Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 96
Filter
2.
Case Rep Oncol ; 16(1): 1353-1361, 2023.
Article in English | MEDLINE | ID: mdl-37946745

ABSTRACT

Introduction: Bing-Neel syndrome (BNS) is a rare and heterogenous manifestation of Waldenström macroglobulinemia (WM) involving central nervous system (CNS) infiltration by malignant lymphoplasmacytic cells. Efforts to standardize diagnostic criteria have improved in recent years, as have treatment options including the use of the Bruton tyrosine kinase inhibitor (BTKI) ibrutinib. Case Presentation: Here, we present the case of a 70-year-old male with a remote history of WM previously treated with bendamustine and rituximab, who presented to medical attention with several months of left-sided weakness, headache, and ataxia. Brain magnetic resonance imaging revealed numerous enhancing masses in the bilateral cerebral hemispheres, inferior medulla, and upper cervical spine. Laboratory studies showed serum IgM lambda monoclonal gammopathy and elevated free serum kappa and lambda light chains, while cerebrospinal fluid flow cytometry revealed CD19+ B cells. Stereotactic brain biopsy of a right frontal brain lesion was consistent with lymphoplasmacytic lymphoma, confirmed by a positive MYD88 L265P mutation. He received ibrutinib 420 mg orally daily, and this resulted in appreciable clinical and radiologic responses, which have persisted over a 31-month period. Conclusion: The advent of molecularly targeted agents and novel therapies for WM has provided patients and clinicians with additional therapeutic options. The use of BTK inhibitors with their high-level CNS penetrance, in particular, offers a novel way to treat BNS and improve patient overall survival while maintaining a high level of quality of life. We discuss the importance of MYD88 L265P testing in the context of BNS as well as the expanding role of BTKIs in treating this disease.

3.
Elife ; 122023 10 17.
Article in English | MEDLINE | ID: mdl-37846664

ABSTRACT

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32-1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70-6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83-12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63-3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20-2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66-3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89-22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. Clinical trial number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701.


Subject(s)
Breast Neoplasms , COVID-19 , United States/epidemiology , Humans , Female , Middle Aged , SARS-CoV-2 , Cohort Studies , Breast Neoplasms/epidemiology , Retrospective Studies
4.
Clin Cancer Res ; 29(24): 5038-5046, 2023 12 15.
Article in English | MEDLINE | ID: mdl-37523145

ABSTRACT

PURPOSE: To evaluate the safety, pharmacokinetics, and pharmacodynamic effects of cabozantinib, a CYP3A4 substrate, in people living with human immunodeficiency virus and cancer receiving antiretrovirals (ARV). PATIENTS AND METHODS: Patients received a reduced dose of cabozantinib (20 mg orally daily) with strong CYP3A4 inhibitors (ARV ritonavir or non-ARV cobicistat, stratum A), or a standard 60 mg dose with ARVs that are CYP3A4 inducers (efavirenz or etravirine, stratum B) or noninteracting ARVs (stratum C). Initial dose escalation in stratum A and stratum B was performed on the basis of tolerability. RESULTS: 36 patients received cabozantinib plus ARVs, including 20 in stratum A, 9 in B, and 7 in C. The recommended initial cabozantinib doses for stratum A, B, and C were 20, 60, and 60 mg, respectively. Doses of 40 or 60 mg plus CYP3A4 inhibitors in stratum A and 100 mg plus CYP3A4 inducers in stratum B were associated with excessive toxicity, whereas 60 mg with noninteracting ARVs was not. The steady state minimal concentrations were lower at 20 mg in stratum A or 60 mg in stratum B compared with 60 mg in stratum C, while total exposure was only lower in 60 mg in stratum B compared with 60 mg in stratum C. Activity was observed in Kaposi sarcoma and an AXL-amplified sarcoma. CONCLUSIONS: Cabozantinib as a single agent should be initiated at 20 mg daily and 60 mg daily when taken concurrently with ARVs that are strong CYP3A4 inhibitors and inducers, respectively, with consideration for subsequent escalation per current cabozantinib guidelines. See related commentary by Eisenmann and Sparreboom, p. 4999.


