title: The effects of hematopoietic stem cell transplant on splenic extramedullary hematopoiesis in patients with myeloproliferative neoplasm-associated myelofibrosis.
abstract: OBJECTIVE
  Hematopoietic stem cell transplant (HSCT) is the only curative treatment for myeloproliferative neoplasm-associated myelofibrosis (MPN-MF). The main clinical manifestation of MPN-MF is splenomegaly secondary to extramedullary hematopoiesis (EMH). The effects of HSCT on splenic EMH and associated vascular and stromal changes are unknown. This study compares the findings seen in spleens following HSCT with those of nontransplanted patients, normal controls, and matched bone marrow (BM) samples.
  
  
  METHODS
  This study included three transplanted MPN-MF spleens, three nontransplanted MPN-MF spleens, and three normal controls. Spleens were assessed for: (a) presence/extent of EMH; (b) presence of Gamna-Gandy bodies; (c) splenic fibrosis; (d) CD34-positive microvessel density; (e) CD8-positive sinusoids; (f) frequency of smooth muscle actin-positive myoid cells; and (g) nerve growth factor receptor-positive adventitial reticulum cells. In two cases, matched BM samples were assessed for cellularity, presence of atypical megakaryocytes, and fibrosis.
  
  
  RESULTS
  Compared with normal controls, all MPN-MF spleens were larger in size, had EMH, red pulp fibrosis, higher CD34-positive microvessel density, and decreased CD8-positive sinusoids. Compared with nontransplanted cases, post-HSCT spleens showed disappearance or reduction of EMH. Gamna-Gandy bodies were increased; no differences in the remaining parameters were found. A reduction of splenic EMH was associated with normalization of BM cellularity and megakaryopoiesis.
  
  
  CONCLUSIONS
  HSCT reduces/abrogates splenic EMH and is associated with an increased number of Gamna-Gandy bodies, which may suggest vascular damage. The lack of stromal changes in spleens removed shortly after transplant is in line with similar observations in the BM, where a longer interval is often necessary for resolution of fibrosis.
authors: Division of Hematopathology, Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital/Weill Cornell Medical College, New York, NY, USA; Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy.
authors: Marco
authors: M
authors: Pizzi
authors: Division of Hematology-Oncology, Department of Medicine, New York Presbyterian Hospital/Weill Cornell Medical College, New York, NY, USA.
authors: Usama
authors: U
authors: Gergis
authors: Division of Hematopathology, Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital/Weill Cornell Medical College, New York, NY, USA.
authors: Felicia
authors: F
authors: Chaviano
authors: Division of Hematopathology, Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital/Weill Cornell Medical College, New York, NY, USA. Electronic address: ato9002@med.cornell.edu.
authors: Attilio
authors: A
authors: Orazi
mesh_terms: D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000473:pathology; D019046:Bone Marrow Neoplasms / Q000473:pathology / Q000628:therapy*; D005260:Female; D006411:Hematopoiesis, Extramedullary; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D055728:Primary Myelofibrosis / Q000473:pathology / Q000628:therapy*; D013154:Spleen / Q000473:pathology*
keywords: Hematopoietic stem cell transplant; Myelofibrosis; Myeloproliferative neoplasms; Spleen