Outcomes of Measurable Residual Disease in Pediatric Acute Myeloid Leukemia before and after Hematopoietic Stem Cell Transplant: Validation of Difference from Normal Flow Cytometry with Chimerism Studies and Wilms Tumor 1 Gene Expression.

We enrolled 150 patients in a prospective multicenter study of children with acute myeloid leukemia undergoing hematopoietic stem cell transplantation (HSCT) to compare the detection of measurable residual disease (MRD) by a "difference from normal" flow cytometry (ΔN) approach with assessment of Wilms tumor 1 (WT1) gene expression without access to the diagnostic specimen. Prospective analysis of the specimens using this approach showed that 23% of patients screened for HSCT had detectable residual disease by ΔN (.04% to 53%). Of those patients who proceeded to transplant as being in morphologic remission, 10 had detectable disease (.04% to 14%) by ΔN. The disease-free survival of this group was 10% (0 to 35%) compared with 55% (46% to 64%, P < .001) for those without disease. The ΔN assay was validated using the post-HSCT specimen by sorting abnormal or suspicious cells to confirm recipient or donor origin by chimerism studies. All 15 patients who had confirmation of tumor detection relapsed, whereas the 2 patients with suspicious phenotype cells lacking this confirmation did not. The phenotype of the relapse specimen was then used retrospectively to assess the pre-HSCT specimen, allowing identification of additional samples with low levels of MRD involvement that were previously undetected. Quantitative assessment of WT1 gene expression was not predictive of relapse or other outcomes in either pre- or post-transplant specimens. MRD detected by ΔN was highly specific, but did not identify most relapsing patients. The application of the assay was limited by poor quality among one-third of the specimens and lack of a diagnostic phenotype for comparison.

Reduced-Intensity Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Solid Tumors in Pediatric and Young Adult Patients.

High-risk, recurrent, or refractory solid tumors in pediatric, adolescent, and young adult (AYA) patients have an extremely poor prognosis despite current intensive treatment regimens. We piloted an allogeneic bone marrow transplant platform using reduced-intensity conditioning (RIC) and partially HLA-mismatched (haploidentical) related donors for this population of pediatric and AYA solid tumor patients. Sixteen patients received fludarabine, cyclophosphamide, melphalan, and low-dose total body irradiation RIC haploidentical BMT (haploBMT) followed by post-transplantation cyclophosphamide (PTCy), mycophenolate mofetil, and sirolimus. All assessable patients were full donor chimeras on day 30 with a median neutrophil recovery of 19 days and platelet recovery of 21 days. One patient (7%) exhibited secondary graft failure associated with concomitant infection. The median follow-up time was 15 months. Overall survival was 88%, 56%, and 21% at 6, 12, and 24 months, respectively. Median survival from transplant date was 14 months with a median progression-free survival 7 months. We observed limited graft-versus-host disease in 3 patients and nonrelapse mortality in 1 patient. We demonstrated that RIC haploBMT with PTCy is feasible and has acceptable toxicities in patients with incurable pediatric and AYA solid tumors; thus, this approach serves as a platform for post-transplant strategies to prevent relapse and optimize progression-free survival.

Nonmyeloablative Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide for Pediatric and Young Adult Patients with High-Risk Hematologic Malignancies.

Lower-intensity conditioning regimens for haploidentical blood or marrow transplantation (BMT) are safe and efficacious for adult patients with hematologic malignancies. We report data for pediatric/young adult patients with high-risk hematologic malignancies (n = 40) treated with nonmyeloablative haploidentical BMT with post-transplantation cyclophosphamide from 2003 to 2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, and total body irradiation. Post-transplantation immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, and tacrolimus. Donor engraftment occurred in 29 of 32 (91%), with median time to engraftment of neutrophils >500/µL of 16 days (range, 13 to 22) and for platelets >20,000/µL without transfusion of 18 days (range, 12 to 62). Cumulative incidences of acute graft-versus-host disease (GVHD) grades II to IV and grades III and IV at day 100 were 33% and 5%, respectively. The cumulative incidence of chronic GVHD was 23%, with 7% moderate-to-severe chronic GVHD, according to National Institutes of Health consensus criteria. Transplantation-related mortality (TRM) at 1 year was 13%. The cumulative incidence of relapse at 2 years was 52%. With a median follow-up of 20 months (range, 3 to 148), 1-year actuarial overall and event-free survival were 56% and 43%, respectively. Thus, we demonstrate excellent rates of engraftment, GVHD, and TRM in pediatric/young adult patients treated with this regimen. This approach is a widely available, safe, and feasible option for pediatric and young adult patients with high-risk hematologic malignancies, including those with a prior history of myeloablative BMT and/or those with comorbidities or organ dysfunction that preclude eligibility for myeloablative BMT.

