Background: After a hematopoietic stem cell transplantation (HSCT), patients are left with little to no immunity to prevent infections. Importantly, this includes immunity gained from previous exposures, including vaccinations. This loss of immunity is a direct result of previous chemotherapy, radiation, and conditioning regimens the patients receive. It is critical to revaccinate patients post-HSCT to ensure protective immunity against vaccine-preventable diseases. Before 2017, all patients at our institution were referred to their pediatrician at approximately 12-month post-HSCT to be revaccinated. Clinical concern was raised at our institution regarding nonadherence and errors in vaccine schedules. Methods: To understand the magnitude of the problem with revaccination, we performed an internal audit of post-vaccine adherence in patients who received an HSCT between 2015 and 2017. A multidisciplinary team was developed to review the audit results and make recommendations. Results: This audit revealed delays in the initiation of the vaccine schedule, incomplete adherence to the recommended revaccination schedule, and errors in administration. Discussion: Based on the review of the data, the multidisciplinary team recommended an approach for systematic assessment of vaccine readiness and centralization of the administration of vaccines to be done within the stem cell transplant outpatient center.

Revaccination after hematopoietic cell transplantation (HCT) is critical to prevent morbidity and mortality from vaccine-preventable illnesses. The global aim of our quality improvement initiative was to enhance timely, correct, and effective revaccination after pediatric HCT. The SMART aim of our project was to decrease median unvaccinated time by 4 months by decreasing the time to vaccine eligibility, time from eligibility to vaccine initiation, and time to completion of the vaccine series. A multidisciplinary group performed a cross-sectional quantitative and qualitative evaluation of revaccination practices at our institution. We identified factors associated with delayed, incorrect, or incomplete revaccination. Several plan-do-study-act interventions were implemented to address these drivers, including revising immune readiness criteria, increasing auditing of primary care administered immunizations, and, importantly, establishing a dedicated revaccination clinic within the HCT clinic at our center. The time to vaccine eligibility decreased from 12.6 months to 10 months (a 20% decrease), and the time to complete the vaccine series decreased from 19.3 months to 15.7 months (a 19% decrease). With a quality improvement initiative, we addressed the many causes of delayed or incomplete revaccination post-HCT and through a team-based approach successfully decreased the time to vaccine start and time to vaccine completion at our center.

Topic Significance & Study Purpose/Background/Rationale Children undergoing hematopoietic stem cell transplant (HSCT) lose their prior immunity post-allogeneic transplant and need reimmunization post-transplant. Traditionally, immunizations post-HSCT were administered at a pediatrician's office (PO), but studies in adult patients have shown compliance with re-vaccination to be low and no data exists on adherence in pediatrics. An internal audit of HSCT patients who received vaccinations at a PO revealed delays in starting vaccines when eligible, non-completion of the schedule in its entirety happened often, and there was an extended length of time for completion of the schedule. Methods, Intervention, & Analysis Through the establishment of an outpatient re-vaccination clinic (RC) within our transplant center, we aimed to: 1. Increase the percentage of patients starting re-vaccination within one month, after deemed eligible for vaccination by standard immune parameters 2. Decrease the duration of time from start to completion of immunizations as compared with retrospective data 3. Increase the proportion of patients who complete the entire re-vaccination schedule to greater than 90% A post-transplant re-immunization clinic was started at our center and prospective data was been collected for the first year of the clinic's operation (2018) and was compared to a retrospective cohort of patients who were transplanted between 2015-2017. Data collected in both periods included time from vaccine eligibility to start of re-vaccination, proportion completing the entire series, and time from start to completion of series. Findings & Interpretation 55% of post-HSCT patients who received immunizations at a PO from 2015-2017 started within one month of being immune-eligible for vaccines. This increased to 80% when patients were revaccinated through our RC (p = 0.0128).Historically, only 9% of patients re-vaccinated in a PO completed the entire series as compared with 69% completing the schedule in our RC (p Discussion & Implications Establishing a post-HSCT re-vaccination clinic in a transplant center should be considered when delivering immunizations. Time to initiation of vaccines, the proportion of patients completing vaccines, and length of time for completion of series substantially improved all three metrics when delivering vaccines in a specialty RC as compared to in a PO.

