Durable Response to PD1 Inhibitor Pembrolizumab in a Metastatic, Metaplastic Breast Cancer.

Metaplastic breast cancer (MBC) is a rare and aggressive subtype of breast cancer. Tumor characteristics typically feature estrogen receptor, progesterone receptor, and HER2-negative, triple-negative breast cancer (TNBC), with a poorer prognosis relative to pure invasive ductal or lobular disease. Resistance to chemotherapy often leads to local recurrence and distant metastasis. Genomic profiling has identified multiple molecular abnormalities that may translate to targetable therapies in MBC. These tumors are known to display higher PD-L1 expressivity than other subtypes of breast cancer, and disease control with pembrolizumab and chemotherapy has been documented. We identify a patient with metastatic, metaplastic TNBC, with mesenchymal components and osseous differentiation, who completed 2 years of pembrolizumab treatment and has remained without evidence of disease after 32 months of observation, while maintaining good quality of life. Future efforts should focus on immunotherapy response with respect to the various subtypes of MBC, and treatment should continue to be incorporated in clinical trials to maximize disease response.

Spontaneous recovery in a patient with acquired thrombotic thrombocytopenic purpura (TTP): observation of a 'subclinical' TTP state.

OBJECTIVES: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy that can have high mortality rates without prompt treatment. Standard treatment is urgent plasma exchange (PLEX), which leads to disease remission in the vast majority of patients. Deficiency of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) alone is not sufficient to cause the clinical manifestations characteristic of TTP. We present a case of acquired TTP, where spontaneous recovery was observed prior to initiation of any TTP-specific therapy. CLINICAL PRESENTATION: A 73-year-old asymptomatic female presented with new-onset mild haemolytic anaemia and thrombocytopenia. Further testing revealed a significantly reduced ADAMTS13 activity level and an ADAMTS13 inhibitor, concerning for acquired TTP. On reassessment, the patient's haematologic parameters had been corrected prior to initiation of therapy. During subsequent follow-up three months later, she developed acute worsening thrombocytopenia indicative of relapsed, acute TTP. The patient was then successfully managed with PLEX and rituximab and achieved a sustained remission. DISCUSSION AND CONCLUSION: TTP is a haematologic emergency that requires urgent therapy to reduce morbidity and mortality. However, it is well documented that individuals with hereditary TTP and a proportion with acquired TTP in clinical remission can have low or nearly absent ADAMTS13 activity levels without evidence of microangiopathic haemolytic anaemia (MAHA) or thrombotic manifestations. Our patient represents a unique case of confirmed ADAMTS13 deficiency due to a documented inhibitor, leading to mild haemolytic anaemia and thrombocytopenia both of which recovered spontaneously. We propose that this scenario could represent a 'subclinical' TTP state that precedes the development of clinically significant disease.

Impact of Insurance Status on Survival Outcomes in Adults With Acute Lymphoblastic Leukemia (ALL): A Single-center Experience.

BACKGROUND: Socioeconomic factors including race, ethnicity, and poverty level have been associated with disparities in survival among adult patients with acute leukemia. Insurance status is also likely to affect survival outcomes in these patients but has not been well studied. We investigated the impact of insurance status at time of diagnosis on survival in adult patients with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Adult patients diagnosed with B-lineage ALL between January 1, 2007 and October 31, 2017 were included, with follow-up through January 19, 2018. Kaplan-Meier survival curves were used to estimate overall survival (OS) and progression-free survival (PFS) for the 2 groups. Cox proportional hazard regression methods were used for univariate and multivariate analyses. RESULTS: A total of 136 patients were included in the study, 29 without insurance and 107 with insurance at time of diagnosis. Patients without insurance were younger and more likely to be Hispanic or Latino compared with insured patients. When controlling for confounding variables, patients without insurance had worse PFS. There was no statistically significant difference in OS between the 2 groups. Hispanic or Latino ethnicity was associated with improved PFS and OS in multivariate analyses. CONCLUSIONS: Adult patients with ALL without health insurance at time of diagnosis had worse PFS when controlling for other relevant clinical factors. Lack of insurance may be an obstacle to timely, effective maintenance therapy in the outpatient setting. Further research is needed to understand how insurance status impacts survival and ways to mitigate any disparities.

Higher-risk myelodysplastic syndromes with del(5q): does the del(5q) matter?

Introduction: Myelodysplastic Syndrome (MDS) represents a group of cancers characterized by abnormal blood cell formation and maturation, leading to various degrees of cytopenias and potential transformation to acute myeloid leukemia. Deletion of the long arm of chromosome 5 (del(5q)) is the most common clonal chromosomal anomaly in MDS, yet the population in this disease subtype is quite heterogeneous. This manuscript analyzes literature on high-risk MDS with del(5q) abnormalities.Areas covered: The paper will review outcomes with lenalidomide among high-risk MDS patients with del(5q). It will discuss the implications of harboring TP53 gene mutations, and share the data for allogeneic hematopoietic stem cell transplantations in this setting. Finally, the report evaluates the risk of disease progression in these patients.Expert commentary: Improved characterization of MDS has enhanced our understanding of patients with anomalies involving del(5q). Emerging literature is exploring combination therapy beyond lenalidomide, and next-generation sequencing may identify secondary mutations that could be an additional avenue for treatment.

Prolonged Survival of Acute Lymphoblastic Leukemia with Intrathecal Treatments for Isolated Central Nervous System Relapse.

