Cell-free EBV DNA as a biomarker during clinical management of nasopharyngeal carcinoma in a nonendemic region.

Nasopharyngeal carcinoma (NPC) is the most common malignant tumor of the nasopharynx. Although NPC is not endemic in India, higher incidences were observed in its North-Eastern regions particularly Sikkim, Nagaland, Manipur, and Mizoram. Early detection of NPC is difficult because the nasopharynx is not readily amenable to clinical examination and symptoms of NPC are nonspecific. The development of suitable biomarkers for early diagnosis of NPC as well as accurate monitoring of treatment response is needed urgently. In this exploratory pilot study, we have investigated the clinical significance of assessing plasma Epstein-Barr virus (EBV) DNA load at diagnosis and during treatment. We found that EBV DNA is detectable at diagnosis in the majority of patients with nonendemic NPC and the absolute copy number of circulating EBV DNA per milliliter increases progressively with the stage of the disease. The viral load declined significantly with induction chemotherapy and definitive chemoradiation but showed a sharp rise at relapse. Patients with EBV DNA levels ≥1500 copies/ml had a higher risk of disease progression or relapse when compared with patients who had EBV DNA <1500 copies/ml at baseline. Estimation of plasma EBV DNA may serve as an excellent noninvasive tool to monitor disease extent, response to therapy, and for better prediction of future relapse or progression-free survival in a nonendemic NPC patient population.

Autologous Hematopoietic Stem Cell Transplant: A Potential Option for Relapsed Pediatric Acute Myeloid Leukemia With Lack of Matched Sibling Donor and Resource Challenge.

Though allogeneic hematopoietic stem cell transplant (HSCT) is standard for relapsed pediatric acute myeloid leukemia, often it may not be accessible due to donor unavailability and resource limitations. We retrospectively analyzed outcomes of 26 children (mean age: 10.9±4.5 y) who underwent autologous HSCT in complete remission 2. Three-year event-free survival and overall survival were 50.1±10.7% and 63.3±9%, respectively; with 1 treatment-related death and 46% relapse rate. Notwithstanding the retrospective study design and somewhat favorable patient characteristics, the outcomes are comparable with those of other series and our own allogeneic HSCT data. Autologous HSCT is a potential alternative to allogeneic HSCT, especially in countries with poorly maintained donor registries.

Allogeneic hematopoietic stem cell transplant in pediatric acute myeloid leukemia: Lessons learnt from a tertiary care center in India.

There is paucity of data on outcomes of MSD-HSCT in children with relapsed or high-risk AML from developing countries, which have unique challenges including adverse host factors and resource constraints. We retrospectively reviewed records of children (age ≤ 18 years) who underwent MSD-HSCT for AML at our center from 2009 to 2019 to evaluate clinical outcome and its predictors using Cox proportional hazards model. There were 46 children (36 boys and 10 girls) with mean age 10.7 ± 4.8 years. Indication for HSCT was relapsed AML in CR2 (n = 37), primary refractory (n = 3), or relapsed refractory disease (n = 3); high-risk (n = 1) or secondary (n = 2) AML in CR1. Five-year EFS and OS were 33.3 ± 7.2% and 36.3 ± 7.6%, respectively. On multivariate analysis, CR1 duration less than 12 months, presence of active disease at transplant, and use of bone marrow stem cell graft were associated with poorer EFS and OS. There was one (2.2%) TRM, while disease relapse occurred in 20/40 patients who underwent HSCT in remission. Though the 5-year EFS and OS were inferior to results reported from high-income countries, relapse (and not TRM) was the major cause of treatment failure. A well-sustained CR1, achievement of disease remission, and use of peripheral blood allograft seem imperative to a successful transplant. Targeted therapy along with HSCT may be the option for those with early relapse.

A prospective study from south India to compare the severity of malaria caused by Plasmodium vivax, P. falciparum and dual infection.

BACKGROUND & OBJECTIVES: Traditionally, Plasmodium falciparum has been attributed to cause severe malaria, whereas P. vivax is considered to cause "benign" tertian malaria. Recently, there has been an increasing body of evidence challenging this conviction. However, the spectrum and degree of severity of the disease caused by P. vivax, as per World Health Organization (2012) remains unclear. Thus, in this prospective study, we aimed at comparing the severity of malaria caused by P. vivax, P. falciparum and dual infection. METHODS: Adult patients presenting to Christian Medical College, Vellore from October 2012 to September 2013 with microscopically confirmed malaria were included in the study. Their clinical and laboratory parameters were recorded and analyzed. Paired t-test and chi-square with 95% CI and post-hoc analyses using the Scheffι post-hoc criterion were used to assess the statistical significance at the level of α <0.05. RESULTS: In total, 131 cases of malaria were identified during the study period, comprising 83 cases of P. vivax, 35 cases of P. falciparum and 13 cases of mixed vivax and falciparum infections. The spectrum and degree of hematological, hepatic, renal, metabolic, central nervous system complications of vivax malaria was not different from that of falciparum group. Thrombocytopenia and hyperbilirubinemia were the most common laboratory abnormalities identified in all the groups. INTERPRETATION & CONCLUSION: This cross-sectional comparative study clearly demonstrates that clinical features, complications and case-fatality rates in vivax malaria can be as severe as in falciparum malaria. Hence, vivax malaria could not be considered benign; and appropriate preventive strategies along with antimalarial therapies should be adopted for control and elimination of this disease.

