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8. Safety and efficacy of rituximab in patients with diffuse large B-cell lymphoma in Malawi: a prospective, single-arm, non-randomised phase 1/2 clinical trial

Author

Kimani, Stephen, Painschab, Matthew S, Kaimila, Bongani, Kasonkanji, Edwards, Zuze, Takondwa, Tomoka, Tamiwe, Mulenga, Maurice, Nyasosela, Richard, Chikasema, Maria, Mtangwanika, Asekanadziwa, Chawinga, Mena, Mhango, Wilberforce, Nicholas, Simon, Chimzimu, Fred, Kampani, Coxcilly, Krysiak, Robert, Lilly, Amy, Randall, Cara, Seguin, Ryan, Westmoreland, Katherine D, Montgomery, Nathan D, Fedoriw, Yuri, and Gopal, Satish

Published
2021
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10. Comprehensive genomic profiling reveals molecular subsets of ASXL1 -mutated myeloid neoplasms

Author

Johnson, Steven M., primary, Haberberger, James, additional, Galeotti, Jonathan, additional, Ramkissoon, Lori, additional, Coombs, Catherine C., additional, Richardson, Daniel R., additional, Foster, Matthew C., additional, Duncan, Daniel, additional, Montgomery, Nathan D., additional, Ferguson, Naomi L., additional, and Zeidner, Joshua F., additional

Published
2023
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12. Proficiency Testing of Standardized Samples Shows High Interlaboratory Agreement for Clinical Next-Generation Sequencing-Based Hematologic Malignancy Assays With Survey Material-Specific Differences in Variant Frequencies

Author

Keegan, Alissa, Bridge, Julia A., Lindeman, Neal I., Long, Thomas A., Merker, Jason D., Moncur, Joel T., Montgomery, Nathan D., Nagarajan, Rakesh, Rothberg, Paul G., Routbort, Mark J., Vasalos, Patricia, Xian, Rena, and Kim, Annette S.

Subjects
Illumina Inc. -- International economic relations, Cancer -- Surveys, Medical societies -- Surveys, Health
Abstract

Context.--As laboratories increasingly turn from single-analyte testing in hematologic malignancies to next-generation sequencing-based panel testing, there is a corresponding need for proficiency testing to ensure adequate performance of these next-generation sequencing assays for optimal patient care. Objective.--To report the performance of laboratories on proficiency testing from the first 4 College of American Pathologists Next-Generation Sequencing Hematologic Malignancy surveys. Design.--College of American Pathologists proficiency testing results for 36 different engineered variants and/or allele fractions as well as a sample with no pathogenic variants were analyzed for accuracy and associated assay performance characteristics. Results.--The overall sensitivity observed for all variants was 93.5% (2190 of 2341) with 99.8% specificity (22 800 of 22 840). The false-negative rate was 6.5% (151 of 2341), and the largest single cause of these errors was difficulty in identifying variants in the sequence of CEBPA that is rich in cytosines and guanines. False-positive results (0.18%; 40 of 22 840) were most likely the result of preanalytic or postanalytic errors. Interestingly, the variant allele fractions were almost uniformly lower than the engineered fraction (as measured by digital polymerase chain reaction). Extensive troubleshooting identified a multifactorial cause for the low variant allele fractions, a result of an interaction between the linearized nature of the plasmid and the Illumina TruSeq chemistry. Conclusions.--Laboratories demonstrated an overall accuracy of 99.2% (24 990 of 25 181) with 99.8% specificity and 93.5% sensitivity when examining 36 clinically relevant somatic single-nucleotide variants with a variant allele fraction of 10% or greater. The data also highlight an issue with artificial linearized plasmids as survey material for next-generation sequencing. doi: 10.5858/arpa.2019-0352-CP, The number of clinical laboratories using next-generation sequencing (NGS) methods for the assessment of somatic variants has been growing rapidly. (1,2) This explosion has been driven by the increasing numbers [...]

Published
2020
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13. Comprehensive genomic profiling reveals molecular subsets of ASXL1-mutated myeloid neoplasms.

Author

Johnson, Steven M., Haberberger, James, Galeotti, Jonathan, Ramkissoon, Lori, Coombs, Catherine C., Richardson, Daniel R., Foster, Matthew C., Duncan, Daniel, Montgomery, Nathan D., Ferguson, Naomi L., and Zeidner, Joshua F.