Tolerance and effectiveness of nivolumab after pediatric T-cell replete, haploidentical, bone marrow transplantation: A case report.

To date, there has been a lack of pediatric experience regarding the efficacy and tolerability of immune checkpoint inhibitors after haploidentical hematopoietic stem cell transplant (HSCT). We present the case of a 22-year-old female with multiple-relapsed Hodgkin lymphoma (HL) who presented with a new relapse after haploidentical (post-haplo) HSCT. Anti-PD-1 therapy with nivolumab resulted in significant objective disease response and clinical improvement without notable side effects, including the absence of a graft-versus-host disease (GVHD). This case report suggests that immune checkpoint inhibition may be safely tolerated even in the setting of haploidentical HSCT, without triggering overt GVHD.

Alternative-Donor Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide for Nonmalignant Disorders.

Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many nonmalignant pediatric disorders, including hemoglobinopathies, bone marrow failure syndromes, and immunodeficiencies. There is great success using HLA-matched related donors for these patients; however, the use of alternative donors has been associated with increased graft failure, graft-versus-host disease (GVHD), and transplant-related mortality (TRM). HSCT using alternative donors with post-transplantation cyclophosphamide (PT/Cy) for GVHD prophylaxis has been performed for hematologic malignancies with engraftment, GVHD, and TRM comparable with that seen with HLA-matched related donors. There are limited reports of HSCT in nonmalignant pediatric disorders other than hemoglobinopathies using alternative donors and PT/Cy. We transplanted 11 pediatric patients with life-threatening nonmalignant conditions using reduced-intensity conditioning, alternative donors, and PT/Cy alone or in combination with tacrolimus and mycophenolate mofetil. We observed limited GVHD, no TRM, and successful engraftment sufficient to eliminate manifestations of disease in all patients. Allogeneic HSCT using alternative donors and PT/Cy shows promise for curing nonmalignant disorders; development of prospective clinical trials to confirm these observations is warranted.

Persistent Multiyear Control of Relapsed T-Cell Acute Lymphoblastic Leukemia With Successive Donor Lymphocyte Infusions: A Case Report.

There are few therapeutic options for patients with T-cell acute lymphoblastic leukemia (T-ALL) who have recurrent disease after initial matched sibling hematopoietic stem cell transplantation. While a second hematopoietic stem cell transplant (HSCT) from a haploidentical donor offers the conceptual possibility of greater graft versus leukemia effect, there is minimal literature to describe the efficacy of this approach in recurrent pediatric T-ALL. We present the case of a now 9-year-old female in whom second haploidentical HSCT, followed by successive donor lymphocyte infusions in response to minimal residual disease reemergence, has led to 3+ years of ongoing disease control without graft versus host disease and excellent quality of life.

Automated Functional Imaging by 2D Speckle Tracking Echocardiography Reveals High Incidence of Abnormal Longitudinal Strain in a Cohort of Pediatric Oncology Patients.