Differential effect of body mass index (BMI) on outcomes of patients treated with docetaxel in prostate cancer - An exploratory analysis.

OBJECTIVE: There are contradictory data on differential effect of docetaxel based on BMI in patients with breast and prostate cancer. We performed an exploratory analysis to determine if the benefit of docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC) is modified by BMI. METHODS: We performed a post hoc analysis of the data retrieved from the ENTHUSE M1C study. BMI (kg/m2) was categorized as: 18.5 to <25 as lean; 25 to <30 as overweight; and ≥30 as obese. Cox regression models were constructed to determine the impact of BMI on progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 466 patients were eligible for the current analysis. The median PFS was 7.3, 7.7 and 8.4 months (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.81 to 1.06; P = 0.261) in lean, overweight and obese patients. The median OS was 16.6, 20.1 and 21.4 months (HR, 0.75; 95% CI, 0.63 to 0.89; P = 0.002) for lean, overweight and obese patients. After adjusting for baseline and tumor characteristics, there was no association of BMI with PFS (overweight, HR, 0.89; 95% CI, 0.71 to 1.13; P = 0.353; obese, HR, 0.86; 95% CI, 0.66 to 1.13; P = 0.277) while overweight (HR, 0.68; 95% CI, 0.51 to 0.89; P = 0.006) and obese (HR, 0.59; 95% CI, 0.41 to 0.83; P = 0.003) patients had significantly better OS compared with lean patients. CONCLUSIONS: There was no effect of BMI on PFS in patients with mCRPC receiving docetaxel. Interestingly, overweight and obese patients had a longer OS compared with lean patients, which is in contradiction to a recent study in breast cancer; and warrants further investigation.

Neoadjuvant pertuzumab plus trastuzumab in combination with anthracycline- free chemotherapy regimen in patients with HER2 positive breast cancer-Real-world data from a single center in India.

BACKGROUND: Dual targeted therapy with chemotherapy is one of the therapeutic approaches as neoadjuvant treatment in HER2/neu positive breast cancer (BC). However, the safety and efficacy data of dual-targeted, chemotherapy regimen (docetaxel, carboplatin, trastuzumab, & pertuzumab [TCH-P] is limited from the Indian subcontinent. METHODS: This retrospective study aims to evaluate the efficacy and toxicity of neoadjuvant TCH-P regimen in early, locally advanced, and oligometastatic (OM) HER2-positive BC, at All India Institute of Medical Sciences, New Delhi, India, in between the period 2015-2020. Total 6 cycles of 3-weekly neoadjuvant chemotherapy (NACT) protocol containing docetaxel (75 mg/m2), carboplatin (AUC = 6), trastuzumab (8 mg/kg loading followed by 6 mg/kg) and pertuzumab (840 mg loading followed by 420 mg) were planned. Subcutaneous peg-filgrastim was prophylactically administered on day 2 of each cycle. The primary outcome was the pathological complete response (pCR), and secondary outcomes were clinical overall response rate (ORR), rate of breast conservation surgery (BCS) for patients for whom modified radical mastectomy (MRM) was planned and toxicity. RESULTS: Forty-five patients with a median age of 48 years (31-65) were included in this study. The TNM (AJCC-7th edition) stage distribution was stage II, 14 (31.1%); stage III, 29 (64.5%); and stage IV (OM), 2 (4.4%). Clinical node positivity disease was found in 26 (57.8%) cases. Nineteen (42.2%) patients had hormone-positive and 26 (57.8%) cases were premenopausal. The clinical ORR and CR were seen in 100% and 60% respectively. Overall pCR rate was observed in 25 (55.6%) patients (70% in stage II). BCS was performed in 23 (51.1%) cases. In 12 (26.6%) cases, planned MRM was changed to BCS following NACT. Grade 3 and 4 toxicities were diarrhea 7 cases, thrombocytopenia in 6, neutropenia in 4, febrile neutropenia in 1, and anaemia in 2 cases. Ten patients required dose modification. No patient had congestive heart failure or induction death. CONCLUSIONS: This is the first study of the non-anthracycline-based neoadjuvant protocol in HER2 positive BC from India. The TCH-P is an effective, safe, and well tolerated protocol with a pCR rate of 55.6% and 26.6% BCS conversion rate from planned MRM.

Is cerebrospinal fluid lactate useful in differentiating scrub typhus meningitis from aseptic, bacterial and tuberculous meningitis?

