18 results on '"Lee, Shawn H R"'
Search Results
2. Maintenance therapy for acute lymphoblastic leukemia: basic science and clinical translations
- Author
-
Toksvang, Linea N., Lee, Shawn H. R., Yang, Jun J., and Schmiegelow, Kjeld
- Published
- 2022
- Full Text
- View/download PDF
3. Additive effects of TPMT and NUDT15 on thiopurine toxicity in children with acute lymphoblastic leukemia across multiethnic populations.
- Author
-
Maillard, Maud, Nishii, Rina, Yang, Wenjian, Hoshitsuki, Keito, Chepyala, Divyabharathi, Lee, Shawn H R, Nguyen, Jenny Q, Relling, Mary V, Crews, Kristine R, Leggas, Mark, Singh, Meenu, Suang, Joshua L Y, Yeoh, Allen E J, Jeha, Sima, Inaba, Hiroto, Pui, Ching-Hon, Karol, Seth E, Trehan, Amita, Bhatia, Prateek, and Klussmann, Federico G Antillon
- Subjects
LYMPHOBLASTIC leukemia ,ACUTE leukemia ,CONSORTIA - Abstract
Background Thiopurines such as mercaptopurine (MP) are widely used to treat acute lymphoblastic leukemia (ALL). Thiopurine-S-methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15) inactivate thiopurines, and no-function variants are associated with drug-induced myelosuppression. Dose adjustment of MP is strongly recommended in patients with intermediate or complete loss of activity of TPMT and NUDT15. However, the extent of dosage reduction recommended for patients with intermediate activity in both enzymes is currently not clear. Methods MP dosages during maintenance were collected from 1768 patients with ALL in Singapore, Guatemala, India, and North America. Patients were genotyped for TPMT and NUDT15, and actionable variants defined by the Clinical Pharmacogenetics Implementation Consortium were used to classify patients as TPMT and NUDT15 normal metabolizers (TPMT/NUDT15 NM), TPMT or NUDT15 intermediate metabolizers (TPMT IM or NUDT15 IM), or TPMT and NUDT15 compound intermediate metabolizers (TPMT/NUDT15 IM/IM). In parallel, we evaluated MP toxicity, metabolism, and dose adjustment using a Tpmt / Nudt15 combined heterozygous mouse model (Tpmt
+/− / Nudt15+/− ). Results Twenty-two patients (1.2%) were TPMT/NUDT15 IM/IM in the cohort, with the majority self-reported as Hispanics (68.2%, 15/22). TPMT/NUDT15 IM/IM patients tolerated a median daily MP dose of 25.7 mg/m2 (interquartile range = 19.0-31.1 mg/m2 ), significantly lower than TPMT IM and NUDT15 IM dosage (P < .001). Similarly, Tpmt+/− / Nudt15+/− mice displayed excessive hematopoietic toxicity and accumulated more metabolite (DNA-TG) than wild-type or single heterozygous mice, which was effectively mitigated by a genotype-guided dose titration of MP. Conclusion We recommend more substantial dose reductions to individualize MP therapy and mitigate toxicity in TPMT/NUDT15 IM/IM patients. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
4. Associations of T-Cell Receptor Repertoire Diversity with L-Asparaginase Allergy in Childhood Acute Lymphoblastic Leukemia
- Author
-
Lee, Shawn H. R., primary, Li, Zhenhua, additional, Lim, Evelyn H. Z., additional, Chin, Winnie H. N., additional, Jiang, Nan, additional, Chiew, Kean Hui, additional, Chen, Zhiwei, additional, Oh, Bernice L. Z., additional, Tan, Ah Moy, additional, Ariffin, Hany, additional, Yang, Jun J., additional, and Yeoh, Allen E. J., additional
- Published
- 2023
- Full Text
- View/download PDF
5. Fratricide-resistant CD7-CAR T cells in T-ALL
- Author
-
Oh, Bernice L. Z., Shimasaki, Noriko, Coustan-Smith, Elaine, Chan, Esther, Poon, Limei, Lee, Shawn H. R., Yeap, Frances, Tan, Lip Kun, Chai, Louis Y. A., Le Bert, Nina, Tan, Nicole, Bertoletti, Antonio, Chen, Siew Peng, Del Bufalo, Francesca, Becilli, Marco, Locatelli, Franco, Yeoh, Allen E. J., and Campana, Dario