BACKGROUND: Automated functional imaging (AFI) was introduced to two-dimensional speckle-tracking echocardiography to facilitate strain assessment in the clinical settings. In patients treated with cardiotoxic anthracyclines, AFI may be helpful in the detection of early myocardial injury when left ventricular ejection fraction (LVEF) remains normal. METHODS: We retrospectively assessed feasibility of AFI in 143 echocardiograms on 102 subjects aged 0.4-22 years (mean 12.3) obtained over a 12-month period. We computed a Z-score for apical four-chamber longitudinal strain using published normal data to assess for abnormal strain in patients with and without previous exposure to anthracyclines. RESULTS: AFI was feasible in 95.1% of echocardiograms, with low inter- and intraobserver variability. There was a statistically significant association between abnormal longitudinal strain Z-score (SZ < -2.0) and depressed LVEF (<55%, P < 0.001). However, 46% of echocardiograms with normal LVEF had abnormal SZ; half of which had no prior anthracycline exposure. The correlation between SZ and LVEF was strongest in subjects exposed to anthracyclines (r(2) = 0.12, P < 0.01). Increasing age was associated with decreasing SZ. Total cumulative dose, after adjusting for age, was inversely associated with SZ (r(2) = 0.42, P < 0.001). Time from last dose of anthracycline had no significant association with SZ. CONCLUSIONS: AFI is highly feasible in the clinical settings. The observed high prevalence of abnormal longitudinal strain in our cohort emphasizes the importance of obtaining baseline measurements prior to anthracycline treatment. The effects of anthracycline on longitudinal strain may be dose and age dependent, with younger children less likely to show abnormalities.

High-dose Cyclophosphamide is Effective Therapy for Pediatric Severe Aplastic Anemia.

OBJECTIVE: Use of high-dose cyclophosphamide without hematopoietic stem cell transplant to treat severe aplastic anemia (SAA) has been controversial due to concern for increased infectious toxicity as compared with antithymocyte globulin and cyclosporine A. As children often tolerate dose-intensive therapy better than adults, we sought to perform a detailed retrospective analysis of both treatment response and toxicity in 28 patients younger than 22 years of age treated with 29 courses of high-dose cyclophosphamide as the sole form of immunosuppression. STUDY DESIGN: Children and adolescents with SAA who lacked an human leukocyte antigen-matched sibling donor were treated with cyclophosphamide 50 mg/kg/d for 4 consecutive days then received daily granulocyte colony stimulating factor until neutrophil recovery, transfusion support, and antimicrobial prophylaxis. RESULTS: Overall survival was 85%, with hematologic response of 79% and complete response of 66%. Cumulative incidences of bacterial infection (86%) and fungal infection (62%) were high but deaths due to infection were rare, as were clonal evolution (1/28), clinically relevant paroxysmal nocturnal (1/28), and relapse (2/28). CONCLUSIONS: Response rates and survival following high-dose cyclophosphamide in pediatric patients with SAA exceed those seen in adults and compare favorably to antithymocyte globulin/cyclosporine A with manageable infectious toxicity.

Bringing central line-associated bloodstream infection prevention home: catheter maintenance practices and beliefs of pediatric oncology patients and families.

BACKGROUND: A study was conducted to investigate (1) the extent to which best-practice central line maintenance practices were employed in the homes of pediatric oncology patients and by whom, (2) caregiver beliefs about central line care and central line-associated blood stream infection (CLABSI) risk, (3) barriers to optimal central line care by families, and (4) educational experiences and preferences regarding central line care. METHODS: Researchers administered a survey to patients and families in a tertiary care pediatric oncology clinic that engaged in rigorous ambulatory and inpatient CLABSI prevention efforts. RESULTS: Of 110 invited patients and caregivers, 105 participated (95% response rate) in the survey (March-May 2012). Of the 50 respondents reporting that they or another caregiver change central line dressings, 48% changed a dressing whenever it was soiled as per protocol (many who did not change dressings per protocol also never personally changed dressings); 67% reported the oncology clinic primarily cares for their child's central line, while 29% reported that an adult caregiver or the patient primarily cares for the central line. Eight patients performed their own line care "always" or "most of the time." Some 13% of respondents believed that it was "slightly likely" or "not at all likely" that their child will get an infection if caregivers do not perform line care practices perfectly every time. Dressing change practices were the most difficult to comply with at home. Some 18% of respondents wished they learned more about line care, and 12% received contradictory training. Respondents cited a variety of preferences regarding line care teaching, although the majority looked to clinic nurses for modeling line care. CONCLUSIONS: Interventions aimed at reducing ambulatory CLABSIs should target appropriate educational experiences for adult caregivers and patients and identify ways to improve compliance with best-practice care.