Acute lymphoblastic leukemia is commonly cured when diagnosed in the pediatric population. It portends a poorer prognosis if present in adult patients. Although adults frequently achieve complete remission, relapse rates are substantial, particularly among the elderly and high-risk populations. In the absence of prophylactic intrathecal chemotherapy, more than half of patients may develop CNS involvement or relapse, which is associated with significant risk for systemic illness. This report describes a patient with acute lymphoblastic leukemia with repeated isolated CNS relapses. This case should remind clinicians that isolated CNS disease in the absence of systemic recurrence could successfully respond to intrathecal therapy and offer patients a favorable quality of life.

Dramatic mixed response of lymphangitic pulmonary metastases in newly diagnosed prostate cancer.

Prostate adenocarcinoma, the most common cancer in males in the United States, is often diagnosed in the nonmetastatic setting. The prognosis with metastatic prostate cancer is less favorable, though treatment options are typically effective in controlling the disease for an extended period. Hormonal therapy is the backbone to the management of prostate cancer metastases, decreasing the level of the prostate-specific antigen and reducing the patient's cancer-related symptoms. Pulmonary metastases, a relatively uncommon initial site of disease involvement, are expected to respond in a similar fashion to hormonal therapy as other organ or bone involvement. This report describes a patient with a newly diagnosed metastatic prostate cancer and a dramatic mixed response to hormonal therapy. This case should remind clinicians that pulmonary disease from prostate cancer may be an early metastatic finding, and can potentially progress even in the setting of an otherwise appropriate response to treatment.

Lactobacillus rhamnosus GG probiotic enteric regimen does not appreciably alter the gut microbiome or provide protection against GVHD after allogeneic hematopoietic stem cell transplantation.

Graft-versus-host disease (GVHD) is a major adverse effect associated with allogeneic stem cell transplant. Previous studies in mice indicated that administration of the probiotic Lactobacillus rhamnosus GG can reduce the incidence of GVHD after hematopoietic stem cell transplant. Here we report results from the first randomized probiotic enteric regimen trial in which allogenic hematopoietic stem cell patients were supplemented with Lactobacillus rhamnosus GG. Gut microbiome analysis confirmed a previously reported gut microbiome association with GVHD. However, the clinical trial was terminated when interim analysis did not detect an appreciable probiotic-related change in the gut microbiome or incidence of GVHD. Additional studies are necessary to determine whether probiotics can alter the incidence of GVHD after allogeneic stem cell transplant.

Hip-related toxicity after prostate radiotherapy: Treatment related or coincidental?

BACKGROUND AND PURPOSE: To evaluate the incidence and predictors of hip toxicity postradiotherapy for localized prostate cancer. METHODS AND MATERIALS: 4067 prostate cancer patients were treated with external beam radiotherapy (EBRT; n=2569; 63%) or brachytherapy with or without supplemental EBRT (n=1508; 27%). 43% (n=1738) were treated with neo-adjuvant and concurrent ADT and 57% (n=2329) with radiotherapy alone. Hip toxicity was defined as moderate or severe pain upon ambulation with or without the need for hip-revision surgery. Median follow-up was 7years (range, 3-21years). RESULTS: One hundred twenty-one (2.7%) patients developed moderate-to-severe hip pain after radiotherapy affecting ambulation. Of these, 73 (60%) required hip replacement secondary to persistent hip pain. Among patients with baseline degenerative joint disease (DJD) changes on scans, 10-year incidence of hip-related toxicity was 11% versus 3% for those without such changes (P<.001). The only variables on multivariate analysis associated with hip-related toxicity post-radiotherapy were baseline DJD on imaging (P<.0001) and prolonged ADT for salvage therapy (P<.0001). CONCLUSIONS: Prostate EBRT or brachytherapy is associated with low incidence of long-term hip-related toxicity. The only variables identified associated with hip toxicity posttherapy was the presence of baseline DJD and prolonged salvage ADT posttreatment for patients developing recurrence.

Clinical significance of HER2-positive and triple-negative status in small (≤ 1 cm) node-negative breast cancer.

BACKGROUND: Data regarding the clinical significance of HER2(+) and TN status in patients with small node-negative tumors are limited and conflicting. It remains unclear who, among those with small lesions, might benefit from more aggressive adjuvant therapy. PATIENTS AND METHODS: We identified all node-negative breast cancer patients with tumor size ≤ 1 cm diagnosed between January 1, 1995 and December 31, 2008 using our institutional breast service database. Patients were classified according to their receptor status into 3 groups: (1) hormone receptor (HR)-positive (estrogen receptor [ER]- or progesterone receptor [PR]-positive, HER2(-)); (2) HER2(+) (immunohistochemistry 3(+) or fluorescence in situ hybridization amplification ≥ 2); and (3) TN (ER(-), PR(-), and HER2(-)). RFS was calculated using Kaplan-Meier methods. RESULTS: Among 656 patients with tumors ≤ 1 cm, 494 (75%) of the patients were HR(+), 107 (16%) were HER2(+), and 55 (9%) were TN. Median age was 59 years (range, 27-92 years). Median follow-up was 3.5 years. The 5-year RFS rates were 98.2%, 97.1%, and 83.5% in patients with HR(+), HER2(+), and TN tumors, respectively (P < .001). In multivariate analysis, TN status was associated with worse RFS (hazard ratio, 6.70; 95% confidence interval [CI], 3.02-14.86), and HER2(+) was not (hazard ratio, 1.64; 95% CI, 0.73-3.69). CONCLUSION: TN, but not HER2(+) status, was associated with worse RFS in patients with T1abN0 tumors, and adjuvant chemotherapy might be considered in patients with TN breast cancer.