- Abstract
T cell acute lymphoblastic leukemia (T-ALL) is difficult to treat when it relapses after therapy or is chemoresistant; the prognosis of patients with relapsed or refractory T-ALL is generally poor. We report a case series of 17 such patients who received autologous chimeric antigen receptor (CAR) T cells expressing an anti-CD7 CAR and an anti-CD7 protein expression blocker (PEBL), which prevented CAR T cell fratricide. Despite high leukemic burden and low CAR T cell dosing, 16 of the 17 patients attained minimal residual disease-negative complete remission within 1 month. The remaining patient had CD7−T-ALL cells before infusion, which persisted after infusion. Toxicities were mild: cytokine release syndrome grade 1 in ten patients and grade 2 in three patients; immune effector cell-associated neurotoxicity syndrome grade 1 in two patients. Eleven patients remained relapse-free (median follow-up, 15 months), including all nine patients who received an allotransplant. The first patient is in remission 55 months after infusion without further chemotherapy or transplantation; circulating CAR T cells were detectable for 2 years. T cells regenerating after lymphodepletion lacked CD7 expression, were polyclonal and responded to SARS-CoV-2 vaccination; CD7+immune cells reemerged concomitantly with CAR T cell disappearance. In conclusion, autologous anti-CD7 PEBL-CAR T cells have powerful antileukemic activity and are potentially an effective option for the treatment of T-ALL.
- Published
- 2024
- Full Text
- View/download PDF
6. Association of Genetic Ancestry With the Molecular Subtypes and Prognosis of Childhood Acute Lymphoblastic Leukemia
- Author
-
Lee, Shawn H. R., primary, Antillon-Klussmann, Federico, additional, Pei, Deqing, additional, Yang, Wenjian, additional, Roberts, Kathryn G., additional, Li, Zhenhua, additional, Devidas, Meenakshi, additional, Yang, Wentao, additional, Najera, Cesar, additional, Lin, Hai Peng, additional, Tan, Ah Moy, additional, Ariffin, Hany, additional, Cheng, Cheng, additional, Evans, William E., additional, Hunger, Stephen P., additional, Jeha, Sima, additional, Mullighan, Charles G., additional, Loh, Mignon L., additional, Yeoh, Allen E. J., additional, Pui, Ching-Hon, additional, and Yang, Jun J., additional
- Published
- 2022
- Full Text
- View/download PDF
7. Life‐threatening infections during treatment for acute lymphoblastic leukemia on the Malaysia‐Singapore 2003 and 2010 clinical trials: A risk prediction model
- Author
-
Oh, Bernice L. Z., primary, Fan, Lijia, additional, Lee, Shawn H. R., additional, Foo, Koon Mian, additional, Chiew, Kean Hui, additional, Seeto, Zelia Z. L., additional, Chen, Zhi Wei, additional, Neoh, Cheryl C. C., additional, Liew, Germaine S. M., additional, Eng, Jing Jia, additional, Lam, Joyce C. M., additional, Quah, Thuan Chong, additional, Tan, Ah Moy, additional, Chan, Yiong Huak, additional, and Yeoh, Allen E. J., additional
- Published
- 2022
- Full Text
- View/download PDF
8. Curing the Curable: Managing Low-Risk Acute Lymphoblastic Leukemia in Resource Limited Countries
- Author
-
Oh, Bernice L. Z., primary, Lee, Shawn H. R., additional, and Yeoh, Allen E. J., additional
- Published
- 2021
- Full Text
- View/download PDF
9. Genetic Alterations in Childhood Acute Lymphoblastic Leukemia: Interactions with Clinical Features and Treatment Response
- Author
-
Lee, Shawn H. R., primary, Li, Zhenhua, additional, Tai, Si Ting, additional, Oh, Bernice L. Z., additional, and Yeoh, Allen E. J., additional
