Tafenoquine for Relapsing Babesiosis: A Case Series.

BACKGROUND: Relapsing babesiosis often occurs in highly immunocompromised patients and has been attributed to the acquisition of resistance against drugs commonly used for treatment such as atovaquone, azithromycin, and clindamycin. Tafenoquine, which is approved for malaria prophylaxis and presumptive antirelapse treatment of Plasmodium vivax malaria, has shown activity against Babesia microti in several animal models of acute infection and in a single human case of relapsing babesiosis. Here, we report 5 cases of relapsing babesiosis treated with tafenoquine, including the previous case, and begin to define the conditions for optimal use of tafenoquine in relapsing babesiosis. METHODS: A definitive diagnosis of babesiosis was made by microscopic examination of Giemsa-stained thin blood smears or a real-time polymerase chain reaction (PCR) that targets the parasite 18S rRNA gene. Clearance of B. microti infection was ascertained by use of blood smear and real-time PCR. RESULTS: Tafenoquine was initiated with a loading dose of 600 mg. A weekly maintenance dose consisted of 200 mg or 300 mg; the lower dose was associated with a delayed clearance of B. microti. In 2 cases, all antimicrobial agents but tafenoquine were discontinued prior to clearance of infection. In 2 other cases, clearance was achieved while tafenoquine was administered along with other antimicrobial agents. In 3 of these 4 cases, tafenoquine was used in combination with atovaquone-proguanil. Other agents included atovaquone, azithromycin, and/or clindamycin. In 1 case, tafenoquine was administered alone and failed to prevent relapse. CONCLUSIONS: Tafenoquine can be a useful adjunct for the treatment of highly immunocompromised patients experiencing relapsing babesiosis caused by B. microti.

Immunizing Cancer Patients: Which Patients? Which Vaccines? When to Give?

Patients receiving treatment for cancer should be considered for age- and indication-appropriate vaccinations, and the responsibility for administration of these vaccines is shared between the oncologist and the primary care provider. Certain vaccine-preventable diseases have higher incidence rates among cancer patients and are associated with worse clinical outcomes. The Centers for Disease Control and Prevention and the Advisory Committee on Immunization Practices recommend certain vaccines for routine use in adults, including those with cancer. This article provides guidance to oncology clinicians on vaccine recommendations and safety of use in their patients.

Radiation Oncology AcaDemic Mentorship Program (ROADMAP) for Junior Faculty: One-Year Results of a Prospective Single Institution Initiative.

PURPOSE: Although mentorship has been associated with promotion, job satisfaction, and retention, data are limited on the mentorship experience of clinical- versus research-track physicians as well as feasibility and relative priority of formal program components. METHODS AND MATERIALS: Within a single-institution, multi-site, academic network, we implemented a Radiation Oncology AcaDemic Mentorship Program (ROADMAP) for junior faculty. Validated surveys assessing mentee satisfaction were distributed at baseline and 1 year. The statistical analysis included Wilcoxon rank sum and signed tests. Mentees assessed the likelihood to recommend each program component (10-point Likert-type scale), and means with standard error (SE) are reported. RESULTS: Among 42 eligible junior faculty, 36 (86%) opted into the program. The median time since residency was 2.5 years (interquartile range, 1.75-5.25) on the clinical track (n = 12) and 3 years (interquartile range, 2.75-5.00) on the research track (n = 24). At baseline, research-track physicians reported higher satisfaction with mentoring than physicians on the clinical track (2.92 vs 2.16; P = .02). Among 32 physicians completing 1 year, overall satisfaction with mentoring increased compared with baseline (2.72 vs 3.87; P < .001), which persisted on subset analysis for both clinical- (2.16 vs 4.03; P < .001) and research-track physicians (2.99 vs 3.77; P = .005). At 1 year, 28 mentees (88%) opted to continue the program. Program components were rated 8.25 (SE, 0.37) for mentor-mentee pairings, 7.22 (SE, 0.39) for goal setting, 6.84 (SE, 0.47) for administrative support, 6.69 (SE, 0.44) for peer mentoring, and 6.53 (SE, 0.45) for steering committee oversight. Ratings of peer mentoring were not associated with track (P = .59) or years in practice (P = .29). CONCLUSIONS: Clinical-track physicians may be less satisfied with mentorship than research-track faculty. However, all junior faculty, regardless of track, appeared to benefit from formalizing dyadic mentor-mentee relationships, goal setting, and peer mentoring. Further work is needed to determine the role of mentorship in addressing physician burnout.

Prolonged SARS-CoV-2 Infection in Patients with Lymphoid Malignancies.