Feasibility of treating post-transplantation minimal residual disease in children with acute leukemia.

Outcomes are poor for patients with hematologic malignancies who experience overt relapse after allogeneic hematopoietic stem cell transplantation (HCT). Data on outcomes of post-transplantation minimal residual disease (MRD) are limited. In this single-institution, retrospective cohort analysis of children with acute leukemia and myelodysplastic syndrome, we document the pattern of relapse with a primary focus on outcomes of post-transplantation MRD. Forty of 93 patients (43%) who underwent a first allogeneic HCT and had systematic pretransplantation and post-transplantation MRD evaluations at +30, +60, +90, +180 days and +1 and +2 years post-transplantation experienced relapse. The median time to relapse was 4.8 months post-transplantation, with a median survival of 4 months post-relapse. Despite frequent, systematic, routine post-HCT disease restaging evaluation, 31 patients (78%) presented with overt disease at the time of relapse. Seven patients with acute leukemia who had post-transplantation MRD presented at a median of 1 month post-transplantation. Owing to rapid disease progression or treatment-related mortality, there was no improvement in survival in those patients whose leukemia was detected in a state of MRD post-transplantation. Our results suggest that early intervention strategies targeting post-transplantation MRD for relapse prevention in acute leukemia may not be feasible.

Factors predictive of relapse of acute leukemia in children after allogeneic hematopoietic cell transplantation.

The presence of minimal residual disease (MRD) before transplantation is the most important prognostic risk factor predictive of post-transplantation relapse in hematologic malignancies. However, MRD alone does not adequately predict relapse in all patients. To improve upon the ability to identify patients likely to relapse, we evaluated risk factors, in addition to MRD, that may be associated with development of post-transplantation relapse. In this single institution, retrospective cohort study of children with acute leukemia or myelodysplastic syndrome who had undergone a first allogeneic transplantation and had pretransplantation MRD evaluation, 40 of 93 patients (43%) experienced relapse. Univariate analysis demonstrated that African American race, high initial white blood cell count, central nervous system (CNS) disease at diagnosis, short first complete remission, nonmyeloablative (NMA) conditioning, lack of remission, and MRD before transplantation were associated with worse relapse-free survival (RFS). In a Cox multivariable analysis, CNS disease (P = .009), lack of remission (P = .01), and NMA conditioning (P = .04) were independently associated with inferior RFS. Among those in a morphologic complete remission who underwent a myeloablative transplantation, having both CNS disease at diagnosis (specifically in acute lymphoblastic leukemia) and MRD positivity was an independent risk factor predictive of relapse, which has not been previously reported. Results from our study support the existence of risk factors complimentary to pretransplantation MRD. Validation in a larger independent homogenous cohort is needed to develop a prognostic tool for clinical use to predict post-transplantation relapse.

Understanding the Information Needs of Pharmacy Staff Using CancelRx: A Qualitative Study of the Use of Prescription E-cancellation.

Background: Although electronic prescription cancellation such as via CancelRx can facilitate critical communication between prescribers and pharmacy staff about discontinued medications, there is little work that explores whether CancelRx meets the needs of pharmacy staff users. Objective: This study leverages qualitative interviews with pharmacy staff to address the following question: When medication changes are made by a prescriber using CancelRx, what information is needed by pharmacy staff to make correct and effective decisions in their roles in medication management? Methods: We conducted an inductive thematic analysis of interviews with 11 pharmacy staff members (pharmacists and pharmacy technicians) across three outpatient community pharmacy sites within an academic health care system. Results: Three information needs themes were consistently identified by both pharmacists and pharmacy technicians: prescriber intent when initiating the CancelRx, clinical rationale for the medication change, and intended medication regimen. Notably, both pharmacists and pharmacy technicians often reported seeking multiple information needs not fully addressed by CancelRx in the electronic health record (EHR) to achieve the shared goals of correct dispensing of medications and supporting patient self-management. Conclusions: Our qualitative analysis reveals that outpatient community pharmacy staff in an academic health care system often seek additional information from the (EHR) following medication changes communicated by CancelRx to meet their information needs. Ideally, the prescriber would provide sufficient information through CancelRx to automatically identify all discontinued prescriptions. These limitations highlight the need for design features that support routine communication of needed information at the time of a medication change, such as structured data elements.

