Donor leukocyte infusions in acute lymphocytic leukemia

Collins, Robert H.; Goldstein, Steven C.; Giralt, Sergío; Levine, John E.; Porter, David; Drobyski, William R.; Barrett, John; Johnson, Mark D.; Kirk, Allan D.; Horowitz, Mary M.; Parker, Pablo

doi:10.1038/sj.bmt.1702555

Cited by 218 publications

(115 citation statements)

References 30 publications

(40 reference statements)

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“…The onset of acute GVHD after conventional DLI occurs a median of 28-32 days after infusion. [5,20] The range reported, however, is quite broad, and GVHD can occur several months to years after DLI. Interestingly, the timing and severity of GVHD is affected by manipulation of DLI cell number and content.…”

Section: Clinical Presentation Of Gvhd After DLImentioning

confidence: 99%

“…Chronic GVHD occurs in 33-61% of patients, and deaths attributable to GVHD are in the range 6-11%. [4,5,7,[19][20][21][22] Most studies demonstrate a strong correlation between GVHD and GVT effects. For instance, a retrospective multicenter North American study evaluated outcomes in 140 patients who received DLI for relapsed disease after SCT.…”

Section: Graft-versus-host Disease After DLImentioning

confidence: 99%

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Graft-versus-host disease after donor leukocyte infusions: presentation and management

Frey

Porter

2008

Best Practice & Research Clinical Haematology

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Donor lymphocyte infusion (DLI) is used after both myeloablative and non-myeloablative stem-cell transplantation to treat and prevent relapse, to establish full donor chimerism, and to treat and prevent infections. The major treatment-related complication of DLI is graft-versus-host disease (GVHD). The presentation and treatment of GVHD after DLI is similar to its presentation and treatment after stem-cell transplantation, with some notable exceptions. While GVHD and graft-versus-tumor (GVT) effects are highly correlated after DLI, some patients experience remission without GVHD. Studies to define tumor-specific target antigens and GVT effector cells, as well as strategies of donor T-cell manipulation and optimization of DLI dose and schedule, may ultimately lead to the consistent ability to separate GVHD from GVT activity, improvement in the safety and specificity of DLI, and enhancement of the anti-tumor activity of donor T cells. Keywordsdonor lymphocyte infusion; immunotherapy; graft-versus-host disease; graft-versus-tumor effect; CD8 + depletion; T-cell inactivation; suicide gene It is well established that the success of allogeneic stem-cell transplantation (SCT) relies in part on the graft-versus-tumor (GVT) effect of donor-derived T cells.[1,2] Donor lymphocyte infusions (DLIs) are frequently used to harness this GVT activity in patients who relapse after SCT and have otherwise limited treatment options. DLI is dramatically effective in inducing sustained remissions and cure in patients with chronic myelogenous leukemia (CML) in chronic phase, but is less successful in inducing initial and sustained remissions in patients with advanced-phase CML or acute leukemia. [3][4][5][6][7] Optimizing the effectiveness of DLI for non-CML disorders is the subject of numerous trials. [8,9] The broadening applications of allogeneic SCT and expansion of non-conventional conditioning regimens have resulted in the increased use of DLI for several other indications (Table 1). In addition to the treatment of relapsed disease after SCT, DLI is being used as prophylaxis after SCT for patients with a high risk of relapse due either to advanced disease stage or in conjunction with T-cell-depleted grafts. [10][11][12] In addition, DLI has been used successfully to treat graft failure, post-transplant lymphoproliferative disorder (PTLD), viral infections, and as a method to facilitate immune reconstitution after allogeneic SCT. [13][14][15][16] *Corresponding author. Tel.: +1-215-662-2867; Fax : +1-215-662-4064. E-mail address: david.porter@uphs.upenn.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply ...

