Cytogenetic analysis of chimerism and leukemia relapse in chronic myelogenous leukemia patients after T cell-depleted bone marrow transplantation Journal Article


Authors: Offit, K.; Burns, J. P.; Cunningham, I.; Jhanwar, S. C.; Black, P.; Kernan, N. A.; O'Reilly, R. J.; Chaganti, R. S. K.
Article Title: Cytogenetic analysis of chimerism and leukemia relapse in chronic myelogenous leukemia patients after T cell-depleted bone marrow transplantation
Abstract: Serial cytogenetic studies were performed on 64 patients with chronic myelogenous leukemia (CML) after T cell-depleted allogeneic bone marrow transplantation (BMT). Forty patients with CML in chronic phase (CP) received cytoreduction followed by BMT with HLA-matched T cell-depleted allogeneic marrow. The remaining 24 patients were transplanted in second chronic accelerated or blastic phase, or received T cell-depleted grafts with a dose of T cells added back. The Y chromosome and autosomal heteromorphisms were used to distinguish between donor and host cells. Mixed hematopoietic chimerism (presence of donor and host cells) was identified in 90% of patients in first CP. The Philadelphia (Ph) chromosome reappeared in 16 of the 40 first CP CML patients. As expected, patients who had detectable Ph chromosome positive cells at any time during the posttransplant period had a high likelihood of subsequent clinical relapse. Transient disappearance of the Ph positive clone was rarely observed, and was followed by reappearance of the Ph chromosome or clinical relapse. A subset of engrafted patients with greater than 25% host cells within 3 months post-BMT had a significantly shorter survival time free of cytogenetic or clinical relapse compaed with other patients. In patients who had received donor T cells added to the T cell-depleted graft, there was a higher proportion of complete chimerism. Clonal progression of Ph positive as well as negative cells was observed and may be the result of radiation induced breakage. Serial cytogenetic studies of patients post-BMT can provide useful information regarding the biologic and clinical behavior of CML.
Keywords: adult; child; transplantation, homologous; human cell; major clinical study; t lymphocyte; bone marrow cells; cytogenetics; cyclophosphamide; chronic myeloid leukemia; chimera; graft rejection; chromosome aberrations; bone marrow transplantation; karyotyping; lymphocyte depletion; hla system; middle age; philadelphia chromosome; leukemia, myeloid, chronic; chromosome disorders; prognosis; human; male; female; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; host vs graft reaction
Journal Title: Blood
Volume: 75
Issue: 6
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 1990-03-15
Start Page: 1346
End Page: 1355
Language: English
PUBMED: 2310831
PROVIDER: scopus
DOI: 10.1182/blood.V75.6.1346.1346
DOI/URL:
Notes: Article -- Export Date: 27 January 2020 -- Source: Scopus
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MSK Authors
  1. Nancy Kernan
    512 Kernan
  2. Kenneth Offit
    788 Offit
  3. Raju S K Chaganti
    391 Chaganti
  4. Suresh C Jhanwar
    293 Jhanwar
  5. Richard O'Reilly
    747 O'Reilly
  6. Patricia   Black
    31 Black