Publications by authors named "Sripad Banavali"

11 Publications

  • Page 1 of 1

A novel case of intrachromosomal amplification and insertion of RUNX1 on derivative chromosome 2 in pediatric AML.

Cancer Genet 2021 Jun 15;254-255:65-69. Epub 2021 Feb 15.

Department of Pediatric Oncology, Tata Memorial Hospital, Dr. E. Borges Road, Parel. Mumbai 400012, India; Cancer Cytogenetics Department, Room No. 6, CCE building, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Sector-22, Kharghar, Navi Mumbai 410210 India. Electronic address:

Intrachromosomal amplification of RUNX1 gene on chromosome 21 (iAMP21) is a rare occurrence in acute myeloid leukemia (AML). Herein, we describe a case of AML with amplification of RUNX1 and its insertion on chromosome 2 detected by conventional karyotyping and confirmed by metaphase FISH. A six-year-old female was diagnosed as acute myeloid leukemia with monocytic differentiation. The patient's bone marrow revealed 74% blasts which were MPO negative. Conventional karyotyping revealed a complex karyotype, with rearrangements in chromosomes 1, 2, 7, 8 and hsr(21). FISH on interphase cells with LSI RUNX1-RUNX1T1 dual colour dual fusion translocation probe showed 6-7 copies of RUNX1 signal. Metaphase FISH with LSI RUNX1-RUNX1T1 probe confirmed amplification of RUNX1 and insertion of amplified RUNX1 sequences on long arm of chromosome 2. Induction chemotherapy was initiated, however, the patient died within one month of diagnosis suggesting poor outcome associated with this novel finding. Insertion of amplified RUNX1 on another chromosome has not yet been reported so far.
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http://dx.doi.org/10.1016/j.cancergen.2021.02.004DOI Listing
June 2021

Cytogenetic profile and outcome of a pediatric acute promyelocytic leukemia patient presenting with isolated isochromosome 17q in absence of RARA rearrangement.

Blood Cells Mol Dis 2021 May 3;88:102443. Epub 2020 May 3.

Department of Pediatric Oncology, Tata Memorial Hospital, Dr. E. Borges Road, Parel, Mumbai 400012, India; Homi Bhabha National Institute (HBNI), Anushaktinagar, Mumbai 400094, India.

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http://dx.doi.org/10.1016/j.bcmd.2020.102443DOI Listing
May 2021

Retrospective Analysis of Outcomes of Patients with Relapsed, Refractory and Metastatic Sarcomas who have received Metronomic Chemotherapy.

Gulf J Oncolog 2019 May;1(30):22-28

Tata Memorial Hospital, Department Of medical Oncology, Mumbai, India.

Introduction: Paediatric soft tissue sarcoma treatments and outcomes have improved significantly in the last few decades. However, a significant number of patients still succumb to the disease. In low-middle income countries there are dual problems of advanced disease at presentation and financial burden leading to poor compliance to therapy. Hence, we designed a low-cost oral metronomic chemotherapy protocol for these patients and studied the responses and toxicities to therapy in a tertiary referral hospital.

Patients And Methods: This is retrospective, single institutional, observational study. We retrospectively reviewed data of patients with relapsed, refractory or metastatic soft tissue sarcoma (STS) [ Ewing Sarcoma (ES); Rhabdomyosarcoma (RMS) or other STS] who were treated with the metronomic protocol of oral Tamoxifen, Etoposide and Cyclophosphamide (TEC) during the period April 1998 to September 2013, at the Tata Memorial Hospital, Parel, Mumbai. Patients with ES and RMS were primarily treated on our Institutional protocols. The patients included in the analysis were those who had relapsed after the primary protocols and then treated with metronomic TEC protocol; or those with primary refractory or metastatic disease (RMS, ES) and received metronomic TEC therapy.

Results: 49 patients were enrolled. Among the 49 patients, 32 were diagnosed ES, 13 RMS and 4 other STS. For the whole cohort response rates (RR) were 59% and clinical benefit rate (CBR) was 79%. Patients in the study were grouped into the following subgroups. Systemic recurrent/relapsed disease (N=24), metastatic disease at presentation (N=15) and local disease (refractory/recurrent) (N=10). None of the patients required blood or platelet support or admission for supportive care. The PFS for the above groups were 16.8 months, 12.5 months and 126.68 months respectively. This compares favorably with other historical cohorts in a similar setting.

