Identifying at risk populations amongst breast cancer survivors and their common symptoms and concerns.

PURPOSE: The survival rate amongst breast cancer survivors (BCS) have been increasing, with a 5-year survival rate of almost 90%. These women face many quality of life (QOL) issues either due to either cancer itself or the complex treatment regimen. Our retrospective analysis aims to identify at risk populations among the BCS and their most common concerns. METHODS: This is a single-institution, retrospective, descriptive analysis of patients who were seen at our Breast Cancer Survivorship Program from October 2016 to May 2021. Patients completed a comprehensive survey which assessed self-reported symptoms, their concerns and degree of worry and recovery to baseline. The descriptive analysis on the patient characteristics included age, cancer stage and treatment type. The bivariate analysis included the relationship between the patient characteristics and their outcomes. Analysis of group differences was completed with Chi-square test. When the expected frequencies were five or less, Fisher exact test was used. Logistic regression models were developed to identify significant predictors for outcomes. RESULTS: 902 patients (age 26-94; median 64) were evaluated. Majority of women had stage 1 breast cancer. The most common self-reported concerns affecting the patients were fatigue (34%), insomnia (33%), hot flashes (26%), night sweats (23%), pain (22%), trouble concentrating (19%), and neuropathy (21%). Though 13% of BCS felt isolated at least 50% of their time, the majority of patients (91%) reported having a positive outlook and felt that they have a sense of purpose (89%). Younger patients were more likely to worry about their cancer more than 50% of the time (p < 0.0001). Patients that were less likely to return back to at least 50% of their pre-treatment baseline were younger (age ≤ 45) (p = 0.0280), had higher stage breast cancer (Stage 2-4) (p = 0.0061), and had chemotherapy either alone or as part of their multi-modality treatment (p < 0.0001). CONCLUSION: According to our study, younger patients, those with higher stage breast cancer and survivors who had chemotherapy may experience significant QOL issues. Fortunately, majority of BCS report a positive and optimistic outlook post treatment. Identifying common concerns after treatments and vulnerable populations are especially important to deliver quality care and to optimize interventions. IMPLICATIONS FOR CANCER SURVIVORS: Our study identified the most common self-reported concerns affecting BCS. In addition, our results suggest that younger patients, patients with higher stage breast cancer and survivors who had chemotherapy were more likely to have QOL issues. Despite this, our study showed, the majority of BCS reported positive outlooks and emotions.

CD34+ selection and the severity of oropharyngeal mucositis in total body irradiation-based allogeneic stem cell transplantation.

OBJECTIVE: The purpose of the present study was to evaluate the impact of ex vivo T cell depleted (TCD) by CD34+ selection on the incidence and severity of oropharyngeal mucositis (OM) after myeloablative allogeneic stem cell transplant (allo-SCT) with total body irradiation (TBI) conditioning. This approach has the advantage of avoiding methotrexate for graft versus host disease (GVHD) prophylaxis. PATIENTS AND METHODS: We analyzed the incidence and severity of OM in a cohort of 105 consecutive patients who underwent CD34+ selected (peripheral blood stem cells (PBSCs) from human leukocyte antigen (HLA)-identical siblings) allo-SCT with total body irradiation (TBI) conditioning. OM was graded by the World Health organization (WHO) and the Bearman regimen-related toxicity (RRT) scales. RESULTS: The incidence of WHO grade 3-4 OM was 34.3 %. There were no cases of grade 3-4 OM by the RRT scale. Significant correlation was found between the severity of OM and the use of intravenous (IV) narcotic medications (r (2) = 0.15, p = 0.004), total parenteral nutrition (TPN; r (2) = 0.68, p < 0.001), and hospital length of stay (LOS) (r (2) = 0.12, p = 0.01). DISCUSSION: TBI-induced OM can inflict significant morbidity in the early transplant period, and the incidence of WHO grade 3-4 OM can exceed 50 % when methotrexate is used for GVHD prophylaxis. In the CD34+ selected setting, methotrexate is avoided and the incidence of WHO grade 3-4 OM, use of TPN, and need for narcotic analgesia appear to be lower than historic evidence from standard T-replete allogeneic transplantation. CONCLUSION: We conclude that toxicity from OM is tolerable in CD34+ selected allo-SCT and should be prospectively measured in randomized trials comparing CD34+ selection versus T-replete transplantation.

Epidemiology of Candida kefyr in patients with hematologic malignancies.

