DLBCL Subtypes and Prognosis Based on Immunophenotyping

DLBCL is the most common type of NHL diagnosed in the world. It is a highly heterogeneous disease with variable prognosis and is generally managed with standard chemo-immunotherapy and its variations. Immunohistochemistry has been found to be useful method to both sub-classify and to predict prognosis of this disease. IHC utilises various CD markers like CD10, BCL2 and IRF4 to divide DLBCL into GCB and non-GCB subtype. In clinical trials, GCB subtype has been shown to have a better prognosis and a response to treatment when compared to non-GCB subtype. Double hit/double expressor is a newer variant of DLBCL that stains positive for MYC and BCL2 or BCL6 and has been found to do better with more aggressive forms of therapy. Significance of various other CD markers is still largely unknown and further research is required in this area to better elucidate their clinical application

Presynaptic BK channel localization is dependent on the hierarchical organization of alpha-catulin and dystrobrevin and fine-tuned by CaV2 calcium channels

BACKGROUND: Large conductance, calcium-activated BK channels regulate many important physiological processes, including smooth muscle excitation, hormone release and synaptic transmission. The biological roles of these channels hinge on their unique ability to respond synergistically to both voltage and cytosolic calcium elevations. Because calcium influx is meticulously regulated both spatially and temporally, the localization of BK channels near calcium channels is critical for their proper function. However, the mechanism underlying BK channel localization near calcium channels is not fully understood. RESULTS: We show here that in C. elegans the localization of SLO-1/BK channels to presynaptic terminals, where UNC-2/CaV2 calcium channels regulate neurotransmitter release, is controlled by the hierarchical organization of CTN-1/alpha-catulin and DYB-1/dystrobrevin, two proteins that interact with cortical cytoskeletal proteins. CTN-1 organizes a macromolecular SLO-1 channel complex at presynaptic terminals by direct physical interaction. DYB-1 contributes to the maintenance or stabilization of the complex at presynaptic terminals by interacting with CTN-1. We also show that SLO-1 channels are functionally coupled with UNC-2 calcium channels, and that normal localization of SLO-1 to presynaptic terminals requires UNC-2. In the absence of UNC-2, SLO-1 clusters lose the localization specificity, thus accumulating inside and outside of presynaptic terminals. Moreover, CTN-1 is also similarly localized in unc-2 mutants, consistent with the direct interaction between CTN-1 and SLO-1. However, localization of UNC-2 at the presynaptic terminals is not dependent on either CTN-1 or SLO-1. Taken together, our data strongly suggest that the absence of UNC-2 indirectly influences SLO-1 localization via the reorganization of cytoskeletal proteins. CONCLUSION: CTN-1 and DYB-1, which interact with cortical cytoskeletal proteins, are required for the presynaptic punctate localization of SLO-1 in a hierarchical manner. In addition, UNC-2 calcium channels indirectly control the fidelity of SLO-1 puncta localization at presynaptic terminals. We suggest that the absence of UNC-2 leads to the reorganization of the cytoskeletal structure that includes CTN-1, which in turn influences SLO-1 puncta localization

Clinicopathological Profile of Pure Neuroendocrine Neoplasms of the Esophagus: A South Indian Center Experience

Purpose. Neuroendocrine neoplasms (NENs) of the esophagus are very uncommon with only a few studies published worldwide. Studies on clinical profile, management, and outcomes are very uncommon. Methods. We report the largest single institution retrospective review of 43 patients of pure esophageal NENs out of our registry of gastrointestinal neuroendocrine tumors treated between 2005 and 2014. Data on the incidence, tumor location, clinical symptoms, stage at presentation, grading, treatment protocol, and treatment outcomes was collected and analyzed. Results. Among 1293 cases of esophageal cancers, pure esophageal NENs were diagnosed in 43 cases. The mean patient age was 55.8 years. The male : female ratio was 1.5 : 1. 81.4% of the tumors were located in the lower third of the esophagus and gastroesophageal junction. Neuroendocrine carcinomas (NEC; G3) accounted for the vast majority of NENs (83.7%). 53.5% patients were Stage IV and 32.5% were Stage III at presentation. The combined median survival of stages II and III patients was 18.25 months, with treatment. The median survival of treated patients with metastatic disease was 6.5 months. Conclusion. Esophageal NENs most commonly were neuroendocrine carcinomas, presented in metastatic stage and were associated with poor prognosis. Grade 2 (G2) tumors had better outcomes than NEC (G3). In nonmetastatic disease, presence of lymph node metastasis and unresectable disease had poorer outcomes

Head and Neck Lymphomas: Tip of the Iceberg?

