PMID- 9578312
OWN - NLM
STAT- MEDLINE
DCOM- 19980616
LR  - 20071115
IS  - 0268-3369 (Print)
IS  - 0268-3369 (Linking)
VI  - 21
IP  - 7
DP  - 1998 Apr
TI  - Monitoring of lineage-specific chimaerism allows early prediction of response 
      following donor lymphocyte infusions for relapsed chronic myeloid leukaemia.
PG  - 711-9
AB  - Donor lymphocyte infusions (DLI) have been shown to enhance the 
      graft-versus-leukaemia (GVL) effect and induce haematological and molecular 
      remission in patients with relapsed CML following allogeneic bone marrow 
      transplantation (BMT). The potent donor cell-mediated cytolysis following DLI may 
      lead to a short period of aplasia before the re-establishment of donor 
      haematopoiesis. The absence of detectable donor cells in patients prior to DLI 
      infusion may result in permanent aplasia in certain patients. We report on four 
      patients who relapsed 1, 3, 6.5 and 7 years post-BMT for chronic phase CML and 
      were treated with DLI from their original BMT donor. Polymorphic short tandem 
      repeats (STRs) were used to assess haematological chimaerism both prior to and 
      following DLI. At the time of relapse, STR-PCR indicated the presence of donor 
      cells in all four patients, at levels ranging from 1-40%. A clinical and 
      molecular response was seen in 4/4 patients following a short period of cytopenia 
      and all patients remain in clinical remission with a follow-up of 2 months-3 
      years post-DLI. STR-PCR indicated that a response was occurring during the period 
      of pancytopenia when metaphase analysis was unsuccessful. Lineage-specific 
      analysis of the cellular response to DLI was monitored using STR-PCR of 
      peripheral blood (PB) and bone marrow (BM) lymphocyte-enriched fractions and 
      CD2-positive and -negative T cell fractions. In one patient BM and PB 
      CD34-positive and -negative fractions were also assessed. A change in the ratio 
      of donor:recipient cells in the PB lymphocyte fraction was the earliest molecular 
      indication of an anti-leukaemic response. Subsequent conversion to donor 
      chimaerism occurred in the other lineages and the granulocyte fraction was the 
      last lineage to convert. In conclusion, lineage-specific STR-PCR permits detailed 
      monitoring of subtle changes in donor/recipient cell dynamics in specific 
      lineages following DLI during the crucial pancytopenic phase and may be a useful 
      predictor of haematological response to DLI therapy.
FAU - Gardiner, N
AU  - Gardiner N
AD  - Department of Haematology, St James Hospital, Dublin, Ireland.
FAU - Lawler, M
AU  - Lawler M
FAU - O'Riordan, J M
AU  - O'Riordan JM
FAU - Duggan, C
AU  - Duggan C
FAU - De Arce, M
AU  - De Arce M
FAU - McCann, S R
AU  - McCann SR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Bone Marrow Transplant
JT  - Bone marrow transplantation
JID - 8702459
SB  - IM
MH  - Adult
MH  - *Cell Lineage
MH  - Humans
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*pathology/*therapy
MH  - *Lymphocyte Transfusion
MH  - Predictive Value of Tests
MH  - Prognosis
MH  - Recurrence
MH  - *Transplantation Chimera
MH  - Transplantation, Homologous
EDAT- 1998/05/13 00:00
MHDA- 1998/05/13 00:01
CRDT- 1998/05/13 00:00
PHST- 1998/05/13 00:00 [pubmed]
PHST- 1998/05/13 00:01 [medline]
PHST- 1998/05/13 00:00 [entrez]
AID - 10.1038/sj.bmt.1701154 [doi]
PST - ppublish
SO  - Bone Marrow Transplant. 1998 Apr;21(7):711-9. doi: 10.1038/sj.bmt.1701154.