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1. Standardizing Definitions of Hematopoietic Recovery, Graft Rejection, Graft Failure, Poor Graft Function, and Donor Chimerism in Allogeneic Hematopoietic Cell Transplantation: A Report on Behalf of the American Society for Transplantation and Cellular Therapy.

Author

Kharfan-Dabaja, Mohamed A., Kumar, Ambuj, Ayala, Ernesto, Aljurf, Mahmoud, Nishihori, Taiga, Marsh, Rebecca, Burroughs, Lauri M., Majhail, Navneet, Al-Homsi, A. Samer, Al-Kadhimi, Zaid S., Bar, Merav, Bertaina, Alice, Boelens, Jaap J., Champlin, Richard, Chaudhury, Sonali, DeFilipp, Zachariah, Dholaria, Bhagirathbhai, El-Jawahri, Areej, Fanning, Suzanne, Fraint, Ellen, Gergis, Usama, Giralt, Sergio, Hamilton, Betty K., Hashmi, Shahrukh K., Horn, Biljana, Inamoto, Yoshihiro, Jacobsohn, David A., Jain, Tania, Johnston, Laura, Kanate, Abraham S., Kansagra, Ankit, Kassim, Adetola, Kean, Leslie S., Kitko, Carrie L., Knight-Perry, Jessica, Kurtzberg, Joanne, Liu, Hien, MacMillan, Margaret L., Mahmoudjafari, Zahra, Mielcarek, Marco, Mohty, Mohamad, Nagler, Arnon, Nemecek, Eneida, Olson, Timothy S., Oran, Betul, Perales, Miguel-Angel, Prockop, Susan E., Pulsipher, Michael A., Pusic, Iskra, Riches, Marcie L., Rodriguez, Cesar, Romee, Rizwan, Rondon, Gabriela, Saad, Ayman, Shah, Nina, Shaw, Peter J., Shenoy, Shalini, Sierra, Jorge, Talano, Julie, Verneris, Michael R., Veys, Paul, Wagner, John E., Savani, Bipin N., Hamadani, Mehdi, Carpenter, Paul A., Kharfan-Dabaja, Mohamed A., Kumar, Ambuj, Ayala, Ernesto, Aljurf, Mahmoud, Nishihori, Taiga, Marsh, Rebecca, Burroughs, Lauri M., Majhail, Navneet, Al-Homsi, A. Samer, Al-Kadhimi, Zaid S., Bar, Merav, Bertaina, Alice, Boelens, Jaap J., Champlin, Richard, Chaudhury, Sonali, DeFilipp, Zachariah, Dholaria, Bhagirathbhai, El-Jawahri, Areej, Fanning, Suzanne, Fraint, Ellen, Gergis, Usama, Giralt, Sergio, Hamilton, Betty K., Hashmi, Shahrukh K., Horn, Biljana, Inamoto, Yoshihiro, Jacobsohn, David A., Jain, Tania, Johnston, Laura, Kanate, Abraham S., Kansagra, Ankit, Kassim, Adetola, Kean, Leslie S., Kitko, Carrie L., Knight-Perry, Jessica, Kurtzberg, Joanne, Liu, Hien, MacMillan, Margaret L., Mahmoudjafari, Zahra, Mielcarek, Marco, Mohty, Mohamad, Nagler, Arnon, Nemecek, Eneida, Olson, Timothy S., Oran, Betul, Perales, Miguel-Angel, Prockop, Susan E., Pulsipher, Michael A., Pusic, Iskra, Riches, Marcie L., Rodriguez, Cesar, Romee, Rizwan, Rondon, Gabriela, Saad, Ayman, Shah, Nina, Shaw, Peter J., Shenoy, Shalini, Sierra, Jorge, Talano, Julie, Verneris, Michael R., Veys, Paul, Wagner, John E., Savani, Bipin N., Hamadani, Mehdi, and Carpenter, Paul A.

Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for certain hematologic malignancies and nonmalignant diseases. The field of allo-HCT has witnessed significant advances, including broadening indications for transplantation, availability of alternative donor sources, less toxic preparative regimens, new cell manipulation techniques, and novel GVHD prevention methods, all of which have expanded the applicability of the procedure. These advances have led to clinical practice conundrums when applying traditional definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism, because these may vary based on donor type, cell source, cell dose, primary disease, graft-versus-host disease (GVHD) prophylaxis, and conditioning intensity, among other variables. To address these contemporary challenges, we surveyed a panel of allo-HCT experts in an attempt to standardize these definitions. We analyzed survey responses from adult and pediatric transplantation physicians separately. Consensus was achieved for definitions of neutrophil and platelet recovery, graft rejection, graft failure, poor graft function, and donor chimerism, but not for delayed engraftment. Here we highlight the complexities associated with the management of mixed donor chimerism in malignant and nonmalignant hematologic diseases, which remains an area for future research. We recognize that there are multiple other specific, and at times complex, clinical scenarios for which clinical management must be individualized.

