PURPOSE This study aimed to describe and assess the regional experience of a pediatric hematology/oncology fellowship program based in Guatemala. METHODS The Unidad Nacional de Oncología Pediátrica ...(UNOP) in Guatemala City, Guatemala, is the only hospital in Central America dedicated exclusively to childhood and adolescent cancer. To address the regional need for specialists, a fellowship program in pediatric hematology/oncology was launched in 2003. The UNOP fellowship program comprises 3 years of training. Although the program is based at UNOP, it also includes rotations locally and internationally to enhance clinical exposure. The curriculum is based on international standards to cover clinical expertise, research, professionalism, communication, and health advocacy. Trainees are selected according to country or facility-level need for pediatric hematologists/oncologists, with a plan for them to be hired immediately after completing their training. RESULTS Forty physicians from 10 countries in Latin America have completed training. In addition, there are currently 13 fellows from five countries in training. Of the graduates, 39 (98%) are now practicing in pediatric hematology/oncology in Latin America. Moreover, many of them have leadership positions within their institutions and participate in research, advocacy, and policy making. Graduates from the UNOP program contribute to institutions by providing care for an increasing number of patients with pediatric cancer. The UNOP program is the first pediatric hematology/oncology fellowship program in the world to be accredited by Accreditation Council for Graduate Medical Education-International, an international body accrediting clinical training programs. CONCLUSION The UNOP program has trained specialists to increase the available care for children with cancer in Latin America. This regional approach to specialist training can maximize resources and serve as a model for other programs and regions.
A fellowship program in Guatemala has a regional impact in strengthening the pediatric cancer workforce.
The profound organ shortage in all types of transplantation has led to broadening of the criteria used to define acceptable organ donors, including those from donors positive for hepatitis C virus ...(HCV) antibodies. These organs are primarily given to recipients with pre-existing chronic HCV infection, but in selected cases they are also placed into recipients without HCV. The majority of these patients become viremic and have the potential to develop sequelae of chronic infection, including progressive hepatic fibrosis. They are exposed to the indirect effects of chronic immune activation and the potential to require HCV treatment which has been associated with allograft rejection and accelerated atherosclerosis. Patient and graft outcomes in transplantation of HCV-positive liver, heart, and kidney grafts have now been studied on the national and center levels. The most data are available for patients who received HCV-positive liver grafts. Given the data to date, these organs are likely to continue to be used in HCV-positive but not in HCV-negative recipients. However, when directly acting HCV antiviral therapy becomes widely available, the use of all types of HCV-positive organs could be expanded, even potentially in HCV-negative recipients. This chapter reviews the literature on the transplantation of HCV-positive grafts into recipients with and without chronic HCV, and speculates on future developments as anti-HCV therapy improves in the years to come.
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Background: An international survey we recently conducted indicated that, even today, adults with acute myeloid leukemia (AML) standardly remain hospitalized after completion of induction ...chemotherapy until resolution of cytopenias due to a high risk of infection and frequent need for transfusions. In contrast, over the last five years at our institution, hospital discharge immediately following completion of induction chemotherapy has become routine after a phase 2 trial evaluating an Early Hospital Discharge (EHD) strategy showed this approach to be safe and cost-effective. On the other hand, EHD is a nearly-universal practice following post-remission or “consolidation” therapy. Here, we sought to compare safety and healthcare resource utilization outcomes for patients who are discharged to the outpatient setting following intensive induction vs. consolidation chemotherapy.
Methods: We retrospectively identified all adults aged ≥18 years with newly-diagnosed AML/high-grade myeloid neoplasms (≥10% blasts in peripheral blood/ bone marrow) who started AML-like intensive induction or consolidation chemotherapy (“7+3,” high-dose cytarabine HiDAC, or a regimen of similar/higher intensity) at our institution from 8/1/14 (completion of our phase 2 EHD study) to 7/31/18. EHD was defined as discharge from the hospital within 72 hours of completing chemotherapy (as done in our phase 2 study). Induction therapy was defined as the first course of intensive chemotherapy for untreated disease. Consolidation therapy was defined as intensive therapy if the marrow (and hematologic parameters) prior to starting treatment showed complete remission by standard International Working Group criteria. Patients with relapsed or primary refractory disease were excluded from this analysis. The study period began on the day of initial discharge and ended with count recovery, death, receipt of additional disease-directed therapy, transfer of care, or once 42 days elapsed. We collected baseline demographic and clinical characteristics, logistical information, and treatment regimen. Outcomes of interest including readmission timing/reasons, intensive care unit (ICU) admission, resource utilization (number of lab visits, provider visits, days of IV antimicrobial use, units of transfused red blood cell RBC and platelets) and survival. All analyses accounted for correlation between patients because 100 patients were in both the induction and consolidation datasets and 62 patients had more than 1 consolidation cycle in the dataset.