Ambulatory pediatric oncology CLABSIs: epidemiology and risk factors.

BACKGROUND: To compare the burden of central line-associated bloodstream infections (CLABSIs) in ambulatory versus inpatient pediatric oncology patients, and identify the epidemiology of and risk factors associated with ambulatory CLABSIs. PROCEDURE: We prospectively identified infections and retrospectively identified central line days and characteristics associated with CLABSIs from January 2009 to October 2010. A nested case-control design was used to identify characteristics associated with ambulatory CLABSIs. RESULTS: We identified 319 patients with central lines. There were 55 ambulatory CLABSIs during 84,705 ambulatory central line days (0.65 CLABSIs per 1,000 central line days (95% CI 0.49, 0.85)), and 19 inpatient CLABSIs during 8,682 inpatient central line days (2.2 CLABSIs per 1,000 central lines days (95% CI 1.3, 3.4)). In patients with ambulatory CLABSIs, 13% were admitted to an intensive care unit and 44% had their central lines removed due to the CLABSI. A secondary analysis with a sub-cohort, suggested children with tunneled, externalized catheters had a greater risk of ambulatory CLABSI than those with totally implantable devices (IRR 20.6, P < 0.001). Other characteristics independently associated with ambulatory CLABSIs included bone marrow transplantation within 100 days (OR 16, 95% CI 1.1, 264), previous bacteremia in any central line (OR 10, 95% CI 2.5, 43) and less than 1 month from central line insertion (OR 4.2, 95% CI 1.0, 17). CONCLUSIONS: In pediatric oncology patients, three times more CLABSIs occur in the ambulatory than inpatient setting. Ambulatory CLABSIs carry appreciable morbidity and have identifiable, associated factors that should be addressed in future ambulatory CLABSI prevention efforts.

Bringing central line-associated bloodstream infection prevention home: CLABSI definitions and prevention policies in home health care agencies.

BACKGROUND: A study was conducted to investigate health care agency central line-associated bloodstream infection (CLABSI) definitions and prevention policies and pare them to the Joint Commission National Patient Safety Goal (NPSG.07.04.01), the Centers for Disease Control and Prevention (CDC) CLABSI prevention recommendations, and a best-practice central line care bundle for inpatients. METHODS: A telephone-based survey was conducted in 2011 of a convenience sample of home health care agencies associated with children's hematology/oncology centers. RESULTS: Of the 97 eligible home health care agencies, 57 (59%) completed the survey. No agency reported using all five aspects of the National Healthcare and Safety Network/Association for Professionals in Infection Control and Epidemiology CLABSI definition and adjudication process, and of the 50 agencies that reported tracking CLABSI rates, 20 (40%) reported using none. Only 10 agencies (18%) had policies consistent with all elements of the inpatient-focused NPSG.07.04.01, 10 agencies (18%) were consistent with all elements of the home care targeted CDC CLABSI prevention recommendations, and no agencies were consistent with all elements of the central line care bundle. Only 14 agencies (25%) knew their overall CLABSI rate: mean 0.40 CLABSIs per 1,000 central line days (95% confidence interval [CI], 0.18 to 0.61). Six agencies (11%) knew their agency's pediatric CLABSI rate: mean 0.54 CLABSIs per 1,000 central line days (95% CI, 0.06 to 1.01). CONCLUSIONS: The policies of a national sample of home health care agencies varied significantly from national inpatient and home health care agency targeted standards for CLABSI definitions and prevention. Future research should assess strategies for standardizing home health care practices consistent with evidence-based recommendations.

