Linu Jacob Abraham

Chronic myeloid leukemia in children and adolescents: results of treatment with imatinib mesylate

Abstract Chronic myeloid leukemia (CML) is a rare disease in children, accounting for 2–3% of leukemias in this age group. Few studies have reported on efficacy of imatinib in childhood CML. The purpose of this retrospective study was to determine the efficacy of imatinib in children. A total of 43 patients from age 7 years to 20 years with newly diagnosed CML received imatinib daily at 260 mg/m2. Response rates, survival and toxicity were evaluated. The median follow-up was 43 months. All patients achieved a complete hematological response. Twenty-five (58.1%) patients achieved a complete cytogenetic response and 18 (41.9%) achieved a major molecular response at any time during their follow-up period. Both overall survival and progression-free survival at 43 months’ median follow-up were 100%. Event-free survival was 92.8%. Imatinib was well tolerated. We conclude that imatinib is effective in children and adolescents with CML.

Anaplastic large cell lymphoma: A single institution experience from India

BACKGROUND Systemic anaplastic large cell lymphoma (ALCL) accounts for 2-8% of non-Hodgkins lymphoma in adults and 10-15% in children. While there is ample data in the world literature about the clinical features and outcome of this disease, prognosis in Indian patients is largely unknown. OBJECTIVE To study the clinical, pathologic profile and outcome ALCL. MATERIALS AND METHODS Fifty patients who had pathologically proven diagnosis of systemic ALCL at our institute from June 2003 to May 2011 were included for retrospective analysis. This included 30 cases of anaplastic lymphoma kinase+ (ALK+), ALCL and 20 cases of anaplastic lymphoma kinase- (ALK-), ALCL. The hospital protocol for treatment of these patients included CHOP chemotherapy regimen in >15 years of age and MCP842 protocol with vinblastine for 1 year in <15 years of age. Event free survival was noted. These outcomes were correlated with ALK status, International Prognostic Index (IPI) score, and stage at presentation. RESULTS At a median follow-up of 36 months (range: 6-72 months) ALK- ALCL had a poor outcome. The 3 year event free survival in pediatric ALCL was 66.7%. In adults, this was 60% ALK+ ALCL was 60% and 20% in ALK- ALCL. CONCLUSIONS Systemic ALCL is an aggressive disease. CD3 + positivity is commonly seen in ALK- ALCL and ALK+, epithelial membrane antigen + positivity is seen in ALK+ ALCL. ALK- ALCL, advanced stage III, IV and high IPI score were associated with poor prognosis. The demographic profile and outcome in our study was similar to the world literature. With new drugs like crizotinib and brentuximab vedotin the future looks very promising.

Locally advanced oral cavity squamous cell carcinoma: Barriers related to effective treatment

Background: Oral cavity cancer is a significant health problem in India. Majority of patients present with locally advanced disease requiring multimodality treatment. Compliance to recommended treatment is an important factor affecting outcome. Aims: The aim was to evaluate the outcome of locally advanced oral cavity cancer patients with regards to treatment adherence and to assess reasons of noncompliance. Materials and Methods: This was a prospective observational study. We included patients referred to Department of Medical Oncology for induction chemotherapy in view of locally advanced oral cavity cancer. Results: Only 15 (26%) patients completed planned treatment schedule. Their 1 year overall survival was 93%. The remaining 43 patients who received inadequate treatment had a dismal 21% 1 year overall survival. Illiteracy, poverty, long waiting list for surgery, prolonged delay for health scheme treatment plan approval and dissatisfaction with attitude of hospital staffs are major barriers related to effective treatment of these patients. Conclusions: A detailed discussion with patient and their relatives regarding recommended treatment, proper implementation of health schemes, increasing trained manpower to avoid long waiting list for surgery, provision of additional financial support for family member accompanying the patient and a sympathetic approach toward patients are needed to help these patients overcome the battle.

Lenalidomide in relapsed refractory non-Hodgkin's lymphoma: An Indian perspective.

BACKGROUND Lenalidomide an immunomodulatory agent has shown activity in relapsed/refractory lymphoma. This study was conducted to evaluate its efficacy and optimal dose in Indian patients with relapsed/refractory lymphoma who were unable or unwilling to undergo autologous hematopoietic stem cell transplant. MATERIALS AND METHODS Patients received oral lenalidomide at 20 mg on days 1-21 every 28 days until disease progression or unacceptable toxicity. RESULTS A total of 25 patients received lenalidomide at a starting dose of 20 mg. Majority of patients were diffuse large B-cell lymphoma (DLBCL). The overall response rate (ORR) was 48%, with 16% achieved complete remission (CR)/unconfirmed CR (CRu), 32% partial response (PR) and 16% stable disease (SD) Among patients with DLBCL the ORR was of 33.3%; with CR/CRu 20%, PR (13.3%), 20% had SD, progressive disease (PD) was seen in seven patients (46.6%). All follicular lymphoma patients responded to treatment, with CR in one patient and PR in other two. Among patients with mantle cell lymphoma, ORR was 75% with PR in (75%) and SD in 25%. One case of transformed lymphoma had a PR and peripheral T-cell lymphoma had no response to treatment. The median duration of response was 8.5 months, with a time to response of 3 months. Median progression free survival was not reached in responding patients. CONCLUSION Lenalidomide is an effective treatment option in relapsed refractory non hodgkins lymphoma.