Coronavirus disease 2019 (COVID-19) infection results in both acute mortality and persistent and/or recurrent disease in patients with hematologic malignancies, but the drivers of persistent infection in this population are unknown. We found that B-cell lymphomas were at particularly high risk for persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity. Further analysis of these patients identified discrete risk factors for initial disease severity compared with disease chronicity. Active therapy and diminished T-cell counts were drivers of acute mortality in COVID-19-infected patients with lymphoma. Conversely, B cell-depleting therapy was the primary driver of rehospitalization for COVID-19. In patients with persistent SARS-CoV-2 positivity, we observed high levels of viral entropy consistent with intrahost viral evolution, particularly in patients with impaired CD8+ T-cell immunity. These results suggest that persistent COVID-19 infection is likely to remain a risk in patients with impaired adaptive immunity and that additional therapeutic strategies are needed to enable viral clearance in this high-risk population. SIGNIFICANCE: We describe the largest cohort of persistent symptomatic COVID-19 infection in patients with lymphoid malignancies and identify B-cell depletion as the key immunologic driver of persistent infection. Furthermore, we demonstrate ongoing intrahost viral evolution in patients with persistent COVID-19 infection, particularly in patients with impaired CD8+ T-cell immunity.This article is highlighted in the In This Issue feature, p. 1.

Performance of Severe Acute Respiratory Syndrome Coronavirus 2 Real-Time RT-PCR Tests on Oral Rinses and Saliva Samples.

Access to rapid and accurate detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is essential for controlling the current global pandemic of coronavirus disease 2019. In this study, the use of oral rinses (ORs) and posterior oropharyngeal saliva as an alternative to swab collection methods from symptomatic and asymptomatic health care workers for the detection of SARS-CoV-2 RNA by RT-PCR was evaluated. For saliva samples, the overall agreement with oropharyngeal swabs was 93% (Ƙ = 0.84), with a sensitivity of 96.7% (95% CI, 83.3%-99.8%). The agreement between saliva and nasopharyngeal swabs was 97.7% (Ƙ = 0.93), with a sensitivity of 94.1% (95% CI, 73.0%-99.7%). ORs were compared with nasopharyngeal swabs only, with an overall agreement of 85.7% (Ƙ = 0.65), and a sensitivity of 63% (95% CI, 46.6%-77.8%). The agreement between a laboratory-developed test based on the CDC RT-PCR and two commercial assays, the Xpert Xpress SARS-CoV-2 and the Cobas SARS-CoV-2, was also evaluated. The overall agreement was >90%. Finally, SARS-CoV-2 RNA in saliva samples was shown to be stable, with no changes in viral loads over 24 hours at both room temperature and 4°C. Although the dilution of SARS-CoV-2 in ORs precluded its acceptability as a sample type, posterior oropharyngeal saliva was an acceptable alternative sample type for SARS-CoV-2 RNA detection.

Determinants of COVID-19 disease severity in patients with cancer.

As of 10 April 2020, New York State had 180,458 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 9,385 reported deaths. Patients with cancer comprised 8.4% of deceased individuals1. Population-based studies from China and Italy suggested a higher coronavirus disease 2019 (COVID-19) death rate in patients with cancer2,3, although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-194. This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. From 10 March to 7 April 2020, 423 cases of symptomatic COVID-19 were diagnosed at Memorial Sloan Kettering Cancer Center (from a total of 2,035 patients with cancer tested). Of these, 40% were hospitalized for COVID-19, 20% developed severe respiratory illness (including 9% who required mechanical ventilation) and 12% died within 30 d. Age older than 65 years and treatment with immune checkpoint inhibitors (ICIs) were predictors for hospitalization and severe disease, whereas receipt of chemotherapy and major surgery were not. Overall, COVID-19 in patients with cancer is marked by substantial rates of hospitalization and severe outcomes. The association observed between ICI and COVID-19 outcomes in our study will need further interrogation in tumor-specific cohorts.

Vaccination of the Stem Cell Transplant Recipient and the Hematologic Malignancy Patient.

Patients with hematologic malignancy or those who undergo hematopoietic stem cell transplantation experience variable degrees of immunosuppression, dependent on underlying disease, therapy received, time since transplant, and complications, such as graft-versus-host disease. Vaccination is an important strategy to mitigate onset and severity of certain vaccine-preventable illnesses, such as influenza, pneumococcal disease, or varicella zoster infection, among others. This article highlights vaccines that should and should not be used in this patient population and includes general guidelines for timing of vaccination administration and special considerations in the context of newer therapies, recent vaccine developments, travel, and considerations for household contacts.

Patient Death Debriefing Sessions to Support Residents' Emotional Reactions to Patient Deaths.

BACKGROUND: There is no standard way to help residents deal with the emotional impact of patient deaths. Most available curricula are time and resource intensive. OBJECTIVE: We introduced "Patient Death Debriefing Sessions" into an inpatient medical oncology rotation at Memorial Sloan Kettering Cancer Center to provide a structured yet practical way to address residents' emotional reactions following the death of a patient. A questionnaire was used to evaluate the impact of these sessions. METHODS: Patient Death Debriefing Sessions consist of a brief (~10 minutes), real-time (within 24-48 hours), consistent (following each death), attending physician-led debriefing that focuses on internal medicine residents' emotional reactions following patient deaths. Sessions were guided by a pocketcard tool and did not require faculty training. Residents completing a 4-week medical oncology rotation were surveyed before and after their rotation. Prerotation and postrotation mean differences were evaluated based on the number of sessions they participated in (0 to ≥ 3) using analyses of variance. RESULTS: Ninety-one of 92 participants spanning all training levels completed questionnaires (99% response rate). Of these, 79 (87%) encountered a patient death and were included in the analyses. Overall, residents found debriefing sessions helpful, educational, and appreciated attending physician leadership. The number of debriefing sessions positively influenced residents' perception of received support. CONCLUSIONS: This high-yield, novel pilot curriculum supported residents' emotional reactions to patient deaths and may foster communication with team members, including supervising attending physicians. This program is easily implemented and could be adapted for use in other clinical settings.