Subject(s)
Antineoplastic Agents , HIV Infections , Neoplasms , Humans , Cytochrome P-450 CYP3A/genetics , HIV , Cytochrome P-450 CYP3A Inhibitors/adverse effects , Cytochrome P-450 CYP3A Inducers/adverse effects , Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Protein Kinase Inhibitors/adverse effects , HIV Infections/drug therapy
5.
medRxiv ; 2023 Mar 10.
Article in English | MEDLINE | ID: mdl-37205429

ABSTRACT

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1,383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32 - 1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70 - 6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83 - 12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63 - 3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20 - 2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66 - 3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89 - 22.6]). Hispanic ethnicity, timing and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to Non-Hispanic White patients.

6.
Qual Life Res ; 32(8): 2293-2304, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37020153

ABSTRACT

PURPOSE: To determine whether treatment of anal high-grade squamous intraepithelial lesions (HSIL), vs active monitoring, is effective in reducing incidence of anal cancer in persons living with HIV, the US National Cancer Institute funded the Phase III ANal Cancer/HSIL Outcomes Research (ANCHOR) clinical trial. As no established patient-reported outcomes (PRO) tool exists for persons with anal HSIL, we sought to estimate the construct validity and responsiveness of the ANCHOR Health-Related Symptom Index (A-HRSI). METHODS: The construct validity phase enrolled ANCHOR participants who were within two weeks of randomization to complete A-HRSI and legacy PRO questionnaires at a single time point. The responsiveness phase enrolled a separate cohort of ANCHOR participants who were not yet randomized to complete A-HRSI at three time points: prior to randomization (T1), 14-70 (T2), and 71-112 (T3) days following randomization. RESULTS: Confirmatory factor analysis techniques established a three-factor model (i.e., physical symptoms, impact on physical functioning, impact on psychological functioning), with moderate evidence of convergent validity and strong evidence of discriminant validity in the construct validity phase (n = 303). We observed a significant moderate effect for changes in A-HRSI impact on physical functioning (standardized response mean = 0.52) and psychological symptoms (standardized response mean = 0.60) from T2 (n = 86) to T3 (n = 92), providing evidence of responsiveness. CONCLUSION: A-HRSI is a brief PRO index that captures health-related symptoms and impacts related to anal HSIL. This instrument may have broad applicability in other contexts assessing individuals with anal HSIL, which may ultimately help improve clinical care and assist providers and patients with medical decision-making.


Subject(s)
Anus Neoplasms , HIV Infections , Squamous Intraepithelial Lesions , Humans , Quality of Life/psychology , Squamous Intraepithelial Lesions/diagnosis , Squamous Intraepithelial Lesions/pathology , Anal Canal , Surveys and Questionnaires , Anus Neoplasms/pathology , HIV Infections/pathology
7.
N Engl J Med ; 386(24): 2273-2282, 2022 06 16.
Article in English | MEDLINE | ID: mdl-35704479

ABSTRACT

BACKGROUND: The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking. METHODS: We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer. RESULTS: Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test). CONCLUSIONS: Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.).


Subject(s)
Anus Neoplasms , HIV Infections , Precancerous Conditions , Squamous Intraepithelial Lesions , Watchful Waiting , Adult , Anus Neoplasms/etiology , Anus Neoplasms/pathology , Anus Neoplasms/prevention & control , Anus Neoplasms/therapy , Biopsy , Female , HIV Infections/complications , Homosexuality, Male , Humans , Male , Papillomavirus Infections/complications , Precancerous Conditions/etiology , Precancerous Conditions/pathology , Precancerous Conditions/therapy , Prospective Studies , Squamous Intraepithelial Lesions/etiology , Squamous Intraepithelial Lesions/pathology , Squamous Intraepithelial Lesions/therapy
8.
J Oncol Pharm Pract ; 28(4): 1003-1008, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35037777

ABSTRACT

INTRODUCTION: Although rare, Kaposi sarcoma is the most common malignant neoplasm associated with human immunodeficiency virus (HIV) infection. Several agents have now been approved in the treatment of this malignancy and are used with varying degrees of success. CASE REPORT: We present a unique case of a 64-year-old man with well-controlled HIV infection who developed necrotizing leg gangrene from invasive cutaneous Kaposi sarcoma. He responded very well to systemic chemotherapy, thereby avoiding limb amputation. MANAGEMENT AND OUTCOME: Pegylated liposomal doxorubicin (PLD) at a dose of 20 mg/m2 every 3 weeks was utilized, with a near-complete response after six cycles of therapy. The patient continues to receive maintenance treatment with PLD. His HIV infection remains in excellent control, with a high-normal CD4 T-cell count. Periodic echocardiogram evaluations have not shown any decline in left ventricular ejection fraction (LVEF) over time. CONCLUSION: Most patients with Kaposi sarcoma achieve partial responses to treatment with PLD. Our case illustrates that near complete and complete responses are possible with this agent, leading to potential limb salvage in necrotizing gangrene.


