RESUMO
BACKGROUND: Tumor boards are part of standard care of patients with complex cancers, but appropriate multidisciplinary expertise and infrastructure are often not available in low- and middle-income countries (LMIC) for pediatric cancers, such as neuroblastoma. Our goal was to review results of a Global Neuroblastoma Network (GNN) tumor board accessible to LMIC. METHODS: De-identified clinical cases presented via internet conference during a weekly GNN virtual tumor board from 2010 through 2020 were evaluated in a standardized format, including diagnostic imaging, pathology, therapy information, resource limitations, and questions for discussion. Information summarized included the presentations, a survey of the impact on care, and a resource questionnaire. RESULTS: Registered GNN participants included 575 individuals from 77 countries, with a median of 39 participants per session. Total 412 cases were presented from 32 countries, including 351 unique neuroblastoma patients, 52 follow-up cases, and nine non-neuroblastoma diagnoses. Twenty-eight educational sessions were presented. Limited critical resources for diagnostics and staging of cases included MYCN analysis (54.7%), metaiodobenzylguanidine (MIBG) scans (38.7%), and International Neuroblastoma Pathology Classification (49%). Therapies were also limited, with markedly decreased use of radiation and autologous stem cell transplant for high-risk cases, and no availability of anti-GD2 antibody in LMIC. Limited sampling with a post-presentation survey showed that 100% found the GNN helpful, and 70% altered the care plan based on the discussion. CONCLUSION: This report shows the utility of an international tumor board for LMIC focused on a challenging solid tumor where local expertise may be limited, with international multidisciplinary expert participation and educational sessions.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Neuroblastoma , 3-Iodobenzilguanidina , Criança , Humanos , Neuroblastoma/patologia , Cintilografia , Transplante AutólogoRESUMO
ABO incompatibility is not a barrier to allogeneic stem cell transplant but may result in acute hemolytic reactions. As stem cell product manipulation is cumbersome, we are reporting the effectiveness and safety of donor-type red cell infusion as a method of reducing acute hemolytic reaction while using marrow as stem cell source. In major ABO-mismatched bone marrow transplants, manipulation of marrow product requires expertise and expensive equipment, which may not be readily available to transplant centers in low- and middle-income regions. The aim behind our study is to report a safe and effective strategy to reduce isohemagglutinin titers and prevent donor marrow infusion reactions in major ABO-mismatched transplants. We retrospectively analyzed 303 consecutive allogeneic bone marrow transplants (BMTs) for beta thalassemia major, between August 2015 and March 2020, with either major (n = 41) or bidirectional (n = 14) mismatches. When isohemagglutinin titers were 1:32 or higher, donor-type packed red blood cell was divided into 4 aliquots, irradiated and administered over 4 days at incremental volumes. Patients were observed for hemolytic reaction, and if no reaction, bone marrow was infused without manipulation. Out of 55 patients, 20 received donor-type blood infusion. Twelve patients showed evidence of mild hemolysis. None developed severe hemolytic or anaphylactic reaction. Titers were rechecked in 14 patients and all had reduction in titers, except for one. Our experience demonstrated that donor-type PRBC infusion is safe and effective in preventing acute hemolysis in major ABO-mismatched stem cell transplants even with bone marrow as graft source.
Assuntos
Sistema ABO de Grupos Sanguíneos/sangue , Incompatibilidade de Grupos Sanguíneos/sangue , Transplante de Medula Óssea/métodos , Transfusão de Eritrócitos/métodos , Hemaglutininas/sangue , Adolescente , Transplante de Medula Óssea/efeitos adversos , Criança , Pré-Escolar , Feminino , Hemólise , Humanos , Masculino , Estudos Retrospectivos , Doadores de Tecidos , Transplante HomólogoRESUMO
Severe thalassemia syndromes (ST) are highly curable by bone marrow transplant (BMT), but rejection may still occur. We retrospectively analyzed our fully matched related donor transplants to establish if isolated splenomegaly is an independent risk factor for rejection and if this risk can be reduced by modifying the conditioning protocol. In this study, we compared rejection rates between patients with and without splenomegaly in 189 consecutive low-risk ST transplants across 2 sequential conditioning regimens: regimen A (August 2013 to December 2016): busulfan (14 mg/kg oral, not adjusted to serum levels), cyclophosphamide (200 mg/kg), and anti-thymocyte globulin (ATG) (Genzyme (Sanofi, Paris, France) 4 mg/kg or Fresenius (Grafalon, Neovii Biotech GmbH, Gräfelfing Germany) 16 mg/kg on days -12 to -10), and regimen B: same backbone as regimen A except fludarabine total dose of 150 mg was added upfront and ATG dose was increased to 7 mg/kg in case of splenomegaly and/or sex-mismatched transplants (January 2017 to September 2018). Compared with regimen A, in regimen B, both overall rejection rates (RRs) (16% versus 6.5%, P = .023) and treatment-related mortality (TRM) (9.9% versus 2.8%, P = .038) improved significantly. By Cox regression analysis, the improvement in RR between the 2 protocols was particularly significant in patients with splenomegaly (RR 54.5% versus 6.5%, P = .00015; TRM 18.2% versus 6.5%, P = .25) (hazard ratio, 4.13; confidence interval, 1.61 to 10.6; P = .003). The increased risk of rejection related to splenomegaly can be overcome by adding fludarabine to the standard ATG-Busulfan- Cyclophosphamide (ATG-Bu-Cy) protocol without significantly increasing transplant-related morbidity and mortality or resorting to splenectomy pre-BMT.