- Published
- 2021
- Full Text
- View/download PDF
10. Genome-Wide Association Study of Susceptibility Loci for TCF3-PBX1 Acute Lymphoblastic Leukemia in Children.
- Author
-
Lee, Shawn H. R, Qian, Maoxiang, Yang, Wentao, Diedrich, Jonathan D, Raetz, Elizabeth, Yang, Wenjian, Dong, Qian, Devidas, Meenakshi, Pei, Deqing, Yeoh, Allen, Cheng, Cheng, Pui, Ching-Hon, Evans, William E, Mullighan, Charles G, Hunger, Stephen P, Savic, Daniel, Relling, Mary V, Loh, Mignon L, Yang, Jun J, and Lee, Shawn H R
- Subjects
- *
GENOME-wide association studies , *LYMPHOBLASTIC leukemia , *ACUTE leukemia , *CHILDHOOD cancer , *CELL fusion , *SOMATIC mutation , *PROTEINS , *RESEARCH , *SEQUENCE analysis , *RESEARCH methodology , *EVALUATION research , *COMPARATIVE studies , *DISEASE susceptibility , *RESEARCH funding , *ACUTE diseases - Abstract
Acute lymphoblastic leukemia (ALL) is the most common cancer in children. TCF3-PBX1 fusion defines a common molecular subtype of ALL with unique clinical features, but the molecular basis of its inherited susceptibility is unknown. In a genome-wide association study of 1494 ALL cases and 2057 non-ALL controls, we identified a germline risk locus located in an intergenic region between BCL11A and PAPOLG: rs2665658, P = 1.88 × 10-8 for TCF3-PBX1 ALL vs non-ALL, and P = 1.70 × 10-8 for TCF3-PBX1 ALL vs other-ALL. The lead variant was validated in a replication cohort, and conditional analyses pointed to a single causal variant with subtype-specific effect. The risk variant is located in a regulatory DNA element uniquely activated in ALL cells with the TCF3-PBX1 fusion and may distally modulate the transcription of the adjacent gene REL. Our results expand the understanding of subtype-specific ALL susceptibility and highlight plausible interplay between germline variants and somatic genomic abnormalities in ALL pathogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
11. Genome-Wide Association Study of Susceptibility Loci for TCF3-PBX1 Acute Lymphoblastic Leukemia in Children
- Author
-
Lee, Shawn H. R, primary, Qian, Maoxiang, additional, Yang, Wentao, additional, Diedrich, Jonathan D, additional, Raetz, Elizabeth, additional, Yang, Wenjian, additional, Dong, Qian, additional, Devidas, Meenakshi, additional, Pei, Deqing, additional, Yeoh, Allen, additional, Cheng, Cheng, additional, Pui, Ching-Hon, additional, Evans, William E, additional, Mullighan, Charles G, additional, Hunger, Stephen P, additional, Savic, Daniel, additional, Relling, Mary V, additional, Loh, Mignon L, additional, and Yang, Jun J, additional