Published
2021

2. Lymphoid and myeloid immune cell reconstitution after nicotinamide-expanded cord blood transplantation

Author

CTI Nierkens, Infection & Immunity, Cancer, CTI Pandit, SCT patientenzorg, Child Health, Regenerative Medicine and Stem Cells, CDL Patiëntenzorg MI, CTI Research, de Koning, Coco, Tao, Weiyang, Lacna, Amelia, van Veghel, Karin, Horwitz, Mitchell E., Sanz, Guillermo, Jagasia, Madan H., Wagner, John E., Stiff, Patrick J., Hanna, Rabi, Cilloni, Daniela, Valcárcel, David, Peled, Tony, Galamidi Cohen, Einat, Goshen, Uri, Pandit, Aridaman, Lindemans, Caroline A., Jan Boelens, Jaap, Nierkens, Stefan, CTI Nierkens, Infection & Immunity, Cancer, CTI Pandit, SCT patientenzorg, Child Health, Regenerative Medicine and Stem Cells, CDL Patiëntenzorg MI, CTI Research, de Koning, Coco, Tao, Weiyang, Lacna, Amelia, van Veghel, Karin, Horwitz, Mitchell E., Sanz, Guillermo, Jagasia, Madan H., Wagner, John E., Stiff, Patrick J., Hanna, Rabi, Cilloni, Daniela, Valcárcel, David, Peled, Tony, Galamidi Cohen, Einat, Goshen, Uri, Pandit, Aridaman, Lindemans, Caroline A., Jan Boelens, Jaap, and Nierkens, Stefan

Published
2021

3. The influence of stem cell source on transplant outcomes for pediatric patients with acute myeloid leukemia

Author

Keating, Amy K., Langenhorst, Jurgen, Wagner, John E., Page, Kristin M., Veys, Paul, Wynn, Robert F., Stefanski, Heather, Elfeky, Reem, Giller, Roger, Mitchell, Richard, Milano, Filippo, O’Brien, Tracey A., Dahlberg, Ann, Delaney, Colleen, Kurtzberg, Joanne, Verneris, Michael R., Boelens, Jaap Jan, Keating, Amy K., Langenhorst, Jurgen, Wagner, John E., Page, Kristin M., Veys, Paul, Wynn, Robert F., Stefanski, Heather, Elfeky, Reem, Giller, Roger, Mitchell, Richard, Milano, Filippo, O’Brien, Tracey A., Dahlberg, Ann, Delaney, Colleen, Kurtzberg, Joanne, Verneris, Michael R., and Boelens, Jaap Jan

Published
2019

4. Phase I/II Study of Stem-Cell Transplantation Using a Single Cord Blood Unit Expanded Ex Vivo With Nicotinamide

Author

Horwitz, Mitchell E, Wease, Stephen, Blackwell, Beth, Valcarcel, David, Frassoni, Francesco, Boelens, Jaap Jan, Nierkens, Stefan, Jagasia, Madan, Wagner, John E, Kuball, Jurgen, Koh, Liang Piu, Majhail, Navneet S, Stiff, Patrick J, Hanna, Rabi, Hwang, William Y K, Kurtzberg, Joanne, Cilloni, Daniela, Freedman, Laurence S, Montesinos, Pau, Sanz, Guillermo, Horwitz, Mitchell E, Wease, Stephen, Blackwell, Beth, Valcarcel, David, Frassoni, Francesco, Boelens, Jaap Jan, Nierkens, Stefan, Jagasia, Madan, Wagner, John E, Kuball, Jurgen, Koh, Liang Piu, Majhail, Navneet S, Stiff, Patrick J, Hanna, Rabi, Hwang, William Y K, Kurtzberg, Joanne, Cilloni, Daniela, Freedman, Laurence S, Montesinos, Pau, and Sanz, Guillermo

Published
2019

5. The influence of stem cell source on transplant outcomes for pediatric patients with acute myeloid leukemia

Author

Keating, Amy K., Langenhorst, Jurgen, Wagner, John E., Page, Kristin M., Veys, Paul, Wynn, Robert F., Stefanski, Heather, Elfeky, Reem, Giller, Roger, Mitchell, Richard, Milano, Filippo, O’Brien, Tracey A., Dahlberg, Ann, Delaney, Colleen, Kurtzberg, Joanne, Verneris, Michael R., Boelens, Jaap Jan, Keating, Amy K., Langenhorst, Jurgen, Wagner, John E., Page, Kristin M., Veys, Paul, Wynn, Robert F., Stefanski, Heather, Elfeky, Reem, Giller, Roger, Mitchell, Richard, Milano, Filippo, O’Brien, Tracey A., Dahlberg, Ann, Delaney, Colleen, Kurtzberg, Joanne, Verneris, Michael R., and Boelens, Jaap Jan

