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28 results on '"Forman, Stephen"'

1. State-transition modeling of blood transcriptome predicts disease evolution and treatment response in chronic myeloid leukemia

Author

Frankhouser, David E, Frankhouser, David E, Rockne, Russell C, Uechi, Lisa, Zhao, Dandan, Branciamore, Sergio, O’Meally, Denis, Irizarry, Jihyun, Ghoda, Lucy, Ali, Haris, Trent, Jeffery M, Forman, Stephen, Fu, Yu-Hsuan, Kuo, Ya-Huei, Zhang, Bin, Marcucci, Guido, Frankhouser, David E, Frankhouser, David E, Rockne, Russell C, Uechi, Lisa, Zhao, Dandan, Branciamore, Sergio, O’Meally, Denis, Irizarry, Jihyun, Ghoda, Lucy, Ali, Haris, Trent, Jeffery M, Forman, Stephen, Fu, Yu-Hsuan, Kuo, Ya-Huei, Zhang, Bin, and Marcucci, Guido

Abstract

Chronic myeloid leukemia (CML) is initiated and maintained by BCR::ABL which is clinically targeted using tyrosine kinase inhibitors (TKIs). TKIs can induce long-term remission but are also not curative. Thus, CML is an ideal system to test our hypothesis that transcriptome-based state-transition models accurately predict cancer evolution and treatment response. We collected time-sequential blood samples from tetracycline-off (Tet-Off) BCR::ABL-inducible transgenic mice and wild-type controls. From the transcriptome, we constructed a CML state-space and a three-well leukemogenic potential landscape. The potential's stable critical points defined observable disease states. Early states were characterized by anti-CML genes opposing leukemia; late states were characterized by pro-CML genes. Genes with expression patterns shaped similarly to the potential landscape were identified as drivers of disease transition. Re-introduction of tetracycline to silence the BCR::ABL gene returned diseased mice transcriptomes to a near healthy state, without reaching it, suggesting parts of the transition are irreversible. TKI only reverted the transcriptome to an intermediate disease state, without approaching a state of health; disease relapse occurred soon after treatment. Using only the earliest time-point as initial conditions, our state-transition models accurately predicted both disease progression and treatment response, supporting this as a potentially valuable approach to time clinical intervention, before phenotypic changes become detectable.

Published
2024

2. Isoform-specific knockdown of long and intermediate prolactin receptors interferes with evolution of B-cell neoplasms.

Author

Taghi Khani, Adeleh, Taghi Khani, Adeleh, Kumar, Anil, Sanchez Ortiz, Ashly, Radecki, Kelly C, Aramburo, Soraya, Lee, Sung June, Hu, Zunsong, Damirchi, Behzad, Lorenson, Mary Y, Wu, Xiwei, Gu, Zhaohui, Stohl, William, Sanz, Ignacio, Meffre, Eric, Müschen, Markus, Forman, Stephen J, Koff, Jean L, Walker, Ameae M, Swaminathan, Srividya, Taghi Khani, Adeleh, Taghi Khani, Adeleh, Kumar, Anil, Sanchez Ortiz, Ashly, Radecki, Kelly C, Aramburo, Soraya, Lee, Sung June, Hu, Zunsong, Damirchi, Behzad, Lorenson, Mary Y, Wu, Xiwei, Gu, Zhaohui, Stohl, William, Sanz, Ignacio, Meffre, Eric, Müschen, Markus, Forman, Stephen J, Koff, Jean L, Walker, Ameae M, and Swaminathan, Srividya

Abstract

Prolactin (PRL) is elevated in B-cell-mediated lymphoproliferative diseases and promotes B-cell survival. Whether PRL or PRL receptors drive the evolution of B-cell malignancies is unknown. We measure changes in B cells after knocking down the pro-proliferative, anti-apoptotic long isoform of the PRL receptor (LFPRLR) in vivo in systemic lupus erythematosus (SLE)- and B-cell lymphoma-prone mouse models, and the long plus intermediate isoforms (LF/IFPRLR) in human B-cell malignancies. To knockdown LF/IFPRLRs without suppressing expression of the counteractive short PRLR isoforms (SFPRLRs), we employ splice-modulating DNA oligomers. In SLE-prone mice, LFPRLR knockdown reduces numbers and proliferation of pathogenic B-cell subsets and lowers the risk of B-cell transformation by downregulating expression of activation-induced cytidine deaminase. LFPRLR knockdown in lymphoma-prone mice reduces B-cell numbers and their expression of BCL2 and TCL1. In overt human B-cell malignancies, LF/IFPRLR knockdown reduces B-cell viability and their MYC and BCL2 expression. Unlike normal B cells, human B-cell malignancies secrete autocrine PRL and often express no SFPRLRs. Neutralization of secreted PRL reduces the viability of B-cell malignancies. Knockdown of LF/IFPRLR reduces the growth of human B-cell malignancies in vitro and in vivo. Thus, LF/IFPRLR knockdown is a highly specific approach to block the evolution of B-cell neoplasms.

Published
2023

3. State-Transition Analysis of Time-Sequential Gene Expression Identifies Critical Points That Predict Development of Acute Myeloid Leukemia.

Author

Branciamore, Sergio, Branciamore, Sergio, Qi, Jing, Frankhouser, David, OMeally, Denis, Hua, Wei-Kai, Cook, Guerry, Carnahan, Emily, Zhang, Lianjun, Marom, Ayelet, Wu, Herman, Maestrini, Davide, Wu, Xiwei, Yuan, Yate-Ching, Liu, Zheng, Wang, Leo, Forman, Stephen, Carlesso, Nadia, Kuo, Ya-Huei, Marcucci, Guido, Rockne, Russell, Branciamore, Sergio, Branciamore, Sergio, Qi, Jing, Frankhouser, David, OMeally, Denis, Hua, Wei-Kai, Cook, Guerry, Carnahan, Emily, Zhang, Lianjun, Marom, Ayelet, Wu, Herman, Maestrini, Davide, Wu, Xiwei, Yuan, Yate-Ching, Liu, Zheng, Wang, Leo, Forman, Stephen, Carlesso, Nadia, Kuo, Ya-Huei, Marcucci, Guido, and Rockne, Russell

Abstract

Temporal dynamics of gene expression inform cellular and molecular perturbations associated with disease development and evolution. Given the complexity of high-dimensional temporal genomic data, an analytic framework guided by a robust theory is needed to interpret time-sequential changes and to predict system dynamics. Here we model temporal dynamics of the transcriptome of peripheral blood mononuclear cells in a two-dimensional state-space representing states of health and leukemia using time-sequential bulk RNA-seq data from a murine model of acute myeloid leukemia (AML). The state-transition model identified critical points that accurately predict AML development and identifies stepwise transcriptomic perturbations that drive leukemia progression. The geometry of the transcriptome state-space provided a biological interpretation of gene dynamics, aligned gene signals that are not synchronized in time across mice, and allowed quantification of gene and pathway contributions to leukemia development. Our state-transition model synthesizes information from multiple cell types in the peripheral blood and identifies critical points in the transition from health to leukemia to guide interpretation of changes in the transcriptome as a whole to predict disease progression. SIGNIFICANCE: These findings apply the theory of state transitions to model the initiation and development of acute myeloid leukemia, identifying transcriptomic perturbations that accurately predict time to disease development.See related commentary by Kuijjer, p. 3072 GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/15/3157/F1.large.jpg.

Published
2020

4. Identifying CD38+ cells in patients with multiple myeloma: first-in-human imaging using copper-64-labeled daratumumab.

Author

Krishnan, Amrita, Krishnan, Amrita, Adhikarla, Vikram, Poku, Erasmus, Palmer, Joycelynne, Chaudhry, Ammar, Biglang-Awa, Van, Bowles, Nicole, Nathwani, Nitya, Rosenzweig, Michael, Sahebi, Firoozeh, Karanes, Chatchada, Simpson, Jennifer, Sanchez, James, Yamauchi, Dave, Parayno, Maria, Chowdhury, Arnab, Caserta, Enrico, Marcucci, Guido, Wu, Anna, Wong, Jeffrey, Forman, Stephen, Colcher, David, Yazaki, Paul, Shively, John, Pichiorri, Flavia, Rockne, Russell, Krishnan, Amrita, Krishnan, Amrita, Adhikarla, Vikram, Poku, Erasmus, Palmer, Joycelynne, Chaudhry, Ammar, Biglang-Awa, Van, Bowles, Nicole, Nathwani, Nitya, Rosenzweig, Michael, Sahebi, Firoozeh, Karanes, Chatchada, Simpson, Jennifer, Sanchez, James, Yamauchi, Dave, Parayno, Maria, Chowdhury, Arnab, Caserta, Enrico, Marcucci, Guido, Wu, Anna, Wong, Jeffrey, Forman, Stephen, Colcher, David, Yazaki, Paul, Shively, John, Pichiorri, Flavia, and Rockne, Russell

Abstract

18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is one of the most widely used imaging techniques to detect multiple myeloma (MM). Intracellular FDG uptake depicts in vivo metabolic activity, which can be seen in both malignant and nonmalignant cells, resulting in limited sensitivity and specificity. Our group showed preclinically that tracing MM dissemination using a CD38-directed human antibody, daratumumab, that is radioconjugated with 64Cu via the chelator DOTA (64Cu-daratumumab), led to improved sensitivity and specificity over that of FDG. Here, we report the results of a phase 1 trial designed to (1) assess the safety and feasibility of 64Cu-daratumumab PET/CT and (2) preliminarily evaluate and characterize the ability of 64Cu-daratumumab to accurately detect or exclude MM lesions. A total of 12 daratumumab-naive patients were imaged. Prior to the injection of 15 mCi/5 mg of 64Cu-daratumumab, patients were treated with 0 (n = 3), 10 (n = 3), 45 (n = 3), or 95 mg (n = 3) of unlabeled daratumumab to assess its effect on image quality. No significant adverse events were observed from either unlabeled daratumumab or 64Cu-daratumumab. Of the dose levels tested, 45 mg unlabeled daratumumab was the most optimal in terms of removing background signal without saturating target sites. 64Cu-daratumumab PET/CT provided safe whole-body imaging of MM. A trial comparing the sensitivity and specificity of 64Cu-daratumumab PET/CT with that of FDG PET/CT is planned. This trial was registered at www.clinicaltrials.gov as #NCT03311828.