Conclusions: This study provides a preliminary evidence efficacy and tolerability of metronomic chemotherapy in poor risk ES and RMS. It also demonstrates that with this low-cost low risk treatment few patients could go into long term remissions despite high disease burden.
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May 2019

Osteosarcoma journey over two decades in India: Small steps, big changes.

Pediatr Blood Cancer 2019 09 17;66(9):e27877. Epub 2019 Jun 17.

Department of Medical Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India.

Background: The management of osteosarcoma is challenging especially in lower-income and middle-income countries, and there is an unmet need to evolve efficient and sustainable chemotherapy regimens.

Methods: We compared the outcomes in nonmetastatic osteosarcoma patients treated with three sequential non-high-dose methotrexate-based combination chemotherapy protocols at a single tertiary care center over two decades. The first protocol, OGS-99, involved dose-intense, alternating dyads of three drugs: doxorubicin (Dox), cisplatin (CDDP), and ifosfamide (Ifo). The second protocol, OGS-99 enhanced, included OGS-99 drugs with etoposide and enhanced supportive care. The OGS-12 protocol involved dose-dense administration of eight sequential dyads of Dox, CDDP and Ifo, universal growth factor prophylaxis and targeted nutritional support. Event-free survival (EFS), overall survival (OS), and toxicity were reported using a retrospective chart review in the OGS-99 and OGS-99 enhanced protocols and prospectively in the OGS-12 protocol.

Results: A total of 41, 94, and 385 treatment-naïve, consecutive, nonmetastatic patients with extremity osteosarcoma were treated with the OGS-99 (2000-2005), OGS-99 enhanced (2010), and OGS-12 (2011-2016), respectively. At a median follow-up of 19, 86, and 39 months, the five-year EFS rates were 38%, 50%, and 62% in the OGS-99, OGS-99 enhanced, and OGS-12, respectively. The corresponding rates of five-year OS were nonevaluable, 60% and 77%, respectively, with acceptable rates of grade 3-4 toxicities: febrile neutropenia (40%), thrombocytopenia (36%), anemia (51%), and 1% deaths related to toxicity.

Conclusions: Sequential selection of an intelligent, dose-dense chemotherapy regimen together with enhanced supportive care resulted in marked improvement in outcomes of nonmetastatic osteosarcoma and this "small steps-big changes" model deserves wider recognition and usage.
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http://dx.doi.org/10.1002/pbc.27877DOI Listing
September 2019

Actionable Activating Oncogenic ERBB2/HER2 Transmembrane and Juxtamembrane Domain Mutations.

Cancer Cell 2018 11 25;34(5):792-806.e5. Epub 2018 Oct 25.

Molecular Biology Department, Genentech Inc., South San Francisco, CA 94080, USA. Electronic address:

Deregulated HER2 is a target of many approved cancer drugs. We analyzed 111,176 patient tumors and identified recurrent mutations in HER2 transmembrane domain (TMD) and juxtamembrane domain (JMD) that include G660D, R678Q, E693K, and Q709L. Using a saturation mutagenesis screen and testing of patient-derived mutations we found several activating TMD and JMD mutations. Structural modeling and analysis showed that the TMD/JMD mutations function by improving the active dimer interface or stabilizing an activating conformation. Further, we found that HER2 G660D employed asymmetric kinase dimerization for activation and signaling. Importantly, anti-HER2 antibodies and small-molecule kinase inhibitors blocked the activity of TMD/JMD mutants. Consistent with this, a G660D germline mutant lung cancer patient showed remarkable clinical response to HER2 blockade.
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http://dx.doi.org/10.1016/j.ccell.2018.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248889PMC
November 2018

Treatment of Langerhans cell histiocytosis with a modified risk-adapted protocol-experience from a tertiary cancer institute in India.

Pediatr Blood Cancer 2018 08 7;65(8):e27028. Epub 2018 Mar 7.

Pediatric Hematolymphoid Disease Management Group, Department of Medical Oncology, Tata Memorial Center, Mumbai, India.

Background: Involvement of risk-organs (RO+) in Langerhans cell histiocytosis (LCH) and inadequate early response identifies patients at high risk for relapse and mortality requiring intensive salvage therapy including stem cell transplant, adding cost and toxicity. To mitigate this, we used a standard induction, augmented with metronomic etoposide, and prolonged maintenance-similarly augmented for RO+, and retrospectively analyzed its impact.