Published
2019

6. Phase I/II Study of Stem-Cell Transplantation Using a Single Cord Blood Unit Expanded Ex Vivo With Nicotinamide

Author

Horwitz, Mitchell E, Wease, Stephen, Blackwell, Beth, Valcarcel, David, Frassoni, Francesco, Boelens, Jaap Jan, Nierkens, Stefan, Jagasia, Madan, Wagner, John E, Kuball, Jurgen, Koh, Liang Piu, Majhail, Navneet S, Stiff, Patrick J, Hanna, Rabi, Hwang, William Y K, Kurtzberg, Joanne, Cilloni, Daniela, Freedman, Laurence S, Montesinos, Pau, Sanz, Guillermo, Horwitz, Mitchell E, Wease, Stephen, Blackwell, Beth, Valcarcel, David, Frassoni, Francesco, Boelens, Jaap Jan, Nierkens, Stefan, Jagasia, Madan, Wagner, John E, Kuball, Jurgen, Koh, Liang Piu, Majhail, Navneet S, Stiff, Patrick J, Hanna, Rabi, Hwang, William Y K, Kurtzberg, Joanne, Cilloni, Daniela, Freedman, Laurence S, Montesinos, Pau, and Sanz, Guillermo

Published
2019

7. The influence of stem cell source on transplant outcomes for pediatric patients with acute myeloid leukemia

Author

Keating, Amy K., Langenhorst, Jurgen, Wagner, John E., Page, Kristin M., Veys, Paul, Wynn, Robert F., Stefanski, Heather, Elfeky, Reem, Giller, Roger, Mitchell, Richard, Milano, Filippo, O’Brien, Tracey A., Dahlberg, Ann, Delaney, Colleen, Kurtzberg, Joanne, Verneris, Michael R., Boelens, Jaap Jan, Keating, Amy K., Langenhorst, Jurgen, Wagner, John E., Page, Kristin M., Veys, Paul, Wynn, Robert F., Stefanski, Heather, Elfeky, Reem, Giller, Roger, Mitchell, Richard, Milano, Filippo, O’Brien, Tracey A., Dahlberg, Ann, Delaney, Colleen, Kurtzberg, Joanne, Verneris, Michael R., and Boelens, Jaap Jan

Published
2019

8. Phase I/II Study of Stem-Cell Transplantation Using a Single Cord Blood Unit Expanded Ex Vivo With Nicotinamide

Author

Horwitz, Mitchell E, Wease, Stephen, Blackwell, Beth, Valcarcel, David, Frassoni, Francesco, Boelens, Jaap Jan, Nierkens, Stefan, Jagasia, Madan, Wagner, John E, Kuball, Jurgen, Koh, Liang Piu, Majhail, Navneet S, Stiff, Patrick J, Hanna, Rabi, Hwang, William Y K, Kurtzberg, Joanne, Cilloni, Daniela, Freedman, Laurence S, Montesinos, Pau, Sanz, Guillermo, Horwitz, Mitchell E, Wease, Stephen, Blackwell, Beth, Valcarcel, David, Frassoni, Francesco, Boelens, Jaap Jan, Nierkens, Stefan, Jagasia, Madan, Wagner, John E, Kuball, Jurgen, Koh, Liang Piu, Majhail, Navneet S, Stiff, Patrick J, Hanna, Rabi, Hwang, William Y K, Kurtzberg, Joanne, Cilloni, Daniela, Freedman, Laurence S, Montesinos, Pau, and Sanz, Guillermo

Published
2019

9. Phase I/II Study of Stem-Cell Transplantation Using a Single Cord Blood Unit Expanded Ex Vivo With Nicotinamide

Author

CTI Nierkens, CTI Research, Infection & Immunity, CDL Patiëntenzorg MI, CTI UDAIR, MS Hematologie, Cancer, Regenerative Medicine and Stem Cells, CTI Kuball, Horwitz, Mitchell E, Wease, Stephen, Blackwell, Beth, Valcarcel, David, Frassoni, Francesco, Boelens, Jaap Jan, Nierkens, Stefan, Jagasia, Madan, Wagner, John E, Kuball, Jurgen, Koh, Liang Piu, Majhail, Navneet S, Stiff, Patrick J, Hanna, Rabi, Hwang, William Y K, Kurtzberg, Joanne, Cilloni, Daniela, Freedman, Laurence S, Montesinos, Pau, Sanz, Guillermo, CTI Nierkens, CTI Research, Infection & Immunity, CDL Patiëntenzorg MI, CTI UDAIR, MS Hematologie, Cancer, Regenerative Medicine and Stem Cells, CTI Kuball, Horwitz, Mitchell E, Wease, Stephen, Blackwell, Beth, Valcarcel, David, Frassoni, Francesco, Boelens, Jaap Jan, Nierkens, Stefan, Jagasia, Madan, Wagner, John E, Kuball, Jurgen, Koh, Liang Piu, Majhail, Navneet S, Stiff, Patrick J, Hanna, Rabi, Hwang, William Y K, Kurtzberg, Joanne, Cilloni, Daniela, Freedman, Laurence S, Montesinos, Pau, and Sanz, Guillermo

