Valeria Cortez Ginani

Oral ciprofloxacin vs. intravenous ceftriaxone administered in an outpatient setting for fever and neutropenia in low-risk pediatric oncology patients: randomized prospective trial.

BACKGROUND Infections are one of the major complications in children undergoing chemotherapy. Monotherapy with either ciprofloxacin or ceftriaxone is safe and efficient in low-risk patients (solid tumors and stage I/II lymphomas). The same drugs may be used in an outpatient setting, decreasing costs and the risk of nosocomial infections. PROCEDURE Low-risk patients (N = 70) with episodes of fever and neutropenia (N = 116) were randomized to receive either oral ciprofloxacin or intravenous ceftriaxone as outpatients. Only one patient had a central venous catheter. RESULTS Episodes of fever and neutropenia were classified as fever of unknown origin (41% vs. 32%) or clinically documented infection (56% vs. 63%) in the ciprofloxacin and ceftriaxone groups, respectively. Most of these infections were of upper respiratory tract, skin, or gastrointestinal origin. The mean duration of neutropenia was 5 vs. 6 days. Fever persisted for 1-9 days (mean 2 vs. 3 days). Therapy was successful with no modifications in 83% vs. 75% of the episodes. Patients were admitted in 7% vs. 4% of the episodes. No bone or joint side effects were seen in either group. All patients survived. CONCLUSIONS Outpatient therapy with either oral ciprofloxacin or intravenous ceftriaxone for fever and neutropenia is effective and safe in pediatric patients with solid tumors and stage I/II non-Hodgkin lymphoma (low-risk patients).

Use of amifostine in the therapy of osteosarcoma in children and adolescents.

Amifostine protects normal tissue from the cytotoxic damage induced by radiation and chemotherapy. In this study, 39 consecutive newly diagnosed children with osteosarcoma were assessed; 20 received amifostine and 19 did not. The chemotherapy regimen included an induction phase of three cycles of cisplatin (100 mg/m2), carboplatin (500 mg/m2), and doxorubicin (60 mg/m2), followed by surgery. Alternating cycles of cisplatin/ifosfamide (9 mg/m2), ifosfamide/doxorubicin, carboplatin/doxorubicin, and ifosfamide/carboplatin were administered every 3 weeks to complete 26 weeks of treatment. Amifostine was administered 15 minutes before the infusions of cisplatin and carboplatin in a total of 193 infusions. Side effects during infusions and renal, hearing, and bone marrow toxicities were evaluated and compared between the two groups. Hypotension was observed in 28 (14.5%) infusions. No patient required discontinuation of therapy. Fewer than two episodes of vomiting occurred in 130 (71%) infusions and two to five episodes occurred in 51 (28%) infusions, and no patient had grade 4 toxicity. There was no difference between the two groups regarding renal toxicity (creatinine clearance). Neutropenia and leukopenia were significantly less frequent in the amifostine group. No difference was observed in platelet and hearing toxicities. Amifostine was well tolerated in doses of 740 mg/m2 in children and adolescents, and myelotoxicity was less severe in the amifostine group. This was a pilot study for further evaluation in a larger randomized trial.

Rapid, low-cost MR imaging protocol to document central nervous system and sinus abnormalities prior to pediatric hematopoietic stem cell transplantation.

Patients undergoing bone marrow transplant (BMT) are at risk for infectious complications, including those of the sinus. Central nervous system (CNS) abnormalities related to the chemotherapy or radiation that the patient received for the treatment of underlying malignancy or to transplant-related effects are also commonly seen. The only effective way to differentiate pre- and post-transplant causes is to have a baseline evaluation prior to the admission for transplant. The current method used to evaluate these patients is head CT. However, CT is not accurate to demonstrate CNS abnormalities and exposes the patient to radiation. MRI, despite better sensitivity for white matter abnormalities, has not been routinely used because of the higher cost and longer duration of the exam. Therefore, we designed a fast, low-cost and radiation-free MRI-based protocol to simultaneously evaluate sinus and brain abnormalities.

Indicações de transplante de células-tronco hematopoéticas em pediatria: consenso apresentado no I Encontro de Diretrizes Brasileiras em Transplante de Células-Tronco Hematopoéticas - Sociedade Brasileira de Transplante de Medula Óssea, Rio de Janeiro, 2009

