Rituximab for the treatment of refractory autoimmune hemolytic anemia in children

Autoimmune hemolytic anemia (AIHA) in children is sometimes characterized by a severe course, requiring prolonged administration of immunosuppressive therapy. Rituximab is able to cause selective in vivo destruction of B lymphocytes, with abrogation of antibody production. In a prospective study, we have evaluated the use of rituximab for the treatment of AIHA resistant to conventional treatment. Fifteen children with AIHA were given rituximab, 375 mg/m(2)/dose for a median of 3 weekly doses. All patients had previously received 2 or more courses of immunosuppressive therapy; 2 patients had undergone splenectomy. After completing treatment, all children received intravenous immunoglobulin for 6 months. Treatment was well tolerated. With a median follow-up of 13 months, 13 patients (87%) responded, whereas 2 patients did not show any improvement. Median hemoglobin levels increased from 7.7 g/dL to a 2-month posttreatment level of 11.8 g/dL (P <.001). Median absolute reticulocyte counts decreased from 236 to 109 x 10(9)/L (P <.01). An increase in platelet count was observed in patients with concomitant thrombocytopenia (Evans syndrome). Three responder patients had relapse, 7, 8, and 10 months after rituximab infusion, respectively. All 3 children received a second course of rituximab, again achieving disease remission. Our data indicate that rituximab is both safe and effective in reducing or even abolishing hemolysis in children with AIHA and that a sustained response can be achieved in the majority of cases. Disease may recur, but a second treatment course may be successful in controlling the disease.     

Isolated breast relapse after allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia

Unusual sites of relapses following bone marrow transplantation (BMT) for childhood acute lymphoblastic leukemia (ALL) are rarely reported. We report the case of a 16-year-old girl who presented with an isolated right breast relapse 8 months after allogeneic BMT for ALL in second remission. Biopsy showed an ALL infiltrate. Bone marrow and CSF were normal. The girl never showed before extramedullary involvement. She was treated with local radiotherapy and mild systemic chemotherapy. Nine months after breast relapse, she presented an isolated central nervous system relapse. The treatment of isolated extramedullary relapses following BMT is still controversial.     

SIOP working committee on psychosocial issues in pediatric oncology

Recognizing the importance of psycho-social issues in the care and cure of the child with cancer, the board of the International Society of Pediatric Oncology (SIOP) in 1991 constituted a Working Committee on Psychosocial Issues in Pediatric Oncology, with Giuseppe Masera as chair and John Spinetta as co-chair. This committee met for the first time in Rhodes, Greece, in October 1991. The committee discussed various psychosocial issues and developed a document on Aims and Recommendations, summarizing the experiences of major centers. This document was approved by the SIOP board, which recommended diffusion of the document to the pediatric oncology community. © 1993 Wiley-Liss, Inc.     

Analysis of Y chromosome microdeletions and CFTR gene mutations as genetic markers of infertility in Serbian men

BACKGROUND/AIM: Impaired fertility of a male partner is the main cause of infertility in up to one half of all infertile couples. At the genetic level, male infertility can be caused by chromosome aberrations or gene mutations. The presence and types of Y chromosome microdeletions and cystic fybrosis transmembrane conductance regulator (CFTR) gene mutations as genetic cause of male infertility was tested in Serbian men. The aim of this study was to analyze CFTR gene mutations and Y chromosome microdelations as potential causes of male infertility in Serbian patients, as well as to test the hypothesis that CFTR mutations in infertile men are predominantly located in the several last exons of the gene. METHODS: This study has encompassed 33 men with oligo- or azoospermia. The screening for Y chromosome microdeletions in the azoospermia factor (AZF) region was performed by multiplex PCR analysis. The screening of the CFTR gene was performed by denaturing gradient gel electrophoresis (DGGE) method. RESULTS: Deletions on Y chromosome were detected in four patients, predominantly in AZFc region (four of total six deletions). Mutations in the CFTR gene were detected on eight out of 66 analyzed chromosomes of infertile men. The most common mutation was F508del (six of total eight mutations). CONCLUSION: This study confirmed that both Y chromosome microdeletions and CFTR gene mutations played important role in etiology of male infertility in Serbian infertile men. Genetic testing for Y chromosome microdeletions and CFTR gene mutations has been introduced in routine daignostics and offered to couples undergoing assisted reproduction techniques. Considering that both the type of Y chromosome microdeletion and the type of CFTR mutation have a prognostic value, it is recomended that AZF and CFTR genotyping should not only be performed in patients with reduced sperm quality before undergoing assisted reproduction, but also for the purpose of preimplantation and prenatal diagnostics in couples in which in vitro fertilization has been performed successfully.     

