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Alpha-interferon with very-low-dose donor lymphocyte infusion for hematologic or cytogenetic relapse of chronic myeloid leukemia induces rapid and durable complete remissions and is associated with acceptable graft-versus-host disease.
Biol Blood Marrow Transplant 2004; 10(3):204-12BB

Abstract

Donor lymphocyte infusion (DLI) results in complete cytogenetic remission (CCR) of relapsed chronic-phase chronic myeloid leukemia (CML-CP) after allogeneic stem cell transplantation (SCT) in up to 80% of patients. The main complication of DLI is graft-versus-host disease (GVHD). Decreasing the dose of DLI is associated with less GVHD but also with a longer interval between treatment and CCR. We postulated that combining alpha-interferon (alpha-IFN) with DLI would enable us to decrease the dose of DLI, thereby limiting GVHD, and at the same time to decrease the interval between DLI and CCR for patients with either a hematologic or cytogenetic relapse. For molecular relapses, we hypothesized that because of a lower tumor load, very low doses of DLI without alpha-IFN could be an effective treatment. Two groups of CML-CP patients treated with DLI at a very low dose of 0.5 to 1.0 x 10(7) mononuclear cells per kilogram, containing 2 to 6 x 10(6) CD3+ T cells per kilogram, were analyzed: 13 patients with a cytogenetic or a hematologic relapse after allogeneic SCT (group A) were treated with additional alpha-IFN therapy at a dose of 3 x 10(6) U 5 d/wk, and 8 patients with a molecular relapse were treated without alpha-IFN (group B). Twelve patients from group A reached a CCR. The median interval between DLI and CCR was 7 weeks (range, 5-18 weeks) for group A. All patients with a CCR reached complete donor chimerism at a median of 10 weeks after DLI (range, 6-121 weeks). Eleven patients reached molecular remission at a median of 15 weeks after DLI (range, 8-34 weeks). In group B, all patients reached a molecular remission at a median of 14 weeks (range, 12-29 weeks). Five patients from group A developed acute GVHD grade II to IV and extensive chronic GVHD. In group B, 1 patient developed acute GVHD grade II to IV and subsequently developed extensive chronic GVHD. With a median follow-up of 62 months, 10 patients in group A are alive and in continuous CCR. One patient had a molecular relapse, for which she successfully received additional DLI; another patient reached molecular remission only after 5 doses of DLI. Two patients from group A died of a gram-negative sepsis, and 1 died of an acute myocardial infection. In group B, all patients are alive and in molecular remission with a median follow-up of 20 months. One patient's disease progressed but was successfully treated with DLI plus alpha-IFN. In conclusion, very-low-dose DLI in combination with alpha-IFN as treatment for cytogenetic or hematologic relapses of CML-CP after allogeneic SCT reduced the interval to obtain a CCR with acceptable GVHD when compared with the literature. Patients with a CCR also reached complete donor chimerism and complete molecular remissions. For patients with a molecular relapse, very-low-dose DLI alone is sufficient to induce molecular remissions in most patients and is associated with limited GVHD.

Authors+Show Affiliations

Department of Hematology, Leiden University Medical Center, The Netherlands. posthuma@rdgg.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

