Clinical UM Guideline

This document addresses the use of donor lymphocyte infusions after an allogeneic hematopoietic progenitor cell transplant to treat a hematologic malignancy (for example, cancer of the blood or bone marrow, such as leukemia or lymphoma). Donor lymphocyte infusion (DLI) is a form of adoptive immunotherapy in which a transplant recipient is infused with lymphocytes obtained in a leukapheresis procedure from the original allogeneic hematopoietic progenitor cell donor. This procedure attempts to induce a beneficial graft-versus-leukemia (GVL) response without the need for additional bone marrow harvest from the donor or further high-dose chemotherapy for the recipient.

Note: Please see the following related documents for additional information:

• MED.00147 Cellular Therapy Products for Allogeneic Stem Cell Transplantation
• TRANS.00023 Hematopoietic Stem Cell Transplantation for Multiple Myeloma and Other Plasma Cell Dyscrasias

Note: For a high-level overview of this document, please see “Summary for Members and Families” below.

Medically Necessary:

Donor* lymphocyte infusion is considered medically necessary for individuals following a medically necessary allogeneic (myeloablative or non-myeloablative) hematopoietic progenitor cell transplant used to treat a hematologic malignancy.

*Note: The donor for the lymphocytes is the same individual whose hematopoietic progenitor cells were used for the transplant procedure.

Collection and cryopreservation of donor lymphocytes is considered medically necessary prior to, at the time of, or after a medically necessary allogeneic or non-myeloablative allogeneic hematopoietic progenitor cell transplant.

Not Medically Necessary:

Donor lymphocyte infusion is considered not medically necessary in all other cases.

Genetic modification of donor lymphocytes as an adjunct to donor lymphocyte infusion is considered not medically necessary.

This document describes clinical studies and expert recommendations, and explains when donor lymphocyte infusion (DLI) is clinically appropriate. The following summary does not replace the medical necessity criteria or other information in this document. The summary may not contain all of the relevant criteria or information. This summary is not medical advice. Please check with your healthcare provider for any advice about your health.

Key Information

DLI is a treatment used after a stem cell transplant from a donor to help treat blood cancers such as leukemia or lymphoma. It works by giving the person immune cells (called lymphocytes) from the same donor who gave the original transplant. These cells may help the body attack cancer cells, called a graft-versus-leukemia effect. DLI may be used if the cancer comes back, does not fully go away, or is still present at a low level after transplant. The cells are collected from the donor through a process called leukapheresis, which removes certain white blood cells from the blood. These cells can be used right away or frozen for later. DLI may help some people avoid another transplant or more chemotherapy, but it can also cause side effects such as graft-versus-host disease, where donor cells attack healthy tissue.

What the Studies Show

Studies show that DLI can be very effective for chronic myeloid leukemia. Many people with this type of cancer have long-lasting remission after treatment. For other blood cancers, such as acute leukemia, multiple myeloma, or lymphoma, DLI can still help, but the results are less consistent. Some small studies show that DLI can shrink cancer or slow its growth. More research with larger groups is needed to know how well it works for these cancers.

DLI may also be used earlier, before cancer clearly returns, in people at high risk. Some studies suggest this early use may improve survival. However, DLI can cause serious side effects. The most common is graft-versus-host disease, which can be severe and may require hospital care. Other risks include infection or damage to healthy tissues. New approaches, such as changing the donor cells in a lab, are being studied to improve results and reduce harm. However, these modified treatments are still being researched, and better studies are needed to know if they improve health.

When is Donor Lymphocyte Infusion Clinically Appropriate?

Donor lymphocyte infusion may be appropriate in these situations:

• A person has had a medically necessary donor stem cell transplant for a blood cancer; and
• The donor lymphocytes come from the same donor as the original transplant

Collection and freezing of donor lymphocytes may also be appropriate before, during, or after the transplant to allow for future treatment.

When is this not Clinically Appropriate?

Donor lymphocyte infusion is not clinically appropriate in scenarios other than those listed above.

Genetic modification of donor lymphocytes (changing the cells in a lab before infusion) is not clinically appropriate because it has not been proven to improve health. Studies are still ongoing, and results are not yet clear.