Candida kefyr is an emerging pathogen among patients with hematologic malignancies (HM). We performed a retrospective study at Johns Hopkins Hospital to evaluate the epidemiology of C. kefyr colonization and infection in HM patients between 2004 and 2010. Eighty-three patients were colonized and/or infected with C. kefyr, with 8 (9.6%) having invasive candidiasis (IC). The yearly incidence of C. kefyr colonization and candidemia increased over the study period (P < 0.01), particularly after 2009. In 2010, C. kefyr caused 16.7% of candidemia episodes. The monthly incidence of C. kefyr was higher during the summer throughout the study. In a cohort of patients with acute myelogenic leukemia receiving induction chemotherapy, risks for C. kefyr colonization included the summer season (odds ratio [OR], 3.1; P = 0.03); administration of an azole (OR, 0.06; P < 0.001) or amphotericin B (OR, 0.35; P = 0.05) was protective. Fingerprinting of 16 isolates by repetitive sequence-based PCR showed that all were different genotypes. The epidemiology of C. kefyr candidemia was evaluated in another hospital in Montreal, Canada; data confirmed higher rates of C. kefyr infection in the summer. C. kefyr appears to be increasing in HM patients, with prominent summer seasonality. These findings raise questions about the effect of antifungal agents and health care exposures (e.g., yogurt) on the epidemiology of this yeast.

The clinical and financial burden of pre-emptive management of cytomegalovirus disease after allogeneic stem cell transplantation-implications for preventative treatment approaches.

BACKGROUND AIMS: Although cytomegalovirus (CMV) infection after allogeneic stem cell transplantation (SCT) is rarely fatal, the management of CMV by pre-emptive medication for viral reactivation has toxicity and carries a financial burden. New strategies to prevent CMV reactivation with vaccines and antiviral T cells may represent an advance over pre-emptive strategies but have yet to be justified in terms of transplantation outcome and cost. METHODS: We compared outcomes and post-transplantation treatment cost in 44 patients who never required pre-emptive CMV treatment with 90 treated patients undergoing SCT at our institute between 2006 and 2012. Eighty-one subjects received CD34+ selected myeloablative SCT, 12 umbilical cord blood transplants, and 41 T-replete non-myeloablative SCT. One hundred nineteen patients (89%) were at risk for CMV because either the donor or recipient was seropositive. Of these, 90 patients (75.6%) reactivated CMV at a median of 30 (range 8-105) days after transplantation and received antivirals. RESULTS: There was no difference in standard transplantation risk factors between the two groups. In multivariate modeling, CMV reactivation >250 copies/mL (odds ratio = 3, P < 0.048), total duration of inpatient IV antiviral therapy (odds ratio = 1.04, P < 0.001), type of transplantation (T-deplete vs. T-replete; odds ratio = 4.65, P < 0.017) were found to be significantly associated with increased non-relapse mortality. The treated group incurred an additional cost of antiviral medication and longer hospitalization within the first 6 months after SCT of $58,000 to $74,000 per patient. CONCLUSIONS: Our findings suggest that to prevent CMV reactivation, treatment should be given within 1 week of SCT. Preventative treatment may improve outcome and have significant cost savings.

Atrial flutter associated with carboplatin administration.

OBJECTIVE: To report a novel case of atrial flutter associated with carboplatin administration and review chemotherapy-related cardiac toxicities, focusing on platinum-containing compounds. CASE REPORT: A 69-year-old man with extensive small cell lung cancer and asymptomatic cardiovascular and cerebrovascular disease was inconsistently adherent to his medication regimen. While undergoing carboplatin infusion, he developed atrial flutter. He had no other immediate arrhythmogenic causes of atrial flutter and the arrhythmia spontaneously reverted to sinus rhythm after 24 hours. His condition remained stable until he died 8 days later. The cause of death was unknown and the family declined postmortem examination. DISCUSSION: Although this patient's cardiac history and nonadherence to his medications may have increased his susceptibility to develop atrial arrhythmias, the Naranjo probability scale reveals a possible relationship between atrial flutter and infusion of carboplatin. A literature search revealed other adverse cardiac events due to platinum compounds; however, to our knowledge, this case is the first to describe an association with atrial flutter. A definitive causal link cannot be determined, but this may have been the result of a direct arrhythmogenic effect of treatment or to a novel hypersensitivity reaction. Given the potential deleterious impact of drug-induced arrhythmias, we have reported this case to the Food and Drug Administration as a new adverse effect of carboplatin. CONCLUSIONS: Providers should consider cardiac monitoring during carboplatin infusion in patients with known cardiac disease or at high risk of cardiac complications.