Subject(s)
HIV Infections , Sarcoma, Kaposi , Skin Neoplasms , Antibiotics, Antineoplastic/therapeutic use , Doxorubicin/analogs & derivatives , Doxorubicin/therapeutic use , Gangrene/complications , Gangrene/drug therapy , HIV Infections/complications , HIV Infections/drug therapy , Humans , Leg/pathology , Male , Middle Aged , Polyethylene Glycols/therapeutic use , Sarcoma, Kaposi/drug therapy , Skin Neoplasms/complications , Skin Neoplasms/drug therapy , Stroke Volume , Ventricular Function, Left
9.
Am J Case Rep ; 22: e929249, 2021 May 27.
Article in English | MEDLINE | ID: mdl-34039947

ABSTRACT

BACKGROUND Cardiac tamponade is a life-threatening pericardial compressive disorder that is a common downstream manifestation of infections, malignancy, and metabolic disorders. Hypothyroidism is a rare cause of tamponade that is attributed to the slow accumulation of effusive fluid into the intrapericardial space. In individuals living with HIV/AIDS, tamponade is commonly associated with infection or malignancy. To our knowledge, this is the first reported case of a patient with HIV/AIDS to have been identified with tamponade secondary to hypothyroidism. CASE REPORT Herein, we describe the case of a 52-year-old male patient with a history of AIDS, who presented with nausea, vomiting, diarrhea, and episodic gastrointestinal discomfort for the past several weeks, in conjunction with progressive fatigue. At initial presentation, he had no hemodynamic or clinical signs of tamponade, but pericardial effusion was incidentally found on imaging. Further investigations revealed an undiagnosed Hashimoto's thyroiditis as a function of restored immunocompetency, which ultimately led to the impending tamponade in this patient. We describe his clinical course through diagnosis of autoimmune hypothyroidism, review cardiac tamponade and hypothyroidism in the context of people living with HIV/AIDS, and discuss this rare manifestation of restored immunocompetency. CONCLUSIONS Hypothyroidism should be ruled out in all patients presenting with pericardial effusions or cardiac tamponade, even in people living with HIV/AIDS or those with a history of immune deficiencies.


Subject(s)
Acquired Immunodeficiency Syndrome , Cardiac Tamponade , Hashimoto Disease , Hypothyroidism , Pericardial Effusion , Cardiac Tamponade/diagnosis , Cardiac Tamponade/etiology , Hashimoto Disease/complications , Hashimoto Disease/diagnosis , Humans , Male , Middle Aged , Pericardial Effusion/etiology
10.
Clin Med Insights Blood Disord ; 14: 2634853521994094, 2021.
Article in English | MEDLINE | ID: mdl-33679144

ABSTRACT

Despite representing 30% to 40% of newly diagnosed cases of adult non-Hodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL) rarely presents (1) in the leukemic phase (2) with dysregulation of the TP53 tumor suppressor gene and (3) an elevated serum lactic acid level. In this case report and literature review, we highlight this unfortunate triad of poor prognostic features associated with an aggressive and fatal clinical course in a 53-year-old man with recrudescent DLBCL. A leukemic presentation of de novo or relapsed DLBCL is rare and may be related to differential expressions of adhesion molecules on cell surfaces. In addition, TP53 gene mutations are present in approximately 20% to 25% of DLBCL cases and foreshadow worse clinical outcomes. Finally, an elevated serum lactic acid level in DLBCL that is not clearly associated with sepsis syndrome is a poor prognostic factor for survival and manifests as type B lactic acidosis through the Warburg effect.

