Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Oct 15:10:572918.
doi: 10.3389/fonc.2020.572918. eCollection 2020.

Donor Lymphocyte Infusions After Allogeneic Stem Cell Transplantation in Acute Leukemia: A Survey From the Gruppo Italiano Trapianto Midollo Osseo (GITMO)

Francesca Patriarca  1   2 , Alessandra Sperotto  1 , Francesca Lorentino  3 , Elena Oldani  4 , Sonia Mammoliti  5 , Miriam Isola  6 , Alessandra Picardi  7 , William Arcese  8 , Giorgia Saporiti  9 , Roberto Sorasio  10 , Nicola Mordini  10 , Irene Cavattoni  11 , Maurizio Musso  12 , Carlo Borghero  13 , Caterina Micò  4 , Renato Fanin  1   2 , Benedetto Bruno  14 , Fabio Ciceri  3 , Francesca Bonifazi  15
Affiliations

Donor Lymphocyte Infusions After Allogeneic Stem Cell Transplantation in Acute Leukemia: A Survey From the Gruppo Italiano Trapianto Midollo Osseo (GITMO)

Francesca Patriarca et al. Front Oncol. .

Abstract

We conducted a retrospective multicenter study including pediatric and adult patients with acute leukemia (AL) who received donor lymphocyte infusions (DLIs) after allogeneic hematopoietic stem cell transplantation (HCT) between January 1, 2010 and December 31, 2015, in order to determine the efficacy and toxicity of the immune treatment. Two hundred fifty-two patients, median age 45.1 years (1.6-73.4), were enrolled from 34 Italian transplant centers. The underlying disease was acute myeloid leukemia in 180 cases (71%). Donors were HLA identical or 1 locus mismatched sibling (40%), unrelated (40%), or haploidentical (20%). The first DLI was administered at a median time of 258 days (55-3,784) after HCT. The main indication for DLI was leukemia relapse (73%), followed by mixed chimerism (17%), and pre-emptive/prophylactic use (10%). Ninety-six patients (38%) received one single infusion, whereas 65 (26%), 42 (17%), and 49 patients (19%) received 2, 3, or ≥4 infusions, respectively, with a median of 31 days between two subsequent DLIs. Forty percent of evaluable patients received no treatment before the first DLI, whereas radiotherapy, conventional chemotherapy or targeted treatments were administered in 3, 39, and 18%, respectively. In informative patients, a few severe adverse events were reported: grade III-IV graft versus host disease (GVHD) (3%), grade III-IV hematological toxicity (11%), and DLI-related mortality (9%). Forty-six patients (18%) received a second HCT after a median of 232 days (32-1,390) from the first DLI. With a median follow-up of 461 days (2-3,255) after the first DLI, 1-, 3-, and 5- year overall survival (OS) of the whole group from start of DLI treatment was 55, 39, and 33%, respectively. In multivariate analysis, older recipient age, and transplants from haploidentical donors significantly reduced OS, whereas DLI for mixed chimerism or as pre-emptive/prophylactic treatment compared to DLI for AL relapse and a schedule including more than one DLI significantly prolonged OS. This GITMO survey confirms that DLI administration in absence of overt hematological relapse and multiple infusions are associated with a favorable outcome in AL patients. DLI from haploidentical donors had a poor outcome and may represent an area of further investigation.

Keywords: acute leukemia; allogeneic stem cell transplantation; donor lymphocyte infusions; pre-emptive treatment; relapse.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Overall survival of the 252 patients treated with DLIs.
Figure 2
Figure 2
Overall survival according to DLI indication.
Figure 3
Figure 3
Overall survival according to donor.
Figure 4
Figure 4
Overall survival according to number of allogeneic transplants.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kolb HJ, Mittermuller J, Clemm C, Holler E, Ledderose G, Brehm G, et al. . Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood. (1990) 76:2462–5. - PubMed
    1. Dobyski WR, Keever CA, Roth MS, Koethe S, Hanson G, McFadden P, et al. Salvage immunotherapy using donor leucocyte infusions as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: efficacy and toxicity of a defined T-cell dose. Blood. (1993) 82:2310–8. 10.1182/blood.V82.8.2310.2310 - DOI - PubMed
    1. Dazzi F, Szydlo RM, Cross NC, Craddock C, Kaeda J, Kanfer E, et al. . Durability of responses following donor lymphocyte infusions for patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Blood. (2000) 96:2712–6. 10.1182/blood.V96.8.2712 - DOI - PubMed
    1. Collins RH, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R, et al. . Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol. (1997) 15:433–44. 10.1200/JCO.1997.15.2.433 - DOI - PubMed
    1. Verdonck LF, Petersen EJ, Lokhorst HM, Nieuwenhuis HK, Dekker AW, Tilanus MG, et al. . Donor leukocyte infusions for recurrent hematologic malignancies after allogeneic bone marrow transplantation: impact of infused and residual donor T cells. Bone Marrow Transplant. (1998) 22:1057–63. 10.1038/sj.bmt.1701496 - DOI - PubMed