Pharmacy e-Prescription Dispensing Before and After CancelRx Implementation.

Importance: An estimated 1.5% to nearly 5% of medications are dispensed after discontinuation in the electronic health record (EHR), with 34% meeting criteria for high risk of potential harm. Objective: To evaluate the association of the implementation of e-prescription cancellation messaging (CancelRx) with medication dispensing after discontinuation of e-prescriptions in the EHR. Design, Setting, and Participants: This case series with interrupted time series analysis included patients who had at least 1 medication e-prescribed in ambulatory care to a health system pharmacy and discontinued in the 2-year study period from 1 year prior to approximately 1 year after CancelRx implementation (January 15, 2018, to December 7, 2019). Prior to CancelRx implementation, changes to e-prescribed medications within the EHR were not electronically communicated to health system pharmacies, which used separate pharmacy management software. Statistical analysis was performed from November 2020 to June 2023 (primary analysis from March 2021 to May 2022). Exposure: Implementation of CancelRx. Main Outcomes and Measures: The primary outcome was the proportion of e-prescribed medications dispensed and sold to patients by pharmacies within 6 months after discontinuation in the EHR. A medication was defined as dispensed after discontinuation if the timestamp of dispensing was at least 1 minute and less than 6 months after the timestamp of discontinuation in the EHR. A secondary outcome was the proportion of discontinued medications that was reordered within 120 days. Results: A total of 53 298 qualifying e-prescriptions that were discontinued were identified for 17 451 unique patients (mean [SD] age, 50.6 [18.2] years; 9332 women [53.5%]). After CancelRx implementation, 22 443 (85.9%) of the 26 127 discontinued e-prescriptions resulted in a CancelRx transaction. In interrupted time series analysis, the proportion of prescriptions dispensed after discontinuation decreased from a baseline of 8.0% (2162 of 27 171) to 1.4% (369 of 26 127; P < .001), without a significant week-to-week trend (ß = 0.000158; P = .37). Conclusions and Relevance: In this case series with interrupted time series analysis, findings suggest that CancelRx implementation was associated with an immediate and persistent reduction in the proportion of e-prescriptions sold after discontinuation in the EHR. Widespread implementation of CancelRx may significantly improve medication safety through the reduction of medication dispensing after discontinuation by prescribers.

A multidisciplinary pediatric oncofertility team improves fertility preservation and counseling across 7 years.

BACKGROUND: Oncofertility is a developing field of increasing importance, particularly in pediatric oncology, where most patients are likely to survive long-term and have not yet had the opportunity to have children. AIMS: We performed a quality improvement initiative to increase our rates of fertility preservation counseling and referral through the implementation of a pediatric oncofertility team, and we report outcomes 7 years following implementation of our initiative. METHODS AND RESULTS: We compare our baseline oncofertility survey to 44 post-intervention survey respondents and electronic medical record documentation for 149 patients treated in 2019. Ninety-five percent of post-intervention survey respondents recalled fertility counseling (baseline 70%, p = .004) and 89.3% were appropriately referred for fertility preservation (baseline 50%, p = .017). Counseling was documented in 60.4% of charts; 81% of patients analyzed by chart review were appropriately referred for fertility preservation. Fertility preservation outcomes differed by sex assigned at birth. CONCLUSION: Creation of an oncofertility team produced improvements in fertility counseling and fertility preservation referral across an extended period of time.

High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up.

Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder that can be treated with bone marrow transplantation, immunosuppressive therapy, and high-dose cyclophosphamide. Here, we report long-term follow-up on 67 SAA patients (44 treatment-naive and 23 refractory) treated with high-dose cyclophosphamide. At 10 years, the overall actuarial survival was 88%, the response rate was 71% with the majority being complete, and the actuarial event-free survival was 58% in 44 treatment-naive SAA patients. Patients with refractory SAA fared less well after high-dose cyclophosphamide therapy; at 10 years, overall actuarial survival, response, and actuarial event-free survival rates were 62%, 48%, and 27%, respectively. High-dose cyclophosphamide is highly effective therapy for severe aplastic anemia. Large randomized controlled trials will be necessary to establish how results of high-dose cyclophosphamide compare with either bone marrow transplantation or standard immunosuppressive regimens, such as antithymocyte globulin and cyclosporine.