Published
2019

10. The influence of stem cell source on transplant outcomes for pediatric patients with acute myeloid leukemia

Author

Cancer, CTI Nierkens, SCT patientenzorg, Regenerative Medicine and Stem Cells, Keating, Amy K., Langenhorst, Jurgen, Wagner, John E., Page, Kristin M., Veys, Paul, Wynn, Robert F., Stefanski, Heather, Elfeky, Reem, Giller, Roger, Mitchell, Richard, Milano, Filippo, O’Brien, Tracey A., Dahlberg, Ann, Delaney, Colleen, Kurtzberg, Joanne, Verneris, Michael R., Boelens, Jaap Jan, Cancer, CTI Nierkens, SCT patientenzorg, Regenerative Medicine and Stem Cells, Keating, Amy K., Langenhorst, Jurgen, Wagner, John E., Page, Kristin M., Veys, Paul, Wynn, Robert F., Stefanski, Heather, Elfeky, Reem, Giller, Roger, Mitchell, Richard, Milano, Filippo, O’Brien, Tracey A., Dahlberg, Ann, Delaney, Colleen, Kurtzberg, Joanne, Verneris, Michael R., and Boelens, Jaap Jan

Published
2019

11. Transplantation of CCR5∆32 Homozygous Umbilical Cord Blood in a Child With Acute Lymphoblastic Leukemia and Perinatally Acquired HIV Infection.

Author

Rothenberger, Meghan, Rothenberger, Meghan, Wagner, John E, Haase, Ashley, Richman, Douglas, Grzywacz, Bartosz, Strain, Matthew, Lada, Steven, Estes, Jacob, Fletcher, Courtney V, Podany, Anthony T, Anderson, Jodi, Schmidt, Thomas, Wietgrefe, Steve, Schacker, Timothy, Verneris, Michael R, Rothenberger, Meghan, Rothenberger, Meghan, Wagner, John E, Haase, Ashley, Richman, Douglas, Grzywacz, Bartosz, Strain, Matthew, Lada, Steven, Estes, Jacob, Fletcher, Courtney V, Podany, Anthony T, Anderson, Jodi, Schmidt, Thomas, Wietgrefe, Steve, Schacker, Timothy, and Verneris, Michael R

Abstract

BackgroundAllogeneic hematopoietic cell transplantation (allo-HCT) in a CCR5∆32 homozygous donor resulted in HIV cure. Understanding how allo-HCT impacts the HIV reservoir will inform cure strategies.MethodsA 12-year-old with perinatally acquired, CCR5-tropic HIV and acute lymphoblastic leukemia underwent myeloablative conditioning and umbilical cord blood (UCB) transplantation from a CCR5∆32 homozygous donor. Peripheral blood mononuclear cells (PBMCs) and the rectum were sampled pre- and post-transplant. The brain, lung, lymph node (LN), stomach, duodenum, ileum, and colon were sampled 73 days after transplantation (day +73), when the patient died from graft-vs-host disease. Droplet digital polymerase chain reaction (ddPCR) and in situ hybridization (ISH) were used detect the HIV reservoir in tissues. CCR5 and CD3 expression in the LN was assessed using immunohistochemistry (IHC).ResultsHIV DNA (vDNA) was detected in PBMCs by ddPCR pretransplant but not post-transplant. vDNA was detected by ISH in the rectum at days -8 and +22, and in the LN, colon, lung, and brain day +73. vDNA was also detected in the lung by ddPCR. IHC revealed CCR5+CD3+ cells in the LN postmortem.ConclusionsHIV was detected in multiple tissues 73 days after CCR5∆32 homozygous UCB allo-HCT despite myeloablative conditioning and complete donor marrow engraftment. These results highlight the importance of analyzing tissue during HIV cure interventions and inform the choice of assay used to detect HIV in tissue reservoirs.

Published
2018

12. Transplantation of CCR5∆32 Homozygous Umbilical Cord Blood in a Child With Acute Lymphoblastic Leukemia and Perinatally Acquired HIV Infection.

Author

Rothenberger, Meghan, Rothenberger, Meghan, Wagner, John E, Haase, Ashley, Richman, Douglas, Grzywacz, Bartosz, Strain, Matthew, Lada, Steven, Estes, Jacob, Fletcher, Courtney V, Podany, Anthony T, Anderson, Jodi, Schmidt, Thomas, Wietgrefe, Steve, Schacker, Timothy, Verneris, Michael R, Rothenberger, Meghan, Rothenberger, Meghan, Wagner, John E, Haase, Ashley, Richman, Douglas, Grzywacz, Bartosz, Strain, Matthew, Lada, Steven, Estes, Jacob, Fletcher, Courtney V, Podany, Anthony T, Anderson, Jodi, Schmidt, Thomas, Wietgrefe, Steve, Schacker, Timothy, and Verneris, Michael R

