Cost-Effectiveness of Hydroxyurea for Sickle Cell Anemia in a Low-Income African Setting: A Model-Based Evaluation of Two Dosing Regimens.

BACKGROUND AND OBJECTIVE: The disease burden of sickle cell anemia (SCA) in sub-Saharan African (SSA) countries is substantial, with many children dying without an established diagnosis or proper treatment. The global burden of SCA is increasing each year, making therapeutic intervention a high priority. Hydroxyurea is the only disease-modifying therapy with proven feasibility and efficacy suitable for SSA; however, no one has quantified the health economic implications of its use. Therefore, from the perspective of the health care provider, we estimated the incremental cost-effectiveness of hydroxyurea as a fixed-dose regimen or maximum tolerated dose (MTD) regimen, versus SCA care without hydroxyurea. METHODS: We estimated the cost of providing outpatient treatment at a pediatric sickle cell clinic in Kampala, Uganda. These estimates were used in a discrete-event simulation model to project mean costs (2021 US$), disability-adjusted life years (DALYs), and consumption of blood products per patient (450 mL units), for patients between 9 months and 18 years of age. We calculated cost-effectiveness as the ratio of incremental costs over incremental DALYs averted, discounted at 3% annually. To test the robustness of our findings, and the impact of uncertainty, we conducted probabilistic and one-way sensitivity analyses, scenario analysis, and price threshold analyses. RESULTS: Hydroxyurea treatment averted an expected 1.37 DALYs and saved US$ 191 per patient if administered at the MTD, compared with SCA care without hydroxyurea. In comparison, hydroxyurea at a fixed dose averted 0.80 DALYs per patient at an incremental cost of US$ 2. The MTD strategy saved 11.2 (95% CI 11.1-11.4) units of blood per patient, compared with 9.1 (95% CI 9.0-9.2) units of blood per patient at the fixed-dose alternative. CONCLUSIONS: Hydroxyurea at MTD is likely to improve quality of life and reduce the consumption of blood products for children with SCA living in Uganda. Compared with a fixed dose regimen, treatment dosing at MTD is likely to be a cost-effective treatment for SCA, using realistic ranges of hydroxyurea costs that are relevant across SSA. Compared with no use of the drug, hydroxyurea could lead to substantial net savings per patient, while reducing the disease morbidity and mortality and increasing quality of life.

Anemia and transfusion requirements among Ugandan children with severe malaria treated with intravenous artesunate.

Parenteral artesunate for the treatment of severe malaria in non-immune travelers is associated with late-onset hemolysis. In children in sub-Saharan Africa, the hematologic effects of malaria and artesunate are less well documented. Here we report a prospective case series of 91 children with severe malaria treated with parenteral artesunate, managed at a resource-poor hospital in Africa, with longitudinal data on hemoglobin (Hb), lactate dehydrogenase (LDH), haptoglobin, and erythrocyte morphology. The median (range) age was 2 (1-8) years and 43 (47%) were female. The median (IQR) admission Hb level was 69 (55-78) g/L and 20 patients (22%) had severe malarial anemia (Hb < 50 g/L). During hospitalization, 69 patients (76%) received one or more blood transfusions. Fatal outcome in 8 patients was associated with severe anemia in 6/8 cases. Follow-up Hb measurement was performed on 35 patients (38%) at day 14 after initial hospital admission; the remaining patients had no clinical evidence of anemia at the follow-up visit. The convalescent Hb was median (range) 90 (60-138) g/L, which was significantly higher than the paired admission levels (median increase +28 g/L, p < .001). Evidence of hemolysis (elevated LDH and low haptoglobin) was common at admission and improved by day 14. No patient met the standardized definition of post-artemisinin delayed hemolysis (PADH). In this cohort of young children with severe malaria treated with artesunate, anemia was common at admission, required one or more transfusions in a majority of patients, and markers of hemolysis had normalized by day 14.

Paediatric immunisation and chemoprophylaxis in a Ugandan sickle cell disease clinic.