ABSTRACT Background: Lymphomas comprise around 5% of all head and neck neoplasms and is the second most common extra nodal non hodgkin's lymphoma (NHL). However there is sporadic data on this entity from the subcontinent and hence we undertook this study. Methodology: This retrospective observational study was conducted at a tertiary care oncology center in India on diagnosed cases of NHL between January 2007 and December 2013. All patients were diagnosed based on histopathology and immunohistochemistry. Staging work up was done in all patients. Patients were considered as primary Head and Neck lymphomas if there was head and neck as the predominant site with or without regional lymph node involvement. Results: A total of 39 patients were studied. The age at presentation ranged from 29 to 78 years. The most common site of presentation was oral cavity (26%; n=10), followed by parotid and thyroid (18% each; n=7), eye (12%, n=5), maxilla (8%; n=3), paranasal sinuses (8%; n-=3) cheek (8%, n=3), and nasal cavity (2%, n=1). 41% (n=16) cases were in stage I, 43% (n=17) in stage II, 3% (n=1) in stage III, and 13% (n=5) were in stage IV. Most common histology was DLBCL (71%; n=28), followed by plasmablastic (10%; n=4), marginal zone (8%, n=3), mantle cell (3%; n=1), follicular lymphomas (5%; n=2), and NK/T cell lymphoma (3%; n=1). Most of the patients were of low risk (67%; n=26), followed by intermediate (23%; n=9), and high risk (10%; n=4). Patients were treated with anthracycline based chemotherapy +/-radiotherapy. In this study, stage I and stage II patients had a better prognosis and overall survival, median OS 28 months and 11 months, respectively. In stage III and IV, it was 7 and 3 months, respectively. According to site, the best median overall survival was seen with parotid (27 m), paranasal sinus (26m), and oral cavity (23 m), followed by thyroid (18 m) nasal cavity (17 m), maxilla (11 m), eye (8 m), and cheek (7 m)

Aflibercept as a second-line therapy in metastatic colorectal cancer: A limited Indian experience

Introduction: Aflibercept in combination with FOLFIRI has been shown to improve overall survival in the pivotal VELOUR study. Aflibercept has not yet been marketed in India. Sanofi has made available this drug for Indian patients under a program called Named Patient Access Program (NPP). We present a limited clinical experience with the use of aflibercept at our center. Materials and Methods: We analyzed the data of the patients who received aflibercept under NPP. Aflibercept was given in combination with FOLFIRI as second-line for patients who progressed on oxaliplatin based therapy. Aflibercept was given at 4 mg/kg intravenous (IV) every 15 days. Chemotoxicities were assessed as per CTCAE. Response evaluation was done every four cycles. Results: Five patients were enrolled. The median age was 34 years. The median number of aflibercept cycles administered was 12. Common grade 2/3 toxicities were mucositis, diarrhea, neutropenia thrombocytopenia, and hypertension seen in three (60%), three (60%), two (40%), two (40%), and one patient respectively. After four cycles, the response was assessed as: One complete remission (CR), three partial remissions (PR), and one progressive disease (PD). Three patients completed 12 cycles of chemotherapy and aflibercept. At the end of 12 cycles, one patient still in CR and two patients were in PR. Four patients were alive till date. Conclusion: As we had very less number of patients, it was very difficult to compare it with VELOUR data. It is one of option as second-line in metastatic colorectal cancer (mCRC) who progressed on oxaliplatin chemotherapy. Mucositis, diarrhea, and hematological toxicity were the most common toxicity in our patient

Outcome of young adults with chronic myeloid leukemia treated with upfront imatinib: A single institutional experience

Background: Young adult patients with malignancy are a distinct group of the population. In addition to their ailment, psychosocial issues including fertility issues should be addressed. Chronic myeloid leukemia (CML) is a disease of the elderly population. The outcome with imatinib in young population is not known. Aim: To study the clinical profile and outcome of young patients newly diagnosed with CML on imatinib and to compare with those of elderly population in a tertiary cancer center. Materials and Methods: 369 patients with newly diagnosed CML were included in the study. Patients belonging to the age group of 20–39 years were used as the study group and those who were more than 40 years were used as controls. Both the groups were treated with imatinib. They were followed up for a period of 3 years. Milestones in terms of achieving hematological, cytogenetic and molecular responses were noted. Toxicity profile of the imatinib and the compliance of the patients were also recorded. Results: A total of 173 patients were in the study group and 196 patients were in the control group. Rates of achieving a hematological response at 3 months (94.2% vs. 93%), the complete cytogenetic response at 12 months (68% vs. 61%) and major molecular response at 18 months (72.2% vs. 67.6%) were among the study group and control group, respectively. None of them were statistically significant. Three years event free survival among the study group and the control group was (85.2% vs. 83.4%) respectively; however, the difference did not reach statistical significant value. Conclusion: This study shows that the outcome of young adults with CML is comparable to those of the elderly people with imatinib both in terms of response rates and survival

Plasmablastic lymphoma in immunocompetent and in immunocompromised patients: Experience at a regional cancer centre in India

