title: Randomized, Prospective Evaluation Comparing Intensity of Lymphodepletion Before Adoptive Transfer of Tumor-Infiltrating Lymphocytes for Patients With Metastatic Melanoma.
abstract: Adoptive cell transfer, the infusion of large numbers of activated autologous lymphocytes, can mediate objective tumor regression in a majority of patients with metastatic melanoma (52 of 93; 56%). Addition and intensification of total body irradiation (TBI) to the preparative lymphodepleting chemotherapy regimen in sequential trials improved objective partial and complete response (CR) rates. Here, we evaluated the importance of adding TBI to the adoptive transfer of tumor-infiltrating lymphocytes (TIL) in a randomized fashion.
  
  
  
  A total of 101 patients with metastatic melanoma, including 76 patients with M1c disease, were randomly assigned to receive nonmyeloablative chemotherapy with or without 1,200 cGy TBI before transfer of tumor-infiltrating lymphcytes. Primary end points were CR rate (as defined by Response Evaluation Criteria in Solid Tumors v1.0) and overall survival (OS). Clinical and laboratory data were analyzed for correlates of response.
  
  
  
  CR rates were 24% in both groups (12 of 50 v 12 of 51), and OS was also similar (median OS, 38.2 v 36.6 months; hazard ratio, 1.11; 95% CI, 0.65 to 1.91; P = .71). Thrombotic microangiopathy was an adverse event unique to the TBI arm and occurred in 13 of 48 treated patients. With a median potential follow-up of 40.9 months, only one of 24 patients who achieved a CR recurred.
  
  
  
  Adoptive cell transfer can mediate durable complete regressions in 24% of patients with metastatic melanoma, with median survival > 3 years. Results were similar using chemotherapy preparative regimens with or without addition of TBI.
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA. stephanie.goff@nih.gov.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Goff
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Dudley
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Citrin
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Somerville
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: John R
authors.initials: JR
authors.lastname: Wunderlich
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: David N
authors.initials: DN
authors.lastname: Danforth
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Zlott
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Sherry
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Udai S
authors.initials: US
authors.lastname: Kammula
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Klebanoff
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Marybeth S
authors.initials: MS
authors.lastname: Hughes
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Langhan
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Shelton
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Lily
authors.initials: L
authors.lastname: Lu
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Mei Li M
authors.initials: ML
authors.lastname: Kwong
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Sadia
authors.initials: S
authors.lastname: Ilyas
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Klemen
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Eden C
authors.initials: EC
authors.lastname: Payabyab
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Morton
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Toomey
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Donald E
authors.initials: DE
authors.lastname: White
authors.affiliation: Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M. Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D008212:Lymphocyte Depletion; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011446:Prospective Studies; D014916:Whole-Body Irradiation