Subjects
GENOMICS, TUMORS, MOLECULAR genetics, MYELOPROLIFERATIVE neoplasms, MYELOID leukemia
Abstract

A large-scale genomic analysis of patients with ASXL1-mutated myeloid disease has not been performed to date. We reviewed comprehensive genomic profiling results from 6043 adults to characterize clinicopathologic features and co-mutation patterns by ASXL1 mutation status. ASXL1 mutations occurred in 1414 patients (23%). Mutation co-occurrence testing revealed strong co-occurrence (p < 0.01) between mutations in ASXL1 and nine genes (SRSF2, U2AF1, RUNX1, SETBP1, EZH2, STAG2, CUX1, CSF3R, CBL). Further analysis of patients with these co-mutations yielded several novel findings. Co-mutation patterns supported that ASXL1/SF3B1 co-mutation may be biologically distinct from ASXL1/non-SF3B1 spliceosome co-mutation. In AML, ASXL1/SRSF2 co-mutated patients frequently harbored STAG2 mutations (42%), which were dependent on the presence of both ASXL1 and SRSF2 mutation (p < 0.05). STAG2 and SETBP1 mutations were also exclusive in ASXL1/SRSF2 co-mutated patients and associated with divergent chronic myeloid phenotypes. Our findings support that certain multi-mutant genotypes may be biologically relevant in ASXL1-mutated myeloid disease. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Data from Phase II Trial of Pembrolizumab after High-Dose Cytarabine in Relapsed/Refractory Acute Myeloid Leukemia

Author

Zeidner, Joshua F., primary, Vincent, Benjamin G., primary, Ivanova, Anastasia, primary, Moore, Dominic, primary, McKinnon, Karen P., primary, Wilkinson, Alec D., primary, Mukhopadhyay, Rupkatha, primary, Mazziotta, Francesco, primary, Knaus, Hanna A., primary, Foster, Matthew C., primary, Coombs, Catherine C., primary, Jamieson, Katarzyna, primary, Van Deventer, Hendrik, primary, Webster, Jonathan A., primary, Prince, Gabrielle T., primary, DeZern, Amy E., primary, Smith, B. Douglas, primary, Levis, Mark J., primary, Montgomery, Nathan D., primary, Luznik, Leo, primary, Serody, Jonathan S., primary, and Gojo, Ivana, primary

Published
2023
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16. Supplementary Methods from Phase II Trial of Pembrolizumab after High-Dose Cytarabine in Relapsed/Refractory Acute Myeloid Leukemia

Author

Zeidner, Joshua F., primary, Vincent, Benjamin G., primary, Ivanova, Anastasia, primary, Moore, Dominic, primary, McKinnon, Karen P., primary, Wilkinson, Alec D., primary, Mukhopadhyay, Rupkatha, primary, Mazziotta, Francesco, primary, Knaus, Hanna A., primary, Foster, Matthew C., primary, Coombs, Catherine C., primary, Jamieson, Katarzyna, primary, Van Deventer, Hendrik, primary, Webster, Jonathan A., primary, Prince, Gabrielle T., primary, DeZern, Amy E., primary, Smith, B. Douglas, primary, Levis, Mark J., primary, Montgomery, Nathan D., primary, Luznik, Leo, primary, Serody, Jonathan S., primary, and Gojo, Ivana, primary

Published
2023
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17. Human herpesvirus-encoded kinase induces B cell lymphomas in vivo

Author

Anders, Penny M., Montgomery, Nathan D., Montgomery, Stephanie A., Dittmer, Aadra P. BhaDirk P., and Damania, Blossom