(Return to Description)

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

Donor lymphocyte infusion
When services may be Medically Necessary when criteria are met:

When services are Not Medically Necessary:
For the procedure codes listed above when criteria are not met or for all other diagnoses not listed.

Genetic modification of donor lymphocytes
When services are Not Medically Necessary:
When the code describes a procedure designated in the Clinical Indications section as not medically necessary.

Summary

Donor lymphocyte infusion (DLI), previously known as donor leukocyte infusion, is an adoptive immunotherapy used after allogeneic hematopoietic progenitor cell transplantation in which lymphocytes collected from the original donor via leukapheresis are infused to enhance a graft-versus-leukemia or graft-versus-tumor effect without additional chemotherapy or repeat transplantation. The National Comprehensive Cancer Network (NCCN) clinical practice guidelines for hematologic malignancies support the use of DLI following allogeneic transplantation in the setting of relapse, persistent disease, or, in select cases, minimal residual disease. DLI is indicated following a medically necessary allogeneic (myeloablative or non-myeloablative) transplant for hematologic malignancy using lymphocytes from the original donor, and collection and cryopreservation of donor lymphocytes may occur before, during, or after transplant to facilitate treatment. Use outside this context is not supported, and genetic modification of donor lymphocytes as an adjunct to DLI is not considered medically necessary.

Description

Infusing lymphocytes from the original hematopoietic cell donor can be used to treat transplant recipients with hematologic malignancies in relapse following allogeneic hematopoietic progenitor cell transplantation. DLI, which is also referred to as donor leukocyte or buffy coat transfusion, is a form of adoptive immunotherapy and attempts to induce a beneficial GVL or graft-versus-tumor (GVT) response without the need for an additional bone marrow harvest from the donor or further high-dose chemotherapy for the recipient. Collection of donor leukocytes requires the original donor to undergo a leukapheresis procedure. After collection, these cells are either immediately infused into the recipient or frozen for storage for future use.

Leukapheresis is the removal of white blood cells from whole blood. In this procedure, whole blood obtained by phlebotomy is passed through a centrifuge where white blood cells, along with some platelets and a small amount of red blood cells, are removed. The remainder of the cells and plasma are then returned to the donor through a needle or catheter. The procedure is performed in the outpatient setting and takes 2 to 3 hours to complete. DLI can be used as an alternative to a second hematopoietic cell transplant.

DLI has been researched as a treatment for a variety of hematologic malignancies, including most prominently chronic myeloid leukemia (CML), but also acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), multiple myeloma, myelodysplastic syndromes, chronic lymphocytic leukemia, Hodgkin disease, and non-Hodgkin lymphoma. Studies, although limited by size and quality, have provided evidence that DLI can establish a GVL effect.

There is clear clinical evidence that DLI can effectively treat relapsed CML. In addition, infusions using lymphocytes obtained from the original hematopoietic progenitor cell donor can induce long-term, complete, hematological, cytogenetic, and molecular genetic remissions in individuals treated for relapsing CML after an allogeneic hematopoietic cell transplant (HCT). The National Comprehensive Cancer Network^® (NCCN) Clinical Practice Guidelines (CPG, V.1.2026) for CML states “Donor lymphocyte infusion (DLI) is effective in inducing durable molecular remissions in the majority of patients with relapsed CML following allogeneic HCT, though it is more effective in patients with chronic phase relapse than advanced phase relapse.” These recommendations were based on 2A category of evidence and uniform consensus. The results from CML may be extrapolated to individuals with relapsed AML, since there is evidence of a graft-versus-leukemia effect in individuals with AML treated with allogeneic transplants.

Therapy is also effective for relapse of hematologic malignant diseases other than CML, although response rates are lower. The medical evidence currently available for the use of DLI in individuals with relapsed disease from other hematologic malignancies including, but not limited to, ALL, multiple myeloma, Hodgkin disease and non-Hodgkin lymphoma, consists mostly of multiple small case series. However, these studies consistently demonstrate that DLI may induce an anti-tumor response in individuals who have relapsed disease following an allogeneic hematopoietic progenitor cell transplant.