AIM: We aimed to assess the receipt of recommended care for young children with sickle cell disease (SCD) in a central SCD clinic in Kampala Uganda, focusing on standard vaccination and antibacterial and antimalarial prophylaxis. METHODS: A cross-sectional assessment of immunisation status and timeliness and prescribed antibacterial and antimalarial prophylaxis was performed in a sample with SCD aged ≤71 months in Mulago Hospital SCD Clinic. Government-issued immunisation cards and clinic-issued visit records for prescribed prophylaxis were reviewed. RESULTS: Vaccinations were documented by immunisation cards in 104 patients, mean age 31.7 months (range 3-70 months). Only 48 (46.2%) received all doses of each of the four recommended vaccine types, including pneumococcal 10-valent conjugate vaccine (pneumococcal conjugate vaccine (PCV)-10), which became available in 2014. Vaccination completion was associated with younger age and, for polio, maternal employment. PCV-10 series was completed in 54.8% of the sample and in 18.2% of those aged 48-71 months. Of children completing all vaccination types, an average 68.8% were immunised on time, defined as <60 days beyond the recommended age. Only 17 (13.5%) children were both fully and timely vaccinated. In an overlapping sample of 147 children, with a mean age of 38.4 months (4-70 months), 81.6% had ≥1 documented prescription for penicillin and/or antimalarial prophylaxis. CONCLUSIONS: Standardised vaccination and antibacterial and antimalarial protective measures for young children at this central SCD clinic were incomplete, especially PCV-10 for age ≥24 months, and often late. Child age, but not general maternal demographics, were associated with vaccination and chemoprophylaxis. Clinic-based oversight may improve timely uptake of these preventative measures.

Platelet Transfusion for Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update.

Purpose To provide evidence-based guidance on the use of platelet transfusion in people with cancer. This guideline updates and replaces the previous ASCO platelet transfusion guideline published initially in 2001. Methods ASCO convened an Expert Panel and conducted a systematic review of the medical literature published from September 1, 2014, through October 26, 2016. This review builds on two 2015 systematic reviews that were conducted by the AABB and the International Collaboration for Transfusion Medicine Guidelines. For clinical questions that were not addressed by the AABB and the International Collaboration for Transfusion Medicine Guidelines (the use of leukoreduction and platelet transfusion in solid tumors or chronic, stable severe thrombocytopenia) or that were addressed partially (invasive procedures), the ASCO search extended back to January 2000. Results The updated ASCO review included 24 more recent publications: three clinical practice guidelines, eight systematic reviews, and 13 observational studies. Recommendations The most substantial change to a previous recommendation involved platelet transfusion in the setting of hematopoietic stem-cell transplantation. Based on data from randomized controlled trials, adult patients who undergo autologous stem-cell transplantation at experienced centers may receive a platelet transfusion at the first sign of bleeding, rather than prophylactically. Prophylactic platelet transfusion at defined platelet count thresholds is still recommended for pediatric patients undergoing autologous stem-cell transplantation and for adult and pediatric patients undergoing allogeneic stem-cell transplantation. Other recommendations address platelet transfusion in patients with hematologic malignancies or solid tumors or in those who undergo invasive procedures. Guidance is also provided regarding the production of platelet products, prevention of Rh alloimmunization, and management of refractoriness to platelet transfusion ( www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki ).

Platelet transfusion therapy in sub-Saharan Africa: bacterial contamination, recipient characteristics, and acute transfusion reactions.