Subjects
Genetically modified mice -- Models -- Research, Lymphomas -- Development and progression -- Models -- Research, Protein kinases -- Research, Herpesviruses -- Genetic aspects -- Research, Health care industry
Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that is the etiological agent of the endothelial cell cancer Kaposi's sarcoma (KS) and 2 B cell lymphoproliferative disorders, primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). KSHV ORF36, also known as viral protein kinase (vPK), is a viral serine/threonine kinase. We previously reported that KSHV vPK enhances cell proliferation and mimics cellular S6 kinase to phosphorylate ribosomal protein S6, a protein involved in protein synthesis. We created a mouse model to analyze the function of vPK in vivo. We believe this is the first mouse tumor model of a viral kinase encoded by a pathogenic human virus. We observed increased B cell activation in the vPK transgenic mice compared with normal mice. We also found that, over time, vPK transgenic mice developed a B cell hyperproliferative disorder and/or a high-grade B cell non-Hodgkin lymphoma at a greatly increased incidence compared with littermate controls. This mouse model shows that a viral protein kinase is capable of promoting B cell activation and proliferation as well as augmenting lymphomagenesis in vivo and may therefore contribute to the development of viral cancers., Introduction Kaposi's sarcoma-associated herpesvirus (KSHV) is a large double-strand DNA herpesvirus that codes for a myriad of proteins that interfere with normal host cellular processes to promote the viral life [...]

Published
2018
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18. Supplementary Data from Identification of Clonal Hematopoiesis Mutations in Solid Tumor Patients Undergoing Unpaired Next-Generation Sequencing Assays

Author

Coombs, Catherine C., primary, Gillis, Nancy K., primary, Tan, Xianming, primary, Berg, Jonathan S., primary, Ball, Markus, primary, Balasis, Maria E., primary, Montgomery, Nathan D., primary, Bolton, Kelly L., primary, Parker, Joel S., primary, Mesa, Tania E., primary, Yoder, Sean J., primary, Hayward, Michele C., primary, Patel, Nirali M., primary, Richards, Kristy L., primary, Walko, Christine M., primary, Knepper, Todd C., primary, Soper, John T., primary, Weiss, Jared, primary, Grilley-Olson, Juneko E., primary, Kim, William Y., primary, Earp, H. Shelton, primary, Levine, Ross L., primary, Papaemmanuil, Elli, primary, Zehir, Ahmet, primary, Hayes, D. Neil, primary, and Padron, Eric, primary

Published
2023
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25. ‘Discovering’ primary effusion lymphoma in Malawi

Author

Dhungel, Bal Mukunda, Montgomery, Nathan D., Painschab, Matthew S., Mulenga, Maurice, Tomoka, Tamiwe, Kaimila, Bongani, Zuze, Takondwa, Kasonkanji, Edwards, Kampani, Coxcilly, Chimzimu, Fred, Randall, Cara, Krysiak, Robert, Seguin, Ryan, Fedoriw, Yuri, and Gopal, Satish

Published
2018
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26. Plasmablastic lymphoma in Malawi

Author

Zuze, Takondwa, Painschab, Matthew S., Seguin, Ryan, Kudowa, Evarista, Kaimila, Bongani, Kasonkanji, Edwards, Tomoka, Tamiwe, Dhungel, Bal Mukunda, Mulenga, Maurice, Chikasema, Maria, Tewete, Blessings, Ntangwanika, Asekanadziwa, Chiyoyola, Sarah, Chimzimu, Fred, Kampani, Coxcilly, Krysiak, Robert, Montgomery, Nathan D., Fedoriw, Yuri, and Gopal, Satish

Published
2018
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27. Outcomes for paediatric Burkitt lymphoma treated with anthracycline-based therapy in Malawi

Author

Stanley, Christopher C., Westmoreland, Kate D., Heimlich, Brett J., El-Mallawany, Nader K., Wasswa, Peter, Mtete, Idah, Butia, Mercy, Itimu, Salama, Chasela, Mary, Mtunda, Mary, Chikasema, Mary, Makwakwa, Victor, Kaimila, Bongani, Kasonkanji, Edwards, Chimzimu, Fred, Kampani, Coxcilly, Dhungel, Bal M., Krysiak, Robert, Montgomery, Nathan D., Fedoriw, Yuri, Rosenberg, Nora E., Liomba, George N., and Gopal, Satish

Published
2016
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28. Clinical and molecular features of FLT3 juxtamembrane domain missense mutations in acute myeloid leukaemia.

Author

Jensen, Christopher E., Montgomery, Nathan D., Galeotti, Jonathan, Foster, Matthew C., and Zeidner, Joshua F.