Plasmablastic lymphoma: Does prognosis differ with HIV status and site of disease?

Background: Apart from its common occurrence in the oral cavity in HIV-positive patients, plasmablastic lymphoma (PBL) has also been described at extraoral sites and among immunocompetent individuals. There is sparse data quoting prognostication of PBL depending on the site of occurrence and HIV status of patients. Aims: The present study was carried out at a tertiary oncology center to address the issue whether PBLs occurring at oral and extraoral sites differ prognostically and whether HIV status of patient has any impact on prognosis. Materials and Methods: This was a retrospective observational study conducted at our center on consecutive patients diagnosed with PBL, from January 2008 to December 2012. Results: We had four patients with oral PBL; three male and one female. Sites of involvement were oral tongue and buccal mucosa. Two patients died within 6 months of diagnosis due to disease progression while on treatment. One patient was lost to follow-up after achieving complete remission (CR) after chemotherapy. Only one patient completed the prescribed schedule of chemotherapy and radiotherapy and is in CR with 33 months follow-up. There were four extraoral PBL patients; three female and one male. Extraoral sites were ileocaecal region, ovary, clavicle and rectum. Three patients died within 6 months due to progressive disease during treatment. Only one patient has completed chemotherapy and is in CR with18 months follow-up. Among all these eight oral and extraoral PBL patients, four were HIV positive. Two of them are in CR after treatment (18 months and 33 months follow-up). One patient died during treatment and one patient was lost to follow-up after being in CR. Unfortunately, none of the other four HIV-negative patients could survive for more than 6 months after diagnosis. Conclusion: Both oral and extraoral PBLs have aggressive clinical course and an overall unfavorable outcome. Prognosis of HIV-associated PBL seems to be better with addition of highly active antiretroviral therapy to chemotherapy. Further large sample studies are needed to confirm these results.

Colorectal cancer presenting as bone metastasis

Introduction: Bone metastasis is a rare site of metastasis, seen in only 3.7–11% of clinical cases. Isolated bone involvement has been reported very rarely in literature. Moreover, the patients who have bone metastasis at presentation are even rare. Objectives: To discuss the demographic characteristics, carcinoembryonic antigen (CEA) levels, pattern of bone involvement, and their correlation with survival in patients of colorectal cancer that have bone metastasis at the time of presentation. Materials and Methods: Retrospectively, tumor registry was analyzed for the cases of colorectal cancer presenting with bone metastasis between 2008 and 2013. Survival curves were generated by Kaplan–Meier method and analyzed using the log-rank test. Results: Ten such patients were identified (male:female = 7:3) of the total 410 patients. Median age was 41 years (22–50 years). All patients were < 50 years of age. Median CEA level was 147.5 (45–840). Three patients had bone-only metastasis. Most common metastatic site involved was liver (six patients) and lungs (three patients). The most common sites of bone metastasis were vertebra and pelvis (4 each). Chemotherapy was given in seven patients. Median overall survival was 5.5 months (2–36 months). It was higher in males, in those with bone-only involvement and those without liver involvement. Vertebral involvement, pelvic involvement, CEA levels, and chemotherapy did not show any significant survival implication. Conclusions: In this study, the patients of colorectal cancer presenting with bone metastasis were of male sex and younger age. The factors that were associated with reduced survival were extraosseous and liver involvement.

Ki-67 and subtype as prognostic and predictive markers of diffuse large B-Cell lymphoma