- Published
- 2020
- Full Text
- View/download PDF
12. Impact of Age on Pharmacogenomics and Treatment Outcomes of B-Cell Acute Lymphoblastic Leukemia.
- Author
-
Yoshimura S, Li Z, Gocho Y, Yang W, Crews KR, Lee SHR, Roberts KG, Mullighan CG, Relling MV, Yu J, Yeoh AEJ, Loh ML, Saygin C, Litzow MR, Jeha S, Karol SE, Inaba H, Pui CH, Konopleva M, Jain N, Stock W, Paietta E, Jabbour E, Kornblau SM, Evans WE, and Yang JJ
- Subjects
- Humans, Adolescent, Child, Adult, Age Factors, Female, Young Adult, Male, Treatment Outcome, Child, Preschool, Aged, Middle Aged, Pharmacogenetics, Antineoplastic Agents therapeutic use, Infant, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Purpose: Acute lymphoblastic leukemia (ALL) can occur across all age groups, with a strikingly higher cure rate in children compared with adults. However, the pharmacological basis of age-related differences in ALL treatment response remains unclear., Methods: Studying 767 children and 309 adults with newly diagnosed B-cell ALL enrolled on frontline trials at St Jude Children's Research Hospital, MD Anderson Cancer Center, the Alliance for Clinical Trials in Oncology, and the ECOG-ACRIN Cancer Research Group, we determined the ex vivo sensitivity of leukemia cells to 21 drugs. Twenty-three ALL molecular subtypes were identified using RNA sequencing. We systematically characterized the associations between drug response and ALL genomics in children, adolescents and young adults, and elderly adults. We evaluated the effect of age-related gene expression signature on ALL treatment outcomes., Results: Seven ALL drugs (asparaginase, prednisolone, mercaptopurine, dasatinib, nelarabine, daunorubicin, and inotuzumab ozogamicin) showed differential activity between children and adults, of which six were explained by age-related differences in leukemia molecular subtypes. Adolescents and young adults showed similar patterns of drug resistance as older adults, relative to young children. Mercaptopurine exhibited subtype-independent greater sensitivity in children. Transcriptomic profiling uncovered subclusters within CRLF2 -, DUX4 -, and KMT2A -rearranged ALL that were linked to age and cytotoxic drug resistance. In particular, a subset of children had adult-like ALL on the basis of leukemia gene expression patterns across subtypes, despite their chronological age. Resistant to cytotoxic drugs, children with adult-like ALL exhibited poor prognosis in pediatric ALL trials, even after adjusting for age and minimal residual diseases., Conclusion: Our results provide pharmacogenomic insights into age-related disparities in ALL cure rates and identify leukemia prognostic features for treatment individualization across age groups.
- Published
- 2024
- Full Text
- View/download PDF
13. Additive effects of TPMT and NUDT15 on thiopurine toxicity in children with acute lymphoblastic leukemia across multiethnic populations.
- Author
-
Maillard M, Nishii R, Yang W, Hoshitsuki K, Chepyala D, Lee SHR, Nguyen JQ, Relling MV, Crews KR, Leggas M, Singh M, Suang JLY, Yeoh AEJ, Jeha S, Inaba H, Pui CH, Karol SE, Trehan A, Bhatia P, Antillon Klussmann FG, Bhojwani D, Haidar CE, and Yang JJ
- Subjects
- Adolescent, Animals, Child, Child, Preschool, Female, Humans, Male, Mice, Antimetabolites, Antineoplastic adverse effects, Antimetabolites, Antineoplastic administration & dosage, Genotype, Nudix Hydrolases, Mercaptopurine toxicity, Methyltransferases genetics, Methyltransferases metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Pyrophosphatases genetics, Pyrophosphatases metabolism
- Abstract
Background: Thiopurines such as mercaptopurine (MP) are widely used to treat acute lymphoblastic leukemia (ALL). Thiopurine-S-methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15) inactivate thiopurines, and no-function variants are associated with drug-induced myelosuppression. Dose adjustment of MP is strongly recommended in patients with intermediate or complete loss of activity of TPMT and NUDT15. However, the extent of dosage reduction recommended for patients with intermediate activity in both enzymes is currently not clear., Methods: MP dosages during maintenance were collected from 1768 patients with ALL in Singapore, Guatemala, India, and North America. Patients were genotyped for TPMT and NUDT15, and actionable variants defined by the Clinical Pharmacogenetics Implementation Consortium were used to classify patients as TPMT and NUDT15 normal metabolizers (TPMT/NUDT15 NM), TPMT or NUDT15 intermediate metabolizers (TPMT IM or NUDT15 IM), or TPMT and NUDT15 compound intermediate metabolizers (TPMT/NUDT15 IM/IM). In parallel, we evaluated MP toxicity, metabolism, and dose adjustment using a Tpmt/Nudt15 combined heterozygous mouse model (Tpmt+/-/Nudt15+/-)., Results: Twenty-two patients (1.2%) were TPMT/NUDT15 IM/IM in the cohort, with the majority self-reported as Hispanics (68.2%, 15/22). TPMT/NUDT15 IM/IM patients tolerated a median daily MP dose of 25.7 mg/m2 (interquartile range = 19.0-31.1 mg/m2), significantly lower than TPMT IM and NUDT15 IM dosage (P < .001). Similarly, Tpmt+/-/Nudt15+/- mice displayed excessive hematopoietic toxicity and accumulated more metabolite (DNA-TG) than wild-type or single heterozygous mice, which was effectively mitigated by a genotype-guided dose titration of MP., Conclusion: We recommend more substantial dose reductions to individualize MP therapy and mitigate toxicity in TPMT/NUDT15 IM/IM patients., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2024
- Full Text
- View/download PDF
14. Toward a Comprehensive One-Stop Shop for Somatic Genomic Profiling in Childhood Acute Lymphoblastic Leukemia.
- Author
-
Lee SHR
- Subjects
- Humans, Mutation, Genomics, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics
- Abstract
Competing Interests: Disclosure Statement None declared.
