maliha khan - Academia.edu (original) (raw)
Papers by maliha khan
Blood Reviews, 2022
Hodgkin lymphoma can be classified as classical Hodgkin lymphoma (cHL) based on the presence of h... more Hodgkin lymphoma can be classified as classical Hodgkin lymphoma (cHL) based on the presence of hallmark Hodgkin and Reed-Sternberg cells. Through radiotherapy and modern chemotherapy, cHL has an impressive cure rate. We discuss normal B-cell maturation and the pathobiology of cHL, correlate significant cHL maturation steps with the sites of action of novel drugs, and highlight these drugs' efficacy in prior trials. In relapsed cHL, the approved agents brentuximab vedotin and immune checkpoint inhibitors have shown efficacy both alone and in combination with chemotherapy for salvage therapy, as maintenance after an autologous stem cell transplant, and after failure of this transplant. Chimeric antigen receptor T-cell therapy is being explored as a potential treatment option in relapsed/refractory cHL, and ongoing clinical trials show promising data without significant toxicity. We illustrate available novel therapeutic options and their efficacy in frontline and relapsed settings and discuss therapeutic benefit in relation to regimen toxicity.
Cancers, 2021
Simple Summary Peripheral T-cell lymphoma is a rare but aggressive tumor. Due to its rarity, the ... more Simple Summary Peripheral T-cell lymphoma is a rare but aggressive tumor. Due to its rarity, the disease has not been completely understood. In our review, we look at this lymphoma at the molecular level based on available literature. We highlight the mechanism behind the progression and resistance of this tumor. In doing so, we bring forth possible mechanism that could be exploited through novel chemotherapy drugs. In addition, we also look at the current available drugs used in treating this disease, as well as highlight other new drugs, describing their potential in treating this lymphoma. We comprehensively have collected and present the available biology behind peripheral T-cell lymphoma and discuss the available treatment options. Abstract T-cell lymphomas are a relatively rare group of malignancies with a diverse range of pathologic features and clinical behaviors. Recent molecular studies have revealed a wide array of different mechanisms that drive the development of these ...
Full quantitative survey data from Daira's evaluation of Mozilla Science Lab Programs. The qu... more Full quantitative survey data from Daira's evaluation of Mozilla Science Lab Programs. The qualitative word responses are excluded for data privacy reasons.
Lecture Notes in Electrical Engineering, 2021
During recent times, wireless local area network is very important and changed to a vital topic s... more During recent times, wireless local area network is very important and changed to a vital topic since the World Wide Web was introduced in 1995; we have many types of wireless network such as wireless local area network, wireless communication, wireless application protocol (WAP), wireless transaction and WMAN. Among all these types, WLAN gained much popularity and used widely in today's world in many areas for different purposes: office, airport, library, university, hospital, military campus and many more. In another hand, the security of all these functionalities has become a crucial topic in today's WLAN due to not existing any physical border around WLAN channel, so that, the security of information can be leaked by attackers very easy. For these purposes, IEEE introduced very famous security standards like WEP, WPA and WPA2 for securing communication between two endpoints. This survey gives a brief introduction to types of WLAN security, to study types of attack in wireless LAN, the vulnerabilities, and study on the existing security standards and will focus more on WPA2 which fix the problem of WEP and WPA and then explore the vulnerability of each standard; finally, this paper will end up with some useful mitigation and suggestion how to improve the wireless LAN security.
2017 IEEE International Conference on Electrical, Instrumentation and Communication Engineering (ICEICE), 2017
A high-voltage-gain technique employing dc-dc power electronic converters is proposed. The sugges... more A high-voltage-gain technique employing dc-dc power electronic converters is proposed. The suggested topologies can be used as multiport converters and draw continuous current from two input sources. They can also draw continuous current from a single source in an interleaved manner. The proposed converter can easily achieve a gain of 12 while getting a continuous input current. Such a converter can individually link a PV panel to a 100-Vdc bus. The design and component selection procedures have been discussed and a prototype has been developed to validate analytical results.
Hematopoietic Cell Transplantation for Malignant Conditions, 2019
Immune recovery after hematopoietic cell transplant (HCT) is delayed and incomplete, increasing r... more Immune recovery after hematopoietic cell transplant (HCT) is delayed and incomplete, increasing risk of infection and malignant relapse, which can limit transplant success. The post-HCT period is characterized by elevated interleukin-7 and interleukin-15 and clonal homeostatic peripheral expansion of CD8+ T cells. However, there is limited T-cell receptor diversity and impaired adaptive immune function. In the context of HCT, cellular therapies aim to exploit the unique immune status of the lymphodepleted host and focus on three key goals: (1) to reduce infectious morbidity and mortality, (2) to enhance graft-versus-tumor effect, and (3) to limit graft-versus-host disease. Ex vivo cultured multivirus-specific cytotoxic lymphocytes (CTLs) have been successfully infused into post-HCT patients and confer immunity against cytomegalovirus, Epstein–Barr virus, and other infections. Similarly, adoptive transfer of CTLs that target minor histocompatibility and tumor-associated antigens can ...
