A Systematic Review and Meta-Analysis of Front-line Anthracycline-Based Chemotherapy Regimens for Peripheral T-Cell Lymphoma

Anthracycline-based chemotherapy remains standard treatment for peripheral T-cell lymphoma (PTCL) although its benefits have been questioned. We performed systematic literature review and meta-analyses examining the complete response (CR) and overall survival (OS) rates for patients with PTCL. The CR rate for PTCL patients ranged from 35.9% (95% CI 23.4–50.7%) for enteropathy-type T-cell lymphoma (ETTL) to 65.8% (95% CI 54.0–75.9%) for anaplastic large cell lymphoma (ALCL). The 5-year OS was 38.5% (95% CI 35.5–41.6%) for all PTCL patients and ranged from 20.3% (95% CI 12.5–31.2%) for ETTL to 56.5% (95% CI 42.8–69.2%) for ALCL. These data suggest that there is marked heterogeneity across PTCL subtypes in the benefits of anthracycline-based chemotherapy. While anthracyclines produce CR in half of PTCL patients, this yields reasonable 5-year OS for patients with ALCL but not for those with PTCL-NOS or ETTL. Novel agents and regimens are needed to improve outcomes for these patients

Response and Survival Rates in Patients with Peripheral T-Cell Lymphoma Treated with Anthracycline-Based Regimens: A Comprehensive Meta-Analysis.

Abstract Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive non-Hodgkin lymphomas (NHL) for which CHOP-type chemotherapy remains the standard despite its suboptimal results, especially when compared to its outcome in B-cell NHL. The International Peripheral T-Cell Lymphoma Clinical and Pathologic Review Project questioned the role of anthracyclines in the treatment of PTCL. To address this issue, we conducted a systematic literature review and meta-analysis of first-line therapy for untreated PTCL patients examining the complete remission (CR) and overall survival (OS) rates with anthracycline-based regimens. Given the established favorable treatment outcome of anaplastic large cell lymphomas (ALCL) along with the heterogeneity in response and survival rates across PTCL subgroups, we focused our analyses on non-ALCL PTCL and performed subgroup meta-analyses on the outcomes of anthracycline-based regimens for patients with PTCL- not-otherwise-specified (NOS), angio-immunoblastic T-cell lymphoma (AITL) and NK/T-cell NHL. Methods: We searched the ASH and ASCO Annual Meeting Abstracts (2003–2006), MEDLINE (1/1996–6/2007), and Google Scholar. Each search used combinations of the term ’Peripheral T-Cell Lymphoma’, ’PTCL’, ’T Cell Lymphoma’, ’Non Hodgkin Lymphoma’, ’NK/T-cell lymphoma’, ’Angioimminoblastic lymphoma’, ’Anaplastic large cell lymphoma’, ’Enteropathy-type T-cell lymphoma’, ’Alk-negative’, ’Non-Alk positive’, ’Anthracycline’, ’Doxorubicin’, ’Adriamycin’, ’Intensive Chemo Therapy’, and ’CHOP’. Criteria for including studies were: Intervention with chemotherapy with or without radiotherapy Reporting in English of treatment outcome measures for patients with non-ALCL PTCL including CR rate, overall response (OR) rate, and at least one form of survival data. Extracted data included pre-treatment disease status, treatment regimen, median follow up time, progression free survival, overall survival, CR, OR and early treatment-related death. Abstracts subsequently published as papers were excluded. In meta-analyses of selected studies, summary CR and 5-year OS estimates were calculated based on the assumption of fixed effects and using the Mantel-Haenszel method. Results: Thirty-one studies meeting the inclusion criteria for this analysis were initially identified. These studies included data from 2912 patients. Twenty-five studies (n=2011) were evaluable for CR. Eighteen studies (n=1812) provided 5-year OS data. The estimated CR rate for anthracycline-based regimens among non-ALCL PTCL patients was 54.5% (95%CI 52.3%–56.8%), with subgroup CR rates as follows: AITL 54.7% (95%CI 47.3%–61.8%), NK/T 57.0% (95%CI 52.5%–61.5%), PTCL-NOS 55.6% (95%CI 51.8%–59.2%). The estimated 5-year OS for non-ALCL PTCL was 37.3% (95%CI 35.1%–39.6%), and for each subgroup was: AITL 36.5% (95%CI 31.7%–41.7%), NK/T 47.9% (95%CI 42.5%–53.5%), PTCL-NOS 34.0% (95%CI 30.2%–38.1%; Figure). Conclusions: Despite the reasonable CR rates induced by anthracycline-based regimens in PTCL, OS remains poor. Future clinical trials need to focus on subtype-specific treatments for increasing CR and strategies such as stem cell transplantation or maintenance therapy, capable of sustaining CRs. Meta-analysis of 5-year Overall Survival rates by PTCL subtype. Shaded boxes reflect the relative statistical weights each study contributed to the summary estimate. Meta-analysis of 5-year Overall Survival rates by PTCL subtype. . / Shaded boxes reflect the relative statistical weights each study contributed to the summary estimate.</jats:p

