Bone Marrow Graft-versus-Host Disease: Evaluation of Its Clinical Impact on Disrupted Hematopoiesis after Allogeneic Hematopoietic Stem Cell Transplantation

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Bone Marrow Graft-versus-Host Disease: Evaluation of Its Clinical Impact on Disrupted Hematopoiesis after Allogeneic Hematopoietic Stem Cell Transplantation Yusuke Shono, Souichi Shiratori, Mizuha Kosugi-Kanaya, Satoshi Ueha, Junichi Sugita, Akio Shigematsu, Takeshi Kondo, Daigo Hashimoto, Katsuya Fujimoto, Tomoyuki Endo, Mitsufumi Nishio, Satoshi Hashino, Yoshihiro Matsuno, Kouji Matsushima, Junji Tanaka, Masahiro Imamura, Takanori Teshima Biology of Blood and Marrow Transplantation Volume 20, Issue 4, Pages 495-500 (April 2014) DOI: 10.1016/j.bbmt.2013.12.568 Copyright © 2014 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 Cumulative incidences of acute (A) and chronic (B) GVHD after allogeneic hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation 2014 20, 495-500DOI: (10.1016/j.bbmt.2013.12.568) Copyright © 2014 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Assessments of bone marrow biopsy samples from patients up to day 100 after allogeneic hematopoietic stem cell transplantation. aGVHD indicates acute graft-versus-host disease; Bx, biopsy. Biology of Blood and Marrow Transplantation 2014 20, 495-500DOI: (10.1016/j.bbmt.2013.12.568) Copyright © 2014 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Assessments of bone marrow biopsy samples from patients after day 100 after allogeneic hematopoietic stem cell transplantation. (A) Relations between loss of osteoblasts and idiopathic cytopenias. (B) Grades of chronic GVHD and their relations to idiopathic cytopenias. Biology of Blood and Marrow Transplantation 2014 20, 495-500DOI: (10.1016/j.bbmt.2013.12.568) Copyright © 2014 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 Loss of osteoblasts during GVHD and cytopenias. Biopsied bone marrow (BM) samples were stained with hematoxylin and eosin (upper panels for all pictures), as well as with CD56 (lower panels for all pictures) for assessments of cellularity, morphology, and presence or absence of osteoblasts. Magnification for the images is ×400. (A) BM samples from a 47-year-old patient after unrelated bone marrow transplantation who had no episode of GVHD and cytopenias when BM biopsies were performed. Osteoblasts are well preserved. Arrowheads indicate osteoblasts. (B) A 57-year-old patient who underwent related peripheral blood stem cell transplantation and relapsed on day 134 developed symptoms of chronic GVHD and cytopenias after day 160. Complete loss of osteoblasts is shown on day 176, and when he recovered from those symptoms osteoblasts are back on day 521. (C) A 37-year-old patient after related peripheral blood stem cell transplantation gradually developed cytopenias after day 90 with stage 1 skin GVHD. The BM samples on day 127 show clear loss of osteoblasts. On day 260, when his symptoms subsided, osteoblasts recovered to a normal level. (D) A 27-year-old patient who underwent unrelated bone marrow transplantation attained engraftment of white blood cells on day 20; however, cytopenias had persisted and he developed stage 1 skin GVHD on day 34. Partial loss of osteoblasts was observed from day 36 to day 68 and he had been on high demand of red blood cell and platelet transfusions. The BM samples on day 147 indicate complete loss of osteoblasts. Biology of Blood and Marrow Transplantation 2014 20, 495-500DOI: (10.1016/j.bbmt.2013.12.568) Copyright © 2014 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 5 Flow cytometric analyses of BM aspirates in patients after day 100. BM aspiration was performed at the same time of BM biopsy in these patients. Cellularity, nucleated cell count (NCC), CD19+ cells, CD3+ cells, and the ratio of CD4+ to CD8+ cells are shown. Biology of Blood and Marrow Transplantation 2014 20, 495-500DOI: (10.1016/j.bbmt.2013.12.568) Copyright © 2014 American Society for Blood and Marrow Transplantation Terms and Conditions