Blood, 2017
Introduction: Patients with chronic phase chronic myeloid leukemia (CML) who fail to respond to f... more Introduction: Patients with chronic phase chronic myeloid leukemia (CML) who fail to respond to first- and second-line tyrosine kinase inhibitor (TKI) therapy may be treated with third-line TKIs or undergo allogeneic hematopoietic stem cell transplant (alloHSCT). However, data demonstrating the efficacy of third-line TKI therapy is limited other than those coming from industry-sponsored studies for individual drugs. Objective: evaluate the efficacy of various third-line TKIs and identify factors predicting outcomes and response in patients with chronic phase CML Methods: A retrospective study was conducted on 185 patients with chronic phase CML with failure to first- or second-line TKIs. Demographic factors and clinical parameters were noted along with TKI therapies. Treatment response and outcomes, including cytogenetic response, molecular response, overall survival (OS), event-free survival (EFS) and transformation-free survival (TFS) were measured. Events were defined by death on...
Blood, 2021
Introduction Differentiated thyroid cancer (DTC) is the most common endocrine malignancy. Treatme... more Introduction Differentiated thyroid cancer (DTC) is the most common endocrine malignancy. Treatment options include surgery, radioiodine & hormonal therapy. Radioiodine therapy (RAI) is often used after surgery with the purpose of ablation of residual thyroid tissue, adjuvant therapy or clinically evident metastatic disease. However, the use of RAI carries a risk of secondary malignancies, such as leukemias. The 10-yr survival rate of patients with DTC > 90%. However, several studies showed those patients may be at risk for secondary cancers. Therapy related myeloid neoplasm (tMN) can develop after RAI exposure. The relationship between thyroid and myeloid neoplasm (MN) may not be fully explained by exposure to RAI. In this retrospective study, we investigated the association between MN & DTC. Methods This study included patients >18years with DTC and either MN ((Acute Myeloid Leukemia (AML), Myelodysplastic syndrome (MDS), Chronic myelomonocytic leukemia (CMML), or Myeloproli...
Blood, 2021
Introduction In multiple myeloma (MM), the RAS-RAF-MEK-ERK pathway plays a key role in regulation... more Introduction In multiple myeloma (MM), the RAS-RAF-MEK-ERK pathway plays a key role in regulation of cell growth, differentiation, proliferation, and cell death. The BRAF gene, located on chromosome 7, is the most potent component of the RAF group, and usually involves missense mutations clustered in exons 11 and 15. In this retrospective study, we investigated the prevalence of BRAF mutations in MM, the clinical and pathological significance of these mutations, and whether these BRAF mutations occur as initial or acquired mutations. Methods Patient data was retrieved from the clinical database of patients with MM who had been diagnosed and/or treated at The University of Texas MD Anderson Cancer Center during January 2015 through December 2020. To be included, participants had to be aged >18 years, have been diagnosed with MM, and have a positive BRAF mutation, identified using an 81-gene panel that had been performed on their bone marrow samples. The primary outcome variable wa...
Maternal & Child Nutrition, 2021
In Tanzania, suboptimal complementary feeding practices contribute to high stunting rates. Father... more In Tanzania, suboptimal complementary feeding practices contribute to high stunting rates. Fathers influence complementary feeding practices, and effective strategies are needed to engage them. The objectives of this research were to examine the acceptability and feasibility of (1) tailored complementary feeding recommendations and (2) engaging fathers in complementary feeding. We conducted trials of improved practices with 50 mothers and 40 fathers with children 6-18 months. At visit 1, mothers reported current feeding practices and fathers participated in focus group discussions. At visit 2, mothers and fathers received individual, tailored counselling and chose new practices to try. After 2 weeks, at visit 3, parents were interviewed individually about their experiences. Interview transcripts were analysed thematically. The most frequent feeding issues at visit 1 were the need to thicken porridge, increase dietary diversity, replace sugary snacks and drinks and feed responsively. After counselling, most mothers agreed to try practices to improve diets and fathers agreed to provide informational and instrumental support for complementary feeding, but few agreed to try feeding the child. At follow-up, mothers reported improved child feeding and confirmed fathers' reports of increased involvement. Most fathers purchased or provided funds for recommended foods; some helped with domestic tasks or fed children. Many participants reported improved spousal communication and cooperation. Families were able to practice recommendations to feed family foods, but high food costs and seasonal unavailability were challenges. It was feasible
Blood Cancer Journal, 2020
Primary plasma cell leukemia (pPCL) is a rare and aggressive form of multiple myeloma (MM) that i... more Primary plasma cell leukemia (pPCL) is a rare and aggressive form of multiple myeloma (MM) that is characterized by the presence of ≥20% circulating plasma cells. Overall survival remains poor despite advances of anti-MM therapy. The disease biology as well as molecular mechanisms that distinguish pPCL from non-pPCL MM remain poorly understood and, given the rarity of the disease, are challenging to study. In an attempt to identify key biological mechanisms that result in the aggressive pPCL phenotype, we performed whole-exome sequencing and gene expression analysis in 23 and 41 patients with newly diagnosed pPCL, respectively. The results reveal an enrichment of complex structural changes and high-risk mutational patterns in pPCL that explain, at least in part, the aggressive nature of the disease. In particular, pPCL patients with traditional low-risk features such as translocation t(11;14) or hyperdiploidy accumulated adverse risk genetic events that could account for the poor ou...