BACKGROUND: Little data are available on bacterial contamination (BC) of platelet units or acute transfusion reactions to platelet transfusions (PTs) in sub-Saharan Africa (SSA). STUDY DESIGN AND METHODS: This prospective, observational study evaluated the rate of BC in whole blood-derived platelet units (WB-PUs), the utility of performing Gram stains to prevent septic reactions, characteristics of patients receiving PTs, and the rate of acute reactions associated with PTs at the Uganda Cancer Institute in Kampala, Uganda. An aliquot of each WB-PU studied was taken to perform Gram stains and culture using the Bactec 9120 instrument. Study participants were monitored for reactions. RESULTS: In total, 337 WB-PUs were evaluated for BC, of which 323 units were transfused in 151 transfusion episodes to 50 patients. The frequency of BC ranged from 0.3% to 2.1% (according to criteria used to define BC). The Gram stain had high specificity (99.1%) but low sensitivity to detect units with BC. The median platelet count before PT was 10,900 cells/µL (interquartile range, 6000-18,900 cells/µL). Overall, 78% of PTs were given to patients with no bleeding. Acute reactions occurred in 11 transfusion episodes, involving 13 WB-PUs, for a rate of 7.3% (95% confidence interval, 3.7%-12.7%) per transfusion episode. All recipients of units with positive bacterial cultures were receiving antibiotics at the time of transfusion; none experienced a reaction. CONCLUSIONS: The rate of BC observed in this study is lower than previously reported in SSA, but still remains a safety issue. Because Gram staining appears to be an ineffective screening tool, alternate methods should be explored to prevent transfusing bacterially contaminated platelets in sub-Saharan Africa.

Trends in timing of prenatal diagnosis and abortion for fetal chromosomal abnormalities.

OBJECTIVE: Our objective was to evaluate changes in the timing of prenatal diagnosis and abortion for chromosomal abnormalities over the past 10 years. STUDY DESIGN: This retrospective review identified singleton pregnancies with fetal chromosomal abnormalities that were diagnosed from 2005-2014 and included Down syndrome, Trisomy 18, and Trisomy 13. The study period was divided into 3 intervals: 2005-2006; 2007-2011; and 2012-2014. Gestational ages at prenatal diagnosis and abortion were compared over these intervals. RESULTS: The 213 cases included 142 cases of Down syndrome (66.7%), 47 cases of Trisomy 18 (22.1%), and 24 cases of Trisomy 13 (11.3%). Two hundred one women (94.4%) chose to undergo abortion. The median gestational ages at prenatal diagnosis and abortion for Trisomy 18 or 13 were 12 weeks (interquartile range, 12-13 weeks) and 13 weeks (interquartile range, 12-15.5 weeks) and did not change over the study period. In contrast, in pregnancies with Down syndrome, the median gestational age at prenatal diagnosis (16, 13, and 12 weeks; P < .001) and abortion (17, 14, and 13 weeks; P < .001) both decreased significantly over the study intervals. In Down syndrome pregnancies, the proportion of women who underwent chorionic villus sampling significantly increased over the 3 study intervals (36%, 63%, and 86%; P < .001). CONCLUSION: Since 2005, the gestational ages at prenatal diagnosis and abortion for Down syndrome have declined significantly. These changes are likely attributable to improvements in early screening that leads to higher rates of chorionic villus sampling.

Transfusion Medicine in Sub-Saharan Africa: Conference Summary.

In November 2014, a 3-day conference devoted to transfusion medicine in sub-Saharan Africa was held in Kampala, Uganda. Faculty from academic institutions in Uganda provided a broad overview of issues pertinent to transfusion medicine in Africa. The conference consisted of lectures, demonstrations, and discussions followed by 5 small group workshops held at the Uganda Blood Transfusion Service Laboratories, the Ugandan Cancer Institute, and the Mulago National Referral Hospital. Highlighted topics included the challenges posed by increasing clinical demands for blood, the need for better patient identification at the time of transfusion, inadequate application of the antiglobulin reagent during pretransfusion testing, concern regarding proper recognition and evaluation of transfusion reactions, the expanded role for nurse leadership as a means to improve patient outcomes, and the need for an epidemiologic map of blood usage in Africa. Specialty areas of focus included the potential for broader application of transcranial Doppler and hydroxyurea therapy in sickle cell disease, African-specific guidelines for transfusion support of cancer patients, the challenges of transfusion support in trauma, and the importance of African-centered clinical research in pediatric and obstetric transfusion medicine. The course concluded by summarizing the benefits derived from an organized quality program that extended from the donor to the recipient. As an educational tool, the slide-audio presentation of the lectures will be made freely available at the International Society of Blood Transfusion Academy Web site: http://www.isbtweb.org/academy/.

