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Pediatric Blood & Cancer | 2010

Plasmablastic lymphoma of oral cavity in a HIV-negative child

Ajay Gogia; Sameer Bakhshi

To the Editor: Plasmablastic lymphoma (PBL) primarily involves the oral cavity, was first described in patients with human immunodeficiency virus (HIV) [1] and is associated with a short survival [2]. Epstein–Barr virus (EBV) is believed to be closely related to its pathogenesis [3]. PBL is characterized by an immunoblastic/plasmablastic morphology and plasma cell immunophenotype; its differentiation from other large B-cell non-Hodgkin lymphoma (NHL) or plasma cell neoplasms is often difficult. PBL is extremely rare in children. A 2-year-old female presented with a 2-month history of a rapidly increasing 10 × 4 cm mass arising from lower jaw and bulging in the floor of mouth. Computerized tomography (CT) scan of face showed a 8 cm midline soft tissue mass in lower jaw with mandibular destruction (Fig. 1A). Burkitt lymphoma and sarcoma were considered in the differential diagnosis. Chest and abdominal CT scan were normal. Complete blood counts and metabolic profile revealed no abnormalities; HIV was negative. Biopsy of the mass revealed a dense, diffuse infiltrate of large lymphocytes with plasmacytoid features (Fig. 1B); positive staining was observed for CD138 (Fig. 1C) and negative staining for leukocyte common antigen, CD20, CD3, CD10, Bcl-2, Bcl-6, desmin, actin, EMA, S-100, HMB45, Alk-1, HHV8, IgA, IgM, and cytokeratin. Monoclonal rearrangements of immunoglobulin heavy chain gene and clonal restriction of immunoglobulin light chain gene were not performed. Bone marrow biopsy and cerebrospinal fluid cytology did not reveal malignant cells. A final diagnosis of PBL of oral cavity in a HIV-negative patient was made and treatment was initiated as per BFM-90 protocol [4]. After the first cycle of chemotherapy and administration of 4Gy hemostatic radiotherapy, the mass decreased in size (Fig. 1D). She was given second cycle of chemotherapy, but patient died from Acinetobacter sepsis. The World Health Organization has classified PBL as B-NHL occurring predominantly in HIV-positive patients [5]. It accounts for 2.6% of cases of HIV-associated NHL. Of the reported 112 cases of HIV-positive PBL, 65 (58%) occurred within the oral cavity and remaining 47 cases (42%) occurred extraorally. All these cases were in adults except 2: one was a 7-year-old child with PBL in oral cavity [6] and another was an 11-year old with EBV-positive cutaneous PBL [7]. Among HIV-negative individuals, there is a reported immunosuppressed patient treated for Richter syndrome who had oral cavity PBL [8]. There are four other cases of PBL of oral cavity [9], nasal cavity [10], cervical lymph node [11], and stomach [12] in non-immunosuppressed and HIV-negative adult patients. In another series of six cases of PBL from Korea, all patients were HIV-negative and without underlying immunodeficiency; of these, there were two children with involvement of tonsils and meninges, respectively [13]. Pathologically, 5/6 cases revealed loss of B-cell antigens but with expression of CD138 or MUM1 substitution [13]. Our patient was HIV-negative with PBL of oral cavity and had loss of B-cell antigens with only expression of CD138. The case is being reported for its rarity in pediatric age group in a HIV-negative individual. Ajay Gogia, MD Sameer Bakhshi, MD* Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India


Asian Pacific Journal of Cancer Prevention | 2014

Taxane and Anthracycline Based Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer : Institutional Experience

Ajay Gogia; Vinod Raina; Suryanarayan Vishnu Deo; Nootan Kumar Shukla; Bidhu Kalyan Mohanti; Daya Nand Sharma