Journal of Clinical Oncology, 2018
8054Background: Plasma cell leukemia (PCL) is a rare and aggressive disease characterized by a cl... more 8054Background: Plasma cell leukemia (PCL) is a rare and aggressive disease characterized by a clonal proliferation of plasma cells in bone marrow and blood. PCL can present as de novo disease with...
Blood, 2018
Introduction: Primary Plasma Cell Leukemia (pPCL) is a rare form of multiple myeloma (MM) that is... more Introduction: Primary Plasma Cell Leukemia (pPCL) is a rare form of multiple myeloma (MM) that is characterized by an aggressive disease course with >20% peripherally circulating plasma cells (PCs) and poor clinical outcome. Despite the advances of modern anti-MM therapy, pPCL patients continue to experience low median overall survival (OS) suggesting a distinct biological background. Due to its low incidence of 1-2% of all MM patients, studies on physiopathology remain challenging and are limited. The aim of this study was to elucidate the differences in biology and outcome between non-pPCL MM and pPCL, to determine the genetic landscape of pPCL and to identify distinct signatures and pathways that potentially could be used as therapeutic targets. Methods: We performed gene expression profiling (GEP; Affymetrix U133 Plus 2.0) of matched circulating peripheral PCs and bone marrow (BM) PCs from 13 patients. Whole exome sequencing (WES) was performed on purified CD138+ PCs from BM ...
Blood, 2016
BACKGROUND The hypomethylating agents decitabine and 5-azacytidine are commonly used for the init... more BACKGROUND The hypomethylating agents decitabine and 5-azacytidine are commonly used for the initial treatment of acute myeloid leukemia (AML) in elderly patients deemed unfit to receive standard cytotoxic induction chemotherapy. Decitabine at the approved schedule of 20 mg/m2daily for 5 days was shown to be superior to supportive care or low dose cytarabine. (Kantarjian H, JCO; 30(21):2670, 2012). An extended 10-day schedule of decitabine was reported to have a significantly higher response rate (Blum W, PNAS; 107(16):7473, 2010) OBJECTIVES The primary objective of the current study was to compare the response rates of the two schedules of decitabine in patients with AML aged 60 years or older who were deemed ineligible to receive standard cytotoxic induction chemotherapy. Secondary objectives were to compare response durations, survival outcomes, and toxicities between the two schedules. METHODS Patients with AML aged 60 years or older were randomized using a Bayesian adaptive des...
Blood, 2015
Background: Myelodysplastic syndromes (MDS) are malignant clinical disorders characterized by ine... more Background: Myelodysplastic syndromes (MDS) are malignant clinical disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, peripheral cytopenias and a property to transform into acute myeloid leukemia (AML). Standard of care for MDS includes the hypomethylating agents (HMAs) (i.e. azacitidine, decitabine) to improve quality of life, decrease transfusion requirements and improve clinical outcome. However not all patients (pts) respond to HMAs and even in responding pts, cytopenias may persist. HMA-failure MDS has extremely poor prognosis and currently there are no approved therapeutic options for such pts who are often of advanced age with frequent comorbidities. Objectives: The dual primary objectives of this study evaluate the safety and efficacy of the second-generation thrombopoietin-receptor agonist (TPO-RA) eltrombopag (EPAG) for the treatment of MDS pts at the time of HMA-failure. Secondary objectives include incidence of transformation to AML and evaluati...
Asian Pacific Journal of Cancer Prevention, 2019
Primary Myelofibrosis is a BCR-ABL negative myeloproliferative neoplasm with a variety of hematol... more Primary Myelofibrosis is a BCR-ABL negative myeloproliferative neoplasm with a variety of hematological presentations, including thrombosis, bleeding diathesis and marrow fibrosis. It is estimated to have an incidence of 1.5 per 100,000 people each year. Although JAK2 or MPL mutations are seen in PMF, several other mutations have recently been documented, including mutations in CALR, epigenetic regulators like TET, ASXL1, and 13q deletions. The identification of these mutations has improved the ability to develop novel treatment options. These include JAK inhibitors like ruxolitinib, heat shock protein-90 inhibitors like ganetespib, histone deacetylase inhibitors including panobinostat, pracinostat, vorinostat and givinostat, hypomethylating agents like decitabine, hedgehog inhibitors like glasdegib, PI3K, AKT and mTOR inhibitors like everolimus as well as telomerase inhibitors like imtelstat. Research on novel therapeutic options is being actively pursued in order to expand treatment options for primary myelofibrosis however currently, there is no curative therapy other than allogenic hematopoietic stem cell transplantation (ASCT) which is possible in select patients.