Beitinjaneh (2012) reported a higher response rate and longer overall survival when DLI was used preemptively in individuals treated with allogeneic HCT for multiple myeloma. Between July 1996 and June 2008, 23 individuals with multiple myeloma received DLI, 8 as preemptive DLI for residual disease (RD) and 15 as DLI for the treatment of recurrent or progressive disease (PD). With a median follow-up of 24 months, 5 of 23 individuals (22%) achieved a complete response (CR) or a very good partial response (2 CR, 3 very good partial response [VGPR]), and stable disease (SD) in 8 individuals (34%) after DLI. A higher response rate (≥ VGPR 50% vs. 7%, p=0.03), a longer overall survival (28.3 vs. 7.6 months, p=0.03) and a trend toward longer progression-free survival (11.9 vs. 5.2 months, p=0.1) were reported in individuals who received DLI for RD. Five individuals (22%) had Grade II-IV acute graft-versus-host disease (GVHD). The authors concluded that the preemptive use of DLI after an allogeneic HSCT for multiple myeloma may be associated with improved outcomes. Additional clinical trials are encouraged to identify the optimal timing for DLI.

The NCCN CPGs for multiple myeloma (V.5.2026) include the use of DLI in individuals with unresponsive or relapsed disease after allogeneic hematopoietic cell grafting in order to stimulate a beneficial graft-versus-myeloma effect. Similarly, the NCCN CPGs for Acute Lymphoblastic Leukemia (V.1.2026) state that, “For patients with relapsed disease after allogeneic HCT, a second allogeneic HCT and/or donor lymphocyte infusion (DLI) can be considered.”

Sala (2014) reported results from a retrospective series of 18 individuals with relapsed and/or refractory Hodgkin lymphoma after allogeneic HSCT that were treated with a combination of bendamustine followed by DLI. Nine of the participants were eligible for DLI after bendamustine, based on the pre-specified criteria. A median of two DLIs were infused into the individuals. Adverse events from the DLI included 3 individuals with chronic GVHD and 3 cases of Grade IV acute GVHD. Acute hospitalization was required for 3 individuals with acute GVHD. Of those treated with DLI, CR was seen in 3 individuals and PR in 7 individuals, for an overall response rate (ORR) of 55% with a 9-month (range 1-26 months) median duration of response. For the 18 participants, the median overall survival was 11 months (range 1-52 months) and the progression-free survival (PFS) was 6 months (range, 1-28 months). The authors noted the combination of bendamustine followed by DLI demonstrated a response. However, a randomized trial is needed to determine if the treatment effect was due to the bendamustine compared to the DLI or the combination.

Velázquez (2025) published a retrospective, two-center cohort study which evaluated prophylactic and pre-emptive DLI in 83 adults with acute myeloid leukemia (n=75) or myelodysplastic syndromes (n=8) in remission following allogeneic stem cell transplantation, administered for prophylaxis (43%), incomplete chimerism (33%), or minimal residual disease (24%). With a median follow-up of 40 months, 2-year overall survival and leukemia-free survival for the overall cohort were 80% and 67%, respectively, with relapse incidence of 26% and non-relapse mortality of 8%. Pre-emptive DLI demonstrated high response rates (83%), supporting its role in early disease control. Graft-versus-host disease occurred frequently, with 1-year rates of grade II-IV acute and moderate/severe chronic GVHD of 34% and 27%, respectively. The study also introduced a composite “treatment success” endpoint, defined as leukemia-free survival without significant immunosuppression for GVHD, which was achieved in 71% of individuals at 2 years. The authors conclude that DLI is an effective strategy for relapse prevention in this setting, though its use requires careful balancing of anti-leukemic benefit with the risk of GVHD.

Thomson (2010) reported multicenter results of 82 individuals with follicular lymphoma treated with allogeneic stem cell transplantation. All individuals with mixed chimerism or residual or progressive disease were eligible for DLI. Thirteen participants received 25 DLIs with remission in 10 individuals (77%). At a median of 44 months after the last DLI, the ongoing complete response seemed durable. There was no response in 3 individuals treated with DLI. The authors concluded that due to the frequency and duration of response, DLI was an “encouraging strategy to treat follicular lymphoma.”