Blood utilization at a national referral hospital in sub-Saharan Africa.

BACKGROUND: A safe and adequate supply of blood is critical to improving health care systems in sub-Saharan Africa, where little is known about the current use of blood. The aim of this study was to comprehensively describe the use of blood at a tertiary care hospital to inform future efforts to strengthen blood programs in resource-limited settings. STUDY DESIGN AND METHODS: Data were collected from blood bank documentation for all units issued at Mulago Hospital Complex in Kampala, Uganda, from mid-January to mid-April 2014. RESULTS: A total of 6330 units (69% whole blood, 32% red blood cells, 6% platelets, 2% plasma) were issued over the 3-month study period to 3662 unique patients. Transfusion recipients were 58% female and median age was 27 years (interquartile range [IQR], 14-41). Median pretransfusion hemoglobin was 5.6 g/dL (IQR, 4.0-7.2 g/dL, n = 1090). Strikingly, cancer was the top indication for transfusion (33.5%), followed by pregnancy-related complications (12.4%) and sickle cell disease (6.9%). CONCLUSION: This study provides a comprehensive picture of blood use at a national referral hospital in sub-Saharan Africa. Noncommunicable diseases, particularly oncologic conditions, represent a large proportion of demand for transfusion services.

Transfusion-related acute lung injury in the Canadian paediatric population.

BACKGROUND: The incidence of transfusion-related acute lung injury (TRALI) in adults is approximately one per 5000 transfusions. The Canadian Paediatric Surveillance Program undertook the present study to determine the incidence of TRALI in the paediatric population and to describe the characteristics and outcomes of children with TRALI. METHODS: The present surveillance study was conducted over a three-year period. RESULTS: Four TRALI cases were reported, yielding an incidence rate of 1.8 per 100,000 transfusions. The degree of severity varied: in two patients, only supplemental oxygen was necessary, while the other two required mechanical ventilation. CONCLUSION: TRALI was reported much less often in the present study compared with adult studies; therefore, it needs to be determined whether TRALI occurs less frequently in children, or alternatively, whether TRALI is recognized less often in children. The possibility that neonates who undergo cardiac surgery are at greater risk of TRALI than other patients should be addressed in future studies.

HISTORIQUE: L'incidence de syndrome respiratoire aigu post transfusionnel (TRALI) est d'environ un cas sur 5 000 transfusions chez les adultes. Le Programme canadien de surveillance pédiatrique (PCSP) a entrepris cette étude pour déterminer l'incidence de TRALI dans la population pédiatrique et pour décrire les caractéristiques et le sort des enfants qui ont un TRALI. MÉTHODOLOGIE: Les chercheurs ont mené l'étude de surveillance pendant trois ans. RÉSULTATS: Quatre cas de TRALI ont été signalés, pour une incidence de 1,8 cas sur 100 000 transfusions. Le degré de gravité variait : deux patients n'ont eu besoin que d'oxygène d'appoint, tandis que les deux autres ont eu besoin d'une ventilation mécanique. CONCLUSION: Dans le cadre de cette étude, le TRALI était beaucoup moins signalé que dans les études auprès d'adultes. Il faut donc déterminer si le TRALI est moins fréquent ou s'il est moins dépisté chez les enfants. Lors de futures études, il faudra évaluer la possibilité que les nouveau-nés qui subissent une chirurgie cardiaque soient plus vulnérables au TRALI que les autres patients.

Cryoprecipitate use in 25 Canadian hospitals: commonly used outside of the published guidelines.