Assuntos
Doença Enxerto-Hospedeiro , Talassemia , Soro Antilinfocitário/uso terapêutico , Bussulfano , Ciclofosfamida/uso terapêutico , França , Alemanha , Humanos , Estudos Retrospectivos , Esplenomegalia , Condicionamento Pré-TransplanteRESUMO
Three-loci low-resolution (LR) or intermediate-resolution HLA typing is generally considered adequate in the related blood and marrow transplantation (BMT) context. However, a single high-resolution (HR) mismatch may have a similar adverse impact on BMT outcome as an LR one. We sought to determine the frequency of mismatches that may go undetected when standard typing (LR or 3-loci HR) is used compared with 6-loci HR typing for related donor compatibility testing, and to assess its impact on relevant BMT outcomes. We analyzed data from a total of 2554 6-loci (HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1) HR sequence-based typing (full typing [FT]) from 754 patients, 1011 siblings, and 789 parents done at DKMS Germany (www.DKMS.de) between January 1, 2014, and June 21, 2016. We also studied 38 cases in which the family had undergone 3-loci HLA typing (standard typing [ST]). Patients were from India (70%), Pakistan (22%), and Sri Lanka (8%). The IMGT/HLA database (www.ebi.ac.uk/ipd/imgt/hla) was used to tease out nonpermissive DPB1 mismatches. HLA disparity-related outcomes, such as rejection and graft-versus-host disease (GVHD) were assessed in a retrospective matched-pair cohort of 50 patients (25 with ST and 25 with FT) who underwent BMT for severe thalassemia from compatible related donors. We found fully matched (either 12/12 HR matches or with a single permissive DPB1 mismatch) related donors for 285 patients (38%). Of these donors, 89% were siblings and 11% were parents. The likelihood of matching on an individual locus on LR but not on HR was found to be 5%. A total of 9 donors (3%; 7 siblings and 2 parents) who would have been considered a full match by HR typing on A, B, and DRB1 alone were not a match by extended 6-loci HR typing. Five of these 9 donors had a mismatch on C or DQB1, and 4 had a nonpermissive DPB1 mismatch. In this group, 5 donors (56%) belonged to a consanguineous family, in 2 donors (22%) there was no reported consanguinity, and in 2 donors (22%) consanguinity was unknown. We identified 18 donors (6%; 13 siblings and 5 parents) who would have been considered a 12/12 match by LR HLA typing alone but were found not to match on extended HR typing. In this group, 11 donors (61%) were from consanguineous families, 3 donors (17%) had no reported consanguinity, and in 4 donors (22%) consanguinity was unknown. Outcome analysis showed that the actuarial proportion of patients with GVHD was 4% in the FT group compared with 16% in the ST group, with log-rank P = .1952. The ST group included 2 patients with grade III-IV acute GVHD and 1 patient each with moderate and severe chronic GVHD, whereas the FT group only 1 patient with grade III acute GVHD. We conclude that even in the context of related donors, the use of LR and/or 3-loci (A, B, and DRB1) HR HLA typing might result in a sizable risk of missing a clinically relevant mismatch, which may have an adverse impact on transplantation outcomes. In the Indian subcontinent, this observation is not limited to putatively compatible parents or consanguineous families; we recommend full 6-loci HR HLA typing even for matched related BMTs.