Published
2020

5. Massively-Parallelized, Deterministic Mechanoporation for Intracellular Delivery.

Author

Dixit, Harish G, Dixit, Harish G, Starr, Renate, Dundon, Morgan L, Pairs, Pranee I, Yang, Xin, Zhang, Yanyan, Nampe, Daniel, Ballas, Christopher B, Tsutsui, Hideaki, Forman, Stephen J, Brown, Christine E, Rao, Masaru P, Dixit, Harish G, Dixit, Harish G, Starr, Renate, Dundon, Morgan L, Pairs, Pranee I, Yang, Xin, Zhang, Yanyan, Nampe, Daniel, Ballas, Christopher B, Tsutsui, Hideaki, Forman, Stephen J, Brown, Christine E, and Rao, Masaru P

Abstract

Microfluidic intracellular delivery approaches based on plasma membrane poration have shown promise for addressing the limitations of conventional cellular engineering techniques in a wide range of applications in biology and medicine. However, the inherent stochasticity of the poration process in many of these approaches often results in a trade-off between delivery efficiency and cellular viability, thus potentially limiting their utility. Herein, we present a novel microfluidic device concept that mitigates this trade-off by providing opportunity for deterministic mechanoporation (DMP) of cells en masse. This is achieved by the impingement of each cell upon a single needle-like penetrator during aspiration-based capture, followed by diffusive influx of exogenous cargo through the resulting membrane pore, once the cells are released by reversal of flow. Massive parallelization enables high throughput operation, while single-site poration allows for delivery of small and large-molecule cargos in difficult-to-transfect cells with efficiencies and viabilities that exceed both conventional and emerging transfection techniques. As such, DMP shows promise for advancing cellular engineering practice in general and engineered cell product manufacturing in particular.

Published
2020

6. Prognostic Score and Cytogenetic Risk Classification for Chronic Lymphocytic Leukemia Patients : Center for International Blood and Marrow Transplant Research Report

Author

Kim, Haesook T., Ahn, Kwang Woo, Hu, Zhen-Huan, Davids, Matthew S., Volpe, Virginia O., Antin, Joseph H., Sorror, Mohamed L., Shadman, Mazyar, Press, Oliver, Pidala, Joseph, Hogan, William, Negrin, Robert, Devine, Steven, Uberti, Joseph, Agura, Edward, Nash, Richard, Mehta, Jayesh, McGuirk, Joseph, Forman, Stephen, Langston, Amelia, Giralt, Sergio A., Perales, Miguel-Angel, Battiwalla, Minoo, Hale, Gregory A., Gale, Robert Peter, Marks, David I., Hamadani, Mehdi, Ganguly, Sid, Bacher, Ulrike, Lazarus, Hillard, Reshef, Ran, Hildebrandt, Gerhard C., Inamoto, Yoshihiro, Cahn, Jean-Yves, Solh, Melhem, Kharfan-Dabaja, Mohamed A., Ghosh, Nilanjan, Saad, Ayman, Aljurf, Mahmoud, Schouten, Harry C., Hill, Brian T., Pawarode, Attaphol, Kindwall-Keller, Tamila, Saba, Nakhle, Copelan, Edward A., Nathan, Sunita, Beitinjaneh, Amer, Savani, Bipin N., Cerny, Jan, Grunwald, Michael R., Yared, Jean, Wirk, Baldeep M., Nishihori, Taiga, Chhabra, Saurabh, Olsson, Richard, Bashey, Asad, Gergis, Usama, Popat, Uday, Sobecks, Ronald, Alyea, Edwin, Saber, Wael, Brown, Jennifer R., Kim, Haesook T., Ahn, Kwang Woo, Hu, Zhen-Huan, Davids, Matthew S., Volpe, Virginia O., Antin, Joseph H., Sorror, Mohamed L., Shadman, Mazyar, Press, Oliver, Pidala, Joseph, Hogan, William, Negrin, Robert, Devine, Steven, Uberti, Joseph, Agura, Edward, Nash, Richard, Mehta, Jayesh, McGuirk, Joseph, Forman, Stephen, Langston, Amelia, Giralt, Sergio A., Perales, Miguel-Angel, Battiwalla, Minoo, Hale, Gregory A., Gale, Robert Peter, Marks, David I., Hamadani, Mehdi, Ganguly, Sid, Bacher, Ulrike, Lazarus, Hillard, Reshef, Ran, Hildebrandt, Gerhard C., Inamoto, Yoshihiro, Cahn, Jean-Yves, Solh, Melhem, Kharfan-Dabaja, Mohamed A., Ghosh, Nilanjan, Saad, Ayman, Aljurf, Mahmoud, Schouten, Harry C., Hill, Brian T., Pawarode, Attaphol, Kindwall-Keller, Tamila, Saba, Nakhle, Copelan, Edward A., Nathan, Sunita, Beitinjaneh, Amer, Savani, Bipin N., Cerny, Jan, Grunwald, Michael R., Yared, Jean, Wirk, Baldeep M., Nishihori, Taiga, Chhabra, Saurabh, Olsson, Richard, Bashey, Asad, Gergis, Usama, Popat, Uday, Sobecks, Ronald, Alyea, Edwin, Saber, Wael, and Brown, Jennifer R.

Abstract

Purpose: To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT). Experimental Design: We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research. Results: On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P < 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or >= 5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years). Conclusions: In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.

Published
2019
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7. Development of Hematopoietic Stem Cell-Engineered Invariant Natural Killer T Cell Therapy for Cancer.

Author

Zhu, Yanni, Zhu, Yanni, Smith, Drake J, Zhou, Yang, Li, Yan-Ruide, Yu, Jiaji, Lee, Derek, Wang, Yu-Chen, Di Biase, Stefano, Wang, Xi, Hardoy, Christian, Ku, Josh, Tsao, Tasha, Lin, Levina J, Pham, Alexander T, Moon, Heesung, McLaughlin, Jami, Cheng, Donghui, Hollis, Roger P, Campo-Fernandez, Beatriz, Urbinati, Fabrizia, Wei, Liu, Pang, Larry, Rezek, Valerie, Berent-Maoz, Beata, Macabali, Mignonette H, Gjertson, David, Wang, Xiaoyan, Galic, Zoran, Kitchen, Scott G, An, Dong Sung, Hu-Lieskovan, Siwen, Kaplan-Lefko, Paula J, De Oliveira, Satiro N, Seet, Christopher S, Larson, Sarah M, Forman, Stephen J, Heath, James R, Zack, Jerome A, Crooks, Gay M, Radu, Caius G, Ribas, Antoni, Kohn, Donald B, Witte, Owen N, Yang, Lili, Zhu, Yanni, Zhu, Yanni, Smith, Drake J, Zhou, Yang, Li, Yan-Ruide, Yu, Jiaji, Lee, Derek, Wang, Yu-Chen, Di Biase, Stefano, Wang, Xi, Hardoy, Christian, Ku, Josh, Tsao, Tasha, Lin, Levina J, Pham, Alexander T, Moon, Heesung, McLaughlin, Jami, Cheng, Donghui, Hollis, Roger P, Campo-Fernandez, Beatriz, Urbinati, Fabrizia, Wei, Liu, Pang, Larry, Rezek, Valerie, Berent-Maoz, Beata, Macabali, Mignonette H, Gjertson, David, Wang, Xiaoyan, Galic, Zoran, Kitchen, Scott G, An, Dong Sung, Hu-Lieskovan, Siwen, Kaplan-Lefko, Paula J, De Oliveira, Satiro N, Seet, Christopher S, Larson, Sarah M, Forman, Stephen J, Heath, James R, Zack, Jerome A, Crooks, Gay M, Radu, Caius G, Ribas, Antoni, Kohn, Donald B, Witte, Owen N, and Yang, Lili

Abstract

Invariant natural killer T (iNKT) cells are potent immune cells for targeting cancer; however, their clinical application has been hindered by their low numbers in cancer patients. Here, we developed a proof-of-concept for hematopoietic stem cell-engineered iNKT (HSC-iNKT) cell therapy with the potential to provide therapeutic levels of iNKT cells for a patient's lifetime. Using a human HSC engrafted mouse model and a human iNKT TCR gene engineering approach, we demonstrated the efficient and long-term generation of HSC-iNKT cells in vivo. These HSC-iNKT cells closely resembled endogenous human iNKT cells, could deploy multiple mechanisms to attack tumor cells, and effectively suppressed tumor growth in vivo in multiple human tumor xenograft mouse models. Preclinical safety studies showed no toxicity or tumorigenicity of the HSC-iNKT cell therapy. Collectively, these results demonstrated the feasibility, safety, and cancer therapy potential of the proposed HSC-iNKT cell therapy and laid a foundation for future clinical development.

