Donor lymphocyte infusion – pro

DLI is well studied in chronic myelogenous leukemia but less so in other hematological conditions.

DLI induces complete remissions in the majority of patients with chronic myeloid leukemia (CML) in early-stage relapse and in less than 30% of patients with relapsed acute leukemia, myelodysplasia, and multiple myeloma. DLI-induced remissions of chronic phase CML are durable, but as many as half of patients with other diseases ultimately relapse. Complications of DLI include acute and chronic graft-vs-host disease (GVHD) and aplasia, which induce profound immunosuppression and susceptibility to opportunistic infections. There is a strong correlation of GVHD and disease response.
Other hematologic malignancies do not respond to DLI as well as early-stage CM. In general, less than 30% of patients with relapsed acute leukemia,myelodysplasia, and multiple myeloma achieve complete responses to DLI. As many close to half or more of patients who do achieve a complete response may be expected to relapse after DLI. DLI has been researched as a treatment for a variety of hematologic malignancies, including most prominently chronic myeloid leukemia, but also acute myeloid leukemia, acute lymphocytic leukemia, multiple myeloma, myelodysplastic syndromes, chronic lymphocytic leukemia, Hodgkin’s disease, and non-Hodgkin’s lymphoma. Studies are limited due to small numbers but they have provided evidence that DLI can establish a graft-versus-leukemia/lymphoma effect. Whetehr a second DLI adds something to GVHD is not known.

While DLI-induced remissions are achieved in only a small number of AML patients, many of these remissions may be durable. Of 10 patients in the North American registry who had achieved a complete remission (CR) from DLI, only two subsequently relapsed at 1–3 years. At a median follow-up of 1 year, five patients were alive and in CR. The two that relapsed died of disease and three other patients had died of treatment-related causes.

The effects of DLI appear to be similar in patients receiving unrelated donor transplants, although only small numbers of recipients of unrelated DLI (UDLI) have been reported. In collaboration with the National Marrow Donor Program, 23 AML patients received UDLI for relapsed AML. The median follow-up was 10 weeks (range 4–102 weeks). Of the patients evaluable for response to DLI alone, 42% achieved a CR. However, only 4/23 of all patients (17%) had a durable CR. From this study and others, it is clear that the most significant predictor of survival and disease-free survival (DFS) was the time from transplant to relapse. Of interest, there was no dose–response effect identified in the unrelated donor setting though the majority of patients received more than 1  107 mononuclear cells/kg. This might argue agains a second DLI.

Unfortunately, not only response to DLI in AML is disappointing, but also the toxicity is significant. Up to 30% of patients will develop grade III–IV acute GVHD, and treatment-related mortality rates are estimated to be up to 20%. Results have been better in more recent studies and an Evidence Based Guideline concluded that DLI is medically necessary in all hematologic malignancies.

As far as myelofibrosis, there is limited supportive information.

Evgeny Klyuchnikov et al, Donor lymphocyte infusions and second transplantation as salvage treatment for relapsed myelofibrosis after reduced‐intensity allografting. BMJ Volume159, Issue2 October 2012 Pages 172-181

Porter D, Collins R, Hardy C, Kernan N, Drobyski W, Giralt S et al. Treatment of relapsed leukemia after unrelated donor marrow transplantation with unrelated donor leukocyte infusions. Blood 2000; 95: 1214–1221.

Leis J, Porter D. Unrelated donor leukocyte infusions to treat relapse after unrelated donor bone marrow transplantation. Leukemia Lymphoma 2002; 43: 9–17.

Levine J, Braun T, Penza S, Beatty P, Cornetta K, Martino R et al. Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem cell transplantation. J Clin Oncol 2001; 20: 405–412.

Christoph Schmid, Myriam Labopin, Arnon Nagler, Martin Bornhäuser, Jürgen Finke, Athanasios Fassas, Liisa Volin, Günham Gürman, Johan Maertens, Pierre Bordigoni, Ernst Holler, Gerhard Ehninger, Emmanuelle Polge, Norbert-Claude Gorin, Hans-Jochem Kolb, Vanderson Rocha Donor Lymphocyte Infusion in the Treatment of First Hematological Relapse After Allogeneic Stem-Cell Transplantation in Adults With Acute Myeloid Leukemia: A Retrospective Risk Factors Analysis and Comparison With Other Strategies by the EBMT Acute Leukemia Working Party Journal of Clinical Oncology, Vol 25, No 31 (November 1), 2007: pp. 4938-4945

Schmid C, Labopin M, Nagler A, et al. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party. Journal of Clinical Oncology [early online publication]. October 1, 2007.

Zhao, X. S., Wang, Y., Yan, C. H., Wang, J. Z., Zhang, X. H., Xu, L. P., et al. (2014). The cell composition of infused donor lymphocyte has different impact in different types of allogeneic hematopoietic stem cell transplantation. Clinical Transplantation, 28 (8), 926-934.

Donor Lymphocyte Infusion after Allogeneic Stem Cell Transplantation, ASCO Educational Book, January 1, 2008; 2008(1): 334 – 337.

Zeidner, J. F., Zahurak, M., Rosner, G. L., Gocke, C. D., Jones, R., J. & Smith, D. (2015). The evolution of treatment strategies for patients with chronic myeloid leukemia relapsing after allogeneic bone marrow transplantation: Can tyrosine kinase inhibitors replace donor lymphocyte infusions? Leukemia & Lymphoma, 56 (1), 128-134.

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