Concurrent Breast Carcinoma and Follicular Lymphoma: A Case Series.

BACKGROUND The incidence of multiple primaries in cancer patients is 2-17%. However, the synchronous co-occurrence of adenocarcinoma of the breast and follicular lymphoma is rare. CASE REPORT We describe a case series of 3 post-menopausal women who presented to our institute with a breast lump. On further investigations, 2 of them had invasive ductal carcinoma and 1 had invasive lobular carcinoma of the breast. All 3 cancers were estrogen/progesterone receptor (ER/PR)-positive and human epidermal growth factor receptor 2 (HER-2)-negative. During the staging PET scans, all 3 patients had increased FDG uptake in axillary, mesenteric, and inguinal lymph nodes, respectively, raising concerns for metastatic disease. However, subsequent biopsies revealed them as follicular lymphomas occurring as a second concurrent primary malignancy. All patients underwent radical mastectomies with sentinel lymph node dissection followed by chemotherapy and hormonal therapy. Most of the lymphomas were low grade, which the oncologist closely followed. CONCLUSIONS Very few cases of breast cancer and follicular lymphoma co-occur; this is not limited to the axillary lymph nodes and can occur in any part of the lymphatic chain. Regional lymph node enlargement detected on examination or imaging does not always indicate metastasis. A high index of suspicion is needed followed by lymph node biopsy to rule out any second primary malignancy.

Genetic Variation and the Role of Multigene Panel Testing for Hereditary Breast Cancer: A Single-Institution Experience.

Background Breast cancer is the second leading cause of cancer death in women. There are multiple pathogenic mutations in addition to BRCA1/2 that are implicated in causing hereditary breast cancer. Methods and results We conducted a retrospective analysis of 1568 patients with breast cancer diagnosed between January 1, 2015, and December 31, 2018. The age range is 23-87. Among the study population, 26% had genetic testing and 8% of those were found to carry a pathogenic variant, as designated in NCCN (National Comprehensive Cancer Network) Guidelines. Of that 8%, 3.4% were BRCA1 and BRCA2 mutations, and the rest were other prevalent pathogenic variants. Discussion Expanded panel testing has the potential to increase the detection rate of pathogenic variants compared to testing for BRCA1/2 alone. Diagnostic accuracy of genetic causes of breast cancer has a significant clinical impact on patients and their families in terms of targeted treatment and prevention strategies. There is a strong need for further understanding of genetic patterns and variations in hereditary breast cancer. Awareness of the possibility of moderate to low penetrance genes and variants of uncertain significance (VUS) is important to assist with appropriate genetic counseling. We believe that physicians should consider re-testing with an expanded panel if patients previously had BRCA1 and BRCA2 testings only with a negative result as it may identify additional mutations.

Cellular immune profiling after sequential clofarabine and lenalidomide for high risk myelodysplastic syndromes and acute myeloid leukemia.

Patients with high risk myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) are commonly older with multiple co-morbidities, rendering them unsuitable for intensive induction chemotherapy or transplantation. We report preliminary cellular immune profiling of four cases receiving sequential clofarabine and lenalidomide for high risk MDS and AML in a phase I study. Our results highlight the potential of immune profiling for monitoring immune-modifying agents in high risk MDS and AML.

A Rare Consequence of Chronic Graft Versus Host Disease - Peyronie's Disease.

Chronic graft versus host disease (GvHD) after allogeneic stem cell transplantation (SCT) may involve any organ system, but male genital involvement is rare. Peyronie's Disease (PD) is an acquired, localized fibrotic disorder of the tunica albuginea, which leads to penile deformity, pain, and eventually to erectile dysfunction. We report the case of a 52 year old African American male with Acute Myeloid Leukemia who underwent human leucocyte antigen (HLA) matched sibling allogeneic peripheral blood SCT. His post transplant course was complicated by development of acute and multi-organ chronic GvHD requiring prolonged immunosuppression. He developed progressive dorsal curvature of the penis with erections within 1 year of ultra low dose interleukin -2 (IL2) treatment for his chronic GvHD but concealed symptoms for several months. Color Doppler Duplex ultrasound evaluation of the erect penis revealed a 75-degree curvature and appropriate hemodynamic response to prostaglandin injection. He underwent successful incision and grafting of the penile plaque. There is no significant residual curvature and is now able to engage in intercourse. A strong temporal association between GVHD (or its treatment) and Peyronie's is documented here. Awareness of the possible link between PD and chronic GVHD is required in this era of rapid growth in numbers of SCT.