Published
2019

8. Development of Hematopoietic Stem Cell-Engineered Invariant Natural Killer T Cell Therapy for Cancer.

Author

Zhu, Yanni, Zhu, Yanni, Smith, Drake J, Zhou, Yang, Li, Yan-Ruide, Yu, Jiaji, Lee, Derek, Wang, Yu-Chen, Di Biase, Stefano, Wang, Xi, Hardoy, Christian, Ku, Josh, Tsao, Tasha, Lin, Levina J, Pham, Alexander T, Moon, Heesung, McLaughlin, Jami, Cheng, Donghui, Hollis, Roger P, Campo-Fernandez, Beatriz, Urbinati, Fabrizia, Wei, Liu, Pang, Larry, Rezek, Valerie, Berent-Maoz, Beata, Macabali, Mignonette H, Gjertson, David, Wang, Xiaoyan, Galic, Zoran, Kitchen, Scott G, An, Dong Sung, Hu-Lieskovan, Siwen, Kaplan-Lefko, Paula J, De Oliveira, Satiro N, Seet, Christopher S, Larson, Sarah M, Forman, Stephen J, Heath, James R, Zack, Jerome A, Crooks, Gay M, Radu, Caius G, Ribas, Antoni, Kohn, Donald B, Witte, Owen N, Yang, Lili, Zhu, Yanni, Zhu, Yanni, Smith, Drake J, Zhou, Yang, Li, Yan-Ruide, Yu, Jiaji, Lee, Derek, Wang, Yu-Chen, Di Biase, Stefano, Wang, Xi, Hardoy, Christian, Ku, Josh, Tsao, Tasha, Lin, Levina J, Pham, Alexander T, Moon, Heesung, McLaughlin, Jami, Cheng, Donghui, Hollis, Roger P, Campo-Fernandez, Beatriz, Urbinati, Fabrizia, Wei, Liu, Pang, Larry, Rezek, Valerie, Berent-Maoz, Beata, Macabali, Mignonette H, Gjertson, David, Wang, Xiaoyan, Galic, Zoran, Kitchen, Scott G, An, Dong Sung, Hu-Lieskovan, Siwen, Kaplan-Lefko, Paula J, De Oliveira, Satiro N, Seet, Christopher S, Larson, Sarah M, Forman, Stephen J, Heath, James R, Zack, Jerome A, Crooks, Gay M, Radu, Caius G, Ribas, Antoni, Kohn, Donald B, Witte, Owen N, and Yang, Lili

Abstract

Invariant natural killer T (iNKT) cells are potent immune cells for targeting cancer; however, their clinical application has been hindered by their low numbers in cancer patients. Here, we developed a proof-of-concept for hematopoietic stem cell-engineered iNKT (HSC-iNKT) cell therapy with the potential to provide therapeutic levels of iNKT cells for a patient's lifetime. Using a human HSC engrafted mouse model and a human iNKT TCR gene engineering approach, we demonstrated the efficient and long-term generation of HSC-iNKT cells in vivo. These HSC-iNKT cells closely resembled endogenous human iNKT cells, could deploy multiple mechanisms to attack tumor cells, and effectively suppressed tumor growth in vivo in multiple human tumor xenograft mouse models. Preclinical safety studies showed no toxicity or tumorigenicity of the HSC-iNKT cell therapy. Collectively, these results demonstrated the feasibility, safety, and cancer therapy potential of the proposed HSC-iNKT cell therapy and laid a foundation for future clinical development.

Published
2019

9. Molecular response with blinatumomab in relapsed/refractory B-cell precursor acute lymphoblastic leukemia.

Author

Gökbuget, Nicola, Gökbuget, Nicola, Kantarjian, Hagop M, Brüggemann, Monika, Stein, Anthony S, Bargou, Ralf C, Dombret, Hervé, Fielding, Adele K, Heffner, Leonard, Rigal-Huguet, Françoise, Litzow, Mark, O'Brien, Susan, Zugmaier, Gerhard, Gao, Shan, Nagorsen, Dirk, Forman, Stephen J, Topp, Max S, Gökbuget, Nicola, Gökbuget, Nicola, Kantarjian, Hagop M, Brüggemann, Monika, Stein, Anthony S, Bargou, Ralf C, Dombret, Hervé, Fielding, Adele K, Heffner, Leonard, Rigal-Huguet, Françoise, Litzow, Mark, O'Brien, Susan, Zugmaier, Gerhard, Gao, Shan, Nagorsen, Dirk, Forman, Stephen J, and Topp, Max S

Abstract

Minimal residual disease (MRD), where leukemic cell levels are lower than the morphologic detection threshold, is the most important prognostic factor for acute lymphoblastic leukemia (ALL) relapse during first-line chemotherapy treatment and is standard of care in treatment monitoring and decision making. Limited data are available on the prognostic value of MRD response after relapse. We evaluated the relationship between MRD response and outcomes in blinatumomab-treated adults with relapsed/refractory (R/R) B-cell precursor ALL. Of 90 patients with complete remission (CR) or CR with partial hematologic recovery (CRh), 64 (71.1%) achieved a complete MRD response (no detectable individual rearrangements of immunoglobulin/T-cell receptor genes by polymerase chain reaction [PCR] at a minimum sensitivity level of 10-4). Eleven patients had MRD <10-4. Therefore, overall, 75 (83.3%) experienced an MRD response (no detectable MRD or detectable MRD) measured by PCR within the first 2 treatment cycles. Overall survival (OS) and relapse-free survival (RFS) were significantly longer in patients who achieved CR/CRh and MRD response (median, 20.6 and 9.0 months, respectively) compared with CR/CRh patients without MRD response (median, 12.5 and 2.3 months, respectively). In conclusion, longer durations of OS and RFS associated with MRD response support the value of achieving MRD response and its use as a prognostic factor for blinatumomab treatment in R/R ALL. This trial was registered at www.clinicaltrials.gov as #NCT01466179.

Published
2019

10. US Intergroup Study of Chemotherapy Plus Dasatinib and Allogeneic Stem Cell Transplant in Philadelphia Chromosome Positive ALL.

Author

Forman, Stephen, Forman, Stephen, Ha, Chul, Wong, Jeffrey, Tallman, Martin, Paietta, Elisabeth, Racevskis, Janis, Uy, Geoffrey, Horowitz, Mary, Takebe, Naoko, Little, Richard, Borate, Uma, Kebriaei, Partow, Kingsbury, Laura, Kantarjian, Hagop, Radich, Jerald, Erba, Harry, Appelbaum, Frederick, Ravandi, Farhad, Othus, Megan, OBrien, Susan, Forman, Stephen, Forman, Stephen, Ha, Chul, Wong, Jeffrey, Tallman, Martin, Paietta, Elisabeth, Racevskis, Janis, Uy, Geoffrey, Horowitz, Mary, Takebe, Naoko, Little, Richard, Borate, Uma, Kebriaei, Partow, Kingsbury, Laura, Kantarjian, Hagop, Radich, Jerald, Erba, Harry, Appelbaum, Frederick, Ravandi, Farhad, Othus, Megan, and OBrien, Susan

Abstract

This multicenter trial was conducted to determine whether the addition of dasatinib to chemotherapy followed by an allogeneic hematopoietic cell transplant (HCT) in patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) was feasible. Patients ≥ 18 and ≤ 60 years of age with newly diagnosed Ph+ ALL received up to 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate with dasatinib. Patients with an available matched sibling or unrelated donor underwent an allogeneic HCT in first complete remission (CR1) followed by daily dasatinib starting from day 100. Others received maintenance therapy with vincristine and prednisone for 2 years and dasatinib indefinitely. 97 patients (94 evaluable) with median age of 44 years (range, 20 - 60) and median WBC at presentation of 10 × 109/L (range, 1 - 410 × 109/L) were accrued. 83 (88%) patients achieved CR or CR with incomplete count recovery (CRi) and 41 underwent ASCT in CR1. Median follow-up is 36 months (range, 9 - 63). For the overall population, overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) at 3 years were 69%, 55%, and 62%, respectively. The 12-month RFS and OS after transplant were 71% and 87%, respectively. Landmark analysis at 175 days from the time of CR/CRi (longest time to HCT), showed statistically superior advantages for RFS and OS (p=0.038 and 0.037, respectively) for the transplanted patients. Addition of dasatinib to chemotherapy and HCT for younger patients with Ph+ ALL is feasible and warrants further testing.