Assuntos
Transplante de Medula Óssea , Rejeição de Enxerto/prevenção & controle , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA/imunologia , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade/métodos , Talassemia/terapia , Criança , Pré-Escolar , Consanguinidade , Bases de Dados de Proteínas , Família , Feminino , Expressão Gênica , Loci Gênicos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Antígenos HLA/classificação , Antígenos HLA/genética , Humanos , Índia , Lactente , Masculino , Paquistão , Estudos Retrospectivos , Sri Lanka , Talassemia/imunologia , Talassemia/patologia , Doadores não RelacionadosRESUMO
Neuroblastoma is the most common extracranial solid tumor in childhood in high-income countries (HIC), where consistent treatment approaches based on clinical and tumor biological risk stratification have steadily improved outcomes. However, in low- and middle- income countries (LMIC), suboptimal diagnosis, risk stratification, and treatment may occur due to limited resources and unavailable infrastructure. The clinical practice guidelines outlined in this manuscript are based on current published evidence and expert opinions. Standard risk stratification and treatment explicitly adapted to graduated resource settings can improve outcomes for children with neuroblastoma by reducing preventable toxic death and relapse.
Assuntos
Países em Desenvolvimento , Recidiva Local de Neoplasia/mortalidade , Neuroblastoma/diagnóstico , Neuroblastoma/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Recidiva Local de Neoplasia/diagnóstico por imagem , Estadiamento de Neoplasias , Neuroblastoma/diagnóstico por imagem , Pobreza , Radiografia , Cintilografia , Risco , Fatores SocioeconômicosRESUMO
Hematopoietic cell transplantation (HCT) remains the sole available curative option for patients with ß-thalassemia major. Expanded and improved supportive therapies for thalassemia now routinely extend the life span of affected individuals well into adulthood. Consequently, in regions of the world where this care is readily available, HCT has been pursued infrequently, in part owing to concerns about an expected lack of balance between risks and benefits. More recently, however, recognition of significant health problems in older patients with thalassemia, along with recognition of increased risks of graft-versus-host disease (GVHD), graft rejection, and impaired organ function leading to inferior HCT outcomes in this particular group, seem to be turning the wheels and tipping the balance again in the direction of consideration for earlier HCTs. In contrast, in countries where thalassemia is most prevalent (>100,000 new children born each year in Middle East and southeast Asia), lack of supportive care standards together with often insufficient access to dedicated health care facilities, results in the majority of these children not reaching adulthood, further supporting the need for expanded access to HCT for these patients. The cost of HCT is equivalent to that of a few years of noncurative supportive care, such that HCT in low-risk young children with a compatible sibling is justified not only medically and ethically but also financially. International cooperation can play a major role in increasing access to safe and affordable HCT in countries where there is a considerable shortage of transplantation centers. In this article, we review the current status of bone marrow transplantation for thalassemia major, with particular emphasis on a global prospective.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Talassemia beta/terapia , Congressos como Assunto , Rejeição de Enxerto/economia , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/terapia , Doença Enxerto-Hospedeiro/economia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/economia , Hospitais Especializados/economia , Hospitais Especializados/provisão & distribuição , Humanos , Longevidade , Transplante Homólogo , Talassemia beta/economia , Talassemia beta/mortalidadeRESUMO
Thalassemia major (TM) is the most frequent life-threatening noninfectious disease of childhood in the Middle East, South Asia, and Pacific Islands where it accounts for a significant proportion of childhood mortality, morbidity, and related health care expenses. In spite of major advances in supportive care during the last decade, many patients in low-income and middle-income countries still fare poorly because of high treatment costs and lack of accessible multidisciplinary teams, not to consider the risk of blood-borne infections, primarily hepatitis C. In selected low-risk patients with a compatible sibling, TM is highly curable by bone marrow transplantation (BMT), which also improves the quality of life and is cost-effective. Starting in 2008, the Cure2Children Foundation (C2C), an Italian Non-Governmental Organization, has supported a BMT network in Pakistan, which during 2012 was extended to India. The primary aim of this project was to assess feasibility, outcomes, and costs of matched-related BMT for thalassemia in young low-risk children using a well-established and tolerable strategy. A total of 100 matched-related BMTs have been performed to date by partner institutions within this C2C-supported network; in the 50 low-risk cases with TM, over 90% disease-free survival was obtained with procedure expenses within 10,000 USD/BMT, that is, an outcome comparable to that obtained in affluent countries but with a fraction of the expenses. This cure rate was also obtained in start-up BMT centers (1 in Pakistan and 1 in India) within a structured and intensive cooperation program. Twinning and other international cooperation strategies based on shared principles and a common vision may substantially facilitate access to BMT.