Subjects
ACUTE myeloid leukemia, MISSENSE mutation, BONE marrow, KARYOTYPES, SOMATIC mutation, HEMATOPOIETIC stem cell transplantation
Abstract

A next-generation-sequencing (NGS) myeloid mutation panel (siParadigm Diagnostic Informatics) identified a type A I NPM1 i frameshift mutation (p.W288fs, 19.0% variant allele frequency) as well as missense mutations in I DNMT3 i A (c.2645G>A, p.R882H, VAF: 46.1%), I IDH2 i (c.419G>A, p.R140Q, VAF: 40.3%) and the I FLT3 i JMD (c.1775T>G, p.V592G, VAF: 13.0%). Keywords: acute myeloid leukemia; FLT3; Precision medicine EN acute myeloid leukemia FLT3 Precision medicine 6079 6082 4 12/19/22 20221215 NES 221215 FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase involved in regulation of haematopoietic stem cell and progenitor cell proliferation and differentiation.[1] Activating mutations in I FLT3 i are found in 25%-35% of adults with acute myeloid leukaemia (AML), most commonly in-frame internal tandem duplications (ITD) within the intracellular juxtamembrane domain (JMD).[2] This domain, consisting of residues 572-603, serves an autoinhibitory function, in part by preventing the activation loop from unfolding into its active conformation.[3] I FLT3 i -ITD mutations cause a gain-of-function phenotype with increased proliferation and protection from apoptosis[4] and are associated with worse clinical outcomes.[5] Most other activating I FLT3 i mutations are found in the tyrosine kinase domain (TKD),[2] though rare activating JMD deletions have also been described.[[6]] We identified three patients with rare I FLT3 i JMD missense mutations (Table 1). In-house NGS myeloid mutation panel revealed I FLT3- i ITD, a type A I NPM1 i frameshift mutation (VAF: 35.4%) and missense mutations in I DNMT3A i (c.2645G>A, p.R882H, VAF: 26.3%) and the I FLT3 i JMD (c.1775T>G, p.V592G, VAF: 10.6%). Each of these findings was less pronounced among the I FLT3 i JMD missense mutants than in ITD- or TKD-expressing cell lines, suggesting that I FLT3 i JMD missense mutations result in more modest gain of function. [Extracted from the article]

Published
2022
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30. Phase II Trial of Pembrolizumab after High-Dose Cytarabine in Relapsed/Refractory Acute Myeloid Leukemia

Author

Zeidner, Joshua F., primary, Vincent, Benjamin G., additional, Ivanova, Anastasia, additional, Moore, Dominic, additional, McKinnon, Karen P., additional, Wilkinson, Alec D., additional, Mukhopadhyay, Rupkatha, additional, Mazziotta, Francesco, additional, Knaus, Hanna A., additional, Foster, Matthew C., additional, Coombs, Catherine C., additional, Jamieson, Katarzyna, additional, Van Deventer, Hendrik, additional, Webster, Jonathan A., additional, Prince, Gabrielle T., additional, DeZern, Amy E., additional, Smith, B. Douglas, additional, Levis, Mark J., additional, Montgomery, Nathan D., additional, Luznik, Leo, additional, Serody, Jonathan S., additional, and Gojo, Ivana, additional

Published
2021
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32. Multi-omics analyses of radiation survivors identify radioprotective microbes and metabolites

Author

Guo, Hao, primary, Chou, Wei-Chun, additional, Lai, Yunjia, additional, Liang, Kaixin, additional, Tam, Jason, additional, Brickey, W. June, additional, Chen, Liang, additional, Montgomery, Nathan D., additional, Li, Xin, additional, Bohannon, Lauren M., additional, Sung, Anthony D., additional, Chao, Nelson J., additional, Peled, Jonathan U., additional, Gomes, Antonio L.C., additional, van den Brink, Marcel R.M., additional, French, Matthew J., additional, Macintyre, Andrew N., additional, Sempowski, Gregory D., additional, Tan, Xianming, additional, Sartor, R. Balfour, additional, Lu, Kun, additional, and Ting, Jenny P.Y., additional

Published
2021
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35. Genomic characteristics and prognostic significance of co‐mutatedASXL1 / SRSF2acute myeloid leukemia