- Published
- 2024
- Full Text
- View/download PDF
15. Prognostic and Pharmacotypic Heterogeneity of Hyperdiploidy in Childhood ALL.
- Author
-
Lee SHR, Ashcraft E, Yang W, Roberts KG, Gocho Y, Rowland L, Inaba H, Karol SE, Jeha S, Crews KR, Mullighan CG, Relling MV, Evans WE, Cheng C, Yang JJ, and Pui CH
- Subjects
- Humans, Prognosis, Mercaptopurine, Asparaginase therapeutic use, Neoplasm Recurrence, Local, Trisomy genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Purpose: High hyperdiploidy, the largest and favorable subtype of childhood ALL, exhibits significant biological and prognostic heterogeneity. However, factors contributing to the varied treatment response and the optimal definition of hyperdiploidy remain uncertain., Methods: We analyzed outcomes of patients treated on two consecutive frontline ALL protocols, using six different definitions of hyperdiploidy: chromosome number 51-67 (Chr51-67); DNA index (DI; DI1.16-1.6); United Kingdom ALL study group low-risk hyperdiploid, either trisomy of chromosomes 17 and 18 or +17 or +18 in the absence of +5 and +20; single trisomy of chromosome 18; double trisomy of chromosomes 4 and 10; and triple trisomy (TT) of chromosomes 4, 10, and 17. Additionally, we characterized ALL ex vivo pharmacotypes across eight main cytotoxic drugs., Results: Among 1,096 patients analyzed, 915 had B-ALL and 634 had pharmacotyping performed. In univariate analysis, TT emerged as the most favorable criterion for event-free survival (EFS; 10-year EFS, 97.3% v 86.8%; P = .0003) and cumulative incidence of relapse (CIR; 10-year CIR, 1.4% v 8.8%; P = .002) compared with the remaining B-ALL. In multivariable analysis, accounting for patient numbers using the akaike information criterion (AIC), DI1.16-1.6 was the most favorable criterion, exhibiting the best AIC for both EFS (hazard ratio [HR], 0.45; 95% CI, 0.23 to 0.88) and CIR (HR, 0.45; 95% CI, 0.21 to 0.99). Hyperdiploidy and subgroups with favorable prognoses exhibited notable sensitivities to asparaginase and mercaptopurine. Specifically, asparaginase sensitivity was associated with trisomy of chromosomes 16 and 17, whereas mercaptopurine sensitivity was linked to gains of chromosomes 14 and 17., Conclusion: Among different definitions of hyperdiploid ALL, DI is optimal based on independent prognostic impact and also the large proportion of low-risk patients identified. Hyperdiploid ALL exhibited particular sensitivities to asparaginase and mercaptopurine, with chromosome-specific associations.
- Published
- 2023
- Full Text
- View/download PDF
16. Successful toxicity reduction during delayed intensification in the non-high-risk arm of Malaysia-Singapore Acute Lymphoblastic Leukaemia 2010 study.