BACKGROUND The aim of this study was to assess the response rates (clinical and pathological ) with docetaxel and epirubicin combination chemotherapy and its effect on outcome. MATERIALS AND METHODS We retrospectively analysed locally advanced breast cancer (LABC) patients who received NACT from January 2008 to December 2012 in our tertiary care centre. LABC constituted 37% of all breast cancer cases and 120 patients fulfilled the eligibility criteria. The regimens used for NACT were, six cycles of DEC (docetaxel 75 mg/m2, epirubicin 75 mg/ m2, cyclophosphamide 500 mg/m2 on Day 1, 3 weekly) and a sequential regimen (4 cycles of FEC, 5-flurouracil 600 mg/m2, epirubicin 75 mg/m2, cyclophosphamide 600 mg/m2 followed by 4 cycles of docetaxel 85 mg/m2). RESULTS The median age was 47 years (range 23-72). Ninety six ( 80 %) had T4 disease and 90% had clinically palpable lymph nodes at diagnosis. The median size of primary tumor at presentation was 5.9 cm. Hormone receptor positivity was seen in 55% and HER2/neu positivity, in 25%. Triple negative breast cancers constituted 25 % of the cases. The overall clinical response rate ( complete or partial ) was 85% and pathological complete responses were obtained in 15%. Four cases defaulted, 5 patients died of treatment related toxicity and 15% developed febrile neutropenia on DEC. The median duration of follow up was 22 months. The median time to relapse was 20 months and the 3 year relapse free and overall survival rates were 50% and 70% respectively. CONCLUSIONS LABC constituted 37% of all breast cancer cases at our institute. With NACT, pCR was seen in 15% of the cases. Sequential chemotherapy was better tolerated than concurrent anthracyline and taxane chemotherapy with a similar pCR.


Clinical Lymphoma, Myeloma & Leukemia | 2014

Prognostic and Predictive Significance of Smudge Cell Percentage on Routine Blood Smear in Chronic Lymphocytic Leukemia

Ajay Gogia; Vinod Raina; Ritu Gupta; Smeeta Gajendra; Lalit Kumar; Atul Sharma; Rajive Kumar; Sreeniwas Vishnubhatla

INTRODUCTION/BACKGROUND Smudge cells are ruptured lymphocytes present on routine blood smears of chronic lymphocytic leukemia (CLL) patients. We evaluated prognostic and predictive significance of smudge cell percentage on a blood smear in CLL patients. MATERIALS AND METHODS We calculated smudge cell percentages (ratio of smudged to intact cells plus smudged lymphocytes) on archived blood smears of 222 untreated CLL patients registered at Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi over the past 12 years. RESULTS The male:female ratio was 3:1, and median age 60 (range, 28-90) years. Median absolute lymphocyte count was 42 × 10(9)/L. The median smudge cell percentage was 29.6% (range, 4%-79%). We found no correlation of proportion of smudge cells with age, sex, lymphocyte count, organomegaly, or response to therapy, although there was a significant correlation with the Rai stage at diagnosis. Median smudge cell percentage in stage 0 and I was 33% (range, 12%-79%), in stage II 31% (range, 12%-61%), and stage III and IV 21% (range, 4%-51%) (P < .001). Patients with ≤ 30% smudge cells had a shorter median progression-free period (PFP) of 30 months compared with patients who had more than 30% smudge cells (PFP, 45 months; P = .01). The 5-year survival rate was 51% for patients with 30% or fewer smudge cells, and it was 81% for patients with more than 30% smudge cells (P < .001) at a median follow-up of 3.5 years. CONCLUSION Simple and inexpensive detection of smudge cells on routine blood smears seems useful in predicting progression-free and overall survival in CLL patients and might be beneficial in countries with limited resources.


Indian Journal of Cancer | 2014

Triple-negative breast cancer: An institutional analysis.

Ajay Gogia; Vinod Raina; S. V. S. Deo; Nootan Kumar Shukla; Bidhu Kalyan Mohanti

AIM Triple-negative breast cancer (TNBC) is defined by the lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER 2)/neu. It has been identified as an independent poor prognostic factor for survival. The aim of this study was to compare the clinico-pathological characteristics and treatment outcomes of patients with TNBC and non-TNBC. MATERIALS AND METHODS We carried out an analysis of 706 patients with invasive breast cancer between January 2007 and December 2011 in whom information on the status of ER, PR, and HER2/neu were available. RESULTS One hundred and fifty-five patients (21.9%) patients had TNBC. Patients with TNBC had a significantly lower median age [46.2 vs. 49.8 years; P = 0.005, 95% confidence interval (CI): 0.98 to 2.38] and a higher proportion of high-grade tumors as compared to the non-TNBC group (43 vs. 24%; P < 0.0001). After a median follow-up of 30 months, the three-year relapse-free survival (RFS) was significantly lower in the TNBC group (76 vs. 64%; log rank P = 0.002). Three-year overall survival (OS) was lower in the TNBC group but not statistically significant. Age <49 years, higher nodal stage, and larger tumor size (>5 cm) were associated with poor outcome. CONCLUSION TNBC is significantly associated with younger age and high-grade tumors and constitutes 21.9% of all breast cancers in our institute. Triple negativity was a significantly poor prognostic factor for RFS but not OS.