Assuntos
Cooperação Internacional , Talassemia beta/prevenção & controle , Talassemia beta/cirurgia , Ásia , Transplante de Medula Óssea , Países em Desenvolvimento , Humanos , Índia , Oriente Médio , Ilhas do Pacífico , PaquistãoRESUMO
In hemoglobinopathy-prone regions, like the Middle East, thalassemia is the most prevalent noncommunicable life-threatening disorder of children and is highly curable by hematopoietic stem cell transplantation (HSCT). Moreover, transplantation is very cost-effective, and HSCT programs can be established directly in middle-income countries (MICs) at a reduced cost while maintaining quality standards and outcomes consistent with international ones. The aim of the present study was to review and verify the efficacy of the applied methodology through the analysis of 47 consecutive matched-related HSCTs in children with thalassemia. In 2016, the first HSCT unit for adults and children with both malignant and nonmalignant diseases was developed in Iraqi Kurdistan, thanks to a capacity building project funded by the Italian Agency for Development Cooperation. Data on clinical activity were obtained from a cohort of patients treated in the newly established HSCT unit. Primary endpoints were overall survival (OS) and thalassemia-free survival (TFS). Startup of the HSCT unit was completed over a 3-year period. Assessing and meeting minimum requirements were crucial for the startup; moreover, a team of international health care professionals (HCPs), all experts in the field of HSCT, conducted the education and training phase, involving all the clinical and nonclinical professionals in the program. At a median follow-up of 2.6 years, the 3-year TFS and OS were 82.8% (SE, 5.5%) and 87.1% (SE, 4.9%), respectively. TFS and graft-versus-host-disease-free composite survival was 80.6% (SE, 5.8%). At present, the HSCT service is completely autonomous, and more than 250 transplants have been done in both adults and children. The minimal essential requirements for an HSCT startup may be affordable in many MICs. Our results for thalassemia are comparable with international data. A twinning program with an international group of experts and a capacity-building approach is crucial for the success of the program, a strategy that allows for rapid development of HSCT units.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Hemoglobinopatias , Talassemia , Criança , Adulto , Humanos , Iraque/epidemiologia , Talassemia/epidemiologia , Talassemia/terapia , Talassemia/etiologia , Hemoglobinopatias/etiologia , Hemoglobinopatias/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversosRESUMO
Bone marrow (BM) continues to be the preferred source of stem cells in allogenic transplantation for nonmalignant disorders. Granulocyte colony-stimulating factor (G-CSF)-primed BM is associated with low rates of acute graft-versus-host disease (aGVHD) and allows reduced collection volumes while ensuring speedy engraftment. However, variability in BM harvest quality is a concern. This study evaluated the utility of a novel indicator, the Bone Marrow Quality Index (BMQI), to predict aGVHD. We analyzed 184 consecutive first matched related donor bone marrow transplants for thalassemia using G-CSF-primed bone marrow over 6 years from March 2017 to April 2023 across 2 centers in India. BMQI was defined as the ratio of the G-CSF-primed BM WBC count to the peripheral blood WBC count within 24 hours of harvest. European Society for Blood and Marrow Transplantation criteria were used to grade aGVHD. The log-rank test was used to assess the impact of BMQI on aGVHD. The chi-square test was used to compare categorical data, and the Wilcoxon rank-sum test was used to compare the numerical data. A Cox proportional hazards model was used to investigate the association of BMQI vis-à-vis other factors on aGVHD. Of the 184 patients studied, 19 had a BMQI <.9, 18 had a BMQI between .9 and 1, and the remaining 147 had a BMQI >1. The rate of aGVHD grade II-IV was 37% in patients with a BMQI <.9 , 22% in those with BMQI .9 to 1, and 12% in those with BMQI >1 (P = .018). Patients with BMQI <.9 had a 3.1-fold greater chance (95% confidence interval [CI], .9 to 10.6) and those with BMQI .9 to 1 had a 2-fold greater chance (95% CI, .5 to 6.6) of developing aGVHD grade II-IV. BMQI was the significant predictor associated with aGVHD hazard (P = .014). BMQI appears to be the most relevant and controllable predictor of aGVHD. It is a novel, informative, and very simple indicator that could influence aGVHD prophylaxis decision making. Our indicator is accurately measurable, inexpensive, precise, and timely; furthermore, it does not involve any sophisticated equipment and thus may be widely applicable. Prior knowledge of poor BM quality may help intensify prophylaxis and monitoring for aGVHD, as well as trigger a review of collection procedures.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Talassemia , Humanos , Medula Óssea , Transplante Homólogo/métodos , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Fator Estimulador de Colônias de Granulócitos , Talassemia/terapiaRESUMO
