High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy

Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens.     

Dental knowledge of educators and healthcare providers working with children with autism spectrum disorders

Objectives:

To evaluate dental knowledge and attitudes toward oral health care among healthcare providers and educators working with children with autism spectrum disorders (ASD) in central Saudi Arabia.

Methods:

There were 305 questionnaires distributed to 7 special-needs centers between September and November 2014. A total of 217 questionnaires were collected with a response rate of 71.1%. The study took place in the College of Dentistry, King Saud University, Riyadh, Kingdom of Saudi Arabia.

Results:

Approximately 50.2% of the participants did not offer any toothbrushing advice, and 73.3% never recommended dental checkup visits to parents, and 75.6% never performed dental examinations to children under their care. Ten percent thought that children should have their first dental visit after 6 years of age. Almost all participants agreed that children should practice oral hygiene, and 60.4% think they should brush twice per day. In general, the participants choose toothbrushes and toothpaste as the main tools to perform oral hygiene. There were 35% of participants who believed that parents should be responsible for the children’s oral hygiene, and a few participants mentioned teachers and therapists to be responsible. Most of the participants (71.4%) did not receive any dental information from dental professional resources, only 14.3% of participants believed bacteria to be the cause of dental cavities.

Conclusion:

There is a clear lack of dental knowledge and attitudes, and its practical application among the participating group of healthcare providers working with children with ASD in Riyadh.Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disability that affects children at a young age. Children with ASD usually show multiple, complicated deficiencies in their social, emotional, and communicative skills.1 Because of the multiple signs and symptoms of ASD, a multidisciplinary team is required to diagnose and offer comprehensive medical care for affected children. These teams usually include different specialists and subspecialists, such as general practitioners for primary diagnoses, and lead to referrals to relevant professionals or pediatricians who are able to confirm, or refute the ASD diagnosis. Clinical psychologists, psychiatrists, and psychotherapists (who are able to confirm the diagnosis of autism and introduce a customized individual behavior management plan), dieticians (who can provide advice and information concerning nutrition and diet), special educators (who can assess children’s educational needs), social workers (who can assess the care needs of children with ASD and their families), speech and language therapists (who can assess speech, language, and communication abilities), audiologists (who can evaluate possible hearing impairments), opticians (who can assess any visual difficulties that the children might have), in addition to specialists in oral health (OH [such as, pediatric dentist, who can perform early check-ups and introduce both primary and comprehensive preventive and therapeutic oral care]).2 From a medical point of view, the recognition and diagnosis of ASD in its early stages is significant. Early intervention and treatment can control, and in many cases improve, the symptoms.3,4 From a dental point of view, early examinations for intervention and prevention among children in general (and those with special needs specifically) are strongly recommended by major dental academies.2,5 However, because children with ASD have multiple medical issues, their dental issues might not receive equal consideration from healthcare providers (HCPs) trying to provide the best comprehensive care. In addition, several well-documented national and international studies have observed a lack of dental knowledge among primary HCPs,6-15 and educators16-20 who work with children. Most published studies have reported data collected from HCPs who work with healthy children, or those with disabilities, such as cerebral palsy, or Down syndrome, however, no studies have been conducted to assess the dental knowledge of educators and HCPs that interact with children diagnosed with ASD. Therefore, because of the unique characteristics of children with ASD, this study evaluated the dental knowledge of, and attitudes toward oral healthcare among different HCPs and educators interacting with children with ASD in Riyadh, Kingdom of Saudi Arabia (KSA).     

Immune Responses to the O-Specific Polysaccharide Antigen in Children Who Received a Killed Oral Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

Current oral cholera vaccines induce lower levels of protective efficacy and shorter durations of protection in young children than in adults. Immunity against cholera is serogroup specific, and immune responses to Vibrio cholerae lipopolysaccharide (LPS), the antigen that mediates serogroup-specific responses, are associated with protection against disease. Despite this, responses against V. cholerae O-specific polysaccharide (OSP), a key component of the LPS responsible for specificity, have not been characterized in children. Here, we report a comparison of polysaccharide antibody responses in children from a region in Bangladesh where cholera is endemic, including infants (6 to 23 months, n = 15), young children (24 to 59 months, n = 14), and older children (5 to 15 years, n = 23) who received two doses of a killed oral cholera vaccine 14 days apart. We found that infants and young children receiving the vaccine did not mount an IgG, IgA, or IgM antibody response to V. cholerae OSP or LPS, whereas older children showed significant responses. In comparison to the vaccinees, young children with wild-type V. cholerae O1 Ogawa infection did mount significant antibody responses against OSP and LPS. We also demonstrated that OSP responses correlated with age in vaccinees, but not in cholera patients, reflecting the ability of even young children with wild-type cholera to develop OSP responses. These differences might contribute to the lower efficacy of protection rendered by vaccination than by wild-type disease in young children and suggest that efforts to improve lipopolysaccharide-specific responses might be critical for achieving optimal cholera vaccine efficacy in this younger age group.     