Published
2016

11. Intravenous Busulfan Compared with Total Body Irradiation Pretransplant Conditioning for Adults with Acute Lymphoblastic Leukemia

Author

Kebriaei, Partow, Anasetti, Claudio, Zhang, Mei Jie, Wang, Hai Lin, Aldoss, Ibrahim, de Lima, Marcos, Khoury, H. Jean, Sandmaier, Brenda M., Horowitz, Mary M., Artz, Andrew, Bejanyan, Nelli, Ciurea, Stefan, Lazarus, Hillard M., Gale, Robert Peter, Litzow, Mark, Bredeson, Christopher, Seftel, Matthew D., Pulsipher, Michael A., Boelens, Jaap Jan, Alvarnas, Joseph, Champlin, Richard, Forman, Stephen, Pullarkat, Vinod, Weisdorf, Daniel, Marks, David I., Hogan, William, Battiwalla, Minoo, Copelan, Edward, Hildebrandt, Gerhard, Ganguly, Sid, Majhail, Navneet, Woolfrey, Ann, Nivison-Smith, Ian, Hertzberg, Mark, Diaz, Miguel Angel, Jakubowski, Ann, Ustun, Celalettin, Yong, Agnes, Freytes, Cesar, DeFilipp, Zachariah, Inamoto, Yoshi, Cahn, Jean Yves, Savani, Bipin, Yared, Jean, Bajel, Ashish, Bacher, Ulrike, Uy, Geoffrey, Rizzieri, David, Wieduwilt, Matthew, Bierings, Marc, Acute Leukemia Committee of the CIBMTR, Kebriaei, Partow, Anasetti, Claudio, Zhang, Mei Jie, Wang, Hai Lin, Aldoss, Ibrahim, de Lima, Marcos, Khoury, H. Jean, Sandmaier, Brenda M., Horowitz, Mary M., Artz, Andrew, Bejanyan, Nelli, Ciurea, Stefan, Lazarus, Hillard M., Gale, Robert Peter, Litzow, Mark, Bredeson, Christopher, Seftel, Matthew D., Pulsipher, Michael A., Boelens, Jaap Jan, Alvarnas, Joseph, Champlin, Richard, Forman, Stephen, Pullarkat, Vinod, Weisdorf, Daniel, Marks, David I., Hogan, William, Battiwalla, Minoo, Copelan, Edward, Hildebrandt, Gerhard, Ganguly, Sid, Majhail, Navneet, Woolfrey, Ann, Nivison-Smith, Ian, Hertzberg, Mark, Diaz, Miguel Angel, Jakubowski, Ann, Ustun, Celalettin, Yong, Agnes, Freytes, Cesar, DeFilipp, Zachariah, Inamoto, Yoshi, Cahn, Jean Yves, Savani, Bipin, Yared, Jean, Bajel, Ashish, Bacher, Ulrike, Uy, Geoffrey, Rizzieri, David, Wieduwilt, Matthew, Bierings, Marc, and Acute Leukemia Committee of the CIBMTR

Published
2018

12. Intravenous Busulfan Compared with Total Body Irradiation Pretransplant Conditioning for Adults with Acute Lymphoblastic Leukemia

Author

Kebriaei, Partow, Anasetti, Claudio, Zhang, Mei Jie, Wang, Hai Lin, Aldoss, Ibrahim, de Lima, Marcos, Khoury, H. Jean, Sandmaier, Brenda M., Horowitz, Mary M., Artz, Andrew, Bejanyan, Nelli, Ciurea, Stefan, Lazarus, Hillard M., Gale, Robert Peter, Litzow, Mark, Bredeson, Christopher, Seftel, Matthew D., Pulsipher, Michael A., Boelens, Jaap Jan, Alvarnas, Joseph, Champlin, Richard, Forman, Stephen, Pullarkat, Vinod, Weisdorf, Daniel, Marks, David I., Hogan, William, Battiwalla, Minoo, Copelan, Edward, Hildebrandt, Gerhard, Ganguly, Sid, Majhail, Navneet, Woolfrey, Ann, Nivison-Smith, Ian, Hertzberg, Mark, Diaz, Miguel Angel, Jakubowski, Ann, Ustun, Celalettin, Yong, Agnes, Freytes, Cesar, DeFilipp, Zachariah, Inamoto, Yoshi, Cahn, Jean Yves, Savani, Bipin, Yared, Jean, Bajel, Ashish, Bacher, Ulrike, Uy, Geoffrey, Rizzieri, David, Wieduwilt, Matthew, Bierings, Marc, Acute Leukemia Committee of the CIBMTR, Kebriaei, Partow, Anasetti, Claudio, Zhang, Mei Jie, Wang, Hai Lin, Aldoss, Ibrahim, de Lima, Marcos, Khoury, H. Jean, Sandmaier, Brenda M., Horowitz, Mary M., Artz, Andrew, Bejanyan, Nelli, Ciurea, Stefan, Lazarus, Hillard M., Gale, Robert Peter, Litzow, Mark, Bredeson, Christopher, Seftel, Matthew D., Pulsipher, Michael A., Boelens, Jaap Jan, Alvarnas, Joseph, Champlin, Richard, Forman, Stephen, Pullarkat, Vinod, Weisdorf, Daniel, Marks, David I., Hogan, William, Battiwalla, Minoo, Copelan, Edward, Hildebrandt, Gerhard, Ganguly, Sid, Majhail, Navneet, Woolfrey, Ann, Nivison-Smith, Ian, Hertzberg, Mark, Diaz, Miguel Angel, Jakubowski, Ann, Ustun, Celalettin, Yong, Agnes, Freytes, Cesar, DeFilipp, Zachariah, Inamoto, Yoshi, Cahn, Jean Yves, Savani, Bipin, Yared, Jean, Bajel, Ashish, Bacher, Ulrike, Uy, Geoffrey, Rizzieri, David, Wieduwilt, Matthew, Bierings, Marc, and Acute Leukemia Committee of the CIBMTR

Published
2018

13. Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma.

Author

Sullivan, Keith M, Sullivan, Keith M, Goldmuntz, Ellen A, Keyes-Elstein, Lynette, McSweeney, Peter A, Pinckney, Ashley, Welch, Beverly, Mayes, Maureen D, Nash, Richard A, Crofford, Leslie J, Eggleston, Barry, Castina, Sharon, Griffith, Linda M, Goldstein, Julia S, Wallace, Dennis, Craciunescu, Oana, Khanna, Dinesh, Folz, Rodney J, Goldin, Jonathan, St Clair, E William, Seibold, James R, Phillips, Kristine, Mineishi, Shin, Simms, Robert W, Ballen, Karen, Wener, Mark H, Georges, George E, Heimfeld, Shelly, Hosing, Chitra, Forman, Stephen, Kafaja, Suzanne, Silver, Richard M, Griffing, Leroy, Storek, Jan, LeClercq, Sharon, Brasington, Richard, Csuka, Mary E, Bredeson, Christopher, Keever-Taylor, Carolyn, Domsic, Robyn T, Kahaleh, M Bashar, Medsger, Thomas, Furst, Daniel E, SCOT Study Investigators, Sullivan, Keith M, Sullivan, Keith M, Goldmuntz, Ellen A, Keyes-Elstein, Lynette, McSweeney, Peter A, Pinckney, Ashley, Welch, Beverly, Mayes, Maureen D, Nash, Richard A, Crofford, Leslie J, Eggleston, Barry, Castina, Sharon, Griffith, Linda M, Goldstein, Julia S, Wallace, Dennis, Craciunescu, Oana, Khanna, Dinesh, Folz, Rodney J, Goldin, Jonathan, St Clair, E William, Seibold, James R, Phillips, Kristine, Mineishi, Shin, Simms, Robert W, Ballen, Karen, Wener, Mark H, Georges, George E, Heimfeld, Shelly, Hosing, Chitra, Forman, Stephen, Kafaja, Suzanne, Silver, Richard M, Griffing, Leroy, Storek, Jan, LeClercq, Sharon, Brasington, Richard, Csuka, Mary E, Bredeson, Christopher, Keever-Taylor, Carolyn, Domsic, Robyn T, Kahaleh, M Bashar, Medsger, Thomas, Furst, Daniel E, and SCOT Study Investigators

Abstract

BackgroundDespite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma.MethodsWe randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants). The primary end point was a global rank composite score comparing participants with each other on the basis of a hierarchy of disease features assessed at 54 months: death, event-free survival (survival without respiratory, renal, or cardiac failure), forced vital capacity, the score on the Disability Index of the Health Assessment Questionnaire, and the modified Rodnan skin score.ResultsIn the intention-to-treat population, global rank composite scores at 54 months showed the superiority of transplantation (67% of 1404 pairwise comparisons favored transplantation and 33% favored cyclophosphamide, P=0.01). In the per-protocol population (participants who received a transplant or completed ≥9 doses of cyclophosphamide), the rate of event-free survival at 54 months was 79% in the transplantation group and 50% in the cyclophosphamide group (P=0.02). At 72 months, Kaplan-Meier estimates of event-free survival (74% vs. 47%) and overall survival (86% vs. 51%) also favored transplantation (P=0.03 and 0.02, respectively). A total of 9% of the participants in the transplantation group had initiated disease-modifying antirheumatic drugs (DMARDs) by 54 months, as compared with 44% of those in the cyclophosphamide group (P=0.001). Treatment-related mortality in the transplantation group was 3% at 54 months and 6% at 72 months, as compared with 0% in the cyclophosphamide group.ConclusionsMyeloablative autologous hematopoietic stem-cell transplantation achiev

Published
2018

14. Intravenous Busulfan Compared with Total Body Irradiation Pretransplant Conditioning for Adults with Acute Lymphoblastic Leukemia