High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease.

Because of its potent immunosuppressive yet stem cell-sparing activity, high-dose cyclophosphamide was tested as sole prophylaxis of graft-versus-host disease (GVHD) after myeloablative allogeneic bone marrow transplantation (alloBMT). We treated 117 patients (median age, 50 years; range, 21-66 years) with advanced hematologic malignancies; 78 had human leukocyte antigen (HLA)-matched related donors and 39 had HLA-matched unrelated donors. All patients received conventional myeloablation with busulfan/cyclophosphamide (BuCy) and T cell-replete bone marrow followed by 50 mg/kg/d of cyclophosphamide on days 3 and 4 after transplantation. The incidences of acute grades II through IV and grades III through IV GVHD for all patients were 43% and 10%, respectively. The nonrelapse mortality at day 100 and 2 years after transplantation were 9% and 17%, respectively. The actuarial overall survival and event-free survivals at 2 years after transplantation were 55% and 39%, respectively, for all patients and 63% and 54%, respectively, for patients who underwent transplantation while in remission. With a median follow-up of 26.3 months among surviving patients, the cumulative incidence of chronic GVHD is 10%. These results suggest that high-dose posttransplantation cyclophosphamide is an effective single-agent prophylaxis of acute and chronic GVHD after BuCy conditioning and HLA-matched BMT (clinicaltrials.gov no. NCT00134017).

Outcomes of pediatric bone marrow transplantation for leukemia and myelodysplasia using matched sibling, mismatched related, or matched unrelated donors.

Although some trials have allowed matched or single human leukocyte antigen (HLA)-mismatched related donors (mmRDs) along with HLA-matched sibling donors (MSDs) for pediatric bone marrow transplantation in early-stage hematologic malignancies, whether mmRD grafts lead to similar outcomes is not known. We compared patients < 18 years old reported to the Center for International Blood and Marrow Transplant Research with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and myelodysplastic syndrome undergoing allogeneic T-replete, myeloablative bone marrow transplantation between 1993 and 2006. In total, patients receiving bone marrow from 1208 MSDs, 266 8/8 allelic-matched unrelated donors (URDs), and 151 0-1 HLA-antigen mmRDs were studied. Multivariate analysis showed that recipients of MSD transplants had less transplantation-related mortality, acute graft-versus-host disease (GVHD), and chronic GVHD, along with better disease-free and overall survival than the URD and mmRD groups. No differences were observed in transplant-related mortality, acute and chronic GVHD, relapse, disease-free survival, or overall survival between the mmRD and URD groups. These data show that mmRD and 8/8 URD outcomes are similar, whereas MSD outcomes are superior to the other 2 sources. Whether allele level typing could identify mmRD recipients with better outcomes will not be known unless centers alter practice and type mmRD at the allele level.

Discontinuation of outpatient medications: implications for electronic messaging to pharmacies using CancelRx.

Electronic communication of prescription discontinuation, or CancelRx, has the potential to improve medication safety. We aimed to describe the proportion of discontinued outpatient medications that would result in a CancelRx message to understand its impact on medication safety. We used a data report to identify all outpatient medications discontinued in the electronic health record (EHR) of an academic health system in 1 month (October 2018). Among all 63 485 medications discontinued, 23 118 (36.4%) were e-prescribed, 25 982 (40.9%) were patient-reported or reconciled, and the remainder prescribed nonelectronically. Discontinued high-risk medications were more likely to be e-prescribed (2768 of 5896, 47.0%). A discontinuation reason was specified in 37 353 (58.9%) of all discontinued medications. Approximately one-third to one-half of discontinued medications were e-prescribed within the same EHR and would result in a CancelRx message to the pharmacy. Extension of this functionality to medications reconciled in the EHR could significantly expand the impact of CancelRx on medication safety. In addition, complete and accurate discontinuation reasons are needed to optimize CancelRx implementation.