Imatinib resistance mutation analysis: experience from a tertiary oncology center

Purpose: BCR-ABL kinase domain (KD) mutations account for 50-90% of the imatinib resistance observed in patients of CML-chronic phase. In CML-CP patients receiving imatinib first-line, mutation analysis is recommended in case of failure or suboptimal response using European LeukemiaNet (ELN) criteria. The present study was carried out at a tertiary oncology centre in south India to assess which mutations accounted for resistance to imatinib among patients of chronic phase CML being treated with imatinib.Methods: This was a retrospective observational study. We analyzed patients who were tested for imatinib resistance mutation in view of suboptimal responses while on imatinib or imatinib failure. Direct sequencing of the BCR-ABL transcript by the Sanger method was used for IRMA testing.Results: Out of 120 tested for IRMA, 36 (30%) had detectable mutations. We observed a higher frequency of mutations at amino acids T315, F359 and M351T.Conclusions: Among the patients who were tested for imatinib resistance mutation in view of suboptimal responses while on imatinib or imatinib failure, 30% had IRMA +ve mutations. The high incidence of imatinib resistance in present study may be attributed to the fact that our patients were given higher dose of imatinib (600 mg), if they failed to achieve CCyR at 12 months or CHR at 3 months as they could not afford second generation TKIs.</p

Imatinib resistance mutation analysis: experience from a tertiary oncology center

Purpose: BCR-ABL kinase domain (KD) mutations account for 50-90% of the imatinib resistance observed in patients of CML-chronic phase. In CML-CP patients receiving imatinib first-line, mutation analysis is recommended in case of failure or suboptimal response using European LeukemiaNet (ELN) criteria. The present study was carried out at a tertiary oncology centre in south India to assess which mutations accounted for resistance to imatinib among patients of chronic phase CML being treated with imatinib.Methods: This was a retrospective observational study. We analyzed patients who were tested for imatinib resistance mutation in view of suboptimal responses while on imatinib or imatinib failure. Direct sequencing of the BCR-ABL transcript by the Sanger method was used for IRMA testing.Results: Out of 120 tested for IRMA, 36 (30%) had detectable mutations. We observed a higher frequency of mutations at amino acids T315, F359 and M351T.Conclusions: Among the patients who were tested for imatinib resistance mutation in view of suboptimal responses while on imatinib or imatinib failure, 30% had IRMA +ve mutations. The high incidence of imatinib resistance in present study may be attributed to the fact that our patients were given higher dose of imatinib (600 mg), if they failed to achieve CCyR at 12 months or CHR at 3 months as they could not afford second generation TKIs

Methotrexate-induced chemical meningitis in patients with acute lymphoblastic leukemia/lymphoma

Background: Intrathecal methotrexate (ITMTX) is an important component in the treatment as well as prophylaxis of leukemia/lymphoma. ITMTX can cause chemical meningitis characterized by vomiting, headache, and fever lasting 2-5 days with spontaneous resolution of symptoms which differentiates this syndrome from bacterial meningitis. Objective: This prospective observational study was carried out to determine incidence of post-ITMTX syndrome in patients receiving prophylactic ITMTX as part of Berlin-Frankfurt-Munster (BFM) protocol. Materials and Methods: Patients aged 15-50 years receiving BFM 90 or BFM 95 protocol for acute lymphoblastic leukemia or lymphoblastic lymphoma were followed up for post-ITMTX syndrome, defined as vomiting, headache and fever between 38 o and 39 o C following ITMTX. Results: Thirty-three patients received a total of 297 courses of ITMTX. Of the 297 doses of ITMTX, 20 episodes (6.7%) of post-ITMTX syndrome were observed. The incidence of post-ITMTX syndrome was highest after the second dose of ITMTX (24%). The most common symptom of post-ITMTX syndrome was headache which was seen in 17 (85%) patients. Seventeen (85%) patients had vomiting, 10 (50%) patients had fever, and 4 (20%) patients had backache. Meningeal signs were present in 2 (10%) patients. Conclusions: Post-ITMTX syndrome is not uncommon in adult patients receiving prophylactic ITMTX for treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Patients develop a toxic syndrome closely mimicking acute bacterial meningitis but spontaneous recovery is seen without any neurological sequelae

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

Primary Diffuse large B-Cell lymphoma of testis: A single centre experience and review of literature