Abstract

BackgroundAllogeneic hematopoietic cell transplantation (allo-HCT) in a CCR5∆32 homozygous donor resulted in HIV cure. Understanding how allo-HCT impacts the HIV reservoir will inform cure strategies.MethodsA 12-year-old with perinatally acquired, CCR5-tropic HIV and acute lymphoblastic leukemia underwent myeloablative conditioning and umbilical cord blood (UCB) transplantation from a CCR5∆32 homozygous donor. Peripheral blood mononuclear cells (PBMCs) and the rectum were sampled pre- and post-transplant. The brain, lung, lymph node (LN), stomach, duodenum, ileum, and colon were sampled 73 days after transplantation (day +73), when the patient died from graft-vs-host disease. Droplet digital polymerase chain reaction (ddPCR) and in situ hybridization (ISH) were used detect the HIV reservoir in tissues. CCR5 and CD3 expression in the LN was assessed using immunohistochemistry (IHC).ResultsHIV DNA (vDNA) was detected in PBMCs by ddPCR pretransplant but not post-transplant. vDNA was detected by ISH in the rectum at days -8 and +22, and in the LN, colon, lung, and brain day +73. vDNA was also detected in the lung by ddPCR. IHC revealed CCR5+CD3+ cells in the LN postmortem.ConclusionsHIV was detected in multiple tissues 73 days after CCR5∆32 homozygous UCB allo-HCT despite myeloablative conditioning and complete donor marrow engraftment. These results highlight the importance of analyzing tissue during HIV cure interventions and inform the choice of assay used to detect HIV in tissue reservoirs.

Published
2018

13. One-unit versus two-unit cord-blood transplantation for hematologic cancers.

Author

Wagner, John E, Wagner, John E, Eapen, Mary, Carter, Shelly, Wang, Yanli, Schultz, Kirk R, Wall, Donna A, Bunin, Nancy, Delaney, Colleen, Haut, Paul, Margolis, David, Peres, Edward, Verneris, Michael R, Walters, Mark, Horowitz, Mary M, Kurtzberg, Joanne, Blood and Marrow Transplant Clinical Trials Network, Wagner, John E, Wagner, John E, Eapen, Mary, Carter, Shelly, Wang, Yanli, Schultz, Kirk R, Wall, Donna A, Bunin, Nancy, Delaney, Colleen, Haut, Paul, Margolis, David, Peres, Edward, Verneris, Michael R, Walters, Mark, Horowitz, Mary M, Kurtzberg, Joanne, and Blood and Marrow Transplant Clinical Trials Network

Abstract

BackgroundUmbilical-cord blood has been used as the source of hematopoietic stem cells in an estimated 30,000 transplants. The limited number of hematopoietic cells in a single cord-blood unit prevents its use in recipients with larger body mass and results in delayed hematopoietic recovery and higher mortality. Therefore, we hypothesized that the greater numbers of hematopoietic cells in two units of cord blood would be associated with improved outcomes after transplantation.MethodsBetween December 1, 2006, and February 24, 2012, a total of 224 patients 1 to 21 years of age with hematologic cancer were randomly assigned to undergo double-unit (111 patients) or single-unit (113 patients) cord-blood transplantation after a uniform myeloablative conditioning regimen and immunoprophylaxis for graft-versus-host disease (GVHD). The primary end point was 1-year overall survival.ResultsTreatment groups were matched for age, sex, self-reported race (white vs. nonwhite), performance status, degree of donor-recipient HLA matching, and disease type and status at transplantation. The 1-year overall survival rate was 65% (95% confidence interval [CI], 56 to 74) and 73% (95% CI, 63 to 80) among recipients of double and single cord-blood units, respectively (P=0.17). Similar outcomes in the two groups were also observed with respect to the rates of disease-free survival, neutrophil recovery, transplantation-related death, relapse, infections, immunologic reconstitution, and grade II-IV acute GVHD. However, improved platelet recovery and lower incidences of grade III and IV acute and extensive chronic GVHD were observed among recipients of a single cord-blood unit.ConclusionsWe found that among children and adolescents with hematologic cancer, survival rates were similar after single-unit and double-unit cord-blood transplantation; however, a single-unit cord-blood transplant was associated with better platelet recovery and a lower risk of GVHD. (Funded by the National Heart, Lung

Published
2014

14. Second Allogeneic Hematopoietic Cell Transplantation for Patients with Fanconi Anemia and Bone Marrow Failure

Author

Ayas, Mouhab, Eapen, Mary, Le-Rademacher, Jennifer, Carreras, Jeanette, Abdel-Azim, Hisham, Alter, Blanche P., Anderlini, Paolo, Battiwalla, Minoo, Bierings, Marc, Buchbinder, David K., Bonfim, Carmem, Camitta, Bruce M., Fasth, Anders L., Gale, Robert Peter, Lee, Michelle A., Lund, Troy C., Myers, Kasiani C., Olsson, Richard F., Page, Kristin M., Prestidge, Tim D., Radhi, Mohamed, Shah, Ami J., Schultz, Kirk R., Wirk, Baldeep, Wagner, John E., Deeg, H. Joachim, Ayas, Mouhab, Eapen, Mary, Le-Rademacher, Jennifer, Carreras, Jeanette, Abdel-Azim, Hisham, Alter, Blanche P., Anderlini, Paolo, Battiwalla, Minoo, Bierings, Marc, Buchbinder, David K., Bonfim, Carmem, Camitta, Bruce M., Fasth, Anders L., Gale, Robert Peter, Lee, Michelle A., Lund, Troy C., Myers, Kasiani C., Olsson, Richard F., Page, Kristin M., Prestidge, Tim D., Radhi, Mohamed, Shah, Ami J., Schultz, Kirk R., Wirk, Baldeep, Wagner, John E., and Deeg, H. Joachim