11.
Lancet Oncol ; 21(12): e575-e588, 2020 12.
Article in English | MEDLINE | ID: mdl-33271114

ABSTRACT

The EU, the USA, and Japan account for the majority of biological pharmacotherapy use worldwide. Biosimilar regulatory approval pathways were authorised in the EU (2006), in Japan (2009), and in the USA (2015), to facilitate approval of biological drugs that are highly similar to reference products and to encourage market competition. Between 2007 and 2020, 33 biosimilars for oncology were approved by the European Medicines Agency (EMA), 16 by the US Food and Drug Administration (FDA), and ten by the Japan Pharmaceuticals and Medical Devices Agency (PMDA). Some of these approved applications were initially rejected because of manufacturing concerns (four of 36 [11%] with the EMA, seven of 16 [44%] with the FDA, none of ten for the PMDA). Median times from initial regulatory submission before approval of oncology biosimilars were 1·5 years (EMA), 1·3 years (FDA), and 0·9 years (PMDA). Pharmacists can substitute biosimilars for reference biologics in some EU countries, but not in the USA or Japan. US regulation prohibits substitution, unless the biosimilar has been approved as interchangeable, a designation not yet achieved for any biosimilar in the USA. Japan does not permit biosimilar substitution, as prescribers must include the product name on each prescription and that specific product must be given to the patient. Policy Reviews published in 2014 and 2016 in The Lancet Oncology focused on premarket and postmarket policies for oncology biosimilars before most of these drugs received regulatory approval. In this Policy Review from the Southern Network on Adverse Reactions, we identify factors preventing the effective launch of oncology biosimilars. Introduction to the market has been more challenging with therapeutic than for supportive care oncology biosimilars. Addressing region-specific competition barriers and educational needs would improve the regulatory approval process and market launches for these biologics, therefore expanding patient access to these products in the EU, the USA, and Japan.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Biosimilar Pharmaceuticals/therapeutic use , Drug Approval , Hematinics/therapeutic use , Neoplasms/drug therapy , United States Food and Drug Administration , Antineoplastic Agents, Immunological/adverse effects , Bevacizumab/therapeutic use , Biosimilar Pharmaceuticals/adverse effects , Drug Approval/legislation & jurisprudence , Drug Substitution , Erythropoietin/analogs & derivatives , Erythropoietin/therapeutic use , Europe , Filgrastim/therapeutic use , Hematinics/adverse effects , Humans , Japan , Neoplasms/immunology , Neoplasms/mortality , Patient Safety , Policy Making , Polyethylene Glycols/therapeutic use , Risk Assessment , Rituximab/therapeutic use , Trastuzumab/therapeutic use , Treatment Outcome , United States , United States Food and Drug Administration/legislation & jurisprudence
12.
Clin Med Insights Blood Disord ; 13: 1179545X20926188, 2020.
Article in English | MEDLINE | ID: mdl-32565679

ABSTRACT

The spleen is among the most common extranodal sites for Hodgkin and non-Hodgkin lymphomas (NHLs); however, among lymphomas arising from the spleen, primary splenic lymphomas (PSLs) are rare. The group of PSLs includes primary splenic diffuse large B-cell lymphoma (PS-DLBCL), splenic red pulp small B-cell lymphoma, splenic marginal zone lymphoma (SMZL), and a splenic hairy cell leukemia variant. Delineating between the PSL variants can be challenging, especially as fine-needle aspirate and core needle biopsy of the spleen are not routinely offered at most medical centers. Herein, we describe the clinical course of 2 representative patients who presented with non-specific gastrointestinal symptoms, the first who was diagnosed with PS-DLBCL and the second who was diagnosed with SMZL. We review and contrast the clinical presentations, imaging techniques, and laboratory findings of these discrete lymphoma variants and offer strategies on how to delineate between these varied splenic processes. We also examine the use of splenectomy and splenic needle biopsy as diagnostics and, in the case of splenectomy, a therapeutic tool. Finally, we also briefly review treatment options for these varied lymphoma sub-types while acknowledging that randomized trials to guide best practices for PSLs are lacking.