An ASH Education Program review was developed to address variability in clinical practice and clarify the optimal “who, when, and why” of DLI following allogeneic stem cell transplantation in hematologic malignancies (Schonewille, 2025). The review draws on available retrospective studies, limited prospective data, and expert consensus. The authors describe DLI use across prophylactic, preemptive, and therapeutic settings, with recommendations emphasizing appropriate selection based on relapse risk, measurable residual disease (MRD) status, donor chimerism, and transplant platform. Prophylactic DLI is generally considered in high-risk disease in remission without active GVHD and after withdrawal of immunosuppression, while preemptive DLI is guided by MRD positivity or mixed chimerism and relies on close molecular monitoring and timely intervention. Therapeutic DLI for overt relapse is typically combined with cytoreductive or targeted therapy, particularly in acute leukemias where response to DLI alone is limited. Across settings, recommendations highlight the importance of timing relative to transplant, disease kinetics, and immune status, as well as avoidance in the presence of active GVHD or infection. The review underscores that current guidance is largely based on observational data and expert opinion, with emerging evidence supporting MRD-guided approaches and integration with targeted therapies to optimize outcomes while mitigating toxicity.

GVHD is a common occurrence with DLI. As a result, studies continue to investigate various dosing, timing of DLI infusions, and new approaches, including modifications to T-lymphocytes to minimize GVHD complications. The level of evidence is insufficient to permit conclusions in terms of uses of DLI for other than hematologic malignancies that have relapsed following a prior allogeneic hematopoietic progenitor cell transplant or to permit conclusions regarding the use of genetic modification (e.g., modified T-lymphocytes) of donor lymphocytes in the treatment of hematologic malignancies.

Modified DLI

In a study by Alho (2016), the authors observed that the “development and maintenance of immune tolerance after allogeneic hematopoietic stem cell transplantation requires the balanced reconstitution of donor-derived CD4 regulatory T cells (CD4Tregs) as well as effector CD4 (conventional CD4 T cells [CD4Tcons]) and CD8 T cells.” They studied 107 adult participants who received “T-replete stem cell grafts after reduced-intensity conditioning who were monitored” over a 2-year period. The authors found that the imbalances assisted in the “production, expansion, and persistence of effector T cells over CD4Tregs and were associated with the development of chronic GVHD.”

There is ongoing research into the genetic modification of donor or the individual’s own lymphocytes, or chimeric antigen receptor T-cell (CAR-T) therapy. Modified DLIs are designed to enhance GVL effects while minimizing the risk of GVHD. Key modifications may include CD8-depleted DLI, which removes CD8+ T cells to reduce GVHD risk while maintaining GVL activity. Regulatory T-cell depleted DLI enhances GVL responses by depleting regulatory T-cell but may increase GvHD risk. Antigen-specific DLI uses T cells engineered to target leukemia-associated antigens, enhancing their efficacy against malignant cells. NK cell DLI employs NK cells to boost anti-leukemic responses with minimal GVHD risk. Cytokine-induced killer (CIK) cells and cytokine-induced memory-like (CIML) NK cells are developed using cytokines to enhance cytotoxic activities and memory features, respectively. Additional modifications include CD4+ T-cell enrichment, CD8+ T-cell depletion, and invariant NKT-cell expansion, which manipulate immune subsets for improved antileukemic control and reduced GVHD. These strategies aim to optimize therapeutic efficacy while managing potential complications in hematopoietic cell transplantation settings. (Pagliuca, 2024; Qasim, 2023; Rambaldi, 2024). The early studies involving the use of CAR-T therapy in hematologic malignancies have reported promising results when compared to standard DLI (Hua, 2021; Liang, 2023; Tan, 2023). Studies regarding the safety and efficacy of genetic modifications of DLI on GVHD and/or graft-versus-leukemia (GVL) are ongoing. Therapies are being evaluated as part of broader adoptive cell therapy platforms, such as CAR-T or T-cell receptor-engineered therapies which may replace or supplement a standard DLI therapy. The use of modified DLI therapy following an allogeneic hematopoietic progenitor cell transplant is not considered a generally accepted practice.

The outcomes following modified DLI therapy show potential benefits in reducing relapse and improving survival rates. However, the variability in individual responses and potential for GVHD highlight the complexity of this treatment. Pagliuca (2024) noted that despite the promising results of modified DLI therapy, “… simple DLI dosing, on the basis of the number of CD3 T cells in the product is, so far, the only strategy that has been broadly established across transplantation centres.”