Expert Opinion on Drug Metabolism & Toxicology, 2019
Introduction: Venetoclax, an antagonist of BCL-2 protein plays an important role in the pathogene... more Introduction: Venetoclax, an antagonist of BCL-2 protein plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL). It has been approved by the FDA for the treatment of relapsed/refractory CLL with del17p, and by the EMA for patients with del17p/TP53 mutation who have failed a BCR inhibitor, or in patients without those aberrations who have failed previous therapy, regardless of their genetic/molecular profile. Venetoclax in combination with rituximab has been also approved for the treatment of CLL after at least 1 prior therapy, regardless of del17p. Areas covered: This article reviews the chemical structure, mechanisms of action, pharmacokinetic and the clinical applications of venetoclax in monotherapy and in combined treatment of CLL. Publications dated 2010 through March 2019 were obtained from the MEDLINE database. The proceedings of the American Society of Hematology held during the last five years were also included. Expert opinion: Venetoclax shows high efficacy, a favorable toxicity profile and a high rate of minimal residual disease negativity, which is thought to have an impact on overall survival. It is efficient in patients with del17p/TP53 mutations, the incidence of which increases during clonal CLL evolution, and after failure of BCR pathway inhibitors.
Acta Haematologica, 2019
Background: Bibliometric analyses are a tool employed by researchers and funding agencies to esta... more Background: Bibliometric analyses are a tool employed by researchers and funding agencies to establish the most important areas of research in a particular field, and to determine which foci need increased research attention. Such analyses have been published in a variety of clinical specialties; however, a detailed literature search showed that no such study has been done for “myeloid neoplasms.” In order to bridge this gap, we conducted a citation analysis of the 100 most influential articles on myeloid neoplasms. Methods: Two independent researchers extracted relevant articles from the Scopus database. These articles were then ranked in descending order of citations and a list of the top 100 original articles was made. A further, more detailed list was created containing significant discriminating characteristics. Results: The top cited articles were published over a period of 47 years, with most of them being published in the 5-year interval of 2001–2005. The citations ranged fr...
Current Hematologic Malignancy Reports, 2018
Purpose of Review While chemoimmunotherapy has improved outcomes in chronic lymphocytic leukemia ... more Purpose of Review While chemoimmunotherapy has improved outcomes in chronic lymphocytic leukemia (CLL), it is not curative, has significant relapse rates, and is not always well tolerated. Recently, novel targeted therapies have been developed to increase response rates and reduce toxicity, especially in high-risk disease. Current goals of CLL therapies are to produce deep and durable, especially minimal residual disease (MRD)-negative, remissions so as to allow patients to ultimately discontinue treatment for a while. Whether this can be achieved with single agents or combination regimens is being investigated. Here, we comment on what the results of recent and ongoing clinical trials mean for the future of CLL therapy. Recent Findings Large trials have proven the efficacy of novel therapies including small-molecule inhibitors like ibrutinib, idelalisib, and venetoclax. These agents are approved as monotherapy for first-line treatment and/or in the relapsed/refractory setting. However, it appears that combining these drugs with other novel agents or with chemoimmunotherapy can give higher rates of MRD-negative remission, and delay disease resistance. Chimeric antigen receptor-T cells may change the outlook for patients with heavily refractory CLL. Summary Further research will determine which drug combinations are optimal for the various subgroups of CLL patients.
Clinical colorectal cancer, Jan 17, 2018
The mucinous histologic subtype accounts for 5% to 20% of colorectal cancer (CRC) cases but remai... more The mucinous histologic subtype accounts for 5% to 20% of colorectal cancer (CRC) cases but remains poorly characterized. The present study characterized the baseline characteristics, mutational profile, and clinical outcomes of patients diagnosed with mucinous CRC. We identified 1877 patients with metastatic CRC with available histologic findings and molecular profiling and summarized the baseline clinical and pathologic characteristics and overall survival (OS) stratified by the histologic type. The data from separate cohorts with consensus molecular subtype (CMS) and CpG island methylator information were also summarized. The mucinous histologic type was found in 277 of the 1877 patients (14.8%) and was associated with an increased prevalence of microsatellite instability (P < .001) and a right-sided primary (P < .001). An increased frequency of CMS1 (microsatellite instability immune) and lower rates of CMS2 (canonical) were identified, with mucinous compared with nonmucin...