Abstract

A second allogeneic hematopoietic cell transplantation (HCT) is the sole salvage option for individuals who develop graft failure after their first HCT. Data on outcomes after second HCT in patients with Fanconi anemia (FA) are scarce. Here we report outcomes after second allogeneic HCT for FA (n = 81). The indication for second HCT was graft failure after the first HCT. Transplantations were performed between 1990 and 2012. The timing of the second HCT predicted subsequent graft failure and survival. Graft failure was high when the second HCT was performed less than 3 months from the first. The 3-month probability of graft failure was 69% when the interval between the first HCT and second HCT was less than 3 months, compared with 23% when the interval was longer (P < .001). Consequently, the 1-year survival rate was substantially lower when the interval between the first and second HCTs was less than 3 months compared with longer (23% vs 58%; P = .001). The corresponding 5-year probability of survival was 16% and 45%, respectively (P = .006). Taken together, these data suggest that fewer than one-half of patients with FA undergoing a second HCT for graft failure are long-term survivors. There is an urgent need to develop strategies to reduce the rate of graft failure after first HCT.

Published
2015
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15. Second Allogeneic Hematopoietic Cell Transplantation for Patients with Fanconi Anemia and Bone Marrow Failure

Author

Ayas, Mouhab, Eapen, Mary, Le-Rademacher, Jennifer, Carreras, Jeanette, Abdel-Azim, Hisham, Alter, Blanche P., Anderlini, Paolo, Battiwalla, Minoo, Bierings, MB, Buchbinder, David K., Bonfim, Carmem, Camitta, Bruce M., Fasth, Anders L., Gale, Robert Peter, Lee, Michelle A., Lund, Troy C., Myers, Kasiani C., Olsson, Richard F., Page, Kristin M., Prestidge, Tim D., Radhi, Mohamed, Shah, Ami J., Schultz, Kirk R., Wirk, Baldeep, Wagner, John E., Deeg, H. Joachim, Ayas, Mouhab, Eapen, Mary, Le-Rademacher, Jennifer, Carreras, Jeanette, Abdel-Azim, Hisham, Alter, Blanche P., Anderlini, Paolo, Battiwalla, Minoo, Bierings, MB, Buchbinder, David K., Bonfim, Carmem, Camitta, Bruce M., Fasth, Anders L., Gale, Robert Peter, Lee, Michelle A., Lund, Troy C., Myers, Kasiani C., Olsson, Richard F., Page, Kristin M., Prestidge, Tim D., Radhi, Mohamed, Shah, Ami J., Schultz, Kirk R., Wirk, Baldeep, Wagner, John E., and Deeg, H. Joachim

Published
2015

16. Second Allogeneic Hematopoietic Cell Transplantation for Patients with Fanconi Anemia and Bone Marrow Failure

Author

Ayas, Mouhab, Eapen, Mary, Le-Rademacher, Jennifer, Carreras, Jeanette, Abdel-Azim, Hisham, Alter, Blanche P., Anderlini, Paolo, Battiwalla, Minoo, Bierings, MB, Buchbinder, David K., Bonfim, Carmem, Camitta, Bruce M., Fasth, Anders L., Gale, Robert Peter, Lee, Michelle A., Lund, Troy C., Myers, Kasiani C., Olsson, Richard F., Page, Kristin M., Prestidge, Tim D., Radhi, Mohamed, Shah, Ami J., Schultz, Kirk R., Wirk, Baldeep, Wagner, John E., Deeg, H. Joachim, Ayas, Mouhab, Eapen, Mary, Le-Rademacher, Jennifer, Carreras, Jeanette, Abdel-Azim, Hisham, Alter, Blanche P., Anderlini, Paolo, Battiwalla, Minoo, Bierings, MB, Buchbinder, David K., Bonfim, Carmem, Camitta, Bruce M., Fasth, Anders L., Gale, Robert Peter, Lee, Michelle A., Lund, Troy C., Myers, Kasiani C., Olsson, Richard F., Page, Kristin M., Prestidge, Tim D., Radhi, Mohamed, Shah, Ami J., Schultz, Kirk R., Wirk, Baldeep, Wagner, John E., and Deeg, H. Joachim

