Connecting Clinical Capacity and Intervention Sustainability in Resource-Variable Pediatric Oncology Centers in Latin America.

Clinical capacity for sustainability, or the clinical resources needed to sustain an evidence-based practice, represent proximal determinants that contribute to intervention sustainment. We examine the relationship between clinical capacity for sustainability and sustainment of PEWS, an evidence-based intervention to improve outcomes for pediatric oncology patients in resource-variable hospitals. We conducted a cross-sectional survey among Latin American pediatric oncology centers participating in Proyecto Escala de Valoración de Alerta Temprana (EVAT), an improvement collaborative to implement Pediatric Early Warning Systems (PEWS). Hospitals were eligible if they had completed PEWS implementation. Clinicians were eligible to participate if they were involved in PEWS implementation or used PEWS in clinical work. The Spanish language survey consisted of 56 close and open-ended questions about the respondent, hospital, participants' assessment of clinical capacity to sustain PEWS using the clinical sustainability assessment tool (CSAT), and perceptions about PEWS and its use as an intervention. Results were analyzed using a multi-level modeling approach to examine the relationship between individual, hospital, intervention, and clinical capacity determinants to PEWS sustainment. A total of 797 responses from 37 centers in 13 countries were included in the analysis. Eighty-seven percent of participants reported PEWS sustainment. After controlling for individual, hospital, and intervention factors, clinical capacity was significantly associated with PEWS sustainment (OR 3.27, p < .01). Marginal effects from the final model indicate that an increasing capacity score has a positive influence (11% for every additional CSAT point) of predicting PEWS sustainment. PEWS is a sustainable intervention and clinical capacity to sustain PEWS contributes meaningfully to PEWS sustainment.

Zaragoza technique of laparoscopic appendicectomy.

INTRODUCTION: Appendectomy is one of the most frequent emergency surgical procedures, currently with a preference for laparoscopic management worldwide. OBJECTIVE: To report a new laparoscopic appendectomy technique and its results. MATERIAL AND METHODS: Cohort study of patients with a diagnosis of appendicitis who are managed laparoscopically. In a total 1063 patients, 148 were operated on with the Zaragoza technique during the period from January 2002 to December 2018. The technique consists of making a window in the appendicular base between the meso and the appendicular wall, two prolene or silk sutures are placed, and the cecal appendix is cut between the two sutures, finally the mesoappendix is sectioned with a harmonic scalpel or bipolar clamp. RESULTS: From our results, we had 1.4% residual abscesses, 1.4% umbilical surgical wound infection and 0% mortality. DISCUSSION: Various laparoscopic management methods for appendectomy are reported in the literature, with a wide range in the results. We have obtained good results in patients subjected to our technique. CONCLUSIONS: The Zaragoza technique for laparoscopic appendectomy is an effective and safe option that prevents excessive manipulation of the inflamed appendix and is easily reproducible.

Bilateral parotid gland enlargement and palpable nephromegaly in infant acute lymphoblastic leukemia: case report and review of the literature.

Acute lymphoblastic leukemia (ALL) in infants below 1 year of age accounts for 2.5% to 5% of childhood ALL. Most children with ALL present with fever, bruising, mucosal bleeding, bone pain, pallor, hepatosplenomegaly, and lymphadenopathy. Common sites of extramedullary involvement at diagnosis include liver, spleen, lymph nodes, brain, and testes. Nephromegaly has also been reported. We present a novel case of bilateral parotid enlargement along with bilateral palpable nephromegaly in a patient with newly diagnosed infant ALL. This unique presentation highlights the importance of considering ALL in the differential diagnosis of parotid enlargement especially when associated with abnormal blood counts.

An unusual case of donor-derived myelodysplastic syndrome following double-unit umbilical cord blood transplantation in acute lymphoblastic leukemia.

Umbilical cord-blood transplantation is considered an effective treatment strategy for acute lymphoblastic leukemia (ALL) when a human leukocyte antigen (HLA)-matched donor is unavailable. The use of a second unit helps ensure engraftment in larger adults and those with comorbidities, even though only one unit engrafts in most patients. Herein, we present the clinical and laboratory characteristics of a patient who developed donor-derived myelodysplastic syndrome (ddMDS) after double umbilical cord-blood transplantation (dUCB HSCT). To our knowledge, no cases of ddMDS have been described in a patient with a history of ALL in molecular remission after receiving a dUCB HSCT. Current molecular techniques, including analysis of short tandem repeats (STR) and fluorescence in situ hybridization (FISH) allowed us to firmly establish donor origin.

Autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura in pediatric solid organ transplant recipients, report of five cases and review of the literature.

Cytopenias are common among pediatric SOT; however, autoimmune cytopenias are infrequently reported. We report five cases of autoimmune cytopenias in pediatric LT patients: two with isolated IgG-mediated AIHA, two with ITP, and one with Evans syndrome (ITP and AIHA). All patients were maintained on tacrolimus as immunosuppression. Viral illness commonly preceded the autoimmune cytopenias. All patients responded well to medical therapy (steroids, intravenous immunoglobulin, and rituximab) and lowering tacrolimus serum level. Prognosis appears to be worse when more than one cell line (e.g., Evans syndrome) is affected, and/or there is no preceding viral illness. A critical literature review of autoimmune cytopenias in children following SOT is conducted. Autoimmune cytopenias are a rarely reported complication of pediatric SOT, but clinicians taking care of pediatric transplant recipients need to be aware of this complication.

Development of a Spanish HIV/AIDS Symptom Management Guidebook.

PURPOSE: To provide culturally appropriate HIV/AIDS patient care, it is important to develop symptom management patient education materials for patients with different cultural backgrounds. The purpose of this study was to develop a Spanish version of the Symptom Management Guidebook: Strategies for People Living with HIV/AIDS guidelines and verify its content, perceived feasibility, and usefulness with HIV/AIDS care providers and people living with HIV/AIDS in Puerto Rico. DESIGN: The Symptom Management Guidebook includes self-care strategies to manage 14 common HIV-related symptoms. The Spanish version was developed by adopting and translating through forward and backward translation methods. Seven HIV/AID Shealth care providers from San Juan, Puerto Rico, were invited to review and revise the contents. Ten people living with HIV/AIDS from a community AIDS clinic in San Juan participated in a focus group to review the guidebook and discussed its usefulness and feasibility for managing their symptoms. FINDINGS/RESULTS: Participants expressed positive responses and considered an educational guidebook as a helpful tool for self-managing their symptoms. DISCUSSION/CONCLUSIONS: Results suggested that this guidebook may be useful as an intervention strategy for symptom management in HIV/AIDS patients. IMPLICATIONS: Future research can include testing self-managing intervention and its outcomes in culturally diverse HIV/AIDS patients.

The administration of general anesthesia to a patient with croup.

Croup in a young child may lead to severe airway narrowing, and would present a severe risk for administration of anesthesia. To the best of our knowledge, there have been no previous case reports of patients undergoing general anesthesia with croup. In our report, we describe a case of a 31 month old child with croup who required anesthesia.

Rhizomucor variabilis var. regularior and Hormographiella aspergillata infections in a leukemic bone marrow transplant recipient with refractory neutropenia.

Rhizomucor variabilis and Hormographiella aspergillata rarely cause human infections. This report details a fatal case of a 14-year-old female with leukemia posthematopoietic cell transplant and relapse with refractory pancytopenia. The patient first developed an R. variabilis var. regularior palate infection and later developed a cutaneous H. aspergillata infection while on posaconazole and caspofungin therapy.

Sequential administration of sargramostim and filgrastim in pediatric allogeneic stem cell transplantation recipients undergoing myeloablative conditioning.

G-CSF and GM-CSF both hasten myeloid engraftment post-MA-alloSCT; however, GM-CSF is earlier acting and less expensive. The objective was to evaluate efficacy/safety of sequential administration of GM-CSF followed by G-CSF in children post-MA-alloSCT. From January 2001 to June 2005, 31 children received 32 MA-alloSCT: mean age 6.65 yr; MRD BM or PBSC vs. related or unrelated UCB 11:21; malignant vs. non-malignant disorders 22:10. GM-CSF (250 microg/m(2) IV QD) began on day of stem cell infusion. GM-CSF was switched to G-CSF (10 microg/kg IV QD) when WBC >or= 300/mm(3) x 2 days. G-CSF continued until ANC >or= 2500/mm(3) x 2 days, then tapered to maintain ANC >or= 1000/mm(3). Median time to myeloid engraftment (ANC >or= 500/mm(3) x 3 days) was 17 days [13 days vs. 24 days, MRD BM/PBSC vs. UCB (p < 0.0001)], occurring at a median time of two days after switch to G-CSF. Clinically relevant adverse events were bone pain (n = 8) and large pleural effusion (n = 1). It was estimated that sequential GM-CSF/G-CSF was cost-effective compared with G-CSF alone [cost-savings of $1311/patient ($41,952/study), 2007 Red Book Average Wholesale Price]. In summary, it was demonstrated that sequential administration of GM-CSF/G-CSF post-MA-alloSCT was safe, cost-effective and resulted in prompt myeloid engraftment.