- Author
-
Oh BLZ, Lee SHR, Foo KM, Chiew KH, Seeto ZZL, Chen ZW, Neoh CCC, Liew GSM, Eng JJ, Lam JCM, Chan YH, Quah TC, Tan AM, and Yeoh AEJ
- Subjects
- Child, Child, Preschool, Female, History, 21st Century, Humans, Infant, Malaysia, Male, Singapore, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
In non-high-risk (non-HR) patients, the Malaysia-Singapore Acute Lymphoblastic Leukaemia 2003 (MS2003) study achieved good outcomes. However, its delayed-intensification (DI) phase, comprising repeated blocks of protocol III (2003-PIII), was toxic and caused significant treatment delays. The successor MS2010 study attempted to lower DI toxicity by replacing myelosuppressive drugs (doxorubicin, cytarabine) with vincristine and asparaginase., Patients and Methods: We analysed 1748 admissions for fever in 315 Singapore children with non-HR acute lymphoblastic leukaemia (ALL) (MS2003, n = 183; MS2010, n = 132), comprising 76% of the total cohort (n = 413), to study the impact of these changes., Results: The new 2010-PVa which has no doxorubicin, was associated with significantly fewer hospitalisations due to fever (0.08 versus 0.30 admissions per block [A/blk], p < 0.001), as than 2003-PIIIa. Similarly in 2010-PIIIb and PVb, where one block of cytarabine was replaced by two doses of vincristine, admissions for fever were also fewer (0.47 versus 0.74 A/blk, p < 0.001) than in 2003-PIIIb. However, the addition of single doses of vincristine and asparaginase in 2010-PIIIa, even with a mandatory seven-day rest, led to more hospitalisations (0.45 A/blk, p < 0.001), increased risk of bacteraemia (relative-risk (RR) = 7.66, p = 0.005) and critical-care admissions (RR = 4.31, p = 0.13). Despite this, overall treatment-related mortality decreased from 2.7% to 0.8%. Taken together, the reduced phase delays allowed earlier completion of the intensive phase of treatment (standard risk: 38.1 versus 49.4 weeks, p < 0.001; intermediate risk: 50.9 versus 58.8 weeks, p < 0.001), while maintaining excellent 10-year event-free survival of 95.4% and overall survival of 96.2%., Conclusions: In non-HR ALL, replacing doxorubicin/cytarabine with vincristine/asparaginase during some DI blocks is effective in reducing toxicity without compromising outcomes., Clinical Trial Information: NCT0289464., Competing Interests: Conflict of interest statement The authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
17. Pharmacogenomics in acute lymphoblastic leukemia.
- Author
-
Lee SHR and Yang JJ
- Subjects
- Antimetabolites, Antineoplastic adverse effects, Asparaginase administration & dosage, Asparaginase adverse effects, Child, Clinical Trials as Topic, Drug Resistance, Neoplasm genetics, Humans, Mercaptopurine administration & dosage, Mercaptopurine adverse effects, Methotrexate administration & dosage, Methotrexate adverse effects, Methyltransferases genetics, Methyltransferases metabolism, Precision Medicine, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Pyrophosphatases genetics, Pyrophosphatases metabolism, Signal Transduction, Vincristine administration & dosage, Vincristine adverse effects, Antimetabolites, Antineoplastic administration & dosage, Gene Expression Regulation, Leukemic, Molecular Targeted Therapy, Pharmacogenetics methods, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Pharmacogenomics is a fast-growing field of personalized medicine using a patient's genomic profile to determine drug disposition or response to drug therapy, in order to develop safer and more effective pharmacotherapy. Childhood acute lymphoblastic leukemia (ALL), being the most common malignancy in childhood, which is treated with uniform and standardized clinical trials, is remarkably poised for pharmacogenomic studies. In the last decade, unbiased genome-wide association studies have identified multiple germline risk factors that strongly modify host response to drug therapy. Some of these genomic associations (e.g. TPMT, NUDT15 and mercaptopurine dosing) have accumulated a significant level of evidence on their clinical utility such that they are warranted as routine clinical tests to guide modification of treatment. Most of these germline associations however, have not yet reached such actionability. Insights have also been gathered on germline factors that affect host susceptibility to adverse effects of antileukemic agents (eg, vincristine, asparaginase, methotrexate). Further large-scale studies are required, along with the assimilation of both germline and somatic variants, to precisely predict host drug response and drug toxicities, with the eventual aim of executing genomic-based precision-pharmacotherapy in the treatment of ALL., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
18. Acronyms in ophthalmology.
- Author
-
Lee SH, Woo JH, and Au Eong KG
- Subjects
- Clinical Trials as Topic, Humans, Publishing standards, Abbreviations as Topic, Ophthalmology standards
- Published
- 2012
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.