Intro Vaccines have shown to significantly reduce the number of infections from vaccine preventable diseases. Children who undergo hematopoietic stem cell transplants (HSCT) are at an increased risk for infections due to highly suppressed immune systems and loss of prior immunity. As a result, these patients need to get re-vaccinated post-transplant. Traditionally, re-vaccinations post HSCT were administered at a local pediatrician's office, but studies in adult patients have shown compliance with re-vaccination to be low and no data exists on adherence in pediatrics. When received, vaccines are often given based on time from transplant, when immune parameters are expected to recover, and not specifically based on an individual patient's immune reconstitution. At our large academic center's HSCT clinic, we have started an immune-based approach to revaccination to improve compliance, reduce errors, and initiate vaccines at the appropriate time. Objectives 1. Establish an outpatient clinic within our HSCT center focusing on re-vaccination post-pediatric HSCT. 2. Create immune-based screening guidelines to standardize patient eligibility for re-vaccination post pediatric HSCT. 3. Operationalize the immune-based screening and vaccine eligibility and monitor time to first vaccination as compared to historical controls. 4. Document the benefits, feasibility and safety of re-vaccinating post-HSCT in a specialty care center. Methods A retrospective analysis of patients who received immunizations in a pediatrician's office demonstrated inconsistency with timing of vaccine re-initiation, completion of schedule, and administration errors. A multidisciplinary team including HSCT, infectious disease, immunology and pharmacy developed a re-vaccination schedule, and immune-based screening guidelines for determining vaccine eligibility. The HSCT NP's established a re-vaccination clinic, including a dedicated coordinator who schedules all visits to ensure timely follow up and a nurse follows up after each visit to assess for side effects. Results Data collection is ongoing. To date there have been >40 patients who have utilized this clinic. Early experience indicates that patients are starting vaccinations earlier as many are meeting eligibility by 8 months based on immune reconstitution. Increased rates of compliance with vaccine clinic appointments and delivery of vaccines with less delay in moving through the series. Conclusion Through a multidisciplinary approach, creation and application of immune-based eligibility guidelines for revaccination was feasible, as was the creation and operationalization of a vaccination clinic at our large outpatient subspecialty HSCT clinic. Ongoing work will continue to track improvements in time to vaccine readiness and delivery as well as the safety of such a vaccination clinic.