13.
Front Oncol ; 10: 570752, 2020.
Article in English | MEDLINE | ID: mdl-33520695

ABSTRACT

Checkpoint inhibitors (CPIs) increase antitumor activity by unblocking regulators of the immune response. This action can provoke a wide range of immunologic and inflammatory side effects, some of which can be fatal. Recent studies suggest that CPI-induced immune-related adverse events (irAEs) may predict survival and response. However, little is known about the mechanisms of this association. This study was undertaken to evaluate the influence of tumor diagnosis and preexisting clinical factors on the types of irAEs experienced by cancer patients treated with CPIs. The correlation between irAEs and overall survival (OS) was also assessed. All cancer patients treated with atezolizumab (ATEZO), ipilimumab (IPI), nivolumab (NIVO), or pembrolizumab (PEMBRO) at Virginia Mason Medical Center between 2011 and 2019 were evaluated. irAEs were graded according to the Common Terminology Criteria for Adverse Events (Version 5) and verified independently. Statistical analyses were performed to assess associations between irAEs, pre-treatment factors, and OS. Of the 288 patients evaluated, 59% developed irAEs of any grade, and 19% developed irAEs of grade 3 or 4. A time-dependent survival analysis demonstrated a clear association between the occurrence of irAEs and OS (P < 0.001). A 6-week landmark analysis adjusted for body mass index confirmed an association between irAEs and OS in non-Small Cell Lung Cancer (NSCLC) (P < 0.03). An association between melanoma and skin irAEs (P < 0.01) and between NSCLC and respiratory irAEs (P = 0.03) was observed, independent of CPI administered. Patients with preexisting autoimmune disease experienced a higher incidence of severe irAEs (P = 0.01), but not a higher overall incidence of irAEs (P = 0.6). A significant association between irAEs and OS was observed in this diverse patient population. No correlation was observed between preexisting comorbid conditions and the type of irAE observed. However, a correlation between skin-related irAEs and melanoma and between respiratory irAEs and NSCLC was observed, suggesting that many irAEs are driven by a specific response to the primary tumor. In patients with NSCLC, the respiratory irAEs were associated with a survival benefit.

14.
BMC Cancer ; 19(1): 1147, 2019 Nov 27.
Article in English | MEDLINE | ID: mdl-31775673

ABSTRACT

BACKGROUND: The advent of the immunomodulatory imide drugs (IMiDs) lenalidomide and thalidomide for the treatment of patients with plasma cell myeloma (PCM), has contributed to more than a doubling of the overall survival of these individuals. As a result, PCM patients join survivors of other malignancies such as breast and prostate cancer with a relatively new clinical problem - second primary malignancies (SPMs) - many of which are a result of the treatment of the initial cancer. PCM patients have a statistically significant increased risk for acute myeloid leukemia (AML) and Kaposi sarcoma. IMiD treatment has also been associated with an increased risk of myelodysplastic syndrome (MDS), AML, and squamous cell carcinoma of the skin. However, within these overlapping groups, acute lymphoblastic leukemia (ALL) is much less common. CASE PRESENTATION: Herein, we describe an elderly man with PCM and a 14-year cumulative history of IMiD therapy who developed persistent pancytopenia and was diagnosed with B-cell acute lymphoblastic leukemia (B-ALL). He joins a group of 17 other patients documented in the literature who have followed a similar sequence of events starting with worsening cytopenias while on IMiD maintenance for PCM. These PCM patients were diagnosed with B-ALL after a median time of 36 months after starting IMiD therapy and at a median age of 61.5 years old. CONCLUSIONS: PCM patients with subsequent B-ALL have a poorer prognosis than their de novo B-ALL counterparts, however, the very low prevalence rate of subsequent B-ALL and high efficacy of IMiD maintenance therapy in PCM should not alter physicians' current practice. Instead, there should be a low threshold for bone marrow biopsy for unexplained cytopenias.


Subject(s)
Lenalidomide/adverse effects , Multiple Myeloma/diagnosis , Multiple Myeloma/etiology , Neoplasms, Second Primary/diagnosis , Neoplasms, Second Primary/etiology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/etiology , Thalidomide/adverse effects , Aged , Aged, 80 and over , Biomarkers, Tumor , Bone Marrow , Humans , Immunologic Factors/adverse effects , Immunologic Factors/therapeutic use , Lenalidomide/therapeutic use , Male , Thalidomide/therapeutic use
16.
Lancet HIV ; 6(4): e209-e210, 2019 04.
Article in English | MEDLINE | ID: mdl-30826280
18.
Mayo Clin Proc Innov Qual Outcomes ; 3(4): 485-494, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31993568