Fetomaternal microchimerism suggests immunological tolerance between mother and fetus. Thus, we performed primary hematopoietic stem cell transplantation from a mismatched mother to thalassemic patient without an human leukocyte antigen-identical donor. Twenty-two patients with thalassemia major were conditioned with 60 mg/kg hydroxyurea and 3 mg/kg azathioprine from day -59 to -11; 30 mg/m(2) fludarabine from day -17 to -11; 14 mg/kg busulfan starting on day -10; and 200 mg/kg cyclophosphamide, 10 mg/kg thiotepa, and 12.5 mg/kg antithymocyte globulin daily from day -5 to -2. Fourteen patients received CD34(+)-mobilized peripheral blood and bone marrow progenitor cells; 8 patients received marrow graft-selected peripheral blood stem cells CD34(+) and bone marrow CD3/CD19-depleted cells. T-cell dose was adjusted to 2 x 10(5)/kg by fresh marrow cell addback at the time of transplantation. Both groups received cyclosporine for graft-versus-host disease prophylaxis for 2 months after transplantation. Two patients died (cerebral Epstein-Barr virus lymphoma or cytomegalovirus pneumonia), 6 patients reject their grafts, and 14 showed full chimerism with functioning grafts at a median follow-up of 40 months. None of the 14 patients who showed full chimerism developed acute or chronic graft-versus-host disease. These results suggest that maternal haploidentical hematopoietic stem cell transplantation is feasible in patients with thalassemia who lack a matched related donor.
Assuntos
Antígenos CD34/metabolismo , Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/prevenção & controle , Depleção Linfocítica , Transplante de Células-Tronco de Sangue Periférico , Linfócitos T , Talassemia/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Viabilidade , Citometria de Fluxo , Sobrevivência de Enxerto/imunologia , Antígenos HLA/metabolismo , Humanos , Hibridização in Situ Fluorescente , Pessoa de Meia-Idade , Mães , Projetos Piloto , Reação em Cadeia da Polimerase , Estudos Prospectivos , Condicionamento Pré-Transplante , Transplante Homólogo , Adulto JovemRESUMO
The utility of weekly rectal swab surveillance cultures (RSSCs) as a resource to identify gut colonization with extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae carbapenemase (KPC)-producing organisms and guide empirical antibiotic therapy in hematopoietic stem cell transplantation (HSCT) recipients continues to be a subject of interest. There is an urgent need to assess and justify modifications to empirical antibiotics based on regional epidemiology and patient groups. This study aimed to study the utility of weekly rectal swab surveillance cultures (RSSCs) to guide empirical antibiotic therapy and to examine the impact of gut colonization on transplantation outcomes. This retrospective analysis of 317 successive first HSCTs performed mainly for hemoglobinopathies was conducted in 3 pediatric bone marrow transplantation centers in the Indian subcontinent between April 2016 and April 2021. Transplantation, infection control, and febrile neutropenia management protocols were identical in the 3 centers. First-line antibiotics were chosen based on RCCS reports, with meropenem used for ESBL and high-dose meropenem with colistin used for carbapenemase-resistant colonization for first half of the study, with no adjustment made in the second half. Clinical response to antibiotics, long-term outcomes, antibiotic-resistant bacteremia, and acute graft-versus-host disease (GVHD) were analyzed. The log-rank test, chi-square, and Wilcoxon rank-sum tests were used to compare data using R Statistical software. Of the 871 weekly RSSCs done, 162 were positive for ESBL- or KPC-resistant organism. RCCSs were ESBL-positive in 106 patients (33%) and KPC-positive in 10 patients (3%). Among the 97 ESBL-positive patients for whom a antimicrobial susceptibility testing report was available, only 22 (25%) demonstrated clinical resistance to piperacillin-tazobactam (Pip-Taz). Among the 10 KPC-positive patients, only 4 (40%) demonstrated clinical resistance to Pip-Taz and 3 (30%) had clinical resistance to meropenem. Two-thirds of patients with ESBL-positive RSSC in whom first-line empirical antibiotics were used responded clinically. Even among the 15 patients who were resistant to first-line empirical antibiotics (Pip-Taz) on RSSC reports, 67% responded clinically to Pip-Taz. Twenty-seven of these patients (56%) never needed carbapenem therapy. Empirical Pip-Taz therapy in ESBL-positive patients did not prolong meropenem use within 100 days of transplantation (P = .18). All patients with a KPC-positive RSSC who received first-line empirical antibiotics responded clinically, including 4 who were resistant to Pip-Taz and 3 who were meropenem-resistant on RCCS. Comparing patients who were ESBL-positive, KPC-positive, and not positive for either showed no statistically significant differences in overall survival (OS) (P = .95), disease-free survival (DFS) (P = .45), transplantation-related mortality (TRM) (P = .97), graft rejection (P = .68), or