BACKGROUND: Canadian Blood Services' disposition reports suggested considerable variation in cryoprecipitate use and prompted this national audit. STUDY DESIGN AND METHODS: Thirty-one institutions were invited to participate in a 2-month audit. Patient information and relevant laboratory and transfusion data were collected. Cryoprecipitate transfusions were categorized as appropriate if a fibrinogen level (taken 6 hr before/after transfusion) was not more than 1.0 g per L and inappropriate if the pretransfusion fibrinogen level was more than 1.0 g per L and posttransfusion fibrinogen level was more than 1.0 g per L or not performed. Appropriateness was categorized as undetermined if the pretransfusion fibrinogen level was not performed and the posttransfusion fibrinogen level was more than 1.0 g per L or not performed. RESULTS: Overall, 25 of 31 invited hospitals agreed to participate. A total of 4370 units of cryoprecipitate were transfused in 603 events to 453 patients representing 62 percent of cryoprecipitate issued to hospitals during the time period. Comparison of the number of units of cryoprecipitate per 100 units of red blood cells (RBCs) transfused by each institution showed significant variation in practice (mean, 9 per 100 RBCs; range, 2 to 27 units). The single most common indication for cryoprecipitate was cardiac surgery (45.4% of events). Overall, 24 percent of cryoprecipitate transfusions were considered to be appropriate (pretransfusion fibrinogen level

Long-term survival rate of pediatric patients after blood transfusion.

BACKGROUND: Studies in adults report posttransfusion survival rate (PTSR) at 1 to 10 years of 41 to 67 percent. There are no published studies specifically addressing PTSR in pediatric patients. The objectives of this study were to evaluate PTSR and risk factors associated with death in children receiving transfusions. STUDY DESIGN AND METHODS: A database of all patients receiving their first transfusion between 1990 and 1992 at Sainte-Justine Hospital (SJH) was used. Patients' demographic data, primary diagnosis, surgical procedures, and information on all labile components transfused were collected. Death was confirmed by the SJH database, RAMQ (universal health care provider for Québec residents), and the Quebec Commission for Access to Information (death certificate). RESULTS: The study population consisted of 1100 children. Median age was 16 months (range, 0-204 months). The most frequent primary diagnoses were cardiac disease (22%), prematurity (21.5%), malignant disease (11%), and hematologic disease (9.5%). Patients received a median of three transfusions (range, 1-126). PTSR was 86.9 percent at 1 year and 82.3 percent at 10 years. For nonsurvivors, median survival time was 22 days. Multivariate analysis showed that significant risk factors for death are age of less than 1 month, a diagnosis of malignant disease, more than 20 transfusions, and administration of more than one type of blood component. CONCLUSION: PTSR in children receiving their first transfusion between 1990 and 1992 was considerably higher than the PTSR reported in adults. Death occurred early after the first transfusion; survival rate remained relatively stable thereafter.

Complications of apheresis in children.

BACKGROUND: Although the frequency of complications in adults undergoing therapeutic apheresis is low, there are little data in children. STUDY DESIGN AND METHODS: A retrospective study of 186 children who had undergone a total of 1632 apheresis procedures between 1994 and 2002 was conducted. Adverse reactions were prospectively documented. The procedures were plasma exchange (67%), hematopoietic progenitor cell collection (18%), red blood cell exchange (6.9%), leukodepletion (0.7%), and plasma exchange with immunoadsorption (6.7%). RESULTS: Adverse reactions, most minor, were reported in 55 percent of procedures in 82 percent of patients. The most frequent complications, per procedure and per patient during an entire course of therapy, were hypotension (14 and 48.4%), hypotension requiring fluid bolus (4.8 and 26.9%), symptomatic hypocalcemia (9.7 and 28.5%), allergic reactions (4.4 and 5.9%), catheter-related thrombosis (1.7 and 12.4%), catheter-related infection (2.1 and 16.1%), and severe anemia (hemoglobin [Hb] level, <7 g/dL; 2.5 and 17.2%). There were two deaths (1% of patients). Risk factors for complications by multivariate analysis were lower body weight, lower preapheresis Hb level, apheresis in a critical care unit, and number of procedures per patient. The 55 percent incidence of complications per procedure in our pediatric cohort is much higher than the 4.3 to 28 percent incidence reported in adults. The excess of adverse reactions in children are mostly related to citrate toxicity, higher relative vascular volume shifts, and the need for vascular access. CONCLUSION: Pediatric apheresis presents unique challenges and is associated with higher complication rate compared to adults. It is recommended that this procedure be performed in specialized centers.

Guidelines on the use of intravenous immune globulin for neurologic conditions.