COVID-19 Infection and Outcomes at a Comprehensive Sickle Cell Center

Abstract Introduction: The Grady Comprehensive Sickle Cell (SC) center is the largest adult sickle cell center in the United States (US) and has the first 24/7 acute care unit for management of sickle cell vaso-occlusive events (VOE). In 2019, the center provided 3077 sickle cell outpatient visits and 3695 acute care visits. When the COVID-19 pandemic reached the US, the center had a precipitous drop in the number of both outpatient clinic and acute care visits as state regulations for lockdown were passed. This report follows all the COVID-19 cases at a single adult center for sickle cell disease in one year. Methods: The clinical database has been tracking COVID-19 cases reported. Out of a total of 1343 patients, 55 patients contracted COVID-19 and were tracked in the clinical database with IRB approval. Results: Of the 55 patients with COVID-19, 28 were female and 27 were male. By genotype, 64% of patients were SS, 31% were SC and 5% were Sβ+ thalassemia. 35% of patient were on hydroxyurea for disease modification with the majority of them being of the SS genotype and 31% had elevated fetal hemoglobin determined by a percentage fetal hemoglobin above 5% by hemoglobin electrophoresis. Chronic pain (defined as patients experiencing daily pain episodes for more than 4 days a week for the last 3 months) and calculation of daily morphine equivalents were reported in clinic follow-up and the narcotic database utilization. 47% of the patients had chronic pain and the median morphine equivalents was 90 mg daily (45-225mg). The rate of emergency department (ED) visits or hospitalizations for the sickle cell patients with COVID-19 was 80%. 49% of the SC patients' visits were related to VOE and 27% related to COVID-19 primarily. 20% of SC patients with COVID-19 were not seen in any emergency setting or required any hospitalization. The COVID-19 signs and symptoms experienced by the patients were as follows: 58% had pain as the main presenting symptom, followed by cough and fever (40%), dyspnea (31%), and pneumonia with chest x-ray evidence (25%). 2 patients developed acute respiratory distress syndrome (ARDS) and were intubated, and 2 patients died. 29% of the patients had lung findings on imaging and 16 of 55 patients required treatment with the use of Remdesivir in 9, dexamethasone in 8 and red cell products in 7 of the 16 patients. The 2 patients who died had both presented with COVID-19 infection in June and July 2020 respectively. One patient had presented in June 2020 with VOE and was found to have bilateral lung opacities but was asymptomatic and was discharged home to return few days later with clinical picture of multi-organ failure for which a red cell erythrocytapheresis was attempted. The second patient had presented in July 2020 with COVID-19 pneumonia and was treated with Remdesivir and convalescent plasma with development of multi-organ failure and ARDS. Discussion: Several reports were published regarding the rate of COVID-19 related mortality and morbidity in sickle cell disease. The Grady comprehensive sickle cell center experience differs in the fact that 16 out of 55 patients who had contracted COVID-19 required treatment and 2 of those 16 had died. In fact, the deaths occurred early in the course of the pandemic in June and July 2020 when 20 total cases were diagnosed (from March to Septemeber 2020). The remaining 35 cases registered zero deaths (October 2020 to March 2021) with the rate of complicated COVID-19 hospitalizations decreasing with better treatment available. In addition, the timeline for the COVID-19 cases reported fits the population timeline of 2 peaks respectively happening in the summer of 2020 and the Winter of 2021. During the initial peak, we have noted a decrease in the number of clinic and acute care visits respectively. This was anticipated given the statewide lockdown that was implemented. To circumvent that, the center adopted virtual visits to deliver healthcare needs. This measure has aided in protecting patients against COVID-19. Additionally, it is interesting that despite the second peak in the winter of 2021, there were no reported deaths among the patients who developed COVID-19. This finding can suggest that despite the concern for morbidity and mortality of sickle cell patients, their diligence and awareness to stay home during the pandemic has proven crucial in reducing morbidity and mortality and the option of virtual visits for healthcare delivery was key and should be utilized further in sickle cell care. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare. </jats:sec