Author

Richardson, Daniel R., primary, Swoboda, David M., additional, Moore, Dominic T., additional, Johnson, Steven M., additional, Chan, Onyee, additional, Galeotti, Jonathan, additional, Esparza, Sonia, additional, Hussaini, Mohammad O., additional, Van Deventer, Hendrick, additional, Foster, Matthew C., additional, Coombs, Catherine C., additional, Montgomery, Nathan D., additional, Sallman, David A., additional, and Zeidner, Joshua F., additional

Published
2021
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36. High pretreatment plasma Epstein-Barr virus (EBV) DNA level is a poor prognostic marker in HIV-associated, EBV-negative diffuse large B-cell lymphoma in Malawi

Author

Kasonkanji, Edwards, Kamapani, Coxcilly, Kaimila, Bongani, Miller, Melissa B., Zuze, Takondwa, Gopal, Satish, Mulenga, Maurice, Damania, Blossom, Fedoriw, Yuri, Dittmer, Dirk P., Elliott, Avian, Randall, Cara, Painschab, Matthew, Sanders, Marcia K., Seguin, Ryan, Montgomery, Nathan D., Krysiak, Robert, Chimzimu, Fred, and Tomoka, Tamiwe

Subjects
hemic and lymphatic diseases
Abstract

Plasma Epstein-Barr virus (EBV) DNA measurement has established prognostic utility in EBV-driven lymphomas, where it serves as a circulating tumor DNA marker. The value of plasma EBV measurement may be amplified in sub-Saharan Africa (SSA), where advanced imaging and molecular technologies for risk stratification are not typically available. However, its utility in diffuse large B-cell lymphoma (DLBCL) is less certain, given that only a subset of DLBCLs are EBV-positive. To explore this possibility, we measured plasma EBV DNA at diagnosis in a cohort of patients with DLBCL in Malawi. High plasma EBV DNA at diagnosis (≥3.0 log10 copies/mL) was associated with decreased overall survival (OS) (P =.048). When stratified by HIV status, the prognostic utility of baseline plasma EBV DNA level was restricted to HIV-positive patients. Unexpectedly, most HIV-positive patients with high plasma EBV DNA at diagnosis had EBV-negative lymphomas, as confirmed by multiple methods. Even in these HIV-positive patients with EBV-negative DLBCL, high plasma EBV DNA remained associated with shorter OS (P =.014). These results suggest that EBV reactivation in nontumor cells is a poor prognostic finding even in HIV-positive patients with convincingly EBV-negative DLBCL, extending the potential utility of EBV measurement as a valuable and implementable prognostic marker in SSA.

Published
2020
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37. Multi-omics analyses of radiation survivors identify radioprotective microbes and metabolites

Author

Guo, Hao, primary, Chou, Wei-Chun, additional, Lai, Yunjia, additional, Liang, Kaixin, additional, Tam, Jason W., additional, Brickey, W. June, additional, Chen, Liang, additional, Montgomery, Nathan D., additional, Li, Xin, additional, Bohannon, Lauren M., additional, Sung, Anthony D., additional, Chao, Nelson J., additional, Peled, Jonathan U., additional, Gomes, Antonio L. C., additional, van den Brink, Marcel R. M., additional, French, Matthew J., additional, Macintyre, Andrew N., additional, Sempowski, Gregory D., additional, Tan, Xianming, additional, Sartor, R. Balfour, additional, Lu, Kun, additional, and Ting, Jenny P. Y., additional

Published
2020
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41. High pretreatment plasma Epstein‐Barr virus (EBV) DNA level is a poor prognostic marker in HIV‐associated, EBV‐negative diffuse large B‐cell lymphoma in Malawi

Author

Montgomery, Nathan D., primary, Randall, Cara, additional, Painschab, Matthew, additional, Seguin, Ryan, additional, Kaimila, Bongani, additional, Kasonkanji, Edwards, additional, Zuze, Takondwa, additional, Krysiak, Robert, additional, Sanders, Marcia K., additional, Elliott, Avian, additional, Miller, Melissa B., additional, Kampani, Coxcilly, additional, Chimzimu, Fred, additional, Mulenga, Maurice, additional, Damania, Blossom, additional, Tomoka, Tamiwe, additional, Fedoriw, Yuri, additional, Dittmer, Dirk P., additional, and Gopal, Satish, additional