Blood Reviews, 2022
Hodgkin lymphoma can be classified as classical Hodgkin lymphoma (cHL) based on the presence of h... more Hodgkin lymphoma can be classified as classical Hodgkin lymphoma (cHL) based on the presence of hallmark Hodgkin and Reed-Sternberg cells. Through radiotherapy and modern chemotherapy, cHL has an impressive cure rate. We discuss normal B-cell maturation and the pathobiology of cHL, correlate significant cHL maturation steps with the sites of action of novel drugs, and highlight these drugs' efficacy in prior trials. In relapsed cHL, the approved agents brentuximab vedotin and immune checkpoint inhibitors have shown efficacy both alone and in combination with chemotherapy for salvage therapy, as maintenance after an autologous stem cell transplant, and after failure of this transplant. Chimeric antigen receptor T-cell therapy is being explored as a potential treatment option in relapsed/refractory cHL, and ongoing clinical trials show promising data without significant toxicity. We illustrate available novel therapeutic options and their efficacy in frontline and relapsed settings and discuss therapeutic benefit in relation to regimen toxicity.
Cancers, 2021
Simple Summary Peripheral T-cell lymphoma is a rare but aggressive tumor. Due to its rarity, the ... more Simple Summary Peripheral T-cell lymphoma is a rare but aggressive tumor. Due to its rarity, the disease has not been completely understood. In our review, we look at this lymphoma at the molecular level based on available literature. We highlight the mechanism behind the progression and resistance of this tumor. In doing so, we bring forth possible mechanism that could be exploited through novel chemotherapy drugs. In addition, we also look at the current available drugs used in treating this disease, as well as highlight other new drugs, describing their potential in treating this lymphoma. We comprehensively have collected and present the available biology behind peripheral T-cell lymphoma and discuss the available treatment options. Abstract T-cell lymphomas are a relatively rare group of malignancies with a diverse range of pathologic features and clinical behaviors. Recent molecular studies have revealed a wide array of different mechanisms that drive the development of these ...
Full quantitative survey data from Daira's evaluation of Mozilla Science Lab Programs. The qu... more Full quantitative survey data from Daira's evaluation of Mozilla Science Lab Programs. The qualitative word responses are excluded for data privacy reasons.
Lecture Notes in Electrical Engineering, 2021
During recent times, wireless local area network is very important and changed to a vital topic s... more During recent times, wireless local area network is very important and changed to a vital topic since the World Wide Web was introduced in 1995; we have many types of wireless network such as wireless local area network, wireless communication, wireless application protocol (WAP), wireless transaction and WMAN. Among all these types, WLAN gained much popularity and used widely in today's world in many areas for different purposes: office, airport, library, university, hospital, military campus and many more. In another hand, the security of all these functionalities has become a crucial topic in today's WLAN due to not existing any physical border around WLAN channel, so that, the security of information can be leaked by attackers very easy. For these purposes, IEEE introduced very famous security standards like WEP, WPA and WPA2 for securing communication between two endpoints. This survey gives a brief introduction to types of WLAN security, to study types of attack in wireless LAN, the vulnerabilities, and study on the existing security standards and will focus more on WPA2 which fix the problem of WEP and WPA and then explore the vulnerability of each standard; finally, this paper will end up with some useful mitigation and suggestion how to improve the wireless LAN security.
2017 IEEE International Conference on Electrical, Instrumentation and Communication Engineering (ICEICE), 2017
A high-voltage-gain technique employing dc-dc power electronic converters is proposed. The sugges... more A high-voltage-gain technique employing dc-dc power electronic converters is proposed. The suggested topologies can be used as multiport converters and draw continuous current from two input sources. They can also draw continuous current from a single source in an interleaved manner. The proposed converter can easily achieve a gain of 12 while getting a continuous input current. Such a converter can individually link a PV panel to a 100-Vdc bus. The design and component selection procedures have been discussed and a prototype has been developed to validate analytical results.
Hematopoietic Cell Transplantation for Malignant Conditions, 2019
Immune recovery after hematopoietic cell transplant (HCT) is delayed and incomplete, increasing r... more Immune recovery after hematopoietic cell transplant (HCT) is delayed and incomplete, increasing risk of infection and malignant relapse, which can limit transplant success. The post-HCT period is characterized by elevated interleukin-7 and interleukin-15 and clonal homeostatic peripheral expansion of CD8+ T cells. However, there is limited T-cell receptor diversity and impaired adaptive immune function. In the context of HCT, cellular therapies aim to exploit the unique immune status of the lymphodepleted host and focus on three key goals: (1) to reduce infectious morbidity and mortality, (2) to enhance graft-versus-tumor effect, and (3) to limit graft-versus-host disease. Ex vivo cultured multivirus-specific cytotoxic lymphocytes (CTLs) have been successfully infused into post-HCT patients and confer immunity against cytomegalovirus, Epstein–Barr virus, and other infections. Similarly, adoptive transfer of CTLs that target minor histocompatibility and tumor-associated antigens can ...