Liposomal amphotericin B prophylaxis of invasive mold infections in children post allogeneic stem cell transplantation.

BACKGROUND: Invasive mold infections (IMI) are a leading cause of infectious mortality in allogeneic stem cell transplant (AlloSCT) recipients. Fluconazole, the current standard for fungal prophylaxis, is ineffective against molds. We initiated a pilot study to determine the safety and activity of prophylactic liposomal amphotericin B (AMB) in preventing IMI in pediatric and adolescent AlloSCT recipients during the first 100 days. PROCEDURE: Fifty-one patients (57 AlloSCT) were given AMB (3 mg/kg/day) intravenously, day 0-100. Median age 6 years, 32 males, 19 females. Donors: 33 unrelated and 2 related cord blood, 13 related and 1 unrelated peripheral blood stem cell and 8 related bone marrow (BM); 30 received myeloablative and 27 reduced intensity conditioning. Graft-versus-host disease (GVHD) prophylaxis comprised tacrolimus and mycophenolate mofetil. RESULTS: Median follow-up is 557 days. AMB was generally well tolerated. The probability of developing >/=grade II acute GVHD and extensive chronic GVHD was 45% and 7%, respectively. Estimated 1-year OS is 62.4% for all patients with 78.8% and 26.7% for average-risk and poor-risk, respectively. The incidence of IMI was 0%. CONCLUSIONS: These results suggest prophylactic AMB is tolerable and may prevent IMI, especially Aspergillus, during the first 100 days post AlloSCT in pediatric and adolescent patients. A randomized study is needed to determine the efficacy of this approach.

Immunophenotypic identification of possible therapeutic targets in paediatric non-Hodgkin lymphomas: a children's oncology group report.

Immunophenotypic analysis can identify protein epitopes in non-Hodgkin lymphomas (NHL) that may respond to targeted immunotherapies, such as anti-CD20 and anti-CD52. Recent studies suggest additional targets may provide therapeutic benefits in NHL. This study evaluated protein expression of CD25, CD52, CD74 and CD80 in paediatric NHL to determine possible targets for immune-based therapeutic approaches. Patient samples were derived from paediatric NHL clinical trials sponsored by the Children's Cancer Group (CCG, now the Children's Oncology Group, COG) and included Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), disseminated T- and B-cell lymphoblastic lymphoma (T-LBL and B-LBL) and anaplastic large cell (ALCL). Immunophenotypic studies were performed on formalin-fixed, paraffin-embedded diagnostic tissues. CD25 was expressed in 8% of T-LBL and 75% of ALCL cases, but not in BL, DLBCL, or B-LBL. CD52 was expressed in 99% of cases of paediatric NHL of all subtypes. CD74 was expressed in 100% of B-LBL, BL and DLBCL, but was absent in ALCL and T-LBL. CD80 was expressed in 12% of B-LBL, 6% of BL and 10% of DLBCL cases studied, but was not detected in T-cell NHL. These expression patterns suggest that CD25, CD52 and CD74 may represent potential new therapeutic targets in paediatric NHL.

A low incidence of nontuberculous mycobacterial infections in pediatric hematopoietic stem cell transplantation recipients.