rate of acute GVHD grade II-IV (P = .78). No statistically significant differences were seen between the ESBL-positive patients who received and those who did not receive higher-level empirical antibiotics in OS (P = .32), DFS (P = .64), TRM (P = .65), graft rejection (P = .46), acute GVHD grade II-IV (P = .26), or antibiotic-resistant bacteremia (P = .3). In the context of HSCT for nonmalignant hematologic disorders, choosing empiric antibiotic therapy based on RSSCs is not justified, even in regions with a high prevalence of antimicrobial resistance. Antimicrobial susceptibility testing reports in surveillance cultures did not correlate with in vivo clinical response. Colonization reported on weekly RSSCs showed no correlation with clinical outcomes. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
Assuntos
Gestão de Antimicrobianos , Bacteriemia , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Antibacterianos/farmacologia , Bacteriemia/tratamento farmacológico , Criança , Escherichia coli , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Controle de Infecções , Klebsiella pneumoniae , Meropeném/uso terapêutico , Combinação Piperacilina e Tazobactam/uso terapêutico , Estudos Retrospectivos , Estados UnidosRESUMO
Background: Patients with tunneled central venous lines (CVL) may develop bloodstream infections which at times are difficult to control without line removal. Concomitant severe thrombocytopenia with platelet transfusion refractoriness is often considered a major contraindication to any procedure involving a major blood vessel. There is very little literature on the clinical risks of tunneled central line removal in febrile pancytopenia patients. Procedure: We analyzed complications and outcomes in all our patients, a total of 52, who underwent CVL removal with platelets <20,000/µl. Results: CVL removal was done on a median day of 17.5 with 47 of the 52 patients never having achieved platelets engraftment prior to line removal. No bleeding episodes or unplanned transfusions could be associated with CVL removal. No other complications were also reported. All patients had time to hemostasis within 5 min of catheter removal. Removal of CVL under local anesthesia remained complication-free even at platelet counts less than 20,000/ul. A total of 31 patients were febrile at the time of CVL removal, of which 17 became afebrile within 2 days. We found no difference in defervescence when comparing those whose antibiotic therapy was changed/escalated versus those in whom it was not. Conclusion: Our findings suggest that central lines can be safely removed with platelet counts less than 20,000/ul and that this may result in enhanced bloodstream infection control. This might be particularly relevant to neutropenic patients in this day and age of multidrug-resistant organism emergence and paucity of new effective antibiotics.
RESUMO
OBJECTIVE: The objective was twofold. The focus of the study was primarily to determine if the stress of a particularly difficult exam could cause students to lose the normal diurnal variation seen in human cortisol levels and secondarily, to validate the use of a competitive enzyme immunoassay for salivary cortisol. DESIGN: Physical therapy students enrolled in Research Design were asked to participate in the study by collecting baseline evening and morning salivary cortisols during what was regarded as a relatively stress free time in the Fall of 2009. The following spring, the same students were asked for samples the evening before and morning of their first Kinesiology test, traditionally a stressful time. Method validation was accomplished using instrumentation owned by the Medical Laboratory Science (MLS) Program and analysis was performed by MLS faculty and a second year MLS student. SETTING: Participants were enrolled in the College of Health Sciences at the University of Tennessee in Memphis. Sample collection and testing was performed in the student laboratory of the Medical Laboratory Science Program. PARTICIPANTS: Physical therapy students in their first year of a three-year entry level doctorate program, DPT. RESULTS: This group of students did not lose their diurnal variation of cortisol. However, an unexpected finding was noted: the students' salivary cortisol specimen collected in the morning of the fall semester was significantly higher than the salivary cortisol specimen collected the morning of the test in the spring semester (p = .019). Method validation was successful demonstrating a strong correlation ( r = 0.915) when compared to the reference laboratory. CONCLUSIONS: Cortisol diurnal variation was not lost in the study participants, but further studies should be performed due to the low percentage of students completing the study and the lack of demographic diversity. Even though the method validation in the student laboratory setting demonstrates that it is indeed possible to obtain the same excellent correlation as is seen in a clinical setting, the student laboratory is not CLIA certified, so assays can be performed for research use only.