Leukemia & Lymphoma | 2012

Assessment of 285 cases of chronic lymphocytic leukemia seen at single large tertiary center in Northern India

Ajay Gogia; Atul Sharma; Vinod Raina; Lalit Kumar; Sreenivas Vishnubhatla; Ritu Gupta; Rajive Kumar

Abstract Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder in the West accounting for about 30% of leukemias, but about 2–4% in India. There is no large series reported from India, and hence we decided to undertake this study. We assessed the clinicohematological profiles and treatment outcomes in 285 patients seen over 11 years at our center (median age 59 years, 209 males). Sixty-three patients (22%) were asymptomatic and diagnosed incidentally. The median total leukocyte count at presentation was 50 × 109/L. Rai stage distribution was: stage 0, 10%; stage I, 16%; stage II, 33%; stage III, 20%; and stage IV, 21%. Fifty percent of patients required treatment at presentation. Ninety-six patients received chlorambucil-based (overall response rate [ORR] 69%, complete remission [CR] 3%) and 27 patients received fludarabine-based (ORR 89%, CR 44%) chemotherapy. With a median follow-up of 2.9 years, the median overall survival (OS) and event-free survival (EFS) were 5.1 and 4.6 years, respectively. Fludarabine was more toxic, as half of the patients developed febrile neutropenia and various infections. The majority of patients presented with advanced stage disease. Fludarabine was less commonly used as first-line therapy. Advanced clinical stage (Rai III and IV) was associated with poor OS (hazard ratio [HR] 2.46, 95% confidence interval [CI] 1.19–5.11, p = 0.001) and EFS.


Pharmacological Research | 2017

Influence of MDR1 and CYP3A5 genetic polymorphisms on trough levels and therapeutic response of imatinib in newly diagnosed patients with chronic myeloid leukemia

Natarajan Harivenkatesh; Lalit Kumar; Sameer Bakhshi; Atul Sharma; Madhulika Kabra; Thirumurthy Velpandian; Ajay Gogia; Shivaram Shastri; Nihar Ranjan Biswas; Yogendra Kumar Gupta

&NA; Polymorphisms in genes coding for imatinib transporters and metabolizing enzymes may affect imatinib pharmacokinetics and clinical response. Aim of this study was to assess the influence of polymorphisms in MDR1 and CYP3A5 genes on imatinib trough levels, cytogenetic and molecular response in patients with CML. Newly diagnosed patients with chronic‐phase CML started on imatinib therapy were enrolled and followed up prospectively for 24 months. The following single nucleotide polymorphisms were genotyped; C1236T, C3435T, G2677T/A in MDR1 gene and A6986G in CYP3A5 gene. Genotyping was done using PCR‐RFLP method and validated by direct gene sequencing. Trough levels of imatinib were measured using LC–MS/MS. Cytogenetic response was assessed by conventional bone‐marrow cytogenetics. Molecular response was assessed by qRTPCR using international scale. A total of 173 patients were included, out of which 71 patients were imatinib responders, while 102 were non‐responders. Marked inter‐individual variability in trough levels of imatinib was seen. Patients with GG genotype for CYP3A5‐A6986G (P = 0.016) and TT genotype for MDR1‐C3435T (P = 0.013) polymorphisms had significantly higher trough levels of imatinib. Patients with AA genotype for CYP3A5‐A6986G [RR = 1.448, 95% CI (1.126, 1.860), P = 0.029] and CC genotype for MDR1‐C1236T [RR = 1.397, 95% CI (1.066, 1.831), P = 0.06] & MDR1‐C3435T [RR = 1.508, 95% CI (1.186, 1.917), P = 0.018] polymorphisms were at high risk for failure of imatinib therapy. Patients with CGC haplotype for MDR1 polymorphisms had significantly lower imatinib trough levels and were at a higher risk of imatinib failure [RR = 1.547, 95% CI (1.324, 1.808), P < 0.001]. GG vs. non‐GG genotype for CYP3A5‐A6986G [adjusted OR: 0.246; 95% CI (0.116, 0.519); P < 0.001] and TT vs. non‐TT genotype for MDR1‐C1236T [adjusted OR: 0.270; 95% CI (0.110, 0.659); P = 0.004] & MDR1‐C3435T [adjusted OR: 0.289; 95% CI (0.135, 0.615); P = 0.001] polymorphisms were independent factors predicting imatinib response in multivariate analysis. To conclude, MDR1 and CYP3A5 genetic polymorphisms significantly influence plasma trough levels and therapeutic response of imatinib in patients with CML. Genotyping of these polymorphisms could be of value to individualize the therapy and optimize the clinical outcomes. Graphical abstract Figure. No caption available.