ABSTRACT

OBJECTIVE: To assess our adherence to treatment guidelines for diffuse large B-cell lymphoma (DLBCL) established by the American Society of Hematology in 2014 through implementation of a quality improvement initiative (QII) at our institution in 2015. PATIENTS AND METHODS: Patients with newly diagnosed DLBCL treated from January 1, 2006, through December 31, 2017, were identified. Electronic medical records were reviewed for documentation of American Society of Hematology Practice Improvement Module quality measures (eg, key pathologic features of DLBCL, lymphoma staging, and screening for hepatitis B virus [HBV] infection in patients receiving rituximab-based chemotherapy). We also reviewed assessment of prognosis by revised International Prognostic Index score, testing for hepatitis C virus, HBV, and HIV, chemotherapy education, and the addition of rituximab in the treatment regimen of CD20+ DLBCL. RESULTS: Following QII implementation, we saw improvements in most metrics, including reporting of key molecular features (fluorescence in situ hybridization for c-MYC, BCL2, and BCL6, from 45.5% [75 of 165 patients] before QII to 91.7% [22 of 24 patients] after QII; P<.001), screening for HBV (41.8% [69 of 165 patients] to 91.7% [22 of 24 patients]; P<.001) and HIV infections (33.9% [56 of 165 patients] to 87.5% [21 of 24 patients]; P<.0001), providing chemotherapy education (92.7% [153 of 165 patients] to 100%), and use of rituximab for CD20+ DLBCL (83.6% [138 of 165 patients] to 100%; P=.05). All patients had positron emission tomography-computed tomography for DLBCL staging, and there was significantly lower use of bone marrow biopsy (P=.011). CONCLUSION: Implementating a QII and employing standardized metrics can aid in improving quality of care for patients with newly diagnosed DLBCL and allow opportunities to build and ensure better adherence to evolving patient care guidelines.

19.
Mayo Clin Proc Innov Qual Outcomes ; 2(3): 277-285, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30225461

ABSTRACT

OBJECTIVE: To determine the utility of routine measurements of left ventricular ejection fraction (LVEF) before the administration of doxorubicin-based chemotherapy (DOX) in patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: We investigated the frequency of LVEF measurements before the initiation of therapy in 291 patients with DLBCL at our institution from January 1, 2001, through December 31, 2013, and reviewed whether LVEF varied in patients with an underlying risk of cardiac disease (CD), the relationship between LVEF and subsequent DLBCL treatment, and congestive heart failure (CHF) occurrence in DOX-treated patients. RESULTS: Left ventricular ejection fraction was measured in 258 patients before the administration of chemotherapy and was not associated with underlying CHF risk (P=.94). Left ventricular ejection fraction was normal in 243 patients (94%) and low in 15 patients. Doxorubicin-based chemotherapy was administered to 206 patients with normal LVEF (85%) vs 8 patients with low LVEF (53%) (P=.006). However, when previous CD was factored out, LVEF did not influence subsequent treatment decisions (P=.51). Congestive heart failure occurred in 18 patients, and the risk was similar in patients treated with and without DOX. For all patients who had LVEF measured, CHF incidence did not differ between patients who received DOX and those who did not (P>.99). Moreover, there was no difference in CHF incidence after receiving DOX between those who had normal and low LVEF results (P=.45). CONCLUSION: The decision to administer DOX was influenced by LVEF status only when previous CD was factored out. Furthermore, CHF incidence posttreatment did not differ between patients who did and did not receive DOX. These preliminary findings challenge the practice of performing cardiac screening before DOX for patients with DLBCL.

20.
Leuk Res Rep ; 9: 48-53, 2018.
Article in English | MEDLINE | ID: mdl-29892550

ABSTRACT

We describe the cautionary case of a patient with advanced-stage large B-cell lymphoma (DLBCL). After combination chemotherapy, CT-PET revealed a persistent focus of likely DLBCL for which he received radiotherapy. Follow-up CT-PET showed diffuse hypermetabolic adenopathy and recurrent DLBCL was presumed. As part of clinical trial assessment, multiple biopsies showed non-caseating lymphadenitis consistent with sarcoidosis. No treatment for asymptomatic sarcoidosis was required and 18 months later he remains cancer-free. The presentation of sarcoidosis masquerading as recurrent DLBCL highlights the importance of tissue sampling prior to engaging in toxic and potentially life-threatening chemotherapy and the interesting link between DLBCL and sarcoidosis.

SELECTION OF CITATIONS
SEARCH DETAIL
...