Results: We identified 215 induction cycles and 225 consolidation cycles that met our criteria for EHD. As detailed in Table 1, induction EHD patients had worse baseline performance status and higher white blood cell counts than consolidation EHD patients. Consolidation patients spent more time on study (27.8 vs. 24.7 days) and spent a higher proportion of their study time as outpatients (mean of 79% vs. 71% of study time; p<0.001), at least in part because of a lower readmission rate (mean of 0.8 vs. 1.1 readmissions; p<0.001). There were no differences in the proportion of study days spent in the ICU (1.6% after induction vs 0.6% after consolidation; p=0.27). However, the early death rate (within 30 days of study day 1) was higher in the induction EHD group (4% vs. 1%; p=0.03). A higher proportion of study days were spent on IV antimicrobials in the induction group (37% vs. 32% days; p=0.06), and though absolute numbers were small, the induction cohort had more frequent physician (0.07 vs. 0.05; p<0.001) and nurse/advanced practiced practitioner visits (0.09 vs. 0.08; p=0.02) per study day than the consolidation group, respectively. There were no differences in mean lab visits per outpatient study day (p=0.63), in mean number of red blood cell transfusions per study day (p=0.18) or mean number of platelet transfusions per study day (p=0.51).
Conclusion: Although the early death rate, as would be expected given a baseline sicker population, was higher for EHD patients following induction compared to consolidation chemotherapy, there were no differences between the two groups in requirements for ICU care, laboratory monitoring, or transfusion need in the outpatient setting. This suggests that an EHD strategy following induction therapy may be safely and reasonably implemented at centers with infrastructure supporting EHD following standard consolidation therapy.
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Halpern:Pfizer Pharmaceuticals: Research Funding; Bayer Pharmaceuticals: Research Funding. Othus:Glycomimetics: Other: Data Safety and Monitoring Committee; Celgene: Other: Data Safety and Monitoring Committee. Buckley:CTI BioPharma: Employment, Equity Ownership. Percival:Pfizer Inc.: Research Funding; Nohla Therapeutics: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees. Becker:The France Foundation: Honoraria; AbbVie, Amgen, Bristol-Myers Squibb, Glycomimetics, Invivoscribe, JW Pharmaceuticals, Novartis, Trovagene: Research Funding; Accordant Health Services/Caremark: Consultancy. Scott:Novartis: Consultancy; Agios: Consultancy; Incyte: Consultancy; Celgene: Consultancy. Oehler:Pfizer Inc.: Research Funding; Blueprint Medicines: Consultancy; NCCN: Consultancy. Gernsheimer:Fuji film: Consultancy; Bioverativ: Consultancy; Dova pharmaceuticals: Consultancy; Novartis: Honoraria; Cellphire: Consultancy; Amgen: Consultancy, Honoraria; Rigel: Consultancy; Shionogi: Consultancy. Orozco:Actinium Pharmaceuticals: Research Funding. Cassaday:Amgen: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Kite/Gilead: Research Funding; Merck: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Other: Spouse's disclosure: employment, stock and other ownership interests. Shustov:Seattle Genetics, Inc.: Research Funding. Hartley:Pfizer Inc.: Employment, Equity Ownership. Welch:Pfizer Inc: Employment, Equity Ownership. Walter:Agios: Consultancy; Amgen: Consultancy; Amphivena Therapeutics: Consultancy, Equity Ownership; Aptevo Therapeutics: Consultancy, Research Funding; Argenx BVBA: Consultancy; Astellas: Consultancy; BioLineRx: Consultancy; BiVictriX: Consultancy; Boehringer Ingelheim: Consultancy; Boston Biomedical: Consultancy; Covagen: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy; Kite Pharma: Consultancy; New Link Genetics: Consultancy; Pfizer: Consultancy, Research Funding; Race Oncology: Consultancy; Seattle Genetics: Research Funding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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Background: Because infections are a major cause of morbidity and mortality after AML induction chemotherapy, patients typically remain hospitalized for monitoring and rapid antimicrobial therapy ...until hematopoietic recovery. With declining early mortality and improved oral antimicrobials, interest in moving post-induction care to the outpatient setting has emerged. In the 5-year period since completing a prospective phase 2 trial evaluating an Early Hospital Discharge (EHD) strategy, EHD following AML-like induction chemotherapy has become routine at our institution. In recent retrospective analyses, we found >80% of EHD patients required hospital readmission, primarily for neutropenic fever. Still, the EHD strategy was safe and reduced healthcare resource utilization, and EHD patients spent >70% of their post-chemotherapy time as outpatients. Here, we investigated differences in the pattern of infectious complications between patients managed as outpatients following induction chemotherapy and those who remain hospitalized until hematopoietic recovery.