Author

CTI Nierkens, Child Health, Regenerative Medicine and Stem Cells, Haematologie, Kebriaei, Partow, Anasetti, Claudio, Zhang, Mei Jie, Wang, Hai Lin, Aldoss, Ibrahim, de Lima, Marcos, Khoury, H. Jean, Sandmaier, Brenda M., Horowitz, Mary M., Artz, Andrew, Bejanyan, Nelli, Ciurea, Stefan, Lazarus, Hillard M., Gale, Robert Peter, Litzow, Mark, Bredeson, Christopher, Seftel, Matthew D., Pulsipher, Michael A., Boelens, Jaap Jan, Alvarnas, Joseph, Champlin, Richard, Forman, Stephen, Pullarkat, Vinod, Weisdorf, Daniel, Marks, David I., Hogan, William, Battiwalla, Minoo, Copelan, Edward, Hildebrandt, Gerhard, Ganguly, Sid, Majhail, Navneet, Woolfrey, Ann, Nivison-Smith, Ian, Hertzberg, Mark, Diaz, Miguel Angel, Jakubowski, Ann, Ustun, Celalettin, Yong, Agnes, Freytes, Cesar, DeFilipp, Zachariah, Inamoto, Yoshi, Cahn, Jean Yves, Savani, Bipin, Yared, Jean, Bajel, Ashish, Bacher, Ulrike, Uy, Geoffrey, Rizzieri, David, Wieduwilt, Matthew, Bierings, Marc, Acute Leukemia Committee of the CIBMTR, CTI Nierkens, Child Health, Regenerative Medicine and Stem Cells, Haematologie, Kebriaei, Partow, Anasetti, Claudio, Zhang, Mei Jie, Wang, Hai Lin, Aldoss, Ibrahim, de Lima, Marcos, Khoury, H. Jean, Sandmaier, Brenda M., Horowitz, Mary M., Artz, Andrew, Bejanyan, Nelli, Ciurea, Stefan, Lazarus, Hillard M., Gale, Robert Peter, Litzow, Mark, Bredeson, Christopher, Seftel, Matthew D., Pulsipher, Michael A., Boelens, Jaap Jan, Alvarnas, Joseph, Champlin, Richard, Forman, Stephen, Pullarkat, Vinod, Weisdorf, Daniel, Marks, David I., Hogan, William, Battiwalla, Minoo, Copelan, Edward, Hildebrandt, Gerhard, Ganguly, Sid, Majhail, Navneet, Woolfrey, Ann, Nivison-Smith, Ian, Hertzberg, Mark, Diaz, Miguel Angel, Jakubowski, Ann, Ustun, Celalettin, Yong, Agnes, Freytes, Cesar, DeFilipp, Zachariah, Inamoto, Yoshi, Cahn, Jean Yves, Savani, Bipin, Yared, Jean, Bajel, Ashish, Bacher, Ulrike, Uy, Geoffrey, Rizzieri, David, Wieduwilt, Matthew, Bierings, Marc, and Acute Leukemia Committee of the CIBMTR

Published
2018

15. Reporter gene imaging of targeted T cell immunotherapy in recurrent glioma.

Author

Keu, Khun Visith, Keu, Khun Visith, Witney, Timothy H, Yaghoubi, Shahriar, Rosenberg, Jarrett, Kurien, Anita, Magnusson, Rachel, Williams, John, Habte, Frezghi, Wagner, Jamie R, Forman, Stephen, Brown, Christine, Allen-Auerbach, Martin, Czernin, Johannes, Tang, Winson, Jensen, Michael C, Badie, Behnam, Gambhir, Sanjiv S, Keu, Khun Visith, Keu, Khun Visith, Witney, Timothy H, Yaghoubi, Shahriar, Rosenberg, Jarrett, Kurien, Anita, Magnusson, Rachel, Williams, John, Habte, Frezghi, Wagner, Jamie R, Forman, Stephen, Brown, Christine, Allen-Auerbach, Martin, Czernin, Johannes, Tang, Winson, Jensen, Michael C, Badie, Behnam, and Gambhir, Sanjiv S

Abstract

High-grade gliomas are aggressive cancers that often become rapidly fatal. Immunotherapy using CD8+ cytotoxic T lymphocytes (CTLs), engineered to express both herpes simplex virus type 1 thymidine kinase (HSV1-TK) and interleukin-13 (IL-13) zetakine chimeric antigen receptor (CAR), is a treatment strategy with considerable potential. To optimize this and related immunotherapies, it would be helpful to monitor CTL viability and trafficking to glioma cells. We show that noninvasive positron emission tomography (PET) imaging with 9-[4-[18F]fluoro-3-(hydroxymethyl)butyl]guanine ([18F]FHBG) can track HSV1-tk reporter gene expression present in CAR-engineered CTLs. [18F]FHBG imaging was safe and enabled the longitudinal imaging of T cells stably transfected with a PET reporter gene in patients. Further optimization of this imaging approach for monitoring in vivo cell trafficking should greatly benefit various cell-based therapies for cancer.

Published
2017

16. Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia.

Author

Gu, Zhaohui, Gu, Zhaohui, Churchman, Michelle, Roberts, Kathryn, Li, Yongjin, Liu, Yu, Harvey, Richard C, McCastlain, Kelly, Reshmi, Shalini C, Payne-Turner, Debbie, Iacobucci, Ilaria, Shao, Ying, Chen, I-Ming, Valentine, Marcus, Pei, Deqing, Mungall, Karen L, Mungall, Andrew J, Ma, Yussanne, Moore, Richard, Marra, Marco, Stonerock, Eileen, Gastier-Foster, Julie M, Devidas, Meenakshi, Dai, Yunfeng, Wood, Brent, Borowitz, Michael, Larsen, Eric E, Maloney, Kelly, Mattano, Leonard A, Angiolillo, Anne, Salzer, Wanda L, Burke, Michael J, Gianni, Francesca, Spinelli, Orietta, Radich, Jerald P, Minden, Mark D, Moorman, Anthony V, Patel, Bella, Fielding, Adele K, Rowe, Jacob M, Luger, Selina M, Bhatia, Ravi, Aldoss, Ibrahim, Forman, Stephen J, Kohlschmidt, Jessica, Mrózek, Krzysztof, Marcucci, Guido, Bloomfield, Clara D, Stock, Wendy, Kornblau, Steven, Kantarjian, Hagop M, Konopleva, Marina, Paietta, Elisabeth, Willman, Cheryl L, Loh, Mignon L, Hunger, Stephen P, Mullighan, Charles G, Gu, Zhaohui, Gu, Zhaohui, Churchman, Michelle, Roberts, Kathryn, Li, Yongjin, Liu, Yu, Harvey, Richard C, McCastlain, Kelly, Reshmi, Shalini C, Payne-Turner, Debbie, Iacobucci, Ilaria, Shao, Ying, Chen, I-Ming, Valentine, Marcus, Pei, Deqing, Mungall, Karen L, Mungall, Andrew J, Ma, Yussanne, Moore, Richard, Marra, Marco, Stonerock, Eileen, Gastier-Foster, Julie M, Devidas, Meenakshi, Dai, Yunfeng, Wood, Brent, Borowitz, Michael, Larsen, Eric E, Maloney, Kelly, Mattano, Leonard A, Angiolillo, Anne, Salzer, Wanda L, Burke, Michael J, Gianni, Francesca, Spinelli, Orietta, Radich, Jerald P, Minden, Mark D, Moorman, Anthony V, Patel, Bella, Fielding, Adele K, Rowe, Jacob M, Luger, Selina M, Bhatia, Ravi, Aldoss, Ibrahim, Forman, Stephen J, Kohlschmidt, Jessica, Mrózek, Krzysztof, Marcucci, Guido, Bloomfield, Clara D, Stock, Wendy, Kornblau, Steven, Kantarjian, Hagop M, Konopleva, Marina, Paietta, Elisabeth, Willman, Cheryl L, Loh, Mignon L, Hunger, Stephen P, and Mullighan, Charles G

Abstract

Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered.

Published
2016

17. Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia.

Author

Gu, Zhaohui, Gu, Zhaohui, Churchman, Michelle, Roberts, Kathryn, Li, Yongjin, Liu, Yu, Harvey, Richard C, McCastlain, Kelly, Reshmi, Shalini C, Payne-Turner, Debbie, Iacobucci, Ilaria, Shao, Ying, Chen, I-Ming, Valentine, Marcus, Pei, Deqing, Mungall, Karen L, Mungall, Andrew J, Ma, Yussanne, Moore, Richard, Marra, Marco, Stonerock, Eileen, Gastier-Foster, Julie M, Devidas, Meenakshi, Dai, Yunfeng, Wood, Brent, Borowitz, Michael, Larsen, Eric E, Maloney, Kelly, Mattano, Leonard A, Angiolillo, Anne, Salzer, Wanda L, Burke, Michael J, Gianni, Francesca, Spinelli, Orietta, Radich, Jerald P, Minden, Mark D, Moorman, Anthony V, Patel, Bella, Fielding, Adele K, Rowe, Jacob M, Luger, Selina M, Bhatia, Ravi, Aldoss, Ibrahim, Forman, Stephen J, Kohlschmidt, Jessica, Mrózek, Krzysztof, Marcucci, Guido, Bloomfield, Clara D, Stock, Wendy, Kornblau, Steven, Kantarjian, Hagop M, Konopleva, Marina, Paietta, Elisabeth, Willman, Cheryl L, Loh, Mignon L, Hunger, Stephen P, Mullighan, Charles G, Gu, Zhaohui, Gu, Zhaohui, Churchman, Michelle, Roberts, Kathryn, Li, Yongjin, Liu, Yu, Harvey, Richard C, McCastlain, Kelly, Reshmi, Shalini C, Payne-Turner, Debbie, Iacobucci, Ilaria, Shao, Ying, Chen, I-Ming, Valentine, Marcus, Pei, Deqing, Mungall, Karen L, Mungall, Andrew J, Ma, Yussanne, Moore, Richard, Marra, Marco, Stonerock, Eileen, Gastier-Foster, Julie M, Devidas, Meenakshi, Dai, Yunfeng, Wood, Brent, Borowitz, Michael, Larsen, Eric E, Maloney, Kelly, Mattano, Leonard A, Angiolillo, Anne, Salzer, Wanda L, Burke, Michael J, Gianni, Francesca, Spinelli, Orietta, Radich, Jerald P, Minden, Mark D, Moorman, Anthony V, Patel, Bella, Fielding, Adele K, Rowe, Jacob M, Luger, Selina M, Bhatia, Ravi, Aldoss, Ibrahim, Forman, Stephen J, Kohlschmidt, Jessica, Mrózek, Krzysztof, Marcucci, Guido, Bloomfield, Clara D, Stock, Wendy, Kornblau, Steven, Kantarjian, Hagop M, Konopleva, Marina, Paietta, Elisabeth, Willman, Cheryl L, Loh, Mignon L, Hunger, Stephen P, and Mullighan, Charles G

Abstract

Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered.