Published
2019
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43. ASXL1/SRSF2 Co-Mutated Acute Myeloid Leukemia (AML): A Rare but Distinct Subpopulation with Dismal Outcomes

Author

Richardson, Daniel R., primary, Swoboda, David M, additional, Ivanova, Anastasia, additional, Johnson, Steven M, additional, Galeotti, Jonathan, additional, Esparza, Sonia, additional, Chan, Onyee, additional, Foster, Matthew C, additional, Coombs, Catherine C., additional, Montgomery, Nathan D, additional, Sallman, David A, additional, and Zeidner, Joshua F, additional

Published
2019
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44. Whole Exome and Transcriptome Sequencing in 1042 Cases Reveals Distinct Clinically Relevant Genetic Subgroups of Follicular Lymphoma

Author

Li, Xiang, primary, Kositsky, Rachel, primary, Reddy, Anupama, primary, Love, Cassandra, primary, Naresh, Kikkeri, primary, Koff, Jean L., primary, Nystrand, Ilja, primary, Leppä, Sirpa, primary, Pasanen, Annika, primary, Karjalainen-Lindsberg, Marja-Liisa, primary, Dunkel, Johannes, primary, Kovanen, Panu, primary, Qin, Qiu, primary, Bhagat, Govind, primary, Leeman-Neill, Rebecca J, primary, Goswami, Rashmi S., primary, Wildeman, Sarah, primary, Delabie, Jan, primary, Burack, Richard, primary, Evans, Andrew G, primary, Amador, Catalina, primary, Yuan, Ji, primary, Qureishi, Hina Naushad, primary, Li, Shaoying, primary, Xu, Jie, primary, Yin, C. Cameron, primary, Gang, Anne Ortved, primary, Norgaard, Peter H., primary, Pedersen, Mette Ø, primary, Chan, Jason Yongsheng, primary, Cheah, Daryl Ming Zhe, primary, Ong, Shin Yeu, primary, Cheng, Chee Leong, primary, Lee, Lianne, primary, Paulua, Felik, primary, Ondrejka, Sarah L., primary, Hsi, Eric D., primary, Czader, Magdalena, primary, Wang, Lin, primary, Landis, Amber, primary, Churnetski, Michael C., primary, Jaye, David L., primary, Flowers, Christopher R., primary, McCall, Chad M., primary, Neff, Jadee, primary, McKinney, Matthew S., primary, Fedoriw, Yuri, primary, Powers, Eric, primary, Montgomery, Nathan D, primary, Bogusz, Agata M., primary, Stafford Hintz, Andrea, primary, Kovach, Alexandra E., primary, Reddy, Nishitha, primary, Thompson Arildsen, Mary Ann, primary, Mason, Emily F, primary, Juskevicius, Ridas, primary, Choi, William, primary, Au-Yeung, Rex, primary, Tse, Eric, primary, Sarno, Vincent, primary, Chadburn, Amy, primary, Lopez, Rafael, primary, Chapman, Jennifer R, primary, Behdad, Amir, primary, Goldschmidt, Neta, primary, Goodlad, John, primary, Burton, Cathy, primary, Pillai, Raju, primary, Louissaint, Abner, primary, Soliman, Dina Sameh, primary, Panea, Razvan, primary, Dave, Tushar, primary, Xiong, Barbara, primary, Smith, Eileen, primary, and Dave, Sandeep, primary

Published
2019
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45. Modified EPOCH for high‐risk non‐Hodgkin lymphoma in sub‐Saharan Africa

Author

Zuze, Takondwa, primary, Ellis, Grace K., additional, Kasonkanji, Edwards, additional, Kaimila, Bongani, additional, Nyasosela, Richard, additional, Nyirenda, Ruth, additional, Tomoka, Tamiwe, additional, Mulenga, Maurice, additional, Chikasema, Maria, additional, Tewete, Blessings, additional, Mtangwanika, Asekanadziwa, additional, Chiyoyola, Sarah, additional, Chimzimu, Fred, additional, Kampani, Coxcilly, additional, Mhango, Wilberforce, additional, Nicholas, Simon, additional, Randall, Cara, additional, Montgomery, Nathan D., additional, Fedoriw, George, additional, Westmoreland, Katherine D., additional, Painschab, Matthew S., additional, and Gopal, Satish, additional