Clinical and biological predictors of outcome following relapse of CML post-allo-SCT.

Although there are now fewer allo-SCTs performed for CML, leukemic relapse post transplant remains a persistent problem. To better define clinical and biological parameters determining postrelapse outcome, we studied 59 patients with CML relapsing after HLA-identical sibling allo-SCT between 1993 and 2008. Eighteen (30.5%) were transplanted in advanced phase and 41 (69.5%) in chronic phase. With a median follow-up from relapse of 7.9 years, 5-year post relapse survival (PRS) was 62%. Multivariate analysis found disease status at transplant, time to diagnosis of relapse from transplant and pretransplant tyrosine kinase inhibitor (TKI) use as significant factors associated with PRS. Analysis of BCR-ABL transcript expression in the hematopoietic progenitor compartment was performed in 36 patients (22 relapsed, 8 non-relapsed and 6 TKI alone controls). Patients with BCR-ABL expression in their early hematopoietic stem cell compartment (Lineage(-)CD34(+)CD38(-)CD90(+)) had worse survival irrespective of the disease status. We conclude that disease status remains the strongest clinical prognostic factor for PRS in CML following allo-SCT. The persistence of BCR-ABL expression in the progenitor cell compartment in some patients after SCT emphasizes the need to target CML-leukemia stem cells.

A retrospective review of acupuncture use for the treatment of pain in sickle cell disease patients: descriptive analysis from a single institution.

OBJECTIVES: This retrospective study describes the use of acupuncture for adult sickle cell patients in a single institution. MATERIALS AND METHODS: We identified 47 sickle cell disease patients referred for acupuncture at the National Institutes of Health between January 2005 and September 2011. All patients were enrolled in a Study of the Natural History of sickle cell disease and signed consent. We reviewed patient demographics, location of acupuncture treatment sessions (inpatient vs. outpatient), number of sessions received, sites of pain, patient pain reporting, and the use of other complementary therapies. RESULTS: Of the 47 patients (60% women, median age 36 y) referred for acupuncture, 42 had homozygous SS disease (89%) and 5 had SC disease (11%). Over half of the patients (51%) reported >3 sites of pain. Only 24 patients (51%) underwent acupuncture treatment. Of those who elected not to receive acupuncture, a majority (87%) accepted some other forms of complementary therapies. Nine patients underwent only inpatient acupuncture for acute vaso-occlusive crisis. Eleven patients received only outpatient acupuncture treatment for chronic pain, and 4 patients received both inpatient and outpatient treatments. For the patients who received inpatient acupuncture treatment for acute vaso-occlusive crisis, there was a significant reduction of reported pain score immediately after acupuncture treatment with an average pain reduction of 2.1 points on the numeric pain scale (P<0.0001). Excluding the 2 outliers, 75% of patients (n=13) in the outpatient setting described their pain as improved compared with prior session. DISCUSSION: To our knowledge, this is the largest retrospective review of acupuncture use in the sickle cell population. This analysis describes the use of acupuncture and raises the possibility of its use as an adjuvant for pain management in this population. Future clinical trials are needed to evaluate acupuncture's efficacy and effectiveness for pain management in different treatment settings and for various types of pain etiologies among the sickle cell population.

Epidemiology, outcomes, and risk factors of invasive fungal infections in adult patients with acute myelogenous leukemia after induction chemotherapy.

This is a retrospective, single-center study of adult patients with newly diagnosed acute myelogenous leukemia (AML), who received intensive induction timed sequential chemotherapy from 1/2005 to 6/2010. Among 254 consecutive AML patients, 123 (48.4%) developed an invasive fungal infection (IFI): 14 (5.5%) patients with invasive candidiasis (IC) and 108 (42.5%) patients with invasive mould infections (IMI). Among 108 IMI identified, 4 (3.7%) were proven, 1 (0.9%) probable, and 103 (95.4%) were possible, using current definitions. Overall, 6-month mortality was 23.7% (27/114) and 20.6% (26/126) for patients with and without an IFI, respectively. Older age (≥50 years; hazard ratio [HR]: 2.5, P < 0.001), female gender (HR: 1.7, P = 0.006), and baseline renal and/or liver dysfunction (HR: 2.4, P < 0.001) were the strongest mortality predictors. We report relatively low rates of IC despite lack of routine primary antifungal prophylaxis, albeit associated with poor long-term survival. High rates of IMI, the vast majority with a possible diagnosis, were observed. Host-related variables (demographics and baseline organ dysfunction) were identified as the most significant risk factors for IFI and mortality predictors in this series.