Background: Primary testicular lymphoma constitutes 1-2% of Non-Hodgkin′s lymphomas affecting elderly men >60 years of age. Most often it is a Diffuse large B cell lymphoma (DLBCL) and treatment involves multimodality approach involving surgery, chemotherapy and radiotherapy. Outcome remains poor in spite of aggressive therapy. Materials and Methods: We retrospectively reviewed 286 registered cases of DLBCL (aged >14 years) from 2007 to 2011 and found nine primary testicular involvement patients. These cases were analyzed for baseline clinical features, investigations, staging, treatment and outcome. Results: Median age was 58 (46-76) years. All patients presented with testicular swelling, two had the presence of B symptoms, and three with abdominal lymphadenopathy. Six had stage IE disease and three patients had stage IIE. All patients underwent orchiectomy. Eight patients received combination chemotherapy and six completed three or more cycles. Four achieved complete response, among these three relapsed after 32, 42, 70 months and one was lost to follow up. Two had a progressive disease, among these one died of disease and one alive with disease. Complete follow up was available from five patients and median survival was 36 months (11-78 months). Conclusion: Primary testicular DLBCL is uncommon, needs multimodality treatment and central nervous system prophylaxis to improve the survival. The outcome needs to be further investigated using biological approaches (Rituximab based) and/or more aggressive management

Epidemiology and outcomes of nasopharyngeal carcinoma: Experience from a regional cancer center in Southern India

Context: Nasopharyngeal carcinoma (NPC) is a rare head and neck cancer with significant geographical variation. There are limited data on epidemiology and outcomes of NPC reported from Southern India. Settings and Design: Retrospective analysis. Materials and Methods: We analyzed our hospital data between January 2005 and December 2011 with NPC and analyzed their demographic parameters and outcomes with therapy. Results: A total 143 cases of NPC were identified. Median age at presentation was 35 years with male predominance. Majority (84%) of the cases had the WHO Type 3 histology. Nodal metastasis at presentation was seen in 90% of the cases, majority being bilateral. Distant metastasis was seen in 16% of the cases, most commonly at bone, lung, and liver. Concurrent chemoradiation with weekly cisplatin was offered to 84.7% of localized disease while 80% of these also received adjuvant chemotherapy. Complete remission and partial remission were achieved in 66.1% and 15.2% of the cases, respectively. Weekly cisplatin was well tolerated with Grade 3–4 toxicity seen in 22% of cases. At a median follow-up of 20 months, 2-year progression-free survival and overall survival were 67.2% and 79.5%, respectively. Statistical Analysis Used: SPSS software version 20. Conclusion: NPC is a rare head and neck malignancy in Southern India, presenting with advanced stage and more propensity to distant metastasis. It has good outcomes to concurrent chemoradiation with weekly schedule of cisplatin being well-tolerated regime. Further prospective studies to test this schedule and other novel agents in this potentially curable malignancy are warranted

Prognostic significance of bone only metastasis compared to visceral metastasis in patients with carcinoma cervix treated with platinum-based chemotherapy

Context: Carcinoma cervix is a leading cause of cancer in Indian females where 15%–60% of the cases eventually metastasize. Bone only metastasis is rare, and data on its response and survival with systemic therapy as compared to other visceral metastasis are limited. Settings and Design: The study design was a retrospective analysis. Materials and Methods: We retrospectively analyzed our data between May 2013 and April 2015 to identify the cases of bone only metastasis and visceral metastasis and tried to analyze their outcomes with paclitaxel- and carboplatin-based chemotherapy and bisphosphonates (for bone metastasis only). Results: Totally, 12 cases with bone only metastasis (Group 1) and 43 cases with visceral metastasis (Group 2) were identified. Most common sites of bone metastasis were vertebrae (66.67%) and pelvis (25%) while that of visceral metastasis was liver (44.18%) and lung (34.88%). Only 33.33% and 34.88% of cases in Group 1 and Group 2, respectively, could complete all six cycles of chemotherapy. Overall, response rates were 41.67% and 30.32% in Group 1 and Group 2, respectively. Median progression-free survival and overall survival (OS) were 10 months and 14 months, respectively, in Group 1 as compared to 4 months and 9 months, respectively, in Group 2. The difference in survival was statistically significant. Statistical Analysis Used: It was carried out by SPSS software version 20. Conclusion: Bone only metastasis is a rare and distinct entity with favorable outcomes as compared to visceral metastasis. However, disease remains aggressive and poor OS emphasizing the need of further research