Published
2016

18. US Intergroup Study of Chemotherapy Plus Dasatinib and Allogeneic Stem Cell Transplant in Philadelphia Chromosome Positive ALL.

Author

Ravandi, Farhad, Ravandi, Farhad, Othus, Megan, O'Brien, Susan M, Forman, Stephen J, Ha, Chul S, Wong, Jeffrey YC, Tallman, Martin S, Paietta, Elisabeth, Racevskis, Janis, Uy, Geoffrey L, Horowitz, Mary, Takebe, Naoko, Little, Richard, Borate, Uma, Kebriaei, Partow, Kingsbury, Laura, Kantarjian, Hagop M, Radich, Jerald P, Erba, Harry P, Appelbaum, Frederick R, Ravandi, Farhad, Ravandi, Farhad, Othus, Megan, O'Brien, Susan M, Forman, Stephen J, Ha, Chul S, Wong, Jeffrey YC, Tallman, Martin S, Paietta, Elisabeth, Racevskis, Janis, Uy, Geoffrey L, Horowitz, Mary, Takebe, Naoko, Little, Richard, Borate, Uma, Kebriaei, Partow, Kingsbury, Laura, Kantarjian, Hagop M, Radich, Jerald P, Erba, Harry P, and Appelbaum, Frederick R

Abstract

This multicenter trial was conducted to determine whether the addition of dasatinib to chemotherapy followed by an allogeneic hematopoietic cell transplant (HCT) in patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) was feasible. Patients ≥ 18 and ≤ 60 years of age with newly diagnosed Ph+ ALL received up to 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate with dasatinib. Patients with an available matched sibling or unrelated donor underwent an allogeneic HCT in first complete remission (CR1) followed by daily dasatinib starting from day 100. Others received maintenance therapy with vincristine and prednisone for 2 years and dasatinib indefinitely. 97 patients (94 evaluable) with median age of 44 years (range, 20 - 60) and median WBC at presentation of 10 × 109/L (range, 1 - 410 × 109/L) were accrued. 83 (88%) patients achieved CR or CR with incomplete count recovery (CRi) and 41 underwent ASCT in CR1. Median follow-up is 36 months (range, 9 - 63). For the overall population, overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) at 3 years were 69%, 55%, and 62%, respectively. The 12-month RFS and OS after transplant were 71% and 87%, respectively. Landmark analysis at 175 days from the time of CR/CRi (longest time to HCT), showed statistically superior advantages for RFS and OS (p=0.038 and 0.037, respectively) for the transplanted patients. Addition of dasatinib to chemotherapy and HCT for younger patients with Ph+ ALL is feasible and warrants further testing.

Published
2016

19. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia.

Author

Boyiadzis, Michael, Boyiadzis, Michael, Bishop, Michael, Abonour, Rafat, Anderson, Kenneth, Ansell, Stephen, Avigan, David, Barbarotta, Lisa, Barrett, Austin, Van Besien, Koen, Bergsagel, P, Borrello, Ivan, Brody, Joshua, Brufsky, Jill, Cairo, Mitchell, Chari, Ajai, Cohen, Adam, Cortes, Jorge, Forman, Stephen, Friedberg, Jonathan, Fuchs, Ephraim, Gore, Steven, Jagannath, Sundar, Kahl, Brad, Kline, Justin, Kochenderfer, James, Kwak, Larry, Levy, Ronald, de Lima, Marcos, Litzow, Mark, Mahindra, Anuj, Miller, Jeffrey, Munshi, Nikhil, Orlowski, Robert, Pagel, John, Porter, David, Russell, Stephen, Schwartz, Karl, Shipp, Margaret, Siegel, David, Stone, Richard, Tallman, Martin, Timmerman, John, Van Rhee, Frits, Waller, Edmund, Welsh, Ann, Werner, Michael, Wiernik, Peter, Dhodapkar, Madhav, Boyiadzis, Michael, Boyiadzis, Michael, Bishop, Michael, Abonour, Rafat, Anderson, Kenneth, Ansell, Stephen, Avigan, David, Barbarotta, Lisa, Barrett, Austin, Van Besien, Koen, Bergsagel, P, Borrello, Ivan, Brody, Joshua, Brufsky, Jill, Cairo, Mitchell, Chari, Ajai, Cohen, Adam, Cortes, Jorge, Forman, Stephen, Friedberg, Jonathan, Fuchs, Ephraim, Gore, Steven, Jagannath, Sundar, Kahl, Brad, Kline, Justin, Kochenderfer, James, Kwak, Larry, Levy, Ronald, de Lima, Marcos, Litzow, Mark, Mahindra, Anuj, Miller, Jeffrey, Munshi, Nikhil, Orlowski, Robert, Pagel, John, Porter, David, Russell, Stephen, Schwartz, Karl, Shipp, Margaret, Siegel, David, Stone, Richard, Tallman, Martin, Timmerman, John, Van Rhee, Frits, Waller, Edmund, Welsh, Ann, Werner, Michael, Wiernik, Peter, and Dhodapkar, Madhav

Abstract

Increasing knowledge concerning the biology of hematologic malignancies as well as the role of the immune system in the control of these diseases has led to the development and approval of immunotherapies that are resulting in impressive clinical responses. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a hematologic malignancy Cancer Immunotherapy Guidelines panel consisting of physicians, nurses, patient advocates, and patients to develop consensus recommendations for the clinical application of immunotherapy for patients with multiple myeloma, lymphoma, and acute leukemia. These recommendations were developed following the previously established process based on the Institute of Medicines clinical practice guidelines. In doing so, a systematic literature search was performed for high-impact studies from 2004 to 2014 and was supplemented with further literature as identified by the panel. The consensus panel met in December of 2014 with the goal to generate consensus recommendations for the clinical use of immunotherapy in patients with hematologic malignancies. During this meeting, consensus panel voting along with discussion were used to rate and review the strength of the supporting evidence from the literature search. These consensus recommendations focus on issues related to patient selection, toxicity management, clinical endpoints, and the sequencing or combination of therapies. Overall, immunotherapy is rapidly emerging as an effective therapeutic strategy for the management of hematologic malignances. Evidence-based consensus recommendations for its clinical application are provided and will be updated as the field evolves.