Blood, 2017
Introduction: Patients with chronic phase chronic myeloid leukemia (CML) who fail to respond to f... more Introduction: Patients with chronic phase chronic myeloid leukemia (CML) who fail to respond to first- and second-line tyrosine kinase inhibitor (TKI) therapy may be treated with third-line TKIs or undergo allogeneic hematopoietic stem cell transplant (alloHSCT). However, data demonstrating the efficacy of third-line TKI therapy is limited other than those coming from industry-sponsored studies for individual drugs. Objective: evaluate the efficacy of various third-line TKIs and identify factors predicting outcomes and response in patients with chronic phase CML Methods: A retrospective study was conducted on 185 patients with chronic phase CML with failure to first- or second-line TKIs. Demographic factors and clinical parameters were noted along with TKI therapies. Treatment response and outcomes, including cytogenetic response, molecular response, overall survival (OS), event-free survival (EFS) and transformation-free survival (TFS) were measured. Events were defined by death on...
Blood, 2021
Introduction Differentiated thyroid cancer (DTC) is the most common endocrine malignancy. Treatme... more Introduction Differentiated thyroid cancer (DTC) is the most common endocrine malignancy. Treatment options include surgery, radioiodine & hormonal therapy. Radioiodine therapy (RAI) is often used after surgery with the purpose of ablation of residual thyroid tissue, adjuvant therapy or clinically evident metastatic disease. However, the use of RAI carries a risk of secondary malignancies, such as leukemias. The 10-yr survival rate of patients with DTC > 90%. However, several studies showed those patients may be at risk for secondary cancers. Therapy related myeloid neoplasm (tMN) can develop after RAI exposure. The relationship between thyroid and myeloid neoplasm (MN) may not be fully explained by exposure to RAI. In this retrospective study, we investigated the association between MN & DTC. Methods This study included patients >18years with DTC and either MN ((Acute Myeloid Leukemia (AML), Myelodysplastic syndrome (MDS), Chronic myelomonocytic leukemia (CMML), or Myeloproli...
Blood, 2021
Introduction In multiple myeloma (MM), the RAS-RAF-MEK-ERK pathway plays a key role in regulation... more Introduction In multiple myeloma (MM), the RAS-RAF-MEK-ERK pathway plays a key role in regulation of cell growth, differentiation, proliferation, and cell death. The BRAF gene, located on chromosome 7, is the most potent component of the RAF group, and usually involves missense mutations clustered in exons 11 and 15. In this retrospective study, we investigated the prevalence of BRAF mutations in MM, the clinical and pathological significance of these mutations, and whether these BRAF mutations occur as initial or acquired mutations. Methods Patient data was retrieved from the clinical database of patients with MM who had been diagnosed and/or treated at The University of Texas MD Anderson Cancer Center during January 2015 through December 2020. To be included, participants had to be aged >18 years, have been diagnosed with MM, and have a positive BRAF mutation, identified using an 81-gene panel that had been performed on their bone marrow samples. The primary outcome variable wa...
Maternal & Child Nutrition, 2021
In Tanzania, suboptimal complementary feeding practices contribute to high stunting rates. Father... more In Tanzania, suboptimal complementary feeding practices contribute to high stunting rates. Fathers influence complementary feeding practices, and effective strategies are needed to engage them. The objectives of this research were to examine the acceptability and feasibility of (1) tailored complementary feeding recommendations and (2) engaging fathers in complementary feeding. We conducted trials of improved practices with 50 mothers and 40 fathers with children 6-18 months. At visit 1, mothers reported current feeding practices and fathers participated in focus group discussions. At visit 2, mothers and fathers received individual, tailored counselling and chose new practices to try. After 2 weeks, at visit 3, parents were interviewed individually about their experiences. Interview transcripts were analysed thematically. The most frequent feeding issues at visit 1 were the need to thicken porridge, increase dietary diversity, replace sugary snacks and drinks and feed responsively. After counselling, most mothers agreed to try practices to improve diets and fathers agreed to provide informational and instrumental support for complementary feeding, but few agreed to try feeding the child. At follow-up, mothers reported improved child feeding and confirmed fathers' reports of increased involvement. Most fathers purchased or provided funds for recommended foods; some helped with domestic tasks or fed children. Many participants reported improved spousal communication and cooperation. Families were able to practice recommendations to feed family foods, but high food costs and seasonal unavailability were challenges. It was feasible
Blood Cancer Journal, 2020
Primary plasma cell leukemia (pPCL) is a rare and aggressive form of multiple myeloma (MM) that i... more Primary plasma cell leukemia (pPCL) is a rare and aggressive form of multiple myeloma (MM) that is characterized by the presence of ≥20% circulating plasma cells. Overall survival remains poor despite advances of anti-MM therapy. The disease biology as well as molecular mechanisms that distinguish pPCL from non-pPCL MM remain poorly understood and, given the rarity of the disease, are challenging to study. In an attempt to identify key biological mechanisms that result in the aggressive pPCL phenotype, we performed whole-exome sequencing and gene expression analysis in 23 and 41 patients with newly diagnosed pPCL, respectively. The results reveal an enrichment of complex structural changes and high-risk mutational patterns in pPCL that explain, at least in part, the aggressive nature of the disease. In particular, pPCL patients with traditional low-risk features such as translocation t(11;14) or hyperdiploidy accumulated adverse risk genetic events that could account for the poor ou...
