was used in 24 cases; fixators Prospon and Orthofix in one and three cases, respectively. Fifteen patients were treated for congenital short femur, the rest had secondary femoral shortening due to following pathologies: distal femoral epiphysiolysis in five children, proximal femoral osteomyelitis in one child, avascular necrosis of the femoral head in one, diaphyseal femur fracture in one, enchondromatosis of the distal femur with growth plate destruction in one, and contralateral femur overgrowth following a fracture in one child. The average age at the beginning of treatment was 11 (range, 4-16) years. Complications were classified as mild, serious and critical. The results were statistically analysed using several statistical tests. RESULTS: The average parameter values for the group included: total femoral lengthening, 40.2.mm (SD±11.1); osteotomy index (OI), 41 % (SD±9.8); lengthening percentage (LP), 10.9 % (SD±3.8); lengthening index (LI), 14.5 (SD±3.5) days/cm; hea- ling index (HI), 52.6 (SD±20.1) days/cm; and consolidation index (CI), 93.3 (SD±40.0) days/cm. Mild complications were recorded in 11 (39.2 %), and serious and critical in eight patients (28.6 %). Fourteen patients (53.8 %) were free of any complications. Two complications were concurrently found in five patients (17.9 %). There was a statistically significant difference in the LP values related to the number of complications (p=0.019). No significant relationship was recorded on comparison of the HI value with the patient's age at the time of surgery (p=0.836) and patient's gender (p=0.546) (Mann- Whitney test). The relationship of the OI value to the HI value was non-significant (p=0.492), as was the relationship between the osteotomy technique (oscillating or Gigli saw osteotomy) and the occurrence of complications (p=1.000) (Fisher's exact test). Correlation between the LI and HI values was significant (p<0.001). DISCUSSION: The results of healing after lengthening, as assessed by the healing and the consolidation index, were in agreement with other authors' data. The lower number of complications, particularly fractures of bone regenerate, can be explained by the facts that, in our study, the lengthening percentage was lower and that the post-operative care was strictly observed, including dynamic axial loading which stimulates bone consolidation at the lengthened section, with adherence to the proof of three developed cortices. CONCLUSIONS: Our results did not confirm the assumption that slower lengthening will have a favourable effect on the healing index. Key words: femoral lengthening, external fixator, complications.

[A contribution of instrumental gait analysis to the establishment of surgical indications in cerebral palsy]. / Prínos instrumentální pohybové analýzy pro indikaci chirurgické lécby u detské mozkové obrny.

PURPOSE OF THE STUDY: To evaluate our experience with indications for surgery based on instrumental gait analysis in cerebral palsy children, and to compare them with those drawn from the results of clinical examination. MATERIAL AND METHODS: The gait analysis laboratory was built in the Paediatric Hospital of the Faculty of Medicine in Brno in the 2008/09 period with support of the Norwegian funds. It is equipped with eight optical cameras, two auxiliary motion-picture video came- ras, two force platforms and a telemetry system for electromyography. Between June 2009 and March 2010 a total of 297 children with spastic cerebral palsy, 66 with hemiparesis and 231 with diparesis were examined. RESULTS: On the basis of instrumental gait analysis, indications for surgery were established in 19 hemiparetic and 88 diparetic patients, which meant a new indication in 107 children. In 14 children, the results of gait analysis led to abandoning former indications for surgery based on clinical examination only while, in 13 children, they backed up the surgical indications in spite of the negative results of clinical examination. In six children a so-called superclinical decision was made, i.e., the results of repeated clinical examinations over-weighed those of instrumental gait analysis either in favour of or against surgery. DISCUSSION: Based on the gait analysis results, a change in treatment plans was made in 27 out of 297 children (9 %). This is in contrast with the findings of other authors who report a much higher rate of treatment planning changes (52-70 %) In our stu- dy the use of instrumental gait analysis allowed us to decrease the frequency of surgical indications by 4.7 %. Other authors have achieved a higher value, up to 13 %. Unlike other studies, ours did not confirm the effect of gait analysis outcomes on an increase in the number of one-stage multi-level surgical procedures. CONCLUSIONS: Instrumental gait analysis is a great contribution to the diagnosis of movement disorders in children with cerebral palsy.