Published
2016

20. In Support of a Patient-Driven Initiative and Petition to Lower the High Price of Cancer Drugs.

Author

Tefferi, Ayalew, Tefferi, Ayalew, Kantarjian, Hagop, Rajkumar, S Vincent, Baker, Lawrence H, Abkowitz, Jan L, Adamson, John W, Advani, Ranjana Hira, Allison, James, Antman, Karen H, Bast, Robert C, Bennett, John M, Benz, Edward J, Berliner, Nancy, Bertino, Joseph, Bhatia, Ravi, Bhatia, Smita, Bhojwani, Deepa, Blanke, Charles D, Bloomfield, Clara D, Bosserman, Linda, Broxmeyer, Hal E, Byrd, John C, Cabanillas, Fernando, Canellos, George Peter, Chabner, Bruce A, Chanan-Khan, Asher, Cheson, Bruce, Clarkson, Bayard, Cohn, Susan L, Colon-Otero, Gerardo, Cortes, Jorge, Coutre, Steven, Cristofanilli, Massimo, Curran, Walter J, Daley, George Q, DeAngelo, Daniel J, Deeg, H Joachim, Einhorn, Lawrence H, Erba, Harry P, Esteva, Francisco J, Estey, Elihu, Fidler, Isaiah J, Foran, James, Forman, Stephen, Freireich, Emil, Fuchs, Charles, George, James N, Gertz, Morie A, Giralt, Sergio, Golomb, Harvey, Greenberg, Peter, Gutterman, Jordan, Handin, Robert I, Hellman, Samuel, Hoff, Paulo Marcelo, Hoffman, Ronald, Hong, Waun Ki, Horowitz, Mary, Hortobagyi, Gabriel N, Hudis, Clifford, Issa, Jean Pierre, Johnson, Bruce Evan, Kantoff, Philip W, Kaushansky, Kenneth, Khayat, David, Khuri, Fadlo R, Kipps, Thomas J, Kripke, Margaret, Kyle, Robert A, Larson, Richard A, Lawrence, Theodore S, Levine, Ross, Link, Michael P, Lippman, Scott M, Lonial, Sagar, Lyman, Gary H, Markman, Maurie, Mendelsohn, John, Meropol, Neal J, Messinger, Yoav, Mulvey, Therese M, O'Brien, Susan, Perez-Soler, Roman, Pollock, Raphael, Prchal, Josef, Press, Oliver, Radich, Jerald, Rai, Kanti, Rosenberg, Saul A, Rowe, Jacob M, Rugo, Hope, Runowicz, Carolyn D, Sandmaier, Brenda M, Saven, Alan, Schafer, Andrew I, Schiffer, Charles, Sekeres, Mikkael A, Silver, Richard T, Siu, Lillian L, Steensma, David P, Tefferi, Ayalew, Tefferi, Ayalew, Kantarjian, Hagop, Rajkumar, S Vincent, Baker, Lawrence H, Abkowitz, Jan L, Adamson, John W, Advani, Ranjana Hira, Allison, James, Antman, Karen H, Bast, Robert C, Bennett, John M, Benz, Edward J, Berliner, Nancy, Bertino, Joseph, Bhatia, Ravi, Bhatia, Smita, Bhojwani, Deepa, Blanke, Charles D, Bloomfield, Clara D, Bosserman, Linda, Broxmeyer, Hal E, Byrd, John C, Cabanillas, Fernando, Canellos, George Peter, Chabner, Bruce A, Chanan-Khan, Asher, Cheson, Bruce, Clarkson, Bayard, Cohn, Susan L, Colon-Otero, Gerardo, Cortes, Jorge, Coutre, Steven, Cristofanilli, Massimo, Curran, Walter J, Daley, George Q, DeAngelo, Daniel J, Deeg, H Joachim, Einhorn, Lawrence H, Erba, Harry P, Esteva, Francisco J, Estey, Elihu, Fidler, Isaiah J, Foran, James, Forman, Stephen, Freireich, Emil, Fuchs, Charles, George, James N, Gertz, Morie A, Giralt, Sergio, Golomb, Harvey, Greenberg, Peter, Gutterman, Jordan, Handin, Robert I, Hellman, Samuel, Hoff, Paulo Marcelo, Hoffman, Ronald, Hong, Waun Ki, Horowitz, Mary, Hortobagyi, Gabriel N, Hudis, Clifford, Issa, Jean Pierre, Johnson, Bruce Evan, Kantoff, Philip W, Kaushansky, Kenneth, Khayat, David, Khuri, Fadlo R, Kipps, Thomas J, Kripke, Margaret, Kyle, Robert A, Larson, Richard A, Lawrence, Theodore S, Levine, Ross, Link, Michael P, Lippman, Scott M, Lonial, Sagar, Lyman, Gary H, Markman, Maurie, Mendelsohn, John, Meropol, Neal J, Messinger, Yoav, Mulvey, Therese M, O'Brien, Susan, Perez-Soler, Roman, Pollock, Raphael, Prchal, Josef, Press, Oliver, Radich, Jerald, Rai, Kanti, Rosenberg, Saul A, Rowe, Jacob M, Rugo, Hope, Runowicz, Carolyn D, Sandmaier, Brenda M, Saven, Alan, Schafer, Andrew I, Schiffer, Charles, Sekeres, Mikkael A, Silver, Richard T, Siu, Lillian L, and Steensma, David P

Published
2015

21. In Support of a Patient-Driven Initiative and Petition to Lower the High Price of Cancer Drugs.

Author

Tefferi, Ayalew, Tefferi, Ayalew, Kantarjian, Hagop, Rajkumar, S Vincent, Baker, Lawrence H, Abkowitz, Jan L, Adamson, John W, Advani, Ranjana Hira, Allison, James, Antman, Karen H, Bast, Robert C, Bennett, John M, Benz, Edward J, Berliner, Nancy, Bertino, Joseph, Bhatia, Ravi, Bhatia, Smita, Bhojwani, Deepa, Blanke, Charles D, Bloomfield, Clara D, Bosserman, Linda, Broxmeyer, Hal E, Byrd, John C, Cabanillas, Fernando, Canellos, George Peter, Chabner, Bruce A, Chanan-Khan, Asher, Cheson, Bruce, Clarkson, Bayard, Cohn, Susan L, Colon-Otero, Gerardo, Cortes, Jorge, Coutre, Steven, Cristofanilli, Massimo, Curran, Walter J, Daley, George Q, DeAngelo, Daniel J, Deeg, H Joachim, Einhorn, Lawrence H, Erba, Harry P, Esteva, Francisco J, Estey, Elihu, Fidler, Isaiah J, Foran, James, Forman, Stephen, Freireich, Emil, Fuchs, Charles, George, James N, Gertz, Morie A, Giralt, Sergio, Golomb, Harvey, Greenberg, Peter, Gutterman, Jordan, Handin, Robert I, Hellman, Samuel, Hoff, Paulo Marcelo, Hoffman, Ronald, Hong, Waun Ki, Horowitz, Mary, Hortobagyi, Gabriel N, Hudis, Clifford, Issa, Jean Pierre, Johnson, Bruce Evan, Kantoff, Philip W, Kaushansky, Kenneth, Khayat, David, Khuri, Fadlo R, Kipps, Thomas J, Kripke, Margaret, Kyle, Robert A, Larson, Richard A, Lawrence, Theodore S, Levine, Ross, Link, Michael P, Lippman, Scott M, Lonial, Sagar, Lyman, Gary H, Markman, Maurie, Mendelsohn, John, Meropol, Neal J, Messinger, Yoav, Mulvey, Therese M, O'Brien, Susan, Perez-Soler, Roman, Pollock, Raphael, Prchal, Josef, Press, Oliver, Radich, Jerald, Rai, Kanti, Rosenberg, Saul A, Rowe, Jacob M, Rugo, Hope, Runowicz, Carolyn D, Sandmaier, Brenda M, Saven, Alan, Schafer, Andrew I, Schiffer, Charles, Sekeres, Mikkael A, Silver, Richard T, Siu, Lillian L, Steensma, David P, Tefferi, Ayalew, Tefferi, Ayalew, Kantarjian, Hagop, Rajkumar, S Vincent, Baker, Lawrence H, Abkowitz, Jan L, Adamson, John W, Advani, Ranjana Hira, Allison, James, Antman, Karen H, Bast, Robert C, Bennett, John M, Benz, Edward J, Berliner, Nancy, Bertino, Joseph, Bhatia, Ravi, Bhatia, Smita, Bhojwani, Deepa, Blanke, Charles D, Bloomfield, Clara D, Bosserman, Linda, Broxmeyer, Hal E, Byrd, John C, Cabanillas, Fernando, Canellos, George Peter, Chabner, Bruce A, Chanan-Khan, Asher, Cheson, Bruce, Clarkson, Bayard, Cohn, Susan L, Colon-Otero, Gerardo, Cortes, Jorge, Coutre, Steven, Cristofanilli, Massimo, Curran, Walter J, Daley, George Q, DeAngelo, Daniel J, Deeg, H Joachim, Einhorn, Lawrence H, Erba, Harry P, Esteva, Francisco J, Estey, Elihu, Fidler, Isaiah J, Foran, James, Forman, Stephen, Freireich, Emil, Fuchs, Charles, George, James N, Gertz, Morie A, Giralt, Sergio, Golomb, Harvey, Greenberg, Peter, Gutterman, Jordan, Handin, Robert I, Hellman, Samuel, Hoff, Paulo Marcelo, Hoffman, Ronald, Hong, Waun Ki, Horowitz, Mary, Hortobagyi, Gabriel N, Hudis, Clifford, Issa, Jean Pierre, Johnson, Bruce Evan, Kantoff, Philip W, Kaushansky, Kenneth, Khayat, David, Khuri, Fadlo R, Kipps, Thomas J, Kripke, Margaret, Kyle, Robert A, Larson, Richard A, Lawrence, Theodore S, Levine, Ross, Link, Michael P, Lippman, Scott M, Lonial, Sagar, Lyman, Gary H, Markman, Maurie, Mendelsohn, John, Meropol, Neal J, Messinger, Yoav, Mulvey, Therese M, O'Brien, Susan, Perez-Soler, Roman, Pollock, Raphael, Prchal, Josef, Press, Oliver, Radich, Jerald, Rai, Kanti, Rosenberg, Saul A, Rowe, Jacob M, Rugo, Hope, Runowicz, Carolyn D, Sandmaier, Brenda M, Saven, Alan, Schafer, Andrew I, Schiffer, Charles, Sekeres, Mikkael A, Silver, Richard T, Siu, Lillian L, and Steensma, David P

Published
2015

22. Chronic myelogenous leukemia stem and progenitor cells demonstrate chromosomal instability related to repeated breakage-fusion-bridge cycles mediated by increased nonhomologous end joining.