Journal of Clinical Oncology, 2018
8054Background: Plasma cell leukemia (PCL) is a rare and aggressive disease characterized by a cl... more 8054Background: Plasma cell leukemia (PCL) is a rare and aggressive disease characterized by a clonal proliferation of plasma cells in bone marrow and blood. PCL can present as de novo disease with...
Blood, 2018
Introduction: Primary Plasma Cell Leukemia (pPCL) is a rare form of multiple myeloma (MM) that is... more Introduction: Primary Plasma Cell Leukemia (pPCL) is a rare form of multiple myeloma (MM) that is characterized by an aggressive disease course with >20% peripherally circulating plasma cells (PCs) and poor clinical outcome. Despite the advances of modern anti-MM therapy, pPCL patients continue to experience low median overall survival (OS) suggesting a distinct biological background. Due to its low incidence of 1-2% of all MM patients, studies on physiopathology remain challenging and are limited. The aim of this study was to elucidate the differences in biology and outcome between non-pPCL MM and pPCL, to determine the genetic landscape of pPCL and to identify distinct signatures and pathways that potentially could be used as therapeutic targets. Methods: We performed gene expression profiling (GEP; Affymetrix U133 Plus 2.0) of matched circulating peripheral PCs and bone marrow (BM) PCs from 13 patients. Whole exome sequencing (WES) was performed on purified CD138+ PCs from BM ...
Blood, 2016
BACKGROUND The hypomethylating agents decitabine and 5-azacytidine are commonly used for the init... more BACKGROUND The hypomethylating agents decitabine and 5-azacytidine are commonly used for the initial treatment of acute myeloid leukemia (AML) in elderly patients deemed unfit to receive standard cytotoxic induction chemotherapy. Decitabine at the approved schedule of 20 mg/m2daily for 5 days was shown to be superior to supportive care or low dose cytarabine. (Kantarjian H, JCO; 30(21):2670, 2012). An extended 10-day schedule of decitabine was reported to have a significantly higher response rate (Blum W, PNAS; 107(16):7473, 2010) OBJECTIVES The primary objective of the current study was to compare the response rates of the two schedules of decitabine in patients with AML aged 60 years or older who were deemed ineligible to receive standard cytotoxic induction chemotherapy. Secondary objectives were to compare response durations, survival outcomes, and toxicities between the two schedules. METHODS Patients with AML aged 60 years or older were randomized using a Bayesian adaptive des...
Blood, 2015
Background: Myelodysplastic syndromes (MDS) are malignant clinical disorders characterized by ine... more Background: Myelodysplastic syndromes (MDS) are malignant clinical disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, peripheral cytopenias and a property to transform into acute myeloid leukemia (AML). Standard of care for MDS includes the hypomethylating agents (HMAs) (i.e. azacitidine, decitabine) to improve quality of life, decrease transfusion requirements and improve clinical outcome. However not all patients (pts) respond to HMAs and even in responding pts, cytopenias may persist. HMA-failure MDS has extremely poor prognosis and currently there are no approved therapeutic options for such pts who are often of advanced age with frequent comorbidities. Objectives: The dual primary objectives of this study evaluate the safety and efficacy of the second-generation thrombopoietin-receptor agonist (TPO-RA) eltrombopag (EPAG) for the treatment of MDS pts at the time of HMA-failure. Secondary objectives include incidence of transformation to AML and evaluati...
Asian Pacific Journal of Cancer Prevention, 2019
Primary Myelofibrosis is a BCR-ABL negative myeloproliferative neoplasm with a variety of hematol... more Primary Myelofibrosis is a BCR-ABL negative myeloproliferative neoplasm with a variety of hematological presentations, including thrombosis, bleeding diathesis and marrow fibrosis. It is estimated to have an incidence of 1.5 per 100,000 people each year. Although JAK2 or MPL mutations are seen in PMF, several other mutations have recently been documented, including mutations in CALR, epigenetic regulators like TET, ASXL1, and 13q deletions. The identification of these mutations has improved the ability to develop novel treatment options. These include JAK inhibitors like ruxolitinib, heat shock protein-90 inhibitors like ganetespib, histone deacetylase inhibitors including panobinostat, pracinostat, vorinostat and givinostat, hypomethylating agents like decitabine, hedgehog inhibitors like glasdegib, PI3K, AKT and mTOR inhibitors like everolimus as well as telomerase inhibitors like imtelstat. Research on novel therapeutic options is being actively pursued in order to expand treatment options for primary myelofibrosis however currently, there is no curative therapy other than allogenic hematopoietic stem cell transplantation (ASCT) which is possible in select patients.