Procedure: LCH patients from 2009 through 2014 were included. Patients received standard vinblastine and prednisolone therapy weekly till week 25 for RO+. Single site (SS) and multisystem (MS) without risk organ involvement (RO-) received 3-weekly pulses from week 13 till week 25. Maintenance was 3-weekly vinblastine and 5-day prednisolone pulses, daily 6-mercaptopurine (60 mg/m ) and weekly methotrexate (15 mg/m ) for 18 and 9 months for RO+ and MSRO-, respectively. RO+ also received oral etoposide (50 mg/m ) for 21 of every 28-day cycle for the first year.

Results: Fifty consecutive patients were analyzed. Median age was 36 months (4-189 months). SS, MSRO-, and RO+ were 29 (58%), 12 (24%), and nine (18%), respectively. Four were lost to follow-up and excluded from further evaluation. On response evaluation at week 6, 24 (52%) had no active disease (NAD), 17 (37%) had AD-better (where AD is active disease), and one (2%) had AD-worse. In RO+, eight (66.6%) had AD-better and three (25%) had NAD. Forty-five patients had NAD by week 12. Three patients relapsed. With median follow-up of 39 months (8-84), 5-year event free survival was 85.6% (RO- and SS), and 100% for RO+. One patient's death in remission from unrelated causes resulted in overall survival of 97%.

Conclusions: RO+LCH receiving oral etoposide augmented induction and maintenance had early and durable responses. Prolonging maintenance lowered reactivation rates in RO+ and RO-LCH, resulting in excellent survival.
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http://dx.doi.org/10.1002/pbc.27028DOI Listing
August 2018

Epidermal Growth Factor Receptor Mutational Status and Brain Metastases in Non-Small-Cell Lung Cancer.

J Glob Oncol 2017 Jun 20;3(3):208-217. Epub 2016 Jul 20.

, , , , , , and , University of Nebraska Medical Center; , Veteran's Affairs Nebraska-Western Iowa Health Care System, Omaha, NE; and , , , , , , , and , Tata Memorial Hospital, Mumbai, India.

Introduction: Epidermal growth factor receptor () mutations in non-small-cell lung cancers (NSCLC) may be more common in patients with brain metastases. Previous studies, however, did not adjust for effects of confounding variables.

Methods: This retrospective study included 1,522 consecutive patients with NSCLC, whose tumors were diagnosed and tested for mutations at the University of Nebraska Medical Center (Omaha, NE) and Tata Memorial Hospital (Mumbai, India). Multivariate logistic regression was used to identify any association between status and clinical factors.

Results: EGFR mutations were more common in females than males (38.7% 24.8%), Asians than whites (31.3% 13.4%), nonsmokers than smokers (40.2% 14.6%), alcohol nonconsumers than users (32.4% 15.8%), adenocarcinoma than other histology types (32.7% 10.3%), and patients with brain metastases than extracranial or no metastases (39.4% 29.8% 15.1%; < .001 for all comparisons). There was a higher likelihood of an mutation among patients with brain metastases (odds ratio, 1.8; < .001). The median overall survival (OS) was 19.8 months. Patients with brain metastases had a shorter median OS (15 20.6 months; = .02). However, in the cohort of mutation-positive patients, there was no difference in median OS between patients with and without brain metastases (20.8 25.1 months; = .11).

Conclusion: There is a nearly two-fold higher incidence of mutations in NSCLC among patients with brain metastases at diagnosis. mutations did not predict for outcomes from brain metastases.
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http://dx.doi.org/10.1200/JGO.2016.003392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493216PMC
June 2017

Preoperative Chemotherapy and Metronomic Scheduling of Chemotherapy in Locally Advanced Oral Cancers.

Oncology 2016 28;91 Suppl 1:35-40. Epub 2016 Jul 28.

Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India.

Locally advanced oral cavity cancers are treated with a multi-modality approach. Surgery is the most efficient local modality in comparison to chemoradiation in oral cancers. Preoperative chemotherapy has failed its expectations to improve disease-free survival or overall survival in resectable oral cancers. Its use as an organ preservation tool is being studied. Induction chemotherapy followed by assessment for surgery is an appropriate option for borderline resectable or technically unresectable oral cancer. Metronomic chemotherapy is being studied as a bridge to surgery and as adjuvant chemotherapy in locally advanced oral cancers. The role of induction chemotherapy in unresectable oral cancers is unproven. Metronomic chemotherapy has shown improved progression-free survival and overall survival in oral cancers in comparison to intravenous cisplatin. A phase 3 study for confirmation of this finding has begun.
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http://dx.doi.org/10.1159/000447579DOI Listing
January 2017

L-asparginase administration reduces white blood cell count and prevents tumor lysis syndrome in children with hyperleukocytic acute lymphoblastic leukemia.