Introduction: Plasmablastic lymphoma (PBL) is a rare lymphoma associated with immunosuppression. It is strongly associated with immunosuppression (human immunodeficiency virus [HIV]) and often occurs within the oral cavity. PBL is also seen in patients receiving immunosuppressive therapy; however, despite its predisposition for the immunocompromised patients, PBL has been diagnosed in immunocompetent patients. Aim: This study aims to prognostic factors and outcome of PBL in immunocompromised and in immunocompetent patients. Materials and Methods: We conducted a retrospective study at our institute from the year 2008 to 2015. Results: A total of 13 patients (8 males and 5 females) with PBL were identified. Eight patients (61.5%) had extraoral PBL (median age 30.2 years) and 5 patients (38.5%) had oral PBL (median age 44 years). Most common extraoral site was gastrointestinal tract. Eight (61.5%) out of 13 patients were HIV positive. More than 50% of patients had Ann Arbor Stage III or IV. All the cases were CD20 negative and CD138 positive. Seven out of 13 patients had Ki-67 more than 80%. Nine patients received cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. Three patients were on best supportive care due to poor performance status (PS). One patient received intensive chemotherapy with CODOX-M/IVAC. The median overall survival was 9 months in HIV-positive patients and 6 months in HIV-negative patients. The prognosis was worse in patients with Ki-67 of> 80%. Statistical Analysis: Survival curves were generated using the Kaplan–Meier method and analyzed using log-rank test and Fisher's t-test. Conclusion: The present study confirms that PBL in both HIV-positive and in HIV-negative patients has an overall unfavorable outcome. The most important prognostic factors are stage, ki-67, and the Eastern Cooperative Oncology Group PS of the patient at the time of presentation

Plasma Epstein Barr viral load in adult-onset Hodgkin lymphoma in South India

Objective/background: Epstein Barr Virus (EBV) DNA load is increasingly being used as a noninvasive biomarker for detecting EBV association in lymphomas. Since there is a need of data from India, we undertook to prospectively evaluate plasma EBV DNA load as a marker of EBV association in newly diagnosed adult-onset Hodgkin lymphoma (HL). Methods: EBV DNA was quantified using real-time polymerase chain reaction. In a subset of patients, an assay was validated qualitatively with EBV latent membrane protein-1 (LMP1) immunohistochemistry (IHC). Wherever possible, follow-up plasma samples post three cycles of chemotherapy were obtained. Results: Over a period of 10 months, 33 newly diagnosed adult-onset HL were enrolled in the study. Pretherapy plasma EBV DNA was detectable in ∼49% (16/33) patients (viral loads range, 1.0–51.2 × 103 copies/mL) and undetectable in 30 voluntary blood donors. LMP1 IHC was positive in 56% of cases tested (14/25). Sensitivity and specificity of plasma EBV DNA with respect to LMP1 IHC were 86% and 100%, respectively. Of the eight patients in whom follow-up plasma was available, in five EBV baseline-positive patients EBV load reverted to negative postchemotherapy and corroborated with clinical remission. Conclusion: Plasma EBV DNA load estimation may be useful in detecting EBV-association and possibly monitoring the response to therapy in EBV-related HL especially in our country where EBV association of HL is higher than in developed nations. Keywords: Epstein–Barr Virus, Hodgkin lymphoma, LMP1 immunohistochemistry, Real-time PCR, Viral loa

Adult Philadelphia-Positive Acute Lymphoblastic Leukemia: A Single-Institution Experience in Limited-Resource Setting

Abstract L. K. Rajeev Background Adult Philadelphia-positive (Ph + ) acute lymphoblastic leukemia (ALL) is a distinct entity with poor prognosis. Treatment with tyrosine kinase inhibitors improved responses but still with poor outcomes. We evaluated treatment outcomes in these patients treated in limited-resource settings in the absence of availability of allogeneic stem cell transplantation (ASCT). Materials and Methods We studied case record files of the adult patients diagnosed with Ph+ ALL. Results A total of 18 patients were evaluated retrospectively. The median age of presentation was 28 years. Male-to-female ratio was 1:1. Patients presented with fever and fatigue. Six patients (33.33%) presented with cervical lymphadenopathy. Clinical splenomegaly was present in 16 (88.88%) patients on palpation, whereas on ultrasonographic evaluation, all 18 patients had splenomegaly. The median size of the spleen was 15 cm. Hepatomegaly was seen in 5 (27%) patients. All 18 patients had anemia at the time of presentation. Leukocytosis was seen in 17 (94.44%) patients, whereas 1 (5.56%) patient presented with low total leukocyte count. The median platelet count at the time of presentation was 30,000/mm.3 On peripheral smear, median number of blast cells was 55%, and on bone marrow aspiration samples, median blast percentage seen was 70%. Conventional cytogenetics was done in all the patients on bone marrow aspiration samples. Ten patients (55.55%) had t(9;22) – Ph chromosome. One patient (5.56%) on cytogenetics showed double Ph chromosome. The median value of breakpoint cluster region-ABL1 transcript in IS% was 13%. Seventeen (94.44%) received ALL protocol (BFM95) along with tyrosine kinase inhibitor (imatinib). One (5.56%) patient refused aggressive cytotoxic chemotherapy. No patient underwent ASCT. The median duration of follow-up was 7.5 months, ranging from 3 to 16 months. Median overall survival (OS) was 7.5 months and 2-year OS was 33.33%. Conclusion Poor prognosis of this disease, especially in the absence of ASCT, remains a major challenge in the treatment