European Journal of Haematology | 2014

Immunophenotypic analysis of T‐acute lymphoblastic leukemia. A CD5‐based ETP‐ALL perspective of non‐ETP T‐ALL

Anita Chopra; Sameer Bakhshi; Suman Kumar Pramanik; Ravindra Mohan Pandey; Saroj Singh; Smeeta Gajendra; Ajay Gogia; Jagan Chandramohan; Atul Sharma; Lalit Kumar; Rachna Seth; Sandeep Rai; Rajive Kumar

T‐cell antigens [CD5,CD1a,CD8] define early T‐cell precursor acute lymphoblastic leukemia (ETP‐ALL). To understand immature T‐ALL of which ETP‐ALL is part, we used these antigens to subcategorize non‐ETP T‐ALL for examining expression of myeloid/stem cell antigens (M/S) and clinical features. Using CD5 (+/−) to start categorization, we studied 69 routinely immunophenotyped patients with T‐ALL. CD5− was a homogenous (CD8,CD1a)− M/S+ ETP‐ALL group (n = 9). CD5+ cases were (CD8,CD1a)− pre‐T‐ALL (n = 22) or (CD8,CD1a)+ (n = 38) thymic/cortical T‐ALL; M/S+ 20/22 (90.91%) in former and 22/38 (57.89%) in latter (P = 0.007). ETP‐ and pre‐T‐ALL together (CD1a−,CD5−/+ immature T‐ALL group) were nearly always M/S+ (29/31; 93.55%). In multivariate analysis, only ETP‐ALL predicted poor overall survival (P = 0.02). We conclude (i) CD5 negativity in T‐ALL almost always means ETP‐ALL. CD1a and CD8 negativity, as much as CD5, marks immaturity in T‐ALL, and the CD5+/−/CD1a−/CD8− immature T‐ALL group needs further study to understand the biology of the T‐ALL–myeloid interface. (ii) ETP‐ALL patients may be pre‐T‐ALL if CD2+; CD2+, conversely, CD5−/CD1a−/CD8− pre‐T ALL patients are ETP‐ALL. (iii) Immunophenotypic workup of T‐ALL must not omit CD1a, CD5, CD8 and CD2, and positivity of antigens should preferably be defined as recommended for ETP‐ALL, so that this entity can be better evaluated in future studies of immature T‐ALL, a group to which ETP‐ALL belongs. (iv) ETP‐ALL has poor prognosis.


Journal of Pediatric Hematology Oncology | 2013

Systemic mastocytosis associated with childhood acute myeloid leukemia.

Ajay Gogia; Surender Kumar Sharawat; Rajive Kumar; Chitra Sarkar; Sameer Bakhshi

1. Devecioglu O, Anak S, Atay D, et al. Pediatric acute lymphoblastic leukemia complicated by secondary hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2009;53:491–499. 2. Taha R, Al Hijji I, El Omri H, et al. Two ocular infections during conventional chemotherapy in a patient with acute lymphoblastic leukemia: a case report. Case Rep Oncol. 2010;3:234–239. 3. Inde Y, Yamaguchi S, Kamoi S, et al. Transition of cytomegalovirus seropositivity in Japanese puerperal women. J Obstet Gynaecol Res. 2010;36:488–494. 4. Brandalise SR, Pinheiro VR, Aguiar SS, et al. Benefits of the intermittent use of 6-mercaptopurine and methotrexate in maintenance treatment for low-risk acute lymphoblastic leukemia in children: randomized trial from the Brazilian Childhood Cooperative Group-protocol ALL99. J Clin Oncol. 2010;28:1911–1918. 5. Henter JI, Horne A, Aricó M, et al. HLH2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48:124–131. 6. Wada K, Kubota N, Ito Y, et al. Simultaneous quantification of Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 DNA in samples from transplant recipients by multiplex real-time PCR assay. J Clin Microbiol. 2007;45:1426–1432. 7. Jabs DA, Martin BK, Forman MS, et al. Cytomegalovirus (CMV) bloodDNA load, CMV retinitis progression, and occurrence of resistant CMV in patients with CMV retinitis. J Infect Dis. 2005;192:640–649. Systemic Mastocytosis Associated With Childhood Acute Myeloid Leukemia


Graefes Archive for Clinical and Experimental Ophthalmology | 2013

Avoidance of exenteration in orbital sebaceous gland carcinoma with neoadjuvant chemotherapy