Schmid (2021) reviewed the role of both modified and unmodified DLI in the treatment of high-risk hematologic malignancies. The authors summarized that there is still a place for DLI therapy, although there are alternative potential adaptive immunotherapy options under evaluation. The authors note:

Given the increasing availability of innovative, disease modifying drugs, DLI is currently at risk to be superseded by other, more specific treatment options, despite its great biologic potential and low costs.

Allogeneic: Genetically dissimilar; involves a donor and recipient.

Bone marrow: A soft, spongy tissue that fills the cavities inside most bones in the human body. Bone marrow is a source of stem cells that manufacture red blood cells, white blood cells, and platelets.

Graft-versus-host disease (GVHD): A potential complication of transplants associated with the use of blood or tissue from a different person (allogeneic). The transplanted cells recognize the recipient’s tissue as foreign and attack the recipient.

Graft-versus-leukemia/lymphoma effect (GVL): Transplanted white blood cells that recognize residual cancer cells (cells that survived chemotherapy and radiation therapy and continue to grow in the body) and attack them.

Hematologic malignancy: A cancer of the blood or bone marrow, such as leukemia or lymphoma.

Hematopoietic progenitor cells: Primitive cells capable of replication and formation into mature blood cells in order to repopulate the bone marrow. Cells may be obtained from bone marrow, peripheral blood or umbilical cord blood.

Leukocytes: Another term for white blood cells. There are several types of leukocytes: granulocytes (neutrophils, eosinophils, and basophils), monocytes, and lymphocytes.

Lymphocyte: Cells present in the blood and lymphatic tissue derived from stem cells. Comprised of T cells and B cells.

Non-myeloablative allogeneic hematopoietic stem cell transplant: Also called reduced intensity or mini-allogeneic transplant. The conditioning regimen is less intense and does not completely ablate the stem cells in the individual’s bone marrow.

Peripheral blood: Blood derived from the circulatory system (as opposed to blood in the bone marrow where it is made).

Peer Reviewed Publications:

1. Alho AC, Kim HT, Chammas MJ, et al. Unbalanced recovery of regulatory and effector T cells after allogeneic stem cell transplantation contributes to chronic GVHD. Blood. 2016; 127(5):646-657.
2. Beitinjaneh AM, Saliba R, Bashir Q, et al. Durable responses after donor lymphocyte infusion for patients with residual multiple myeloma following non-myeloablative allogeneic stem cell transplant. Leuk Lymphoma. 2012; 53(8):1525-1529.
3. Berglund S, Gertow J, Uhlin M, Mattsson J. Expanded umbilical cord blood T cells used as donor lymphocyte infusions after umbilical cord blood transplantation. Cytotherapy. 2014; 16(11):1528-1536.
4. Chalandon Y, Passweg JR, Guglielmi C, et al.; Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Early administration of donor lymphocyte infusions upon molecular relapse after allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia: a study by the Chronic Malignancies Working Party of the EBMT. Haematologica. 2014; 99(9):1492-1498.
5. Collins RH, Goldstein S, Giralt S, et al. Donor leukocyte infusions in acute lymphocytic leukemia. Bone Marrow Transplant. 2000; 26(5):511-516.
6. Corradini P, Dodero A, Zallio F, et al. Graft-versus-lymphoma effect in relapsed peripheral T-cell non-Hodgkin’s lymphomas after reduced-intensity conditioning followed by allogeneic transplantation of hematopoietic cells. J Clin Oncol. 2004; 22(11):2172-2176.
7. Dazzi F, Szydlo RM, Cross NC, 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(8):2712-2716.
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10. Flowers ME, Leisenring W, Beach K, et al. Granulocyte colony-stimulating factor given to donors before apheresis does not prevent aplasia in patients treated with donor leukocyte infusion for recurrent chronic myeloid leukemia after bone marrow transplantation. Biol Blood Marrow Transplant. 2000; 6(3A):321-326.
11. Guglielmi C, Arcese W, Dazzi F, et al. Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose. Blood. 2002; 100(2):397-405.
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13. Hua J, Zhang J, Zhang X, et al. Donor-derived anti-CD19 CAR T cells compared with donor lymphocyte infusion for recurrent B-ALL after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2021; 56(5):1056-1064.
14. Ishikawa J, Maeda T, Kashiwagi H, et al. Successful second allogeneic peripheral blood stem cell transplantation and donor leukocyte infusion in patients with relapsed acute leukemia using the same donor as for the initial allogeneic bone marrow transplantation. Bone Marrow Transplant. 2003; 31(11):1057-1059.
15. Kolb HJ. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood. 2008; 112(12):4371-4383.
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17. Kumar AJ, Hexner EO, Frey NV, et al. Pilot study of prophylactic ex vivo costimulated donor leukocyte infusion after reduced-intensity conditioned allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2013; 19(7):1094-1101.
18. Levine JE, Braun T, Penza SL, et al. Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem cell transplantation. J Clin Oncol. 2002; 20(2):405-412.
19. Liang Z, Xu H, Zhou X, et al. Donor-derived CAR-T therapy improves the survival of relapsed B-ALL after allogeneic transplantation compared with donor lymphocyte infusion. Hum Cell. 2023; 36(5):1716-1728.
20. Lokhorst HM, Schattenberg A, Cornelissen JJ, et al. donor Leukocyte infusions are effective in relapsed multiple myeloma after allogeneic bone marrow transplantation. Blood. 1997; 90(10):4206-4211.
21. Luznik L, Fuchs EJ. Donor lymphocytes infusions to treat hematologic malignancies in relapse after allogeneic blood or marrow transplantation. Cancer Control. 2002; 9(2):123-134.
22. Orsini E, Alyea EP, Chillemi A, et al. Conversion to full donor chimerism following donor lymphocyte infusion is associated with disease response in patients with multiple myeloma. Biol Blood Marrow Transplant. 2000; 6(4):375-386.
23. Pagliuca S, Schmid C, Santoro N, et al.; Practice Harmonization and Guidelines Committee and the Cellular Therapy and Immunobiology Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Donor lymphocyte infusion after allogeneic haematopoietic cell transplantation for haematological malignancies: basic considerations and best practice recommendations from the EBMT. Lancet Haematol. 2024; 11(6):e448-e458.
24. Peggs KS, Mackinnon S. Cellular therapy: donor lymphocyte infusion. Curr Opin Hematol. 2001; 8(6):349-354.
25. Peggs KS, Sureda A, Qian W, et al.; UK and Spanish Collaborative Groups. Reduced-intensity conditioning for allogeneic haematopoietic stem cell transplantation in relapsed and refractory Hodgkin lymphoma: impact of alemtuzumab and donor lymphocyte infusions on long-term outcomes. Br J Haematol. 2007; 139(1):70-80.
26. Porter DL, Collins RH, Hardy C, et al. Treatment of relapsed leukemia after unrelated donor marrow transplantation with unrelated donor leukocyte infusions. Blood. 2000; 95(4):1214-1221.
27. Przepiorka D, Smith TL, Folloder J, et al. Controlled trial of filgrastim for acceleration of neutrophil recovery after allogeneic blood stem cell transplantation from human leukocyte antigen-matched related donors. Blood. 2001; 97(11):3405-3410.
28. Qasim W. Genome-edited allogeneic donor "universal" chimeric antigen receptor T cells. Blood. 2023; 141(8):835-845.
29. Raiola AM, Van Lint MT, Valbonesi M, et al. Factors predicting response and graft-versus-host disease after donor leukocyte infusions: a study on 593 infusions. Bone Marrow Transplant. 2003; 31(8):687-693.
30. Rambaldi B, Rizzuto G, Rambaldi A, Introna M. Genetically modified and unmodified cellular approaches to enhance graft versus leukemia effect, without increasing graft versus host disease: the use of allogeneic cytokine-induced killer cells. Front Immunol. 2024; 15:1459175.
31. Russell NH, Byrne JL, Faulkner RD, et al. Donor lymphocyte infusions can result in sustained remissions in patients with residual or relapsed lymphoid malignancy following allogeneic haematopoietic stem cell transplantation. Bone Marrow Transplant. 2005; 36(5):437-441.
32. Sala E, Crocchiolo R, Gandolfi S, et al. Bendamustine combined with donor lymphocytes infusion in Hodgkin's lymphoma relapsing after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014; 20(9):1444-1447.
33. Salama M, Nevill T, Marcellus D, et al. Donor leukocyte infusions for multiple myeloma. Bone Marrow Transplant. 2000; 26(11):1179-1184.
34. 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. J Clin Oncol. 2007; 25(31):4938-4945.
35. Schmid C, Kuball J, Bug G. Defining the role of donor lymphocyte infusion in high-risk hematologic malignancies. J Clin Oncol. 2021; 39(5):397-418.
36. Schmidt S, Liu Y, Hu ZH, et al. The role of donor lymphocyte infusion (DLI) in post-hematopoietic cell transplant (HCT) relapse for chronic myeloid leukemia (CML) in the tyrosine inhibitor (TKI) era. Biol Blood Marrow Transplant. 2020; 26:1137-1143.
37. Schonewille P, van Rhenen A, Ham RMT, et al. Posttransplant cells for the win? DLI and adoptive cell therapy to eradicate MRD. Hematology Am Soc Hematol Educ Program. 2025; 2025(1):537-546.
38. Takami A, Yano S, Yokoyama H, et al. Donor lymphocyte infusion for the treatment of relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation: a retrospective analysis by the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2014; 20(11):1785-1790.
39. Tan X, Wang XQ, Zhang C, et al. Donor-derived CD19 CAR-T cells versus chemotherapy plus donor lymphocyte infusion for treatment of recurrent CD19-positive B-ALL after allogeneic hematopoietic stem cell transplantation. Curr Med Sci. 2023; 43(4):733-740.
40. Thomson KJ, Morris EC, Milligan D, et al. T-cell-depleted reduced-intensity transplantation followed by donor leukocyte infusions to promote graft-versus-lymphoma activity results in excellent long-term survival in patients with multiply relapsed follicular lymphoma. J Clin Oncol. 2010; 28(23):3695-3700.
41. Vela-Ojeda J, Garcia-Ruiz Esparza MA, Reyes-Maldonado E, et al. Donor lymphocyte infusions for relapse of chronic myeloid leukemia after allogeneic stem cell transplantation: prognostic significance of the dose of CD3+ and CD4+ lymphocytes. Ann Hematol. 2004; 83(5):295-301.
42. Velázquez GF, Weller JF, Rubeck A, et al. Prophylactic and pre-emptive donor lymphocyte infusion in patients with acute myeloid leukemia and myelodysplastic syndrome: validation of current recommendations and proposal of a modified outcome assessment. Haematologica. 2025; 110(10):2293-2304.
43. Warlick ED, DeFor T, Blazar BR, et al. Successful remission rates and survival after lymphodepleting chemotherapy and donor lymphocyte infusion for relapsed hematologic malignancies postallogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012; 18(3):480-486.

