title: Extramedullary relapse following total marrow and lymphoid irradiation in patients undergoing allogeneic hematopoietic cell transplantation.
abstract: OBJECTIVE
  Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution.
  
  
  METHODS
  Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph node chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy.
  
  
  RESULTS
  A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years.
  
  
  CONCLUSIONS
  EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk.
authors.affiliation: Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California.
authors.forename: Anthony
authors.initials: A
authors.lastname: Stein
authors.affiliation: Department of Biostatistics, City of Hope National Medical Center, Duarte, California.
authors.forename: Nicole
authors.initials: N
authors.lastname: Tsai
authors.affiliation: Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Schultheiss
authors.affiliation: Department of Biostatistics, City of Hope National Medical Center, Duarte, California.
authors.forename: Joycelynne
authors.initials: J
authors.lastname: Palmer
authors.affiliation: Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California.
authors.forename: An
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California; Department of Pediatrics, City of Hope National Medical Center, Duarte, California.
authors.forename: Joseph
authors.initials: J
authors.lastname: Rosenthal
authors.affiliation: Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.affiliation: Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California. Electronic address: jwong@coh.org.
authors.forename: Jeffrey Y C
authors.initials: JY
authors.lastname: Wong
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001752:Blast Crisis / Q000401:mortality / Q000628:therapy*; D001853:Bone Marrow / Q000528:radiation effects; D002066:Busulfan / Q000627:therapeutic use; D002648:Child; D003520:Cyclophosphamide / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy*; D015182:Lymphatic Irradiation / Q000009:adverse effects / Q000379:methods*; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy*; D059351:Organ Sparing Treatments / Q000009:adverse effects; D058958:Organs at Risk; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy*; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D012008:Recurrence; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014916:Whole-Body Irradiation / Q000009:adverse effects / Q000379:methods*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D005047:Etoposide; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008558:Melphalan