IntroductionCytomegalovirus (CMV) viremia after allogeneic hematopoietic cell transplant (HCT) is associated with substantial morbidity. In vivo T cell depletion with alemtuzumab is a known risk factor for CMV reactivation. After observing very early CMV viremia in patients who received distal alemutuzumab in preparation for HCT for hemoglobinopathies, we implemented a quality improvement project to decrease the burden of CMV in this population.ObjectiveTo describe patterns of CMV reactivation before and after changing our CMV prophylaxis and surveillance strategies.MethodsWe reviewed medical records of children undergoing HCT for sickle cell disease (SCD) or beta thalassemia at Children`s Hospital of Philadelphia between 2007-2018, who received distal alemtuzumab containing conditioning regimens. Patients received alemtuzumab (48 mg, starting ∼22 days before transplant) with fludarabine and melphalan. Beginning in February 2014, CMV seropositive (CMV+) patients received prophylaxis with valganciclovir from completion of alemtuzumab through day -1 and foscarnet starting on day 0, as well as weekly CMV surveillance beginning with alemtuzumab administration. Rates of CMV reactivation, as well as balancing metrics [time to engraftment and rate of acute kidney injury (AKI) within 100 days post-HCT] were evaluated before and after implementation of this preventive approach.ResultsTwenty-nine children were included in the analysis. The median age was 11.1 (range: 3.1 to 17.3) years at HCT; 22 (75.9%) patients had SCD and 8 (24.1%) had beta thalassemia. All patients received bone marrow grafts, 22 (75.9%) from HLA-identical siblings and 7 (24.1%) from unrelated donors. Prior to HCT, 13 patients were CMV+. Of those, 11 (84.6%) developed CMV reactivation (7/7 pre-intervention and 4/6 post-intervention). Time from alemtuzumab start to CMV reactivation, regardless of prophylactic strategy, is shown in Figure 1. CMV reactivation occurred at a median of 4 (range: -11 to +13) days after planned HCT. During the post-intervention period, CMV reactivation was identified in 2 patients prior to the start of the proximal cytotoxic phase of conditioning and HCT was delayed until viremia cleared. One CMV seronegative patient developed CMV viremia 47 days post-HCT. Median time to engraftment was similar before and after the intervention (12.5 versus 13 days), as was the proportion of patients with AKI (3/7 versus 1/6).ConclusionIn this cohort, rates of CMV viremia were high and CMV reactivation often occurred very early in the transplant course. In two cases, CMV reactivation was identified prior to transplant day, necessitating a delay in HCT. Consideration should be given to implementing a program of screening or prophylaxis beginning as early as the start of alemtuzumab administration in CMV+ patients. Further research is needed to determine the optimal prophylactic strategy.

Pulmonary mucormycosis diagnosed immediately after hematopoietic stem cell transplantation frequently portends a poor prognosis. However, here we describe two cases in children that were treated successfully to highlight the efficacy of a multidisciplinary approach. Despite diagnosis in the immediate post-transplant period and requirement for ongoing immunosuppression to prevent or treat GVHD, both are long-term survivors due to early surgical debridement with transfusion support and prompt initiation of targeted antifungal therapy. In the absence of evidence-based treatment guidelines, survival of pulmonary mucormycosis is achievable even in high-risk patients with a multidisciplinary team to guide management.

Unrelated donor hematopoietic stem cell transplantation (HSCT) is increasingly being used to cure nonmalignant hematologic diseases (NMHD) in patients who lack HLA matched related donors. Both graft rejection and graft-versus-host disease (GVHD) remain major barriers to safe and effective transplant for these patients requiring unrelated donors. Partial T cell depletion combined with peripheral stem cell transplantation (pTCD-PSCT) has the potential advantages of providing a high stem cell dose to facilitate rapid engraftment, maintaining cells that may facilitate engraftment, and decreasing GVHD risk compared with T cell-replete HSCT. Here, we report a single-institution, retrospective experience of unrelated donor pTCD-PSCT for pediatric patients with NMHD. From 2014 to 2017, 12 pediatric patients with transfusion-dependent NMHD underwent matched unrelated donor (MUD) or mismatched unrelated donor (MMUD) pTCD HSCT in our center using disease-specific conditioning. Donor PSCs underwent CD3(+) T cell and CD19(+) B cell depletion using Clini-MACS, followed by a targeted addback of 1 x 10(5) CD3(+ )T cells/kg to the graft before infusion. All 12 patients demonstrated rapid trilinear engraftment. At a median follow-up of 740 days (range, 279 to 1466), all patients were alive with over 92% total peripheral blood donor chimerism and without transfusion dependence or recurrence of their underlying hematologic disease. Immune reconstitution was rapid and comparable with T cell-replete HSCT. No patients developed severe acute GVHD (grades III to IV) or chronic extensive GVHD, and all patients had discontinued systemic immune suppression. Viral reactivations were common, but no patient developed symptoms of life-threatening infectious disease. Our data indicate that MUD and MMUD pTCD-PSCTs are safe and effective approaches that enable rapid engraftment and immune reconstitution, prevent severe GVHD, and expand availability of HSCT to any patients with NMHD who have closely MUDs. (C) 2018 American Society for Blood and Marrow Transplantation.