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Section: Clinical Presentation Of Gvhd After DLImentioning

confidence: 99%

Section: Graft-versus-host Disease After DLImentioning

confidence: 99%

Graft-versus-host disease after donor leukocyte infusions: presentation and management

Frey

Porter

2008

Best Practice & Research Clinical Haematology

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“…cGVHD occurs in 33-61% of patients, and the deaths attributable to GVHD are in the range of 6-11% when unmanipulated DLI is given for relapsed hematological malignancies after myeloablative related transplants. [69][70][71][72][73] Thus, it is highly desirable that the DLI protocol augments the GVL effect without leading to severe GVHD.…”

Section: Gvhd and Gvl After DLImentioning

confidence: 99%

New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT

Chang

Zang

Xia

2015

Bone Marrow Transplant

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DLI is an effective strategy for patients with recurrent hematological malignancies after allogeneic hematopoietic SCT (allo-HSCT). DLI has been widely applied to boost the graft vs tumor (GVT) or GVL effects. However, given the potentially severe complications associated with conventional DLI and transient GVL effect, new strategies for DLI are emerging. In this review, we have discussed the recent important studies on DLI as a prophylactic or therapeutic modality for relapsed hematological disorders after allo-HSCT. The strategies to separate GVL from GVHD have also been discussed. Leukemia-targeting therapy and lymphodepletion combined with DLI, and prophylactic DLI after allo-HSCT are often employed for patients with high risk of relapse, which has been reviewed as well. In addition, we have also discussed the issues on DLI to be further addressed, such as the doses, timing and frequency of DLI in different clinical settings, leukemic antigen-specific DLI as well as how to augment GVL effect while attenuating GVHD.

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“…Although the anti-leukemia potential of DLI in patients with ALL has been described, [16][17][18][19][20] DLI was thought to have limited benefit in patients with relapsed ALL after BMT. Kolb et al 21 and Collins et al 22 reported poor outcomes in ALL patients given DLI after relapse. The reason for low efficacy of DLI in ALL is uncertain.…”

Section: Discussionmentioning

confidence: 99%

Eradication of residual bcr-abl-positive clones by inducing graft-versus-host disease after allogeneic stem cell transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

Matsue

Tabayashi

Yamada

et al. 2002

Bone Marrow Transplant

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Summary:Persistence of bcr-abl transcripts after marrow grafting is thought to convey a high risk for relapse in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). Donor leukocyte infusion (DLI) is closely associated with development of graftversus-host disease (GVHD) and has well-defined activity against relapsed chronic myelogenous leukemia (CML) but not ALL. We report two patients with Phpositive ALL who remained bcr-abl positive by reverse transcriptase polymerase chain reaction (RT-PCR) after marrow grafting. Residual bcr-abl transcripts in both patients were eliminated following acute GVHD, which was induced by either DLI or rapid reduction of immunosuppression. Both patients have continued in complete molecular remission for 18 months and 8 months following transplantation, respectively. Our observation suggests that induction of GVHD may eliminate minimal residual disease, thereby preventing leukemia relapse in patients transplanted for Ph-positive ALL. Bone Marrow Transplantation (2002) 29, 63-66. DOI: 10.1038/sj/bmt/1703318 Keywords: bcr-abl; MRD; Ph-positive ALL; DLI; stem cell transplantation; GVL The prognosis of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) is much worse than other types of ALL in both children and adults. 1-3 The Ph chromosome t(9;22)(q34;q11) results from a translocation involving the breakpoint cluster region of the bcr gene on chromosome 22 and the abl gene on chromosome 9. This rearrangement is seen in 20 to 26% of adult

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Donor leukocyte infusions in acute lymphocytic leukemia

Cited by 218 publications

References 30 publications

Graft-versus-host disease after donor leukocyte infusions: presentation and management

Graft-versus-host disease after donor leukocyte infusions: presentation and management

New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT

Eradication of residual bcr-abl-positive clones by inducing graft-versus-host disease after allogeneic stem cell transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

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