Assuntos
Hidrocortisona/metabolismo , Técnicas Imunoenzimáticas/métodos , Técnicas Imunoenzimáticas/normas , Saliva/metabolismo , Estresse Psicológico/diagnóstico , Estresse Psicológico/metabolismo , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Diamond Blackfan anemia (DBA) is a rare congenital syndrome presenting primarily as pure red cell aplasia with constitutional abnormalities and cancer predisposition. Established treatment options are corticosteroids, regular erythrocyte transfusions with iron chelation therapy, and hematopoietic stem cell transplantation (HSCT). To date, HSCT is the only definitive curative treatment for the hematological phenotype of DBA, but there is little experience with its use. Given the rarity of the disease and its unique features, an expert panel agreed to draw up a set of recommendations on the use of HSCT in DBA to guide clinical decision-making and practice. The recommendations address indications, pretransplant patient evaluation, donor selection, stem cell sources, conditioning regimens, prophylaxis of rejection and graft versus host disease, and post-transplant follow-up.
Assuntos
Anemia Aplástica , Anemia de Diamond-Blackfan , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Anemia Aplástica/terapia , Anemia de Diamond-Blackfan/genética , Anemia de Diamond-Blackfan/terapia , Transfusão de Eritrócitos , Doença Enxerto-Hospedeiro/prevenção & controle , HumanosRESUMO
Establishing a hematopoietic cell transplantation (HCT) program is complex. Planning is essential while establishing such a program to overcome the expected challenges. Authorities involved in HCT program establishment will need to coordinate the efforts between the different departments required to start up the program. One essential department is pharmacy and the medications required. To help facilitate this, the Worldwide Network for Blood and Marrow Transplantation organized a structured survey to address the essential medications required to start up an HCT program. A group of senior physicians and pharmacists prepared a list of the medications used at the different phases of transplantation. These drugs were then rated by a questionnaire using a scale of necessity based on the stage of development of the transplant program. The questionnaire was sent to 30 physicians, in different parts of the world, who have between 5 and 40 years of experience in autologous and/or allogeneic transplantation. This group of experts scored each medication on a 7-point scale, ranging from an absolute requirement (score of 1) to not required (score of 7). The results are presented here to help guide the prioritization of required medications.
Assuntos
Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Transplante de Medula Óssea , Transplante HomólogoRESUMO
Severe blood disorders and cancer are the leading cause of death and disability from noncommunicable diseases in the global pediatric population and a major financial burden. The most frequent of these conditions, namely sickle cell disease and severe thalassemia, are highly curable by blood or bone marrow transplantation (BMT) which can restore a normal health-related quality of life and be cost-effective. This position paper summarizes critical issues in extending global access to BMT based on ground experience in the start-up of several BMT units in middle-income countries (MICs) across South-East Asia and the Middle East where close to 700 allogeneic BMTs have been performed over a 10-year period. Basic requirements in terms of support systems, equipment, and consumables are summarized keeping in mind WHO's model essential lists and recommendations. BMT unit setup and maintenance costs are summarized as well as those per transplant. Low-risk BMT is feasible and safe in MICs with outcomes comparable to high-income countries but at a fraction of the cost. This report might be of assistance to health care institutions in MICs interested in developing hematopoietic stem cell transplantation services and strengthening context appropriate tertiary care and higher medical education.
Assuntos
Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Transplante de Medula Óssea , Criança , Humanos , Oriente Médio , Qualidade de VidaRESUMO
Hematopoietic stem cell transplantation (HSCT) remains the only established definitive cure for severe hemoglobinopathies, such as sickle cell disease (SCD) and thalassemia-the most prevalent life-threatening non-communicable disease of childhood globally. HSCT can not only cure over 85% of children with a compatible sibling but also restore normal health-related quality of life in most cases who do not have major irreversible organ damage at transplant. In low- and middle-income countries (LMICs), particularly in sub-Saharan Africa, SCD carrier rate can be up to 30% and 1% of live births have SCD. Relatively simple and inexpensive measures such as newborn screening, early diagnosis, caregiver education, and timely institution of anti-pneumococcal prophylaxis and hydroxyurea therapy can substantially reduce SCD-related mortality and morbidity. Improved prevention and early care should proceed in parallel with the development of transplant services and hope for cure. Cure2Children, an Italian NGO, has supported the startup of several bone marrow transplantation programs in LMICs where over 500 transplants have been performed over the last 10 years, with outcomes not substantially different from high-income countries but at a fraction of the cost. This report summarizes this experience and suggests some strategies to set up new HSCT units.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Hemoglobinopatias/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Criança , Pré-Escolar , Países em Desenvolvimento , Feminino , Humanos , Lactente , MasculinoRESUMO
Sickle cell disease is one of the most common, life-threatening, non-communicable diseases in the world and a major public health problem. Following the implementation of simple preventive and therapeutic modalities, infant mortality has almost been abolished in high-income countries, but only a small amount of progress has been made in improving survival in adulthood. Progressive end-organ damage, partly related to a systemic vasculopathy, is increasingly recognised. With the availability of a variety of novel disease-modifying drugs, gene addition and gene editing strategies, matched sibling donor haematopoietic stem cell transplantation (HSCT) in children (offering an overall survival rate of 95% and an event-free survival rate of 92%), and encouraging outcomes after alternative donor HSCT, the new challenge is to risk stratify patients, revise transplantation indications, and define the best therapeutic approach for each patient. The ultimate challenge will be to enable these advances in low-income and middle-income countries, where disease prevalence is highest and where innovative strategies are most needed.