A Sociedade Brasileira de Transplante de Medula (SBTMO) promoveu o I Encontro de Diretrizes do Transplante de Medula Ossea em 2009. Para revisao das indicacoes de transplante em Pediatria baseadas em evidencias foi constituido grupo de trabalho com oncologistas e hematologistas com experiencia em pediatria. Os artigos cientificos foram cuidadosamente avaliados e, para cada doenca, foram definidas as evidencias para recomendacao dos transplantes (de A a C) e a qualidade destas evidencias (de 1 a 3). As recomendacoes incluem doencas hematologicas malignas e nao malignas, tumores solidos, imunodeficiencias e doencas de deposito tratadas com transplantes de celulas-tronco hematopoeticas, quer autologos, alogenicos de irmao HLA compativel ou nao aparentados (doadores adultos ou sangue de cordao umbilical). Como nao existem recomendacoes uniformemente aceitas em pediatria, nao foram incluidas recomendacoes para transplantes de intensidade reduzida, com manipulacao do enxerto e nem parcialmente compativeis. E importante ressaltar que todas as indicacoes sao baseadas no conhecimento atual e podem modificar-se com o tempo. Assim, esta revisao nao deve ser utilizada para aplicacao direta no cuidado do paciente sem levar em conta caracteristicas da doenca, do doador e fatores de risco do proprio paciente. Este trabalho nao deve ainda ser utilizado como documento que limite o acesso do paciente ao transplante adequadamente indicado. Ressaltamos ainda, nesta revisao, diferencas entre transplantes em criancas e em adultos, com algumas recomendacoes especificas para os transplantes em pediatria.

Simultaneous Quantification of the 8 Human Herpesviruses in Allogeneic Hematopoietic Stem Cell Transplantation.

Background Human herpesviruses may cause severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). However, the impact of some of these infections on transplant outcomes is still unclear. A prospective survey on the incidence and clinical features of herpesviruses infections after HSCT has not yet been conducted in Brazilian patients, and the impact of these infections on HSCT outcome remains unclear. Methods We prospectively analyzed the incidence of infection of the eight human herpesviruses simultaneously in 1 045 peripheral blood samples from 98 allogeneic HSCT recipients. Samples were collected weekly starting at the time of transplant until day +100. All herpesviruses were screened and quantified in plasma by quantitative real-time polymerase chain reaction. Median follow up time was 24 months. Results The incidences of infection for each herpesvirus were as follows: cytomegalovirus (CMV), 44%; human herpesvirus [HHV] 6, 18%; HHV8, 6%; Epstein-Barr virus, 3%; herpes simplex virus 1, 3%; varicella zoster virus, 3%; HHV7, 2%; and herpes simplex virus 2, 1%. The CMV infection was significantly more frequent among adults and was associated with a higher risk of developing acute graft-versus-host disease. The HHV6 infection was significantly more frequent after umbilical cord blood transplant and was associated with an increased risk of platelet engraftment failure. There was no significant impact of these infections on the other transplant outcomes. Conclusions Herpesviruses infections were uncommon after HSCT, except for CMV and HHV6, which, although relatively frequent, had no clinically relevant impact on the outcomes.

Adherence and immune response to revaccination following hematopoietic stem cell transplantation at a pediatric onco-hematology reference center

Revaccination after hematopoietic stem cell transplantation (HSCT) is necessary to compensate for the loss of immunological memory. The aims of this study were to evaluate the adherence to revaccination schedule and the humoral immune response to different vaccine antigens in HSCT pediatric and young adult patients.

The influence of cell concentration at cryopreservation on neutrophil engraftment after autologous peripheral blood stem cell transplantation

Background Peripheral blood stem cell concentrations are traditionally adjusted to 20–40 × 106 leukocytes/mL prior to freezing. This low cell concentration at cryopreservation implies larger volumes with more dimethyl sulfoxide being used, and higher cost and toxicity at the time of transplant. Higher cell concentrations have been reported but this is not widely accepted. Moreover, the influence of cell concentration on engraftment has not been well documented. Therefore, this study retrospectively analyzed the influence of peripheral blood stem cell concentration at freezing on engraftment after autologous hematopoietic stem cell transplantation. Method Leukapheresis products were plasma-depleted and cryopreserved with 5% dimethyl sulfoxide, 6% hydroxyethylamide solution and 4% albumin in a −80 °C freezer. Individual patient data from hospital records were reviewed. Results Fifty consecutive patients with oncological diseases underwent 88 leukaphereses. Median age was six years (range: 1–32 years) and median weight was 19 kg (range: 8–94 kg). Median leukocyte concentration was 109 × 106/mL at collection and 359 × 106 (range: 58–676 × 106) at freezing with 78% viability (range: 53–95%); leukocyte recovery after thawing was 95% (range: 70–100%). In multivariate analysis, cell concentration (p-value = 0.001) had a negative impact on engraftment. Patients infused with bags frozen with <200 × 106 leukocytes/mL engrafted after a median of nine days (range: 8–12 days), 200–400 × 106 leukocytes/mL after 11 days (range: 9–20 days); 400–600 × 106 leukocytes/mL after 12 days (range: 8–19 days) and with cell concentrations >600 × 106 leukocytes/mL, engraftment was after 14 days (range: 13–22 days). Conclusion In patients with adequate CD34 cell collections, total leukocyte concentrations of 282 × 106/mL, freezing with 5% dimethyl sulfoxide and 6% hydroxyethylamide solution without a controlled-rate freezer, and storing cells at −80 °C yielded excellent engraftment. Further increases in cell concentration may delay engraftment, without affecting safety.