Published
2015

17. Second Allogeneic Hematopoietic Cell Transplantation for Patients with Fanconi Anemia and Bone Marrow Failure

Author

Ayas, Mouhab, Eapen, Mary, Le-Rademacher, Jennifer, Carreras, Jeanette, Abdel-Azim, Hisham, Alter, Blanche P., Anderlini, Paolo, Battiwalla, Minoo, Bierings, MB, Buchbinder, David K., Bonfim, Carmem, Camitta, Bruce M., Fasth, Anders L., Gale, Robert Peter, Lee, Michelle A., Lund, Troy C., Myers, Kasiani C., Olsson, Richard F., Page, Kristin M., Prestidge, Tim D., Radhi, Mohamed, Shah, Ami J., Schultz, Kirk R., Wirk, Baldeep, Wagner, John E., Deeg, H. Joachim, Ayas, Mouhab, Eapen, Mary, Le-Rademacher, Jennifer, Carreras, Jeanette, Abdel-Azim, Hisham, Alter, Blanche P., Anderlini, Paolo, Battiwalla, Minoo, Bierings, MB, Buchbinder, David K., Bonfim, Carmem, Camitta, Bruce M., Fasth, Anders L., Gale, Robert Peter, Lee, Michelle A., Lund, Troy C., Myers, Kasiani C., Olsson, Richard F., Page, Kristin M., Prestidge, Tim D., Radhi, Mohamed, Shah, Ami J., Schultz, Kirk R., Wirk, Baldeep, Wagner, John E., and Deeg, H. Joachim

Published
2015

18. Bone mineral density in children with fanconi anemia after hematopoietic cell transplantation.

Author

Petryk, Anna, Petryk, Anna, Polgreen, Lynda E, Barnum, Jessie L, Zhang, Lei, Hodges, James S, Baker, K Scott, Wagner, John E, Steinberger, Julia, MacMillan, Margaret L, Petryk, Anna, Petryk, Anna, Polgreen, Lynda E, Barnum, Jessie L, Zhang, Lei, Hodges, James S, Baker, K Scott, Wagner, John E, Steinberger, Julia, and MacMillan, Margaret L

Abstract

Fanconi anemia (FA) is an inherited DNA repair disorder associated with short stature and bone marrow failure, usually requiring hematopoietic cell transplantation (HCT). Although low bone mineral density (BMD) has been reported in leukemia patients after HCT, little is known about BMD in FA children after HCT (FA HCT). This study's goals were to compare BMD in FA HCT to BMD in healthy controls and in children who received HCT for hematologic malignancy (cancer HCT), and to test for associations between BMD and risk factors for bone loss. This cross-sectional study included 20 FA HCT, 13 cancer HCT, and 90 healthy controls, age-matched and <18 years old at evaluation. BMD Z-scores for total body (TBMD) and lumbar spine (LBMD) were measured by dual energy x-ray absorptiometry and adjusted for height-for-age Z-score (HAZ). FA HCT had lower mean TBMDHAZ Z-score (by .8 SD) and higher fraction with Z-score ≤ -1 than healthy controls (42% versus 11%). No LBMD deficits were detected. FA HCT and cancer HCT groups did not differ significantly in TBMD or LBMD Z-scores. In FA HCT patients, lower body mass index and lower percent fat were associated with lower BMD. This study highlights the importance of monitoring BMD to optimize bone health in FA patients.

Published
2015

19. A Dominant Mutation in Human RAD51 Reveals Its Function in DNA Interstrand Crosslink Repair Independent of Homologous Recombination.

Author

Wang, Anderson T, Wang, Anderson T, Kim, Taeho, Wagner, John E, Conti, Brooke A, Lach, Francis P, Huang, Athena L, Molina, Henrik, Sanborn, Erica M, Zierhut, Heather, Cornes, Belinda K, Abhyankar, Avinash, Sougnez, Carrie, Gabriel, Stacey B, Auerbach, Arleen D, Kowalczykowski, Stephen C, Smogorzewska, Agata, Wang, Anderson T, Wang, Anderson T, Kim, Taeho, Wagner, John E, Conti, Brooke A, Lach, Francis P, Huang, Athena L, Molina, Henrik, Sanborn, Erica M, Zierhut, Heather, Cornes, Belinda K, Abhyankar, Avinash, Sougnez, Carrie, Gabriel, Stacey B, Auerbach, Arleen D, Kowalczykowski, Stephen C, and Smogorzewska, Agata

Abstract

Repair of DNA interstrand crosslinks requires action of multiple DNA repair pathways, including homologous recombination. Here, we report a de novo heterozygous T131P mutation in RAD51/FANCR, the key recombinase essential for homologous recombination, in a patient with Fanconi anemia-like phenotype. In vitro, RAD51-T131P displays DNA-independent ATPase activity, no DNA pairing capacity, and a co-dominant-negative effect on RAD51 recombinase function. However, the patient cells are homologous recombination proficient due to the low ratio of mutant to wild-type RAD51 in cells. Instead, patient cells are sensitive to crosslinking agents and display hyperphosphorylation of Replication Protein A due to increased activity of DNA2 and WRN at the DNA interstrand crosslinks. Thus, proper RAD51 function is important during DNA interstrand crosslink repair outside of homologous recombination. Our study provides a molecular basis for how RAD51 and its associated factors may operate in a homologous recombination-independent manner to maintain genomic integrity.