Meetings with Parents After the Death of Their Child from Leukemia

There is a growing interest in the emotional status of parents and siblings after the death of a child with chronic disease. For the past 7 years physicians at our center have systematically contacted parents who lost a child because of leukemia within the first few months after the death. From this experience it appears that most parents needed to talk at least once with the physicians who took care of their child. As expected, some parents and siblings were found to have significant psychological problems and to need psychologic support. We suggest that the opportunity to talk with a physician of the attending staff should be provided routinely to parents shortly after the death of a child from leukemia.     

Impact of influenza-like illness and effectiveness of influenza vaccination in oncohematological children who have completed cancer therapy

In order to evaluate the impact of influenza-like illness and the effectiveness of influenza vaccination in children with oncohematological disease who have completed cancer therapy, 182 children with a diagnosis of oncohematological disease were divided into two subgroups on the basis of the length of time off therapy (<6 months or 6–24 months) and randomised 1:1 to receive influenza vaccination or not. The controls were 91 otherwise healthy children unvaccinated against influenza. The results show that the clinical and socioeconomic impact of influenza-like illnesses and the effectiveness of influenza vaccination in oncohematological children who have completed cancer therapy are related to the length of the off therapy period, and seem to be significantly greater in those who have been off therapy for less than 6 months in comparison with healthy controls. This suggests that the administration of influenza vaccination should be strongly recommended only among oncohematological children who have been off therapy for less than 6 months.     

Thyroid blood flow and uptake of technetium-99m pertechnetate in Graves' disease

The aim of this study was to assess the relation of early thyroid blood flow (EBF) and technetium-99m pertechnetate ((99m)TcO(-)(4)) uptake, as an early diagnostic index in patients with Graves' disease (GD) by dynamic thyroid scintigraphy (40 frames, 3 sec/frame). Thirty patients with GD with mean age 50.0 +/- 9.0 y, range: 35.0-69.0 y, were studied. The results obtained were compared with those of 30 euthyroid individuals (EI) of mean age 46.9 +/- 12.5 y, range: 22.0-68.0 y. The parameters of (99m)TcO(-)(4) EBF and early uptake studied, derived from the background subtracted time activity curves, were as follows: a) The duration of the EBF in sec; b) The perfusion index (PI) - the ratio of counts at the beginning and at the end of the EBF; c) The uptake index 1 (UI1)- the counts ratio between the counts at the end of the EBF and at the 2nd min d) The uptake index 2 (UI2) - the counts ratio between the 1st min and the 2nd min of the uptake curve and e) Delayed (99m)TcO(-)(4) thyroid uptake (TcTU) at 20 min was also calculated as a percentage of net counts activity accumulated in the thyroid gland at 20 min. Results were as follows: a) The mean values of the duration of the EBF were shorter in GD patients (9.90 +/- 2.94 sec) than in EI (15.70 +/- 4.01 sec; P<0.0001); b) PI did not differ significantly (P>0.05); c) The mean UI1 and UI2 values of thyroid uptake of 99m TcO4- were significantly lower in GD (UI1=0.621, UI2=0.772) as compared to EI (UI1=1.106, UI2=0.947; P<0.0001 for both) and d) TcTU values were significantly higher in GD (13.6%) than in the group of EI (1.29%; P<0.0001). A good correlation was found in patients with GD between early (UI1 and UI2) and delayed TcTU (r = -0.562; P=0.010 and r = -0.459; P=0.042 respectively). Also, in patients with GD the EBF correlated poorly with UI1, UI2 and TcTU (P>0.05 for all these parameters). In conclusion, the results of this study indicate that the duration of EBF did not relate significantly to the height of TcTU values in patients with GD. On the contrary, the early uptake, indices UI1 and especially UI2 were shown to be faster in the majority of GD patients and correlated well with the TcTU. These parameters may be used as diagnostic indices for GD. Further investigation is required to support the above findings.     

Precocious puberty and empty sella syndrome in a girl cured of acute lymphoblastic leukemia

We describe a case of precocious puberty in a girl treated with chemoradiotherapy according to the Italian Association of Pediatric Hematology and Oncology ALL 9503 protocol for acute lymphoblastic leukemia (ALL) from the age of 15 months until the age of 3 years and 4 months. The patient was treated with chemotherapy and cranial irradiation (18 Gy in 12 fractions). At 7 years of age, during topical estrogenic treatment for congenital adhesions of the labia minora, she showed bilateral breast development that evolved into precocious puberty. A magnetic resonance imaging of the brain showed an "empty sella" (ES); the etiology of the ES, and the consequent precocious puberty, being presumably iatrogenic. Children treated with cranial radiotherapy should be carefully checked for signs of precocious puberty and the exogenous administration of estrogens should be avoided, as far as possible, because these could act as a trigger factor in a population at higher risk of precocious puberty.