Methods: We retrospectively identified all adults ≥18 years with untreated AML/high-grade myeloid neoplasms (≥10% blasts in blood/ bone marrow) who started intensive induction chemotherapy (“7+3” or a regimen of similar/higher intensity) at our institution from 8/1/2014-7/31/2018. Patients were considered “EHD” if they were discharged from the hospital <72 hours from completing chemotherapy (as done in our phase 2 study); the remaining patients were considered inpatient “controls”. The study period began on the day of discharge (EHD group) or at the completion of chemotherapy (control group) and ended with count recovery, hospital discharge (control group), death, receipt of more chemotherapy, or at 42 days. Table 1 describes baseline variables collected. Outcomes of interest were organism and site of infections, days of IV antimicrobial use, days in intensive care unit (ICU), and survival. Bacterial infections were either culture-documented or probable based on clinical exam/imaging. Fungal infections were proven or probable based on EORTC/MSG Working Group Criteria. Microbiological documentation was required for viral infections.
Results: We identified 354 inductions that met our criteria: 215 (61%) in the EHD group and 139 (39%) in the control group (baseline characteristics in Table 1). For antimicrobial prophylaxis, more EHD patients than controls used levofloxacin vs. other agents (98% vs. 93%; p=0.03) and controls more likely used posaconazole vs. EHD patients (64% vs. 52%; p<0.001). EHD patients more likely had a tunneled central venous catheter (42% vs. 32%; p=0.03) than a peripherally inserted central catheter (53% vs 67%; p=0.03). 53% of EHD patients vs. 39% of controls developed ≥1 infection during the study period (p=0.01). There were no differences between groups in type of organism identified. We then assessed whether the higher infection rate in EHD patients led to inferior outcomes (Table 2). There were no differences in ICU admission (7% vs. 10%; p=0.44) or early death (4% vs. 7%; p=0.24) between EHD and controls. Despite a higher rate of infections, EHD patients spent fewer days on IV antimicrobials. For the whole cohort, however, patients with ≥1 infection more likely required ICU care than those without infection (14% vs 4%, p<0.001) but there was no difference in early death rates between patients who developed an infection and those who did not. Development of gram positive bacteremia was associated with risk of ICU admission, a trend towards early death and a longer hospital stay. Development of fungal infection was also associated with a longer hospital stay (12.7 vs 6.4 days) but not risk of ICU admission or early death. There was no association between type of prophylactic antifungal agent and subsequent diagnosis of fungal infection, between catheter type and risk of bacteremia, or between housing distance to our institution and infection risk (EHD group).
Conclusion: An EHD care strategy following AML-like induction chemotherapy is associated with a higher rate of infection but not an increased risk for ICU stay or early death. Central catheter type, specifics of antimicrobial prophylaxis, and distance to our institution were not associated with infection risk in the EHD group. Further investigation to elucidate the risk factors for the increased rate of infection in the EHD group is warranted.
