The Role of Hematopoietic Stem-Cell Transplantation in First Remission in Pediatric Acute Lymphoblastic Leukemia: A Narrative Review

Context: Survival after allogeneic hematopoietic stem-cell transplantation (HSCT) for children with hematologic malignancies including acute lymphoblastic leukemia (ALL) continues to improve in part due to advancement in HLA typing and enhanced supportive care. Despite improved outcomes with HSCT, the decision to offer it in first remission (CR1) in children with ALL remains a topic of debate and uncertainty. This review aims to discuss the role of HSCT in CR1 for children with high-risk subsets of ALL in the current era. Evidence Acquisition: A thorough review of the literature was performed using electronic databases: PubMed, Google Scholar, and bibliographies. Studies focusing on high-risk subsets of ALL (Primary Induction Failure, Severe Hypodiploidy, Philadelphia-chromosome positive ALL, T-Cell ALL, Infant ALL, ALL with persistent minimal residual disease (MRD), and Philadelphia-like ALL) were included. Publications in non- English language were excluded. Results: Based on our review of the current literature, HSCT should be considered in first remission for patients with primary induction failure, severe hypodiploidy, T-cell ALL with poor response, high-risk infant ALL, and persistently positive MRD. In contrast, HSCT in CR1 may not be warranted for patients with early T-cell progenitor ALL or Philadelphia-chromosome positive ALL. Further data are needed to make specific recommendations regarding Philadelphia-like ALL. Conclusions: As our understanding of high-risk leukemia biology continues to develop, the role of HSCT in ALL CR1 will need to be revisited

Comparative outcomes of percutaneous coronary intervention for ST-segment-elevation myocardial infarction among medicare beneficiaries with multivessel coronary artery disease: An national cardiovascular data registry research to practice project

BACKGROUND: Prior studies on the use of multivessel percutaneous coronary intervention (MV PCI) for patients with STEMI and multivessel coronary artery disease have yielded heterogeneous results. The recent COMPLETE trial demonstrated that MV PCI was superior to culprit-only PCI among patients with STEMI. It is unclear how these trial results apply to clinical decisions encountered in routine practice. METHODS: We studied STEMI admissions among patients >65 years with multivessel disease and CMS-linked data in the NCDR CathPCI Registry® from 7/1/2009–12/31/2017. MV PCI was defined as PCI to a non-culprit lesion ≤45 days of the index procedure. The primary outcome was the composite of death, myocardial infarction, and revascularization from 45 days through 1 year. To account for unmeasured confounders, an instrumental variable analysis (IVA) was used to compare treatment strategies. The instrument was institutional rates of MV PCI. A falsification endpoint of post-discharge major bleeding was utilized to assess for residual confounding. RESULTS: Of 56,332 admissions from 1,102 institutions, 37.7% received MV PCI ≤45 days of index STEMI PCI. Of those undergoing MV PCI, 74.8% received complete revascularization. In unadjusted analysis, MV PCI was associated with a lower cumulative incidence of the composite outcome between 45 days and 1 year (13.9% vs 18.2% for non-MV PCI, p<0.01). In the IVA, there was no association between MV PCI and the composite outcome (adjusted risk difference [RD] −0.97%; 95%CI −3.52%, 1.59%; p=0.46). An association between MV PCI and the falsification endpoint of major bleeding was not observed (RD −2.54%; 95%CI −5.30%, 0.22%; p=0.07). CONCLUSIONS: In this large, nationwide analysis, we did not find benefit of MV PCI by 1 year among older STEMI patients. The clinical benefit of MV PCI may not extend equally outside of trials to include all patients, including those with more extreme ages and more complex decision making

Comparative Outcomes of Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction Among Medicare Beneficiaries With Multivessel Coronary Artery Disease: An National Cardiovascular Data Registry Research to Practice Project

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Late hepatic toxicity surveillance for survivors of childhood, adolescent and young adult cancer: Recommendations from the international late effects of childhood cancer guideline harmonization group

Background: Survivors of childhood, adolescent and young adult (CAYA) cancer may develop treatment-induced chronic liver disease. Surveillance guidelines can improve survivors’ health outcomes. However, current recommendations vary, leading to uncertainty about optimal screening. The International Late Effects of Childhood Cancer Guideline Harmonization Group has developed recommendations for the surveillance of late hepatotoxicity after CAYA cancer. Methods: Evidence-based methods based on the GRADE framework were used in guideline development. A multidisciplinary guideline panel performed systematic literature reviews, developed evidence summaries, appraised the evidence, and formulated recommendations on the basis of evidence, clinical judgement, and consideration of benefits versus the harms of the surveillance while allowing for flexibility in implementation across different health care systems. Results: The guideline strongly recommends a physical examination and measurement of serum liver enzyme concentrations (ALT, AST, gGT, ALP) once at entry into long-term follow-up for survivors treated with radiotherapy potentially exposing the liver (moderate- to high-quality evidence). For survivors treated with busulfan, thioguanine, mercaptopurine, methotrexate, dactinomycin, hematopoietic stem cell transplantation (HSCT), or hepatic surgery, or with a history of chronic viral hepatitis or sinusoidal obstruction syndrome, similar surveillance for late hepatotoxicity once at entry into LTFU is reasonable (low-quality evidence/expert opinion, moderate recommendation). For survivors who have undergone HSCT and/or received multiple red blood cell transfusions, surveillance for iron overload with serum ferritin is strongly recommended once at long-term follow-up entry. Conclusions: These evidence-based, internationally-harmonized recommendations for the surveillance of late hepatic toxicity in cancer survivors can inform clinical care and guide future research of health outcomes for CAYA cancer survivors

Does recipient body mass index inform donor selection for allogeneic haematopoietic cell transplantation?

It is not known whether obesity has a differential effect on allogeneic haematopoietic cell transplantation outcomes with alternative donor types. We report the results of a retrospective registry study examining the effect of obesity [body mass index (BMI) > 30] on outcomes with alternative donors (haploidentical related donor with two or more mismatches and receiving post-transplant cyclophosphamide [haplo] and cord blood (CBU)] versus matched unrelated donor (MUD). Adult patients receiving haematopoietic cell transplantation for haematologic malignancy (2013-2017) (N = 16 182) using MUD (n = 11 801), haplo (n = 2894) and CBU (n = 1487) were included. The primary outcome was non-relapse mortality (NRM). The analysis demonstrated a significant, non-linear interaction between pretransplant BMI and the three donor groups for NRM: NRM risk was significantly higher with CBU compared to haplo at BMI 25-30 [hazard ratio (HR) 1.66-1.71, p < 0.05] and MUD transplants at a BMI of 25-45 (HR, 1.61-3.47, p < 0.05). The results demonstrated that NRM and survival outcomes are worse in overweight and obese transplant recipients (BMI ≥ 25) with one alternative donor type over MUD, although obesity does not appear to confer a uniform differential mortality risk with one donor type over the other. BMI may serve as a criterion for selecting a donor among the three (MUD, haplo and CBU) options, if matched sibling donor is not available