[Subtalar stabilization of pes equinovalgus by conventional open surgery using bicortical iliac crest bone graft (mid-term results)]. / Strednedobé výsledky subtalární stabilizace pes equinovalgus klasickou otevrenou metodou bikortikálním stepem z pánve.

PURPOSE OF THE STUDY: The aim of the study was to analyze the results of subtalar stabilization of the foot by conventional open surgery with the use of bicortical graft in cerebral palsy patients with pes equinovalgus and to compare our results with those of other authors. MATERIAL: A total of 193 operations were performed, with bilateral surgery in 84, surgery on the right foot in nine and surgery on the left foot in 16 patients. The average follow-up was 5 years and 2 months. METHODS: Before and after surgery, the clinical presentation in each patient was evaluated according to our subjective, description- based classification using a I-to-III scale (I, normal foot; II, moderate deformity; III, severe deformity). On lateral radiographs of the foot in a standing position, the talocalcaneal (TC) angle and that between the longitudinal calcaneus axis and foot-supporting surface (CS) were measured. The data was analyzed by statistical methods. RESULTS: The pre-operative findings were compared with the post-operative ones on the basis of our I-III classification system. In all results obtained with the McNemar test, p-values were lower than 0.001; therefore, at a 5 % level, the null hypothesis can be ruled out and a conclusion can be drawn that this surgery has an effect on the change in foot shape, as defined by our classification. Surgery failed in 13 feet (6.7 %), i.e., it did not produce any change in the degree of deformity. Similarly, values of the TC and CS angles were compared. The null hypothesis of Wilcoxon's test is that the patient's condition (TC and CP angles) remains the same before and after surgery. In all cases, the p-values were lower than 0.001; therefore, at a 5 % level, the null hypothesis can be ruled out, with the conclusion that differences between pre- and postoperative conditions were statistically significant. DISCUSSION: The results of this study, as compared with the relevant data, show that, for correction of pes equinovalgus, subtalar stabilization with bicortical iliac crest graft is a sufficiently reliable method even without metal fixation. The failure rate is only 6.7 %. CONCLUSIONS: The method described here achieves good results, the validity of which is supported by statistical analysis. Key words: cerebral palsy, pes equinovalgus, subtalar extra-articular arthrodesis.

Low mortality of children undergoing hematopoietic stem cell transplantation from 7 to 8/10 human leukocyte antigen allele-matched unrelated donors with the use of antithymocyte globulin.

Human leukocyte antigen (HLA)-matched sibling donor hematopoietic stem cell transplantation (HSCT) is available for only approximately 30% patients needing HSCT. Use of alternative donors is associated with a high incidence and severity of graft-versus-host disease (GVHD). Here we report our experience with GVHD prophylaxis using pre-transplant rabbit antithymocyte globulin (rATG), in addition to post transplant cyclosporin A and methotrexate. Seventy-five children received unmanipulated grafts from 7 to 10/10 HLA allele-matched unrelated donors. Median follow-up was 25 months (range, 6-65 months). Only 2/75 patients (2.5%) developed acute GVHD grades III-IV, and 17/75 (25%) developed extensive chronic GVHD. Overall survival was 79%. It was similar in patients receiving grafts from 7 or 8/10 to 9 or 10/10 allele-matched donors, and similar in patients receiving peripheral blood stem cells and marrow. Six (11%) patients died owing to relapse, and 10 (13%) due to transplant-related complications. The addition of rATG appears to result in a low incidence of severe GVHD and overall mortality.