Acta Haematol 2015 26;133(1):6-9. Epub 2014 Jun 26.

Department of Pediatrics, Armed Forces Medical College, Pune, India.

Background: The management of hyperleukocytosis currently involves intensive supportive care for preventing tumor lysis syndrome (TLS)-associated metabolic abnormalities as well as cytoreduction procedures to reduce the white blood cell (WBC) count. These procedures are often equipment-intensive and may not be practised in developing countries with limited resources. Hence, it is not clear what would be the most effective strategy to manage hyperleukocytosis and prevent TLS.

Procedure: All children ≤12 years, diagnosed with acute lymphoblastic leukemia (ALL) and hyperleukocytosis (WBC count >100 × 10(9)/l) were administered L-asparginase (L-asp, 6,000 U/m(2), i.m.) along with standard supportive care consisting of hydration, oral allopurinol administration and alkalization. The complete blood counts and biochemical parameters were monitored for 72 h. After 48 h, if the WBC count was >100 × 10(9)/l, a repeat dose of L-asp was administered.

Results: Twenty-one children (9 boys and 12 girls) with hyperleukocytic ALL were treated with L-asp. The median age of the children was 5.3 years (range 2-11 years). The median initial WBC count was 249 × 10(9)/l (range 151-476 × 10(9)/l). Twenty children received only one dose of L-asp. The mean reduction in WBC count achieved by treatment was 15.7, 42.0, 61.0, 76.4, 85.5 and 90.8% at 12, 24, 36, 48, 60 and 72 h, respectively. None of the patients developed TLS.

Conclusions: Chemical cytoreduction by administering L-asp is an effective means of managing hyperleukocytosis and preventing TLS.
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http://dx.doi.org/10.1159/000358115DOI Listing
February 2015

Pediatric oncology in India: Past, present and future.

Indian J Med Paediatr Oncol 2009 Oct;30(4):121-3

Editor, IJMPO, Associate Professor, Division of Pediatric Oncology, Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai - 400 012, India E-mail:

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http://dx.doi.org/10.4103/0971-5851.65333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930298PMC
October 2009

Single monochrome real-time RT-PCR assay for identification, quantification, and breakpoint cluster region determination of t(9;22) transcripts.

J Mol Diagn 2005 Feb;7(1):40-7

King Fahad National Centre for Children's Cancer and Research, PO Box 3354, MBC # 98-16, Riyadh, 11211, Saudi Arabia.

t(9;22) generates the BCR-ABL fusion gene, the hallmark of chronic myeloid leukemia (CML) but also found in acute lymphoblastic leukemia (ALL). Multiple chimeric transcripts translate to proteins of 190 or 210 kd and, rarely, 230 kd. CML typically carries p210 BCR-ABL while ALL is most often associated with p190. Detection and quantification of these fusion transcripts is useful in clinical management. We have exploited the unique melting profiles of these transcripts to design a new, simple, and cost-effective assay based on monochrome multiplex real-time RT-PCR for identification and quantification of each of these transcripts (b3-a2, b2-a2, and e1-a2) without further manipulation. The sensitivity of this assay was 10(-4) for e1-a2 and 10(-5) for b3-a2/b2-a2, which is appropriate for detection of minimal residual disease (MRD). Inter- and intra-assay variation was minimal. We applied this assay to assess the distribution of p190 and p210 in 260 childhood ALL samples from India. BCR-ABL was detected in 19 (7.3%), including one T-ALL. Eight patients (3.1%) demonstrated mBCR-ABL (p190) and 11 (4.2%) had MBCR-ABL (p210). Transcript levels varied markedly (up to 3000-fold) but e1-a2 were generally expressed at higher levels than b3/b2-a2 (P = 0.05). This simple real-time multiplex assay can thus be easily applied to monitor patients with ALL as well as CML.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867499PMC
http://dx.doi.org/10.1016/S1525-1578(10)60007-4DOI Listing
February 2005