Expert Opinion on Drug Metabolism & Toxicology, 2019
Introduction: Venetoclax, an antagonist of BCL-2 protein plays an important role in the pathogene... more Introduction: Venetoclax, an antagonist of BCL-2 protein plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL). It has been approved by the FDA for the treatment of relapsed/refractory CLL with del17p, and by the EMA for patients with del17p/TP53 mutation who have failed a BCR inhibitor, or in patients without those aberrations who have failed previous therapy, regardless of their genetic/molecular profile. Venetoclax in combination with rituximab has been also approved for the treatment of CLL after at least 1 prior therapy, regardless of del17p. Areas covered: This article reviews the chemical structure, mechanisms of action, pharmacokinetic and the clinical applications of venetoclax in monotherapy and in combined treatment of CLL. Publications dated 2010 through March 2019 were obtained from the MEDLINE database. The proceedings of the American Society of Hematology held during the last five years were also included. Expert opinion: Venetoclax shows high efficacy, a favorable toxicity profile and a high rate of minimal residual disease negativity, which is thought to have an impact on overall survival. It is efficient in patients with del17p/TP53 mutations, the incidence of which increases during clonal CLL evolution, and after failure of BCR pathway inhibitors.
Acta Haematologica, 2019
Background: Bibliometric analyses are a tool employed by researchers and funding agencies to esta... more Background: Bibliometric analyses are a tool employed by researchers and funding agencies to establish the most important areas of research in a particular field, and to determine which foci need increased research attention. Such analyses have been published in a variety of clinical specialties; however, a detailed literature search showed that no such study has been done for “myeloid neoplasms.” In order to bridge this gap, we conducted a citation analysis of the 100 most influential articles on myeloid neoplasms. Methods: Two independent researchers extracted relevant articles from the Scopus database. These articles were then ranked in descending order of citations and a list of the top 100 original articles was made. A further, more detailed list was created containing significant discriminating characteristics. Results: The top cited articles were published over a period of 47 years, with most of them being published in the 5-year interval of 2001–2005. The citations ranged fr...
Current Hematologic Malignancy Reports, 2018
Purpose of Review While chemoimmunotherapy has improved outcomes in chronic lymphocytic leukemia ... more Purpose of Review While chemoimmunotherapy has improved outcomes in chronic lymphocytic leukemia (CLL), it is not curative, has significant relapse rates, and is not always well tolerated. Recently, novel targeted therapies have been developed to increase response rates and reduce toxicity, especially in high-risk disease. Current goals of CLL therapies are to produce deep and durable, especially minimal residual disease (MRD)-negative, remissions so as to allow patients to ultimately discontinue treatment for a while. Whether this can be achieved with single agents or combination regimens is being investigated. Here, we comment on what the results of recent and ongoing clinical trials mean for the future of CLL therapy. Recent Findings Large trials have proven the efficacy of novel therapies including small-molecule inhibitors like ibrutinib, idelalisib, and venetoclax. These agents are approved as monotherapy for first-line treatment and/or in the relapsed/refractory setting. However, it appears that combining these drugs with other novel agents or with chemoimmunotherapy can give higher rates of MRD-negative remission, and delay disease resistance. Chimeric antigen receptor-T cells may change the outlook for patients with heavily refractory CLL. Summary Further research will determine which drug combinations are optimal for the various subgroups of CLL patients.
Clinical colorectal cancer, Jan 17, 2018
The mucinous histologic subtype accounts for 5% to 20% of colorectal cancer (CRC) cases but remai... more The mucinous histologic subtype accounts for 5% to 20% of colorectal cancer (CRC) cases but remains poorly characterized. The present study characterized the baseline characteristics, mutational profile, and clinical outcomes of patients diagnosed with mucinous CRC. We identified 1877 patients with metastatic CRC with available histologic findings and molecular profiling and summarized the baseline clinical and pathologic characteristics and overall survival (OS) stratified by the histologic type. The data from separate cohorts with consensus molecular subtype (CMS) and CpG island methylator information were also summarized. The mucinous histologic type was found in 277 of the 1877 patients (14.8%) and was associated with an increased prevalence of microsatellite instability (P < .001) and a right-sided primary (P < .001). An increased frequency of CMS1 (microsatellite instability immune) and lower rates of CMS2 (canonical) were identified, with mucinous compared with nonmucin...