Published
2019
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46. Venetoclax‐induced tumour lysis syndrome in acute myeloid leukaemia

Author

Esparza, Sonia, primary, Muluneh, Benyam, additional, Galeotti, Jonathan, additional, Matson, Melissa, additional, Richardson, Daniel R., additional, Montgomery, Nathan D., additional, Coombs, Catherine C., additional, Jamieson, Katarzyna, additional, Foster, Matthew C., additional, and Zeidner, Joshua F., additional

Published
2019
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48. Characteristics and survival for HIV‐associated multicentric Castleman disease in Malawi

Author

Gopal, Satish, Liomba, N George, Montgomery, Nathan D., Moses, Agnes, Kaimila, Bongani, Nyasosela, Richard, Chikasema, Maria, Dhungel, Bal M., Kampani, Coxcilly, Sanders, Marcia K., Krysiak, Robert, Dittmer, Dirk P., and Fedoriw, Yuri

Subjects
Lymphoproliferative disorders -- Statistics -- Patient outcomes, HIV infection -- Statistics -- Complications and side effects -- Patient outcomes, Health
Abstract

Introduction: Clinical reports of multicentric Castleman disease (MCD) from sub‐Saharan Africa (SSA) are scarce despite high prevalence of HIV and Kaposi sarcoma‐associated herpesvirus (KSHV). Our objective is to describe characteristics and survival for HIV‐associated MCD patients in Malawi. To our knowledge, this is the first HIV‐associated MCD case series from the region. Methods: We describe HIV‐positive patients with MCD in Lilongwe, and compare them to HIV‐associated lymph node Kaposi sarcoma (KS) and non‐Hodgkin lymphoma (NHL) patients treated at our centre. All patients were enrolled into a prospective longitudinal cohort study at a national teaching hospital and cancer referral centre serving half of Malawi's 16 million people. We included adult patients≥18 years of age with HIV‐associated MCD (n=6), lymph node KS (n=5) or NHL (n=31) enrolled between 1 June 2013 and 31 January 2015. Results and discussion: MCD patients had a median age of 42.4 years (range 37.2–51.8). All had diffuse lymphadenopathy and five had hepatosplenomegaly. Concurrent KS was present for one MCD patient, and four had performance status ≥3. MCD patients had lower median haemoglobin (6.4 g/dL, range 3.6–9.3) than KS (11.0 g/dL, range 9.1–12.0, p=0.011) or NHL (11.2 g/dL, range 4.5–15.1, p=0.0007). Median serum albumin was also lower for MCD (2.1 g/dL, range 1.7–3.2) than KS (3.7 g/dL, range 3.2–3.9, p=0.013) or NHL (3.4 g/dL, range 1.8–4.8, p=0.003). All six MCD patients were on antiretroviral therapy (ART) with median CD4 count 208 cells/µL (range 108–1146), and all with HIV RNA Conclusions: HIV‐associated MCD occurs in Malawi, is diagnosed late and is associated with high mortality. Improvements in awareness, diagnostic facilities, treatment and supportive care are needed to address this likely under‐recognized public health problem in SSA., Introduction HIV‐associated multicentric Castleman disease (MCD) is a lymphoproliferative disorder caused by Kaposi sarcoma‐associated herpesvirus (KSHV) [1–5]. Unlike Kaposi sarcoma (KS), MCD incidence may be increasing in the antiretroviral therapy [...]

Published
2015
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50. Acute Myeloid Leukemia with Co‐mutated ASXL1 and SRSF2 Exhibits Monocytic Differentiation and has a Mutational Profile Overlapping with Chronic Myelomonocytic Leukemia

Author

Johnson, Steven M., primary, Richardson, Daniel R., additional, Galeotti, Jonathan, additional, Esparza, Sonia, additional, Zhu, Anqi, additional, Fedoriw, Yuri, additional, Weck, Karen E., additional, Foster, Matthew C., additional, Coombs, Catherine C., additional, Zeidner, Joshua F., additional, and Montgomery, Nathan D., additional

Published
2019
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