Antibody Avidity in Humoral Immune Responses in Bangladeshi Children and Adults following Administration of an Oral Killed Cholera Vaccine

Antibody avidity for antigens following disease or vaccination increases with affinity maturation and somatic hypermutation. In this study, we followed children and adults in Bangladesh for 1 year following oral cholera vaccination and measured the avidity of antibodies to the T cell-dependent antigen cholera toxin B subunit (CTB) and the T cell-independent antigen lipopolysaccharide (LPS) in comparison with responses in other immunological measurements. Children produced CTB-specific IgG and IgA antibodies of high avidity following vaccination, which persisted for several months; the magnitudes of responses were comparable to those seen in adult vaccinees. The avidity of LPS-specific IgG and IgA antibodies in vaccinees increased significantly shortly after the second dose of vaccine but waned rapidly to baseline levels thereafter. CTB-specific memory B cells were present for only a short time following vaccination, and we did not find significant memory B cell responses to LPS in any age group. For older children, there was a significant correlation between CTB-specific memory T cell responses after the second dose of vaccine and CTB-specific IgG antibody avidity indices over the subsequent year. These findings suggest that vaccination induces a longer-lasting increase in the avidity of antibodies to a T cell-dependent antigen than is measured by a memory B cell response to that antigen and that early memory T cell responses correlate well with the subsequent development of higher-avidity antibodies.     

Refrigerated storage of lyophilized and rehydrated, lyophilized human red cells

Human red cells (RBCs) were collected in CPDA-1 and then freeze-dried in lyoprotective solution. The lyophilized RBCs were then stored at -20 degrees C for 7 days. At the end of the storage period, the lyophilized RBCs were rehydrated and washed in dextrose saline. The washed, reconstituted, lyophilized RBCs were resuspended in final wash solutions of ADSOL, CPDA-1, or a special additive solution containing glucose, citrate, phosphate, adenine, and mannitol, and then they were stored at 4 degrees C for an additional 7 days. The main purpose of this study was to determine whether human RBCs can be lyophilized in such a manner that normal metabolic, rheologic, and cellular properties are maintained during rehydration and subsequent storage in standard blood bank preservative solutions. Our results show that reconstituted, lyophilized RBCs maintained levels of ATP, 2,3 DPG, lactate, and cellular properties that are equal to or better than those in control nonlyophilized RBCs stored for a comparable period in CPDA-1. Reconstituted, lyophilized RBCs stored at 4 degrees C after rehydration also show better maintenance of ATP, 2,3 DPG, and lactate than do control RBCs stored in the same preservative solutions for comparable periods.     

PCR-positivity in harvested bone marrow predicts relapse after transplantation with autologous purged bone marrow in children in second remission of precursor B-cell acute leukaemia

Purging of autologous bone marrow (BM) grafts of children in second remission after a relapse of precursor B acute lymphoblastic leukaemia (ALL) in the BM has been carried out in our laboratory since 1987, initially by complement mediated cell lysis. This protocol was extended by performing an immunorosette depletion before lysis with complement. The aim of the present study was to assess by polymerase chain reaction the presence of residual leukaemic cells in the BM grafts before and after purging. The results were then correlated to clinical outcome. In 24/28 patients a PCR product was obtained by amplification of IgH and/or TcR junctional regions. BM before purging was available for analysis in 13 patients. We found that leukaemic cells could be detected in 8/13 (62%) of these grafts before purging . All these eight patients experienced a relapse, regardless of whether the purging procedure had been successful (defined as achievement of PCR-negativity) or not. In contrast, none of the five patients with PCR-negative grafts before purging relapsed ( P  = 0.0008). One patient died due to transplant-related toxicity. Of the remaining 23 patients, nine patients received a PCR-positive BM graft after purging. All these nine patients experienced a relapse as compared to 6/14 whose BM was PCR-negative after purging ( P  = 0.0072). Two of eight PCR-positive BM grafts could be purged to PCR-negativity. Thus, improvements both in treatment of leukaemia and in purging efficacy are still needed.