Author

Chakraborty, Sujata, Chakraborty, Sujata, Stark, Jeremy M, Sun, Can-Lan, Modi, Hardik, Chen, WenYong, O'Connor, Timothy R, Forman, Stephen J, Bhatia, Smita, Bhatia, Ravi, Chakraborty, Sujata, Chakraborty, Sujata, Stark, Jeremy M, Sun, Can-Lan, Modi, Hardik, Chen, WenYong, O'Connor, Timothy R, Forman, Stephen J, Bhatia, Smita, and Bhatia, Ravi

Abstract

Chromosomal aberrations are an important consequence of genotoxic exposure and contribute to pathogenesis and progression of several malignancies. We investigated the susceptibility to chromosomal aberrations in chronic myelogenous leukemia (CML) progenitors after exposure to ionizing radiation. In normal progenitors, ionizing radiation induced both stable and unstable chromosomal lesions, but only stable aberrations persisted after multiple divisions. In contrast, radiation of chronic phase CML progenitors resulted in enhanced generation of unstable lesions that persisted after multiple divisions. CML progenitors demonstrated active cell cycle checkpoints and increased nonhomologous end joining DNA repair, suggesting that persistence of unstable aberrations was the result of continued generation of these lesions. CML progenitors demonstrated enhanced susceptibility to repeated cycles of chromosome damage, repair, and damage through a breakage-fusion-bridge mechanism. Perpetuation of breakage-fusion-bridge cycles in CML progenitors was mediated by classic nonhomologous end joining repair. These studies reveal a previously unrecognized mechanism of chromosomal instability in leukemia progenitors because of continued generation of unstable chromosomal lesions through repeated cycles of breakage and repair of such lesions.

Published
2012

23. Cost Savings Using Stirrup Reinforcement Instead of Laced Wall Reinforcement Per UFC 3-340-02 (TM 5-1300) December, 2008

Author

WEIDLINGER ASSOCIATES INC MOUNTAIN VIEW CA, Lawver, Darell, Weeks, Jim, Forman, Stephen, Lackey, Robert, Faria, Larry, WEIDLINGER ASSOCIATES INC MOUNTAIN VIEW CA, Lawver, Darell, Weeks, Jim, Forman, Stephen, Lackey, Robert, and Faria, Larry

Abstract

The design of explosive processing facilities for Department of Defense (DoD), Department of Energy (DOE), other government organizations and government contractors has been primarily governed by the November 1990 version of TM5-1300 [1] for almost two decades since its publication. The document contains prescriptive and recommended design procedures for the design of structures to resist the effects of accidental explosions. The procedures were developed from explosive testing-- extensive in some areas, but very limited in others-- and good engineering practice. Since the publication of TM5-1300, the state of the art methods in computational fluid dynamics and structural analysis have improved tremendously in their ability to more accurately predict the response of structural components to blast loading. This has been verified and validated through many government-sponsored test programs [2-11]. These test programs have also improved the accuracy of empirical and simplified engineering tools to predict the response of structural components to blast loading [12-14]. Due to the prescriptive nature of TM5-1300, this body of knowledge is generally not available for use in design. Blast testing of systems is often required to demonstrate their ability to meet the intent of the standard when they fall short of meeting the strict prescriptive requirements of TM5-1300. The testing is not only very costly, but also time consuming which may prevent users from meeting aggressive design and construction schedules. Therefore, most engineering projects conform to the prescriptive requirements of the TM5-1300 standards. In this manner, the design can be reviewed through conventional government channels and delays caused by the testing process are avoided., See also ADM002313. Presented at the Department of Defense Explosives Safety Board Seminar (34th) held in Portland, Oregon on 13-15 July 2010, The original document contains color images.

Published
2010

24. Visual, auditory, sensory, and motor impairments in long-term survivors of hematopoietic stem cell transplantation performed in childhood

Author

Department of Pediatrics, University of Michigan, Ann Arbor, Michigan ; Fax: (734) 764-2599 ; University of Michigan, Division of General Pediatrics, 300 NIB 6E02 Box 0456, 300 N. Ingalls St., Ann Arbor, MI 48109-0456, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, Department of Pediatrics, City of Hope Cancer Center, Duarte, California, Gurney, James G., Ness, Kirsten K., Rosenthal, Joseph, Forman, Stephen J., Bhatia, Smita, Baker, K. Scott, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan ; Fax: (734) 764-2599 ; University of Michigan, Division of General Pediatrics, 300 NIB 6E02 Box 0456, 300 N. Ingalls St., Ann Arbor, MI 48109-0456, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, Department of Pediatrics, City of Hope Cancer Center, Duarte, California, Gurney, James G., Ness, Kirsten K., Rosenthal, Joseph, Forman, Stephen J., Bhatia, Smita, and Baker, K. Scott

Abstract

BACKGROUND Because of treatment-related toxicity, research is increasingly being focused on long-term sequelae secondary to hematopoietic stem cell transplantation (HSCT) in survivor populations. METHODS This study describes the incidence of auditory, sensory, motor, and visual impairments, including cataracts, among 235 individuals who were treated with HSCT during childhood or adolescence. Outcomes were compared with 705 siblings of childhood cancer survivors. Participants completed a survey with questions on posttransplant organ system impairments. Approximately half of survivors were transplanted when younger than 10 years of age. The median length of followup was 11 years. RESULTS The cumulative incidence of cataracts was 36% at 15 years post-HSCT, although cataracts occurred only in those who received total body irradiation as an HSCT conditioning agent or head irradiation before transplant. Persistent pain was reported by 21% of survivors. Loss of hearing in one or both ears, and legal blindness in one or both eyes, each occurred after transplant in 2% of survivors. Occurrences were uncommon, but survivors were 4.3 times (95% confidence interval [CI]: 2.0–9.4) more likely to report coordination problems, 7.7 times (95% CI: 3.2–18.5) more likely to report chewing or swallowing problems, and 3.5 times (3.5; 95% CI: 1.6–7.9) more likely to report muscle weakness than those in the comparison group. Muscle weakness was strongly associated with positive history of chronic graft-versus-host disease. CONCLUSIONS Increased risks were found for motor impairments, hearing loss, vision loss, and persistent pain among study participants. Cataracts were a frequent adverse effect, suggesting that close monitoring with appropriate intervention for preservation of vision, particularly among those who received total body irradiation, should be a primary goal in survivors of HSCT performed in childhood. Cancer 2006. © 2006 American Cancer Society.

Published
2007

25. EVALUATION OF THE MAIN GUN OF THE M60 TANK AGAINST MOVING GROUND TARGETS

Author

RESEARCH ANALYSIS CORP MCLEAN VA, Bruce, Jr., Charles A., Eckles, III, Andrew J., Forman, Stephen B., RESEARCH ANALYSIS CORP MCLEAN VA, Bruce, Jr., Charles A., Eckles, III, Andrew J., and Forman, Stephen B.

Abstract

This paper evaluates employment of the main gun of the M60 tank against moving ground targets. The results are from a live-fire experiment conducted at Ft Stewart, Georgia, during the period 25 Jun-6 Jul 1963. Of chief interest are the hit probabilities against moving targets of armor-piercing discarding-sabot and training-practice rounds for the 105-mm main gun and the accuracy and consistency of observer sensing of firings of those ammunitions. However, such other intermediate results as miss distance and lay error are also reported because they support the results concerning hit probability.

Published
1965

26. A FIELD COMPARISON OF HELICOPTER ANTIARMOR TACTICS

Author

RESEARCH ANALYSIS CORP MCLEAN VA, Forman, Stephen B., Hoppes, Harrison N., Kibel, Barry M., Woods, Arthur R., Edney, Benny E., RESEARCH ANALYSIS CORP MCLEAN VA, Forman, Stephen B., Hoppes, Harrison N., Kibel, Barry M., Woods, Arthur R., and Edney, Benny E.

Abstract

Evaluation of helicopter antiarmor concepts against simulated enemy ground employments is reported. During July 1964 a helicopter antiarmor experiment, designed with Project Advisory Group (PAG) guidance, was conducted. This experiment measured the ability of helicopter antiarmor teams to engage targets assumed to have been acquired by reconnaissance elements of the air cavalry troop. The SS-11/UH-1 crews were found to encounter considerable difficulty in acquiring enemy target vehicles. None of the SS-11/UH-1 teams detected targets on their initial attempts against vehicles in the stationary complexes and only half were able to launch missiles against fluid target vehicles on their initial firing passes. On eight missions involving SS-11/UH-1 teams at least one helicopter was taken under fire by enemy ground personnel prior to the time the first SS-11 missile was launched. Helicopter support of dismounted killer elements did not lead to a noticeable improvement in their performance. Antiarmor teams were markedly more effective in attacking vehicles with a movement mission than in attacking the stationary target complexes; 60% of the target kills expected were scored against fluid vehicles. For the 40 missions observed, helicopters were fired on twice as often on missions against the stationary complexes as on missions against fluid enemy vehicles. (Author)

Published
1966

27. Future Impact of Dissident Elements within the Army on the Enforcement of Discipline, Law, and Order.

Author

RESEARCH ANALYSIS CORP MCLEAN VA, Rae, R. William, Forman, Stephen B., Olson, Howard C., RESEARCH ANALYSIS CORP MCLEAN VA, Rae, R. William, Forman, Stephen B., and Olson, Howard C.

Abstract

The degree to which dissidence may have an impact in the future on the enforcement of discipline, law, and order is of serious concern to Army planners. In this study, an attempt was made to determine the current level of dissidence in the Army and to examine the possible causes of dissident behavior as a basis for estimating what the trend may be in the next few years. (Author)

Published
1972

28. A Method for Predicting Staffing and Space Requirements for Juvenile Court Intake.

Author

RESEARCH ANALYSIS CORP MCLEAN VA, Forman,Stephen B., RESEARCH ANALYSIS CORP MCLEAN VA, and Forman,Stephen B.

Abstract

The paper presents a procedure that juvenile court planners can use to aid them in predicting future personnel and space requirements for juvenile court intake. The procedure involves the utilization of chart and tabular data that were derived during a study of the applicability of modern management techniques to the juvenile court process. (Author)

Published
1970

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