International travel patterns and travel risks for stem cell transplant recipients.

BACKGROUND: Stem cell transplantation (SCT) is being increasingly utilized for multiple medical illnesses. However, there is limited knowledge about international travel patterns and travel-related illnesses of stem cell transplant recipients (SCTRs). METHODS: An observational cross-sectional study was conducted among 979 SCTRs at Memorial Sloan Kettering Cancer Center using a previously standardized and validated questionnaire. International travel post SCT, pre-travel health advice, exposure risks, and travel-related illnesses were queried. RESULTS: A total of 516 SCTRs completed the survey (55% response rate); of these, 40% were allogeneic SCTRs. A total of 229 (44.3%) respondents reported international travel outside the United States and Canada post SCT. The international travel incidence was 32% [95% confidence interval CI 28-36] within 2 years after SCT. Using multivariable Cox regression analysis, variables significantly associated with international travel within first 2 years after SCT were history of international travel prior to SCT [hazard ratio (HR) = 5.3, 95% CI 2.3-12.0], autologous SCT (HR = 2.6, 95% CI 1.6-2.8), foreign birth (HR = 2.3, 95% CI 1.5-3.3), and high income (HR = 2.0, 95% CI 1.8-3.7). During their first trip, 64 travelers (28%) had traveled to destinations that may have required vaccination or malaria chemoprophylaxis. Only 56% reported seeking pre-travel health advice. Of those who traveled, 16 travelers (7%) became ill enough to require medical attention during their first trip after SCT. Ill travelers were more likely to have visited high-risk areas (60 vs 26%, p = 0.005), to have had a longer mean trip duration (24 vs 12 days, p = 0.0002), and to have visited friends and relatives (69 vs 21%, p < 0.0001). CONCLUSIONS: International travel was common among SCTRs within 2 years after SCT and was mainly to low-risk destinations. Although the overall incidence of travel-related illnesses was low, certain subgroups of travelers were at a significantly higher risk. Pre-travel health counseling and interventions were suboptimal.

Tolerability of chemotherapy in HIV-infected women with breast cancer: are there prognostic implications?

Breast cancer is the most commonly diagnosed malignancy in women, but little is known about therapeutic outcomes in patients with both breast cancer and HIV. We performed a retrospective cohort study of women with or without HIV undergoing treatment for breast cancer from 1996 to 2011. Cases with HIV were 1:2 matched to non-HIV controls based on age, sex, race, and date of cancer diagnosis. Dose reduction and/or delay during chemotherapy, overall survival, and development of metastatic disease were studied outcomes. 156 (52 HIV, 104 non-HIV) subjects were analyzed. The majority of breast cancers in both groups were clinical stages 0, I, II, and III (73%). HIV infection preceded cancer diagnosis by a median of 13 years. Median CD4 count at time of cancer diagnosis was 417 cells/mcL. Approximately 87% (45/52) were on HAART, mostly protease inhibitor-based (57%) therapy. HIV-infected women needed more dose reductions and/or delays to chemotherapy due to toxicity (56% vs. 30%; p=0.03). Stage at diagnosis, triple negative receptor status, and dose reduction and/or delay were predictors of metastatic disease and death. HIV-infected women experienced more adverse events during breast cancer treatment, and a potential causative factor could be drug-drug interactions between HAART and chemotherapy.

International travel patterns and travel risks of patients diagnosed with cancer.

BACKGROUND: Immunocompromised travelers living with cancer can be at increased risk of travel-related illnesses. Their international travel patterns and associated risks remain largely unknown. METHODS: This was a retrospective cohort study of all patients diagnosed with cancer who presented for pre-travel health advice between January 1, 2003 and June 30, 2011. Demographics, travel patterns, and infectious diseases exposure risks of immunocompromised travelers were characterized and compared with those of immunocompetent travelers. Reported travel-related illnesses were assessed in both groups. RESULTS: A total of 149 travelers were included in this study. Fifty-one percent had solid tumors, 32% had hematological malignancies, and 17% underwent stem cell transplantation. Seventy travelers (47%) were immunocompromised. Immunocompromised travelers had similar demographics, trip itineraries, and infectious diseases exposure risks to hepatitis A, malaria, typhoid fever, and yellow fever as immunocompetent travelers. Most of the reported travel-related illnesses were of minor nature. CONCLUSION: Travelers with cancer who have impaired immunity had similar infectious diseases exposure risks and travel patterns as travelers whose cancer is cured or in remission. Improved understanding of travel patterns and risks of patients with cancer may assist in providing more focused pre-travel health interventions to this complex subset of travelers.