Canada's per capita use of intravenous immune globulin (IVIG) grew by approximately 115% between 1998 and 2006, making Canada one of the world's highest per capita users of IVIG. It is believed that most of this growth is attributable to off-label usage. To help ensure IVIG use is in keeping with an evidence-based approach to the practice of medicine, the National Advisory Committee on Blood and Blood Products (NAC) and Canadian Blood Services convened a panel of national experts to develop an evidence-based practice guideline on the use of IVIG for neurologic conditions. The mandate of the expert panel was to review evidence regarding use of IVIG for 22 neurologic conditions and formulate recommendations on IVIG use for each. A panel of 6 clinical experts, one expert in practice guideline development and 4 representatives from the NAC met to review the evidence and reach consensus on the recommendations for the use of IVIG. The primary sources used by the panel were 2 recent evidence-based reviews. Recommendations were based on interpretation of the available evidence and, where evidence was lacking, consensus of expert clinical opinion. A draft of the practice guideline was circulated to neurologists in Canada for feedback. The results of this process were reviewed by the expert panel, and modifications to the draft guideline were made where appropriate. This practice guideline will provide the NAC with a basis for making recommendations to provincial and territorial health ministries regarding IVIG use management. Recommendations for use of IVIG were made for 14 conditions, including acute disseminated encephalomyelitis, chronic inflammatory demyelinating polyneuropathy, dermatomyositis, diabetic neuropathy, Guillain-Barré syndrome, Lambert-Eaton myasthenic syndrome, multifocal motor neuropathy, multiple sclerosis, myasthenia gravis, opsoclonus-myoclonus, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, polymyositis, Rasmussen's encephalitis, and stiff person syndrome; IVIG was not recommended for 8 conditions including adrenoleukodystrophy, amyotropic lateral sclerosis, autism, critical illness polyneuropathy, inclusion body, myositis, intractable childhood epilepsy, paraproteinemic neuropathy (IgM variant), and POEMS syndrome. Development and dissemination of evidence-based clinical practice guidelines may help to facilitate appropriate use of IVIG.

Guidelines on the use of intravenous immune globulin for hematologic conditions.

Canada's per capita use of intravenous immune globulin (IVIG) grew by approximately 115% between 1998 and 2006, making Canada one of the world's highest per capita users of IVIG. It is believed that most of this growth is attributable to off-label usage. To help ensure IVIG use is in keeping with an evidence-based approach to the practice of medicine, the National Advisory Committee on Blood and Blood Products of Canada (NAC) and Canadian Blood Services convened a panel of national experts to develop an evidence-based practice guideline on the use of IVIG for hematologic conditions. The mandate of the expert panel was to review evidence regarding use of IVIG for 18 hematologic conditions and formulate recommendations on IVIG use for each. A panel of 13 clinical experts and 1 expert in practice guideline development met to review the evidence and reach consensus on the recommendations for the use of IVIG. The primary sources used by the panel were 3 recent evidence-based reviews. Recommendations were based on interpretation of the available evidence and where evidence was lacking, consensus of expert clinical opinion. A draft of the practice guideline was circulated to hematologists in Canada for feedback. The results of this process were reviewed by the expert panel, and modifications to the draft guideline were made where appropriate. This practice guideline will provide the NAC with a basis for making recommendations to provincial and territorial health ministries regarding IVIG use management. Specific recommendations for routine use of IVIG were made for 7 conditions including acquired red cell aplasia; acquired hypogammaglobulinemia (secondary to malignancy); fetal-neonatal alloimmune thrombocytopenia; hemolytic disease of the newborn; HIV-associated thrombocytopenia; idiopathic thrombocytopenic purpura; and posttransfusion purpura. Intravenous immune globulin was not recommended for use, except under certain life-threatening circumstances, for 8 conditions including acquired hemophilia; acquired von Willebrand disease; autoimmune hemolytic anemia; autoimmune neutropenia; hemolytic transfusion reaction; hemolytic transfusion reaction associated with sickle cell disease; hemolytic uremic syndrome/thrombotic thrombocytopenic purpura; and viral-associated hemophagocytic syndrome. Intravenous immune globulin was not recommended for 2 conditions (aplastic anemia and hematopoietic stem cell transplantation) and was contraindicated for 1 condition (heparin-induced thrombocytopenia). For most hematologic conditions reviewed by the expert panel, routine use of IVIG was not recommended. Development and dissemination of evidence-based guidelines may help to facilitate appropriate use of IVIG.

