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Kinetics of the graft-versus-leukemia response after donor leukocyte infusions for relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation.
Blood. 1998 Nov 15; 92(10):3582-90.Blood

Abstract

Little is known about the mechanisms and the kinetics of the so-called graft-versus-leukemia (GVL) response induced by donor lymphocyte infusions (DLI) in patients with leukemic relapse after allogeneic bone marrow transplantation (BMT). We sought to elucidate this problem by sequentially studying three patients with relapsed chronic myeloid leukemia after sex-mismatched BMT from time before donor leukocyte infusion until achievement of complete molecular remission. Lineage-specific chimerism was assessed longitudinally by a combined fluorescent immunophenotyping and sex chromosome-specific in situ hybridization approach. Results were related to quantitative detection of bcr-abl transcripts by competitive differential reverse transcriptase-polymerase chain reaction (RT-PCR), qualitative bcr-abl RT-PCR, and multiplex PCR-based DNA donor/recipient chimerism. All patients had predominant donor lymphopoiesis at the time of DLI, suggesting a state of tolerance to recipient leukemic and/or normal cells. In contrast, granulopoiesis and erythropoiesis were mainly recipient derived in both patients with hematologic relapse and partly recipient derived in the patient with molecular relapse. Eighty percent, 90%, and 8% of CD34(+) cells, respectively, were found to be of recipient origin at relapse, and few donor stem cells predicted for cytopenia post-DLI. Responses were seen after a time lag of 5 to 13 weeks after DLI and resulted in reversal to full donor chimerism within a critical switch period of 4 to 5 weeks. A sudden decrease in recipient cells was paralleled by a sharp decrease in bcr-abl transcript numbers detectable several weeks before achievement of molecular remission and onset of clinical graft-versus-host disease (GVHD). This response pattern was confirmed by retrospective RT-PCR analysis in an additional five patients. Prospective monitoring of stem cell chimerism and response may enable us to individually tailor adoptive immunotherapy in the future.

Authors+Show Affiliations

Abteilung für Innere Medizin mit Schwerpunkt Hämatologie/Onkologie, Virchow Klinikum der Humboldt Universität zu Berlin, Berlin, Germany. Herrad.Baurmann@t-online.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9808551

Citation

Baurmann, H, et al. "Kinetics of the Graft-versus-leukemia Response After Donor Leukocyte Infusions for Relapsed Chronic Myeloid Leukemia After Allogeneic Bone Marrow Transplantation." Blood, vol. 92, no. 10, 1998, pp. 3582-90.
Baurmann H, Nagel S, Binder T, et al. Kinetics of the graft-versus-leukemia response after donor leukocyte infusions for relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation. Blood. 1998;92(10):3582-90.
Baurmann, H., Nagel, S., Binder, T., Neubauer, A., Siegert, W., & Huhn, D. (1998). Kinetics of the graft-versus-leukemia response after donor leukocyte infusions for relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation. Blood, 92(10), 3582-90.
Baurmann H, et al. Kinetics of the Graft-versus-leukemia Response After Donor Leukocyte Infusions for Relapsed Chronic Myeloid Leukemia After Allogeneic Bone Marrow Transplantation. Blood. 1998 Nov 15;92(10):3582-90. PubMed PMID: 9808551.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Kinetics of the graft-versus-leukemia response after donor leukocyte infusions for relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation. AU - Baurmann,H, AU - Nagel,S, AU - Binder,T, AU - Neubauer,A, AU - Siegert,W, AU - Huhn,D, PY - 1998/11/10/pubmed PY - 1998/11/10/medline PY - 1998/11/10/entrez SP - 3582 EP - 90 JF - Blood JO - Blood VL - 92 IS - 10 N2 - Little is known about the mechanisms and the kinetics of the so-called graft-versus-leukemia (GVL) response induced by donor lymphocyte infusions (DLI) in patients with leukemic relapse after allogeneic bone marrow transplantation (BMT). We sought to elucidate this problem by sequentially studying three patients with relapsed chronic myeloid leukemia after sex-mismatched BMT from time before donor leukocyte infusion until achievement of complete molecular remission. Lineage-specific chimerism was assessed longitudinally by a combined fluorescent immunophenotyping and sex chromosome-specific in situ hybridization approach. Results were related to quantitative detection of bcr-abl transcripts by competitive differential reverse transcriptase-polymerase chain reaction (RT-PCR), qualitative bcr-abl RT-PCR, and multiplex PCR-based DNA donor/recipient chimerism. All patients had predominant donor lymphopoiesis at the time of DLI, suggesting a state of tolerance to recipient leukemic and/or normal cells. In contrast, granulopoiesis and erythropoiesis were mainly recipient derived in both patients with hematologic relapse and partly recipient derived in the patient with molecular relapse. Eighty percent, 90%, and 8% of CD34(+) cells, respectively, were found to be of recipient origin at relapse, and few donor stem cells predicted for cytopenia post-DLI. Responses were seen after a time lag of 5 to 13 weeks after DLI and resulted in reversal to full donor chimerism within a critical switch period of 4 to 5 weeks. A sudden decrease in recipient cells was paralleled by a sharp decrease in bcr-abl transcript numbers detectable several weeks before achievement of molecular remission and onset of clinical graft-versus-host disease (GVHD). This response pattern was confirmed by retrospective RT-PCR analysis in an additional five patients. Prospective monitoring of stem cell chimerism and response may enable us to individually tailor adoptive immunotherapy in the future. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/9808551/Kinetics_of_the_graft_versus_leukemia_response_after_donor_leukocyte_infusions_for_relapsed_chronic_myeloid_leukemia_after_allogeneic_bone_marrow_transplantation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-4971(20)57801-4 DB - PRIME DP - Unbound Medicine ER -