Assuntos
Anemia Falciforme/terapia , Edição de Genes/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Anemia Falciforme/patologia , HumanosRESUMO
In spite of advances in chelation therapy and screening of blood, mortality associated with the most common life-threatening noncommunicable disease of children in India, transfusion-dependent thalassemia (TDT), remains poorly defined. This study aims at estimating death rates and mortality risk factors associated with TDT. The clinical records of 1087 patients from 5 thalassemia centers in India were retrospectively analyzed from 2011 to 2018. Median patient age was 8.5 years, with 107 patients older than 18 years; 656 patients were male and 431 were female. Demographic details and clinical parameters were analyzed at presentation and at last visit. With 41 recorded deaths, actuarial survival at 26.9 years was 50%, and under-5 mortality was 7 times higher than in the general population. Patients with transfusion-transmitted infections (TTIs) had 3.4 times higher risk for death (P = .031). Serum ferritin higher than 4000 ng/dL had 4.6 times higher risk for mortality compared with ferritin lower than 1000 ng/dL (P = .00063). A hemoglobin drop lower than 2 g/dL per week had 7.7 times higher mortality risk compared with a drop of less than 1 g/dL per week (P < .0001). Social determinants (sex, economic status, and distance from center), splenectomy, and even cardiac complications were not associated with higher mortality risk. Main causes of death were infection, iron overload, TTIs, and allo-immunization. Patients who received more than 4 years of adequate care had more than 66% mortality risk reduction (P < .0001). TDT in India continues to result in high mortality. Ineffective transfusion, TTIs, and chelation continue to be the most significant risk factors. Comprehensive care in dedicated day care centers from early age is likely to improve outcomes.
Assuntos
Expectativa de Vida , Talassemia , Criança , Feminino , Humanos , Índia/epidemiologia , Masculino , Estudos Retrospectivos , Fatores de Risco , Síndrome , Talassemia/epidemiologia , Talassemia/terapiaRESUMO
BACKGROUND: Successful models of information and communication technology (ICT) applied to cost-effective delivery of quality care in low- and middle-income countries (LMIC) are an increasing necessity. Severe thalassemia is one of the most common life-threatening noncommunicable diseases of children globally. OBJECTIVE: The aim was to study the impact of ICT on quality of care for severe thalassemia patients in LMIC. METHODS: A total of 1110 patients with severe thalassemia from five centers in India were followed over a 1-year period. The impact of consistent use of a Web-based platform designed to assist comprehensive management of severe thalassemia (ThalCare) on key indicators of quality of care such as minimum (pretransfusion) hemoglobin, serum ferritin, liver size, and spleen size were assessed. RESULTS: Overall improvements in initial hemoglobin, ferritin, and liver and spleen size were significant (P<.001 for each). For four centers, the improvement in mean pretransfusion hemoglobin level was statistically significant (P<.001). Four of five centers achieved reduction in mean ferritin levels, with two displaying a significant drop in ferritin (P=.004 and P<.001). One of the five centers did not record liver and spleen size on palpation, but of the remaining four centers, two witnessed a large drop in liver and spleen size (P<.01), one witnessed moderate drop (P=.05 for liver; P=.03 for spleen size), while the fourth witnessed a moderate increase in liver size (P=.08) and insignificant change in spleen size (P=.12). CONCLUSIONS: Implementation of computer-assisted treatment planning and performance assessment consistently and positively impacted indexes reflecting effective delivery of care to patients suffering from severe thalassemia in LMIC.