Quick Response Code: Abstract Introduction: Since patients with similar International Prognostic Index (IPI) scores have varied outcomes, molecular signatures including Ki‐67 overexpression have been studied to prognosticate diffuse large B‐cell lymphoma (DLBCL), which have shown varied outcomes. Objective: To correlate Ki‐67 expression with survival in two biologic subgroups of DLBCL. Materials and Methods: One hundred and twelve adults with DLBCL between 2008 and 2012 were identified. Ki‐67 overexpression was determined using immunohistochemistry. Results: A total of 112 patients of DLBCL were identified and included in the study. The median age was 54 years (18–78 years), with a male/female ratio of 1.8:1. Median survival was greater in patients with low Ki‐67 (n = 32) as compared to high Ki‐67 (n = 44) (32 m vs. 21.5 m, P = 0.033). In the germinal center B‐cell (GCB) subtype, low Ki‐67 had a better survival as compared to high Ki‐67 (35 m vs. 28 m, P = 0.044), whereas in the non‐GCB (NGCB) subtype, the results were same but statistically insignificant (26.5 m vs. 18 m, P = 0.7). In the high IPI arm, low Ki‐67 had a better survival (26.5 m vs. 17 m, P = 0.02), whereas in low IPI arm, the results were similar but statistically insignificant (39 m vs. 38 m, P = 0.837). Survival analysis was done in each treatment arm (CHOP and R‐CHOP) based on Ki‐67 expression (high or low) in GCB and NGCB arms. No statistically significant difference was noted in any of the four arms; 27.5 m versus 34 m (P = 0.738) in high versus low Ki‐67 in CHOP‐GCB arm, 15 m versus 22 m (P = 0.443) in high versus low Ki‐67 in CHOP‐NGCB arm, 27 m versus 44 m (P = 0.104) in high versus low Ki‐67 in R‐CHOP‐GCB arm, and 31 m versus 35 m (P = 0.861) in high versus low Ki‐67 in R‐CHOP‐NGCB arm. Conclusions: Ki‐67 although an indicator of poor outcome, its use to predict outcomes alone in the absence of study of expression of concomitant markers such as myc/BCL6 would cause a bias in results. Furthermore, its relevance in the rituximab era needs further validation.

Colorectal cancer presenting as ovarian metastasis

Background: Metastatic malignant tumors account for up to 7% of ovarian masses. Approximately 3.6% to 7.4% of patients with colon cancer have ovarian metastasis at the time of initial presentation, of which 45% are mistaken for primary ovarian tumors. Methods: Tumor registry was analyzed retrospectively for the cases of colorectal cancers diagnosed between 2008 and 2013. SPSS version 19 was used for statistical analysis. The survival curves were generated using the Kaplan–Meier method using log-rank test. Results: A total of twenty such patients were identified. Median age was 40 years (22–60 years). Seventeen (85%) patients were below 50 years. Most common symptom was abdominal pain (n = 11; 55). Carcinoembryonic antigen was elevated in 17 (85%) patients and CA-125 in 15 (75%) patients. Involvement of ovary was bilateral in almost half of the patients (n = 11; 55%). Median overall survival was 8 months. It was significantly higher in six patients with ovary-only metastasis as compared to extraovarian involvement, 24 versus 4 months, respectively (P = 0.001). Other factors such as extent of extraovarian metastasis, hepatic and peritoneal involvement, and administration of postoperative therapy did not have a significant survival implication. Conclusion: A female patient, especially in the premenopausal age, presenting with a pelvic mass should always be suspected for ovarian metastasis from colon cancer, and necessary evaluation should be carried out. Postoperative chemotherapy (5-fluorouracil-based or capecitabine-based) should be incorporated in suitable patients. However, further larger studies are required in this regard.

Gemcitabine-induced supraventricular tachycardia: A rare manifestation

Gemcitabine is a cytotoxic drug with superior toxicity profile and widely used in the management of various solid malignancies. The common side effects associated with gemcitabine are myelosuppression, diarrhea, and flu-like symptoms. Cardiac side effects due to gemcitabine are very rare. We present a case of an elderly female aged 69 years, diagnosed to have metastatic carcinoma gallbladder, and without any cardiac risk factors, who developed supraventricular tachycardia 3 days after gemcitabine infusion. We emphasize the need for careful and routine cardiac monitoring in an elderly patient who develops symptoms of tachyarrhythmia when on gemcitabine therapy.

Hairy cell leukemia - clinical profile and treatment outcome from a Tertiary Regional Cancer Institute in South India

Background: Hairy cell leukemia (HCL) is an indolent neoplasm of small mature B lymphoid cells. It is characterized by pancytopenia, splenomegaly, bone marrow fibrosis, and presence of atypical lymphoid cells with hairy projections in peripheral blood, bone marrow and spleen. HCL is potentially curable and treatment with purine analog cladribine induces complete remission (CR). Materials and Methods: This is a retrospective analysis of 10 HCL cases diagnosed in the Department of Medical Oncology at a Tertiary Regional Cancer Institute, South India, over 7 years. The clinical features, laboratory parameters, bone marrow findings, cytochemistry, immunophenotyping, and outcome with treatment were studied. Results: Among 8 cases of HCL who were treated with cladribine, 7 achieved remission and 1 succumbed to infection during course of treatment. Median overall survival in these 7 cases was 61 months. Conclusion: HCL is a chronic lymphoproliferative neoplasm with potentially curative treatment. Cladribine is treatment of choice and majority of patients achieve long-lasting CR. Upon relapse, these patients can be successfully salvaged with cladribine retreatment.