14993886

Citation

Posthuma, Eduardus F M., et al. "Alpha-interferon With Very-low-dose Donor Lymphocyte Infusion for Hematologic or Cytogenetic Relapse of Chronic Myeloid Leukemia Induces Rapid and Durable Complete Remissions and Is Associated With Acceptable Graft-versus-host Disease." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 10, no. 3, 2004, pp. 204-12.
Posthuma EF, Marijt EW, Barge RM, et al. Alpha-interferon with very-low-dose donor lymphocyte infusion for hematologic or cytogenetic relapse of chronic myeloid leukemia induces rapid and durable complete remissions and is associated with acceptable graft-versus-host disease. Biol Blood Marrow Transplant. 2004;10(3):204-12.
Posthuma, E. F., Marijt, E. W., Barge, R. M., van Soest, R. A., Baas, I. O., Starrenburg, C. W., ... Falkenburg, J. H. (2004). Alpha-interferon with very-low-dose donor lymphocyte infusion for hematologic or cytogenetic relapse of chronic myeloid leukemia induces rapid and durable complete remissions and is associated with acceptable graft-versus-host disease. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 10(3), pp. 204-12.
Posthuma EF, et al. Alpha-interferon With Very-low-dose Donor Lymphocyte Infusion for Hematologic or Cytogenetic Relapse of Chronic Myeloid Leukemia Induces Rapid and Durable Complete Remissions and Is Associated With Acceptable Graft-versus-host Disease. Biol Blood Marrow Transplant. 2004;10(3):204-12. PubMed PMID: 14993886.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alpha-interferon with very-low-dose donor lymphocyte infusion for hematologic or cytogenetic relapse of chronic myeloid leukemia induces rapid and durable complete remissions and is associated with acceptable graft-versus-host disease. AU - Posthuma,Eduardus F M, AU - Marijt,Erik W A F, AU - Barge,Renee M Y, AU - van Soest,Ronald A, AU - Baas,Inge O, AU - Starrenburg,C W J Ingrid, AU - van Zelderen-Bhola,Shama L, AU - Fibbe,Willem E, AU - Smit,Wim M, AU - Willemze,Roel, AU - Falkenburg,J H Frederik, PY - 2004/3/3/pubmed PY - 2004/10/8/medline PY - 2004/3/3/entrez SP - 204 EP - 12 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 10 IS - 3 N2 - Donor lymphocyte infusion (DLI) results in complete cytogenetic remission (CCR) of relapsed chronic-phase chronic myeloid leukemia (CML-CP) after allogeneic stem cell transplantation (SCT) in up to 80% of patients. The main complication of DLI is graft-versus-host disease (GVHD). Decreasing the dose of DLI is associated with less GVHD but also with a longer interval between treatment and CCR. We postulated that combining alpha-interferon (alpha-IFN) with DLI would enable us to decrease the dose of DLI, thereby limiting GVHD, and at the same time to decrease the interval between DLI and CCR for patients with either a hematologic or cytogenetic relapse. For molecular relapses, we hypothesized that because of a lower tumor load, very low doses of DLI without alpha-IFN could be an effective treatment. Two groups of CML-CP patients treated with DLI at a very low dose of 0.5 to 1.0 x 10(7) mononuclear cells per kilogram, containing 2 to 6 x 10(6) CD3+ T cells per kilogram, were analyzed: 13 patients with a cytogenetic or a hematologic relapse after allogeneic SCT (group A) were treated with additional alpha-IFN therapy at a dose of 3 x 10(6) U 5 d/wk, and 8 patients with a molecular relapse were treated without alpha-IFN (group B). Twelve patients from group A reached a CCR. The median interval between DLI and CCR was 7 weeks (range, 5-18 weeks) for group A. All patients with a CCR reached complete donor chimerism at a median of 10 weeks after DLI (range, 6-121 weeks). Eleven patients reached molecular remission at a median of 15 weeks after DLI (range, 8-34 weeks). In group B, all patients reached a molecular remission at a median of 14 weeks (range, 12-29 weeks). Five patients from group A developed acute GVHD grade II to IV and extensive chronic GVHD. In group B, 1 patient developed acute GVHD grade II to IV and subsequently developed extensive chronic GVHD. With a median follow-up of 62 months, 10 patients in group A are alive and in continuous CCR. One patient had a molecular relapse, for which she successfully received additional DLI; another patient reached molecular remission only after 5 doses of DLI. Two patients from group A died of a gram-negative sepsis, and 1 died of an acute myocardial infection. In group B, all patients are alive and in molecular remission with a median follow-up of 20 months. One patient's disease progressed but was successfully treated with DLI plus alpha-IFN. In conclusion, very-low-dose DLI in combination with alpha-IFN as treatment for cytogenetic or hematologic relapses of CML-CP after allogeneic SCT reduced the interval to obtain a CCR with acceptable GVHD when compared with the literature. Patients with a CCR also reached complete donor chimerism and complete molecular remissions. For patients with a molecular relapse, very-low-dose DLI alone is sufficient to induce molecular remissions in most patients and is associated with limited GVHD. SN - 1083-8791 UR - https://www.unboundmedicine.com/medline/citation/14993886/Alpha_interferon_with_very_low_dose_donor_lymphocyte_infusion_for_hematologic_or_cytogenetic_relapse_of_chronic_myeloid_leukemia_induces_rapid_and_durable_complete_remissions_and_is_associated_with_acceptable_graft_versus_host_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083879103004774 DB - PRIME DP - Unbound Medicine ER -