PMID- 11064467
OWN - NLM
STAT- MEDLINE
DCOM- 20010301
LR  - 20071115
IS  - 0390-6078 (Print)
IS  - 0390-6078 (Linking)
VI  - 85
IP  - 11
DP  - 2000 Nov
TI  - Need for an accurate molecular diagnosis to assess the donor origin of leukemia 
      relapse after allogeneic stem cell transplantation.
PG  - 1153-7
AB  - BACKGROUND AND OBJECTIVES: Leukemia relapse occurring in donor cells after 
      allogeneic hematopoietic stem cell transplantation has been reported in rare 
      cases. Cytogenetic analysis and molecular probing of variable number of tandem 
      repeats (VNTRs) have been used to confirm this unusual event in the few cases so 
      far reported in the literature. The aim of this study was to demonstrate that 
      extensive molecular characterization of leukemic cells at diagnosis and relapse 
      may be necessary to avoid many technical pitfalls possibly leading to an 
      erroneous diagnosis of leukemia relapse in donor cells after allogeneic 
      transplantation. DESIGN AND METHODS: We report the case of a 49- year old man who 
      received an allogeneic transplantation from his HLA-identical sister because of 
      BCR-ABL+ acute lymphoblastic leukemia (ALL). After having achieved complete 
      hematologic and molecular remission, two years later an overt leukemia relapse 
      occurred with cytogenetic findings suggesting a leukemia relapse in donor cells. 
      The donor or patient origin of leukemic cells at relapse was further investigated 
      by fluorescence in situ hybridization (FISH) karyotyping, reverse transcription 
      (RT) polymerase chain reaction (PCR) analysis of BCR-ABL chimeric transcripts, 
      PCR amplification of several VNTRs and the Y chromosome-specific DYS14 sequence 
      and finally by amplification, cloning and sequencing of the CDRIII region of the 
      immunoglobulin heavy chain (IgH) gene. RESULTS: At the time of relapse, 
      conventional and FISH karyotyping revealed the presence of a Phl+ chromosome and 
      a female karyotype in all the 25 metaphases analyzed and PCR amplification of the 
      Y chromosome-specific DYS14 sequence was negative. Moreover, the molecular 
      evaluation of hematopoietic chimerism performed by the NZ-22 VNTR allowed us to 
      demonstrate that at the time of relapse, a consistent proportion of hematopoietic 
      cells was of donor origin. However, the molecular cloning and sequencing of the 
      CDRIII region of the immunoglobuin heavy chain (IgH) gene rearrangement in 
      leukemic blasts at diagnosis and relapse demonstrated their identity thus 
      formally proving the patient origin of both leukemic clones. INTERPRETATION AND 
      CONCLUSIONS: While the simplest interpretation of the apparent female karyotype 
      at relapse is the consequence of a loss of the Y chromosome which in leukemic 
      blasts took place along with duplication of an X-chromosome, this case strongly 
      emphasizes the need for accurate and extensive molecular characterization to 
      prove the donor origin of a leukemia relapse after allogeneic transplantation.
FAU - Spinelli, O
AU  - Spinelli O
AD  - Divisione di Ematologia e Centro Trasfusionale, Ospedali Riuniti di Bergamo, 
      Italy.
FAU - Giussani, U
AU  - Giussani U
FAU - Borleri, G
AU  - Borleri G
FAU - Lazzari, M
AU  - Lazzari M
FAU - Michelato, A
AU  - Michelato A
FAU - Dotti, G
AU  - Dotti G
FAU - Barbui, T
AU  - Barbui T
FAU - Rambaldi, A
AU  - Rambaldi A
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
SB  - IM
MH  - Base Sequence
MH  - Cell Transformation, Neoplastic
MH  - Cytogenetic Analysis
MH  - Female
MH  - Hematopoietic Stem Cell Transplantation/*adverse effects
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Neoplasms, Second Primary/*etiology/pathology
MH  - Nuclear Family
MH  - Philadelphia Chromosome
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood/*therapy
MH  - Recurrence
MH  - Sequence Analysis, DNA
MH  - Tissue Donors
MH  - Transplantation Chimera
MH  - Transplantation, Homologous
EDAT- 2000/11/07 11:00
MHDA- 2001/03/07 10:01
CRDT- 2000/11/07 11:00
PHST- 2000/11/07 11:00 [pubmed]
PHST- 2001/03/07 10:01 [medline]
PHST- 2000/11/07 11:00 [entrez]
PST - ppublish
SO  - Haematologica. 2000 Nov;85(11):1153-7.