Protocol combining GnRH agonists and GnRH antagonists for rapid suppression and prevention of gonadal damage during cytotoxic therapy.

PURPOSE OF INVESTIGATION: Infertility represents one of the main sequelae of cytotoxic therapy given for various malignant diseases. Because dividing cells are more sensitive to cytotoxic effects than are cells at rest, it has been hypothesized that inhibition of the pituitary-gonadal axis may facilitate the preservation of future gonadal function. The aim of our study was to find a quick, reliable and economic way to suppress the pituitary-gonadal axis by combining GnRH-agonists with GnRH-antagonists in order to preserve future gonadal function. METHODS: A combination of D-Trp6-GnRH-a (3.75 mg) and cetrorelix (3 mg) was used to achieve a quick downregulation in six postmenarchal young women (aged 15.4 +/- 0.7) years with haematological malignancies before the onset of cytotoxic chemotherapy. RESULTS: The combination of D-Trp6-GnRH-a and GnRH-antagonist cetrorelix induced a reliable and long-lasting suppression of gonadotrophin secretion within 96 hours in all patients allowing cytotoxic therapy to be started without any delay. CONCLUSIONS: The combination of GnRH-agonist and GnRH-antagonist enables a rapid, reliable and cost-effective suppression of the pituitary-gonadal axis to be achieved. Future gonadal function of treated patients will be monitored.

Verotoxigenic (enterohaemorrhagic) Escherichia coli in infants and toddlers in Czechoslovakia.

The results of the investigation indicate that verotoxigenic Escherichia coli (VTEC) belonging to enteropathogenic and other serogroups including Escherichia coli O157:H7 or H- are important enteropathogens in infants and toddlers in Czechoslovakia. As to enteropathogenic serotypes, verotoxin (VT) production was proved most frequently in strains of serogroup O26, and also O111 and O128. Diseases caused by them were as a rule manifested by febrile watery diarrhoea with mucus in the stool. In two of five infants with Escherichia coli O26 :H11 with VT1 production in titres of greater than or equal to 1:512 (blood was present) in the stool and one suffered from marked abdominal pain. In one infant haemorrhagic colitis due to Escherichia coli O157:H- was found. Haemolytic uraemic syndrome associated with VTEC of serogroups O157, O26, O18, O5 and O1 with VT1 and/or VT2 was observed in six children including five who contracted the disease during an outbreak in a small town, and the source of infection was probably contaminated water. Five children recovered and one died; the postmortem examination revealed haemorrhagic colitis and necrosis of the renal cortex. Haemorrhagic colitis caused by Escherichia coli O157 in infants and toddlers differed from the course hitherto described in older subjects by fever and the presence of mucus in the stools.

Vero cytotoxin-producing strains of Escherichia coli in children with haemolytic uraemic syndrome and diarrhoea in Czechoslovakia.

The presence of verotoxin-producing strains of Escherichia coli (VTEC) was examined in six children with haemolytic uraemic syndrome and one child with haemorrhagic colitis. Stools were screened for strains of serogroup O157 on sorbitol-MacConkey agar for VTEC of other serogroups by serotyping. Verotoxin (VT) was tested on Vero cell monolayers: the antigenic variant of VT was assessed by neutralization experiments. Strains producing verotoxin 1 or verotoxin 2 or both were detected in the stools of all seven children. Three strains belonged to serogroup O157 (two of them to serotype O157:H7, one was non-motile) and another five belonged to serogroups O26 (two strains), O1, O5 and O18. The faeces of five children available for testing contained free VT. Production of VT was also examined retrospectively in 32 E. coli strains of serotype O26:H11 isolated from children with diarrhoea; eight (25%) of them produced moderate to high levels of verotoxin 1 despite several years storage in vitro. In conclusion, VTEC including strains of serogroup O157 seem to be an important cause of haemolytic uraemic syndrome, haemorrhagic colitis and diarrhoea in children in Czechoslovakia.