Hematopoietic stem cell transplantation (HSCT) is being used to treat a wide spectrum of clinical disorders but opportunistic infection remains an important factor determining outcomes for these patients. Nontuberculous mycobacterial (NTM) infections are being reported more frequently in HSCT recipients and the incidence of NTM infections in adult recipients is reported to be 0.4%-4.9%. However, the incidence and severity of NTM infections are less well described in pediatric HSCT recipients. Centers for Disease Control and Prevention guidelines were used to define definite and probable NTM infection among 132 children undergoing 169 HSCT between January 2000 and December 2004 at our institution. NTM infection was diagnosed in 5 of 132 pediatric recipients (3.8%). There were no NTM infections diagnosed in the autologous HSCT recipients and the incidence of NTM in allogeneic HSCT recipients was 6.4% (95% confidence interval, 0.8-11.9). The mean age of the HSCT recipients who developed NTM infections was 8 years (range, 2-19 years); 3 were male and 2 were female. Four conditioning regimens included alemtuzumab and 3 had antithymocyte globulin. Of the 5 patients with NTM infections, 2 met the criteria for definite infection and 3 for probable infection. Of the 2 patients with definite NTM infection, 1 had disseminated disease with Mycobacterium avium complex and the other had Mycobacterium chelonae catheter-related bloodstream infection. The probable NTM infections were 1 skin infection with Mycobacterium kansasii and 2 lower respiratory tract infections with M avium complex. Median time to NTM infection was 115 days (range, 14-269 days) after HSCT. Two patients had graft-versus-host disease at the time of NTM infection. All 5 patients received 3-4 antimycobacterial drugs and all NTM infections resolved. In summary, the incidence of NTM infection in pediatric HSCT recipients appears similar to that described in adult HSCT recipients and the outcome appears to be excellent with the proper antibiotic therapy. The increased use of anti-T cell antibodies appears to be associated with an increased risk of NTM infections in pediatric HSCT recipients. Multicenter studies are needed to identify the risk factors, early diagnostic criteria, and optimal therapy.

Preliminary results of the safety of immunotherapy with gemtuzumab ozogamicin following reduced intensity allogeneic stem cell transplant in children with CD33+ acute myeloid leukemia.

PURPOSE: Myeloablative allogeneic stem cell transplantation (SCT) has been successful in the treatment of childhood acute myeloid leukemia (AML), but may be associated with significant toxicity and recurrent disease. Reduced-intensity allogeneic SCT may offer a less toxic approach to patients with AML. Targeted immunotherapy with gemtuzumab ozogamicin has been shown to be safe, well tolerated in children, and, as a single agent, gemtuzumab ozogamicin has induced responses in 30% of patients with recurrent CD33+ AML. There are no safety data with gemtuzumab ozogamicin post allogeneic SCT in children. Therefore, we explored the feasibility and toxicity of targeted immunotherapy following reduced-intensity allogeneic SCT in children with CD33+ AML. EXPERIMENTAL DESIGN: Eight patients with CD33+ AML received a reduced-intensity allogeneic SCT following fludarabine 30 mg/m2 for 6 days and busulfan 3.2 mg/kg (<4 years, 4 mg/kg/d) for 2 days. Donor sources included six 6/6 HLA-matched related peripheral blood stem cells, one 6/6 sibling cord blood, and one 4/6 unrelated cord blood. RESULTS: Day 30 and day 60 donor chimerisms in seven of eight evaluable patients were 96 +/- 2% (n = 7) and 94 +/- 3% (n = 6), respectively. Five of six patients (too early for one patient) received two doses of gemtuzumab ozogamicin and one patient received only one dose. After each dose, all patients developed grade 4 neutropenia, with recovery on median days 16 and 13, respectively, after dose 1 and dose 2. Grade 4 thrombocytopenia was only observed in 2 of 11 gemtuzumab ozogamicin courses. No patients have developed dose-limiting toxicity secondary to gemtuzumab ozogamicin. CONCLUSIONS: The administration of gemtuzumab ozogamicin post reduced-intensity allogeneic SCT in children with average risk AML is feasible and well tolerated with minimal toxicity. The maximal tolerated dose has yet to be determined for gemtuzumab ozogamicin post reduced-intensity allogeneic SCT in children with CD33+ AML. Additional studies in a larger group of patients will be required to adequately assess the safety of this approach.

Congenital MLL-positive B-cell acute lymphoblastic leukemia (B-ALL) switched lineage at relapse to acute myelocytic leukemia (AML) with persistent t(4;11) and t(1;6) translocations and JH gene rearrangement.

Congenital acute leukemia is a rare form of childhood leukemia, in which lineage conversion at relapse is very rarely reported. Here we describe a case of congenital B-cell acute lymphoblastic leukemia (B-ALL) with t(4;11) and t(1;6) translocations, which at relapse underwent a switch to monocytic lineage with persistence of the original cytogenetic translocations and clonal rearrangement of the JH gene. Similar to the other described cases of congenital acute leukemia with lineage conversion, our case had a MLL gene rearrangement and followed an aggressive clinical course.