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Halpern:Pfizer Pharmaceuticals: Research Funding; Bayer Pharmaceuticals: Research Funding. Othus:Glycomimetics: Other: Data Safety and Monitoring Committee; Celgene: Other: Data Safety and Monitoring Committee. Buckley:CTI Biopharma: Employment. Percival:Pfizer Inc.: Research Funding; Nohla Therapeutics: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees. Becker:The France Foundation: Honoraria; Accordant Health Services/Caremark: Consultancy; AbbVie, Amgen, Bristol-Myers Squibb, Glycomimetics, Invivoscribe, JW Pharmaceuticals, Novartis, Trovagene: Research Funding. Scott:Incyte: Consultancy; Novartis: Consultancy; Agios: Consultancy; Celgene: Consultancy. Oehler:Pfizer Inc.: Research Funding; Blueprint Medicines: Consultancy; NCCN: Consultancy. Gernsheimer:Bioverativ: Consultancy; Novartis: Honoraria; Dova pharmaceuticals: Consultancy; Shionogi: Consultancy; Rigel: Consultancy; Fuji film: Consultancy; Amgen: Consultancy, Honoraria; Cellphire: Consultancy. Orozco:Actinium Pharmaceuticals: Research Funding. Cassaday:Seattle Genetics: Other: Spouse's disclosure: employment, stock and other ownership interests; Amgen: Consultancy, Research Funding; Merck: Research Funding; Seattle Genetics: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Kite/Gilead: Research Funding. Shustov:Seattle Genetics, Inc.: Research Funding. Hartley:Pfizer Inc.: Employment, Equity Ownership. Welch:Pfizer Inc: Employment, Equity Ownership. Walter:Seattle Genetics: Research Funding; Jazz Pharmaceuticals: Consultancy; Amphivena Therapeutics: Consultancy, Equity Ownership; Agios: Consultancy; Amgen: Consultancy; Aptevo Therapeutics: Consultancy, Research Funding; Argenx BVBA: Consultancy; Astellas: Consultancy; BioLineRx: Consultancy; BiVictriX: Consultancy; Boehringer Ingelheim: Consultancy; Daiichi Sankyo: Consultancy; New Link Genetics: Consultancy; Pfizer: Consultancy, Research Funding; Kite Pharma: Consultancy; Covagen: Consultancy; Boston Biomedical: Consultancy; Race Oncology: Consultancy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Twenty-five patients with high-risk resected stages IIB, III, and IV melanoma were immunized with a vaccine consisting of the minimal epitope, immunodominant 9-amino acid peptide derived from the ...MART-1 tumor antigen (AAGIGILTV) complexed with incomplete Freund's adjuvant. The last three patients received the MART-1(27-35) peptide with incomplete Freund's adjuvant mixed with CRL 1005, a block copolymer adjuvant. Patients were immunized with increasing doses of the MART-1(27-35) peptide in a Phase I trial to evaluate the toxicity, tolerability, and immune responses to the vaccine. Immunizations were administered every 3 weeks for a total of four injections, preceded by leukapheresis to obtain peripheral blood mononuclear cells for immune analyses, followed by a post-vaccine leukapheresis 3 weeks after the fourth vaccination. Skin testing with peptide and standard delayed-type hypersensitivity skin test reagents was also performed before and after vaccinations. Local pain and granuloma formation were observed in the majority of patients, as were fevers or lethargy of grade 1 or 2. No vaccine-related grade III/IV toxicity was observed. The vaccine was felt to be well tolerated. Twelve of 25 patients were anergic to skin testing at the initiation of the trial, and 13 of 25 developed a positive skin test response to the MART-1(27-35) peptide. Immune responses were measured by release of IFN-gamma in an ELISA assay by effector cells after multiple restimulations of peripheral blood mononuclear cells in the presence of MART-1(27-35) peptide-pulsed antigen-presenting cells. An ELISPOT assay was also developed to measure more quantitatively the change in numbers of peptide-specific effector cells after vaccination. Ten of 22 patients demonstrated an immune response to peptide-pulsed targets or tumor cells by ELISA assay after vaccination, as did 12 of 20 patients by ELISPOT. Nine of 25 patients have relapsed with a median of 16 months of follow-up, and 3 patients in this high-risk group have died. Immune response by ELISA correlated with prolonged relapse-free survival. These data suggest a significant proportion of patients with resected melanoma mount an antigen-specific immune response against a peptide vaccine and support further development of peptide vaccines for melanoma.
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