Ajay Gogia; Neelam Pushker; Seema Sen; Sameer Bakhshi

Dear Editor Sebaceous gland carcinoma (SGC), a rare eyelid tumor, comprises <1 % of all eyelid malignancies. The management of localized SGC (confined to eyelid) includes wide surgical excision, while advanced tumors (infiltrating orbital structures other than eyelid) may warrant orbital exenteration. Chemotherapy is not a standard modality in management of SGC, and the role of neoadjuvant chemotherapy (NACT) in SGC is not well-explored. We report a case of locally advanced SGC of upper eyelid which was treated with NACT, with the patient made amenable to organpreserving surgery instead of mutilating surgery. A 48-year-old male presented with mass over right upper eyelid extending to the lateral sclera without visual disturbance for 2 years (Fig. 1a) Computerized tomography (CT) scan of orbit revealed a 5-cm mass on right upper eyelid, with infiltration of lateral rectus muscle but no bony involvement (Fig. 1b and c). Incisional biopsy of the mass revealed SGC. Based on clinical and radiological evaluation, complete resectionwith sparing of globe was not feasible, and the patient was not willing to undergo an exenteration. In view of this, a trial of NACT with cisplatin 50 mg/m on days 1–2, and 5-flurouracil 750 mg/m on days 2–5 was administered to the patient every 3 weeks. After three cycles of chemotherapy, there was a reduction in size of tumor as observed clinically and on orbital CT (Fig. 1d and e). The patient then underwent conservative surgery with negative margins and sparing of the globe. Histopathology of tumor revealed poorly differentiated SGC; tumor cells were vacuolated with abundant pale, foamy cytoplasm and hyperchromatic nuclei (Fig. 1f). Postoperatively, patient received radiotherapy 60 Gy in 30 fractions to the orbit. Presently, he is 10 months after completion of treatment and is disease-free. The main aim of NACT is to downstage the tumor so as to achieve tumor-free margins and also to make the tumor more amenable to a less mutilating and possibly organsparing surgical excision. Its role is well-established in bone sarcomas [1]. Topical and intravenous mitomycin C has been used in adjuvant treatment for SGC of eyelid with pagetoid invasion and recurrent SGC of anal margin in Muir–Torre syndrome respectively, with minimal response [2, 3]. Husain et al. used palliative chemotherapy (docetaxel and carboplatin with bevacizumab) in a 50-year-old female with metastatic SGC, wherein partial response was observed [4]. Murthy et al. reported a 55-year-old female with recurrent SGC who underwent eyelid sparing orbital exenteration post three cycles of NACT [5]. Priyadarshini O et al. reported a 64-year-old male with good response to NACT in recurrent SGC with orbital invasion and regional lymphadenopathy [6]. The above patient is the first of his/her kind who presented initially with locally advanced SGC wherein use of NACT resulted in complete resection of tumor without exenteration. We used a combination of cisplatin and 5-fluorouracil, which is an extrapolation from the chemotherapy used in head and neck squamous cell carcinoma. The above report and the previous two reports suggest that in locally advanced SGC wherein exenteration has to be done, a trial of NACT may be considered so as to possibly down-stage the tumor and perhaps perform a less mutilating surgery. Further, the main concern in these patients is the high recurrence rate and the development of local lymph A. Gogia : S. Bakhshi (*) Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, , All India Institute of Medical Sciences, New Delhi-29, India e-mail: [email protected]


Leukemia & Lymphoma | 2012

Priapism as an initial presentation of chronic lymphocytic leukemia

Ajay Gogia; Atul Sharma; Vinod Raina; Ritu Gupta

Priapism is persistent, prolonged and painful erection of the penis that is present for longer than 6 h without accompanied sexual arousal [1]. Th e most frequent cause of priapism in adults is medication used for erectile dysfunction or impotence, and in children is hematological disorder such as sickle cell anemia [2,3]. Th e incidence of priapism is 1 – 3% in all adult leukemias; however, it is very unusual in patients with chronic lymphocytic leukemia (CLL). We report a case of a 55-year-old male patient with CLL whose initial presentation was priapism. Th e case was successfully managed with antileukemic therapy without surgery. A 55-year-old male presented with a 3-day history of painful penile erection. Th ere was no history of trauma, recent sexual intercourse or medications. His general examination revealed an erected and painful penis, liver palpable 8 cm

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Lalit Kumar

All India Institute of Medical Sciences

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Atul Sharma

All India Institute of Medical Sciences

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Sameer Bakhshi

All India Institute of Medical Sciences

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Vinod Raina

All India Institute of Medical Sciences

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Ritu Gupta

All India Institute of Medical Sciences

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Sandeep Mathur

All India Institute of Medical Sciences

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S. V. S. Deo

All India Institute of Medical Sciences

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Ranjit Kumar Sahoo

All India Institute of Medical Sciences

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Sanjay Thulkar

All India Institute of Medical Sciences

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Mehar Chand Sharma

All India Institute of Medical Sciences

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