Second induction in pediatric patients with recurrent acute lymphoid leukemia using DFCI-ALL protocols.

Between 15% and 30% of children with acute lymphoblastic leukemia (ALL) experience disease recurrence. With the possible exception of patients presenting with late isolated extramedullary relapse, induction of second complete remission (CR) is employed as a stepping stone to allogeneic hematopoietic stem cell transplantation (HSCT). The authors report their institutional experience in the management of children with recurrent ALL using the Dana Farber Cancer Institute (DFCI) ALL protocol in patients treated initially with that same protocol. Successful reinduction was followed by allogeneic HSCT when possible. Between April 1986 and May 2003, 34 patients with recurrent ALL, treated at initial diagnosis with DFCI-ALL protocol therapy, were given the same protocol as repeat induction chemotherapy. The median age was 4.6 years at diagnosis and 7.1 years at recurrence. Median duration of CR1 was 30.3 months. Second CR was obtained in 29 (85%) patients. Twenty went on to allogeneic HSCT; 10 of them currently remain in CR. Two additional patients treated with chemotherapy without HSCT are also in continuous CR2. Overall, 13 (38%) of the 34 patients are alive with a median follow-up of 105 months. There were no toxic deaths due to the reinduction therapy. One child died of cardiac failure after autologous HSCT. The treatment of children with recurrent ALL using the DFCI-ALL protocol induction regimen after initial use of the same protocol is associated with a high rate of second CR with no excess toxicity. However, the overall prognosis in these patients remains unsatisfactory and needs to be improved.

Perioperative blood transfusion therapy in pediatric patients.

In general, transfusion guidelines for non-neonatal pediatric patients are similar to those for adults. However, some differences do exist and certain precautions may be necessary particularly in the setting of massive transfusions. We review these differences as they apply to general pediatric surgery outside of the neonatal period, with respect to the transfusion of red blood cells (RBCs), platelets, fresh-frozen plasma (FFP), and cryoprecipitate. We include a discussion of the indications for transfusion and practical considerations such as dosing and administration. Finally, we briefly review the use of directed donations and specialized (irradiated, CMV seronegative) blood components.

Survey on transfusion practices of pediatric intensivists.

OBJECTIVE: To describe the red blood cell transfusion practices of pediatric intensivists. DESIGN: Cross-sectional self-administered survey. SETTING: Pediatric intensive care units. PATIENTS: Academic pediatric intensivists. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Scenario-based survey among English- or French-speaking intensivists from Canada, France, Belgium, or Switzerland, working in tertiary-care pediatric intensive care units. Respondents were asked to report their decisions regarding transfusion practice with respect to four scenarios: cases of bronchiolitis, septic shock, trauma, and the postoperative care of a patient with Fallot's tetrad. The response rate was 71% (163 of 230). The overall baseline hemoglobin transfusion threshold that would have prompted intensivists to transfuse a patient ranged from 7 to 13 g/dL (70-130 g/L) within almost all scenarios. There was a significant difference between scenarios of the average baseline hemoglobin transfusion thresholds (p < .0001). A low Pao2, a high blood lactate concentration, a high Pediatric Risk of Mortality score, active gastric bleeding, emergency surgery, and age (2 wks) were important determinants of red blood cell transfusion, whereas none of the respondents' personal characteristics were. The average volume of packed red blood cells transfused in the four scenarios did not differ significantly. CONCLUSIONS: This survey documented a significant variation in transfusion practice patterns among pediatric critical care practitioners with respect to the threshold hemoglobin concentration for red blood cell transfusion. The volume of packed red blood cells given was not adjusted to the hemoglobin concentration.