Published
2015

20. Second Allogeneic Hematopoietic Cell Transplantation for Patients with Fanconi Anemia and Bone Marrow Failure

Author

Haematologie, Child Health, Regenerative Medicine and Stem Cells, Ayas, Mouhab, Eapen, Mary, Le-Rademacher, Jennifer, Carreras, Jeanette, Abdel-Azim, Hisham, Alter, Blanche P., Anderlini, Paolo, Battiwalla, Minoo, Bierings, MB, Buchbinder, David K., Bonfim, Carmem, Camitta, Bruce M., Fasth, Anders L., Gale, Robert Peter, Lee, Michelle A., Lund, Troy C., Myers, Kasiani C., Olsson, Richard F., Page, Kristin M., Prestidge, Tim D., Radhi, Mohamed, Shah, Ami J., Schultz, Kirk R., Wirk, Baldeep, Wagner, John E., Deeg, H. Joachim, Haematologie, Child Health, Regenerative Medicine and Stem Cells, Ayas, Mouhab, Eapen, Mary, Le-Rademacher, Jennifer, Carreras, Jeanette, Abdel-Azim, Hisham, Alter, Blanche P., Anderlini, Paolo, Battiwalla, Minoo, Bierings, MB, Buchbinder, David K., Bonfim, Carmem, Camitta, Bruce M., Fasth, Anders L., Gale, Robert Peter, Lee, Michelle A., Lund, Troy C., Myers, Kasiani C., Olsson, Richard F., Page, Kristin M., Prestidge, Tim D., Radhi, Mohamed, Shah, Ami J., Schultz, Kirk R., Wirk, Baldeep, Wagner, John E., and Deeg, H. Joachim

Published
2015

21. Analysis of risk factors influencing outcomes after cord blood transplantation in children with juvenile myelomonocytic leukemia: a EUROCORD, EBMT, EWOG-MDS, CIBMTR study

Author

Locatelli, Franco, Crotta, Alessandro, Ruggeri, Annalisa, Eapen, Mary, Wagner, John E, Macmillan, Margaret L, Zecca, Marco, Kurtzberg, Joanne, Bonfim, Carmem, Vora, Ajay, Díaz de Heredia, Cristina, Teague, Lochie, Stein, Jerry, O'Brien, Tracey A, Bittencourt, Henrique, Madureira, Adrienne, Strahm, Brigitte, Peters, Christina, Niemeyer, Charlotte, Gluckman, Eliane, Rocha, Vanderson, Locatelli, Franco (ORCID:0000-0002-7976-3654), Locatelli, Franco, Crotta, Alessandro, Ruggeri, Annalisa, Eapen, Mary, Wagner, John E, Macmillan, Margaret L, Zecca, Marco, Kurtzberg, Joanne, Bonfim, Carmem, Vora, Ajay, Díaz de Heredia, Cristina, Teague, Lochie, Stein, Jerry, O'Brien, Tracey A, Bittencourt, Henrique, Madureira, Adrienne, Strahm, Brigitte, Peters, Christina, Niemeyer, Charlotte, Gluckman, Eliane, Rocha, Vanderson, and Locatelli, Franco (ORCID:0000-0002-7976-3654)

Abstract

We retrospectively analyzed 110 patients with juvenile myelomonocytic leukemia, given single-unit, unrelated donor umbilical cord blood transplantation. Median age at diagnosis and at transplantation was 1.4 years (age range, 0.1-6.4 years) and 2.2 years (age range, 0.5-7.4 years), respectively. Before transplantation, 88 patients received chemotherapy; splenectomy was performed in 24 patients. Monosomy of chromosome 7 was the most frequent cytogenetic abnormality, found in 24% of patients. All but 8 patients received myeloablative conditioning; cyclosporine plus steroids was the most common graft-versus-host disease prophylaxis. Sixteen percent of units were HLA-matched with the recipient, whereas 43% and 35% had either 1 or 2 to 3 HLAdisparities, respectively. The median number of nucleated cells infused was 7.1x10(7)/kg (range, 1.7-27.6x10(7)/kg). With a median follow-up of 64 months (range, 14-174 months), the 5-year cumulative incidences of transplantation-related mortality and relapse were 22% and 33%, respectively. The 5-year disease-free survival rate was 44%. In multivariate analysis, factors predicting better disease-free survival were age younger than 1.4 years at diagnosis (hazard ratio [HR], 0.42; P=.005), 0 to 1 HLA disparities in the donor/recipient pair (HR, 0.4; P=.009), and karyotype other than monosomy 7 (HR, 0.5; P=.02). Umbilical cord blood transplantation may cure a relevant proportion of children with juvenile myelomonocytic leukemia. Because disease recurrence remains the major cause of treatment failure, strategies to reduce incidence of relapse are warranted.

Published
2013

22. National Service as an Alternative for Military Conscription.

Author

ARMY WAR COLL CARLISLE BARRACKS PA, Wagner, John E., ARMY WAR COLL CARLISLE BARRACKS PA, and Wagner, John E.

Abstract

The essay analyzes National Service as a possible alternative approach to military conscription as a means for providing the necessary manpower to support the armed forces. It considers the requirements of military recruitment, military officer procurement, and retention of trained personnel, in relation to national attitudes, historic precedents, objectives of national service, and other methods for meeting military manpower requirements. (Modified author abstract)

Published
1971

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