Scrub typhus is one of the most common causes of meningo-encephalitis in endemic areas of the Indian subcontinent. Numerous studies have established the reliability of cerebrospinal fluid lactate for differentiation of bacterial meningitis from aseptic meningitis. However, there are no reported data on the predictive value of cerebrospinal fluid lactate in scrub typhus meningitis. We thus conducted a cross-sectional study to examine the diagnostic accuracy of cerebrospinal fluid lactate in the differentiation of different causes of acute meningitis. Over two years, we studied 119 patients, with almost equal gender distribution, whose mean age was 43.58 (±18) years and their overall mean duration of fever was 11.7 (±21.0) days. Commonest clinical features overall were neck stiffness; values of cerebrospinal fluid lactate were lowest in aseptic meningitis, followed by scrub typhus, TB and bacterial meningitis. We conclude that cerebrospinal fluid lactate levels may be a useful adjunct to clinical features and laboratory investigations to differentiate between bacterial, viral, tubercular and scrub meningitis.

Impact of Cell-of-Origin on Outcome of Patients With Diffuse Large B-Cell Lymphoma Treated With Uniform R-CHOP Protocol: A Single-Center Retrospective Analysis From North India.

INTRODUCTION: There is a scarcity of data from India on the impact of cell of origin (COO) on outcomes of diffuse large B-cell lymphoma (DLBCL). This study was conducted to evaluate the impact of COO on outcomes of DLBCL patients treated with uniform rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (RCHOP) protocol. MATERIALS AND METHODS: This retrospective analysis included patients who received uniform RCHOP chemoimmunotherapy during the study period (2014-2020) at the Department of Medical Oncology at All India Institute of Medical Sciences (AIIMS), New Delhi, India. The patients were classified as germinal center B-cell like (GCB) or activated B-cell (ABC) type using the Hans classification. RESULTS: Four hundred seventeen patients with median age of 48 years (range, 18-76) and a male-female ratio of 2:1 were included in the analysis. B symptoms and bulky disease were seen in 42.9% and 35.5%. Extranodal involvement was seen in 50.8% of cases. ECOG performance status (0-2) was present in 65%, and 51% presented with advanced disease. GCB subtype was seen in 43%, and 47% were ABC type. Low- and intermediate-risk international prognostic index (IPI) score was seen in 76% of cases. The overall response rate to RCHOP was 85.8%, including a complete response rate of 74.8%. After a median follow-up of 30 months, the 3-year event-free survival (EFS) and overall survival (OS) were 80% and 88%, respectively. The presence of B symptoms and poor ECOG performance status (3-4) was associated with inferior CR rate. Low albumin (p < 0.001), age >60 years (p = 0.001), bulky disease (p < 0.001), and extranodal involvement (p = 0.001) were associated with inferior EFS, whereas a high IPI risk score was associated with an inferior OS (p < 0.001). EFS and OS were not significantly different between the GCB and ABC subtypes. Grade III/IV anemia, neutropenia, and thrombocytopenia were seen in 7.6%, 13.6%, and 2.7% of patients, respectively. Febrile neutropenia was seen in 8.9% of patients, and there were four treatment-related deaths. CONCLUSIONS: Cell of origin for DLBCL has no impact on CR, EFS, and OS if patients are appropriately treated with standard doses and frequency of RCHOP. RCHOP is well tolerated in our patients, and results are comparable with the Western data.

Good and sustained response to pembrolizumab and pazopanib in advanced undifferentiated pleomorphic sarcoma: a case report.

BACKGROUND: Conventional cytotoxic agents and pazopanib are approved for advanced soft tissue sarcomas but have low response rates and modest survival benefits. Recently, immune checkpoint inhibitors have shown clinically meaningful activity. The combination of pazopanib and immunotherapy has shown synergism in various other malignancies but has not been fully explored in advanced soft tissue sarcomas. CASE PRESENTATION: A 63 year old woman with metastatic undifferentiated pleomorphic sarcoma progressed after two lines of palliative combination chemotherapy-doxorubicin with olaratumab, and gemcitabine with docetaxel. In view of significant symptoms, she was treated with pazopanib in combination with pembrolizumab. She had remarkable radiological and clinical improvement, with a manageable toxicity profile and an ongoing response at ten months of therapy. CONCLUSIONS: Undifferentiated pleomorphic sarcoma is an immunologically active subtype of soft tissue sarcoma, which is particularly amenable to immune checkpoint inhibitors. Pazopanib with immune checkpoint inhibitors is a well-tolerated, yet hitherto underexplored combination that may offer significant clinical benefit in advanced sarcomas-this finding warrants further evaluation in clinical trials.

Palmar-plantar erythrodysesthesia: An uncommon adverse effect of everolimus.

Mammalian target of rapamycin inhibitor everolimus is a novel agent used in endocrine therapy resistant hormone receptor positive metastatic breast cancer. Its use has been associated with clinically significant improvement in the otherwise dismal outcomes of this subset of patients. Rash is a common adverse effect associated with everolimus. However, Hand-foot syndrome is an uncommon toxicity with the use of this drug. We report a case of Grade 3 hand-foot syndrome following institution of everolimus therapy and describe its successful management.

Acute liver failure in dengue haemorrhagic fever.

While dengue virus infection leads to a mild to moderate elevation of liver transaminases in almost all cases, hepatic failure rarely dominates the clinical picture in adults. We present a case of dengue haemorrhagic fever in a young adult, leading to the rare complication of acute liver failure. He was managed with supportive care and discharged after 5 days. At follow-up after 1 week, he had complete recovery and no residual symptoms.