Government Agency, Medical Society, and Other Authoritative Publications:

1. NCCN Clinical Practice Guidelines in Oncology^™. ^©2026 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on April 13, 2026.
   • Acute Lymphoblastic Leukemia (V.1.2026). April 8, 2026.
   • Chronic Myeloid Leukemia (V.1.2026). Revised July 16, 2025.
   • Multiple Myeloma (V.5.2026). Revised January 9, 2026.
   • Myelodysplastic Syndromes (MDS) (V3.2026). Revised January 12, 2026.
   • T-Cell Lymphomas. (V.2.2026). Revised February 13, 2026.

1. American Cancer Society. Types of stem cell transplant and bone marrow transplants. Last revised July 10, 2025. Available at: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/stem-cell-transplant/types-of-transplants.html. Accessed on April 13, 2026.
2. American Society for Transplantation and Cellular Therapy (ASTCT). Available at: http://www.asbmt.org. Accessed on April 13, 2026.
3. National Cancer Institute. About Cancer. Available at: https://www.cancer.gov/about-cancer. Accessed on April 13, 2026.
4. National Marrow Donor Program. Available at: http://www.marrow.org. Accessed on April 13, 2026.

Buffy Coat Transfusion
Donor Leukocyte Infusion|
Donor Lymphocyte Infusion
Leukapheresis

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