Donor lymphocyte infusions for the treatment of minimal residual disease in acute leukemia

Dominietto, Alida; Pozzi, Sarah; Miglino, Maurizio; Albarracin, Flavio; Piaggio, Giovanna; Bertolotti, Francesca; Grasso, Raffaella; Zupo, Simona; Raiola, Anna Maria; Gobbi, Marco; Frassoni, Francesco; Bacigalupo, Andrea

doi:10.1182/blood-2007-02-072470

Cited by 75 publications

(55 citation statements)

References 9 publications

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“…Repeated observations indeed suggested an anti-leukemia effect of such an approach, at least if used at very-low tumor burden. [82][83][84] Bader et al 69 initially reported in a prospective study that, among 46 ALL patients with increasing mixed chimerisms after AlloHCT, the 31 subjected to immunotherapy (withdrawal of immunosuppression and/or low-dose donor lymphocyte infusion (DLI)) had a significantly better 3-year EFS than the 15 who did not receive immunotherapy (37% vs 0%, Po0.001). A follow-up study from the same group confirmed these findings by documenting a probability of EFS of 46% vs 0% for patients with mixed chimerisms receiving (n ¼ 13) vs not receiving (n ¼ 7) immunotherapy, with an EFS estimate of 71% for the subset of patients transplanted while in CR.…”

Section: Using Pre-hct Mrd To Tailor Therapy In Acute Leukemiamentioning

confidence: 99%

Prognostic and therapeutic implications of minimal residual disease at the time of transplantation in acute leukemia

Buckley

Appelbaum

Walter

2012

Bone Marrow Transplant

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Section: Using Pre-hct Mrd To Tailor Therapy In Acute Leukemiamentioning

confidence: 99%

Prognostic and therapeutic implications of minimal residual disease at the time of transplantation in acute leukemia

Buckley

Appelbaum

Walter

2012

Bone Marrow Transplant

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“…Consequently, there is interest in the administration of prophylactic DLI in patients deemed to be at a higher risk of relapse as a strategy to optimize the GVL effect post transplant. 88 The presence of mixed T-cell chimerism after a reduced-intensity allograft is taken to indicate bidirectional tolerance and it can be argued that DLI should be administered in these patients in the first few months post transplant with the aim of achieving full donor T-cell chimerism. 89 Other groups have explored the possibility of restricting the use of DLI to patients who demonstrate MRD positivity post transplant.…”

Section: Strategies To Improve Outcome After Ric Allograftsmentioning

confidence: 99%

Full-intensity and reduced-intensity allogeneic stem cell transplantation in AML

Craddock

2008

Bone Marrow Transplant

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Allogeneic stem cell transplantation represents the most active form of anti-leukaemic therapy in acute myeloid leukaemia (AML). Advances in transplant technology and supportive care have resulted in improved outcomes in patients allografted using a myeloablative conditioning regimen. At the same time the use of reduced-intensity conditioning regimens has allowed an immunologically mediated graft-versus-leukaemia effect to be exploited in older patients who were previously ineligible for transplantation on the grounds of age or comorbidity. This coupled with the increased availability of alternative stem cell sources, in the form of either unrelated or cord blood donations, has established allogeneic transplantation as a key therapeutic strategy in the treatment of both younger and older adults with AML.

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“…The first option is the reinforcement of the GVL effect by immunosuppression reduction or donor lymphocyte infusion (DLI); the second is the application of further cytoreductive therapy, including MoAb or specific tyrosine kinase inhibitors, in the case of BCR/ABL-positive ALL. [18][19][20][21][22][23][24][25][26] The benefit from such therapy has been described in a small proportion of ALL patients. To date, there is no general consent regarding the choice and timing of therapy in case of post transplant MRD positivity.…”

Section: Introductionmentioning

confidence: 99%

B-cell reconstitution after allogeneic SCT impairs minimal residual disease monitoring in children with ALL

Froňková

Mužíková

Mejstříková

et al. 2008

Bone Marrow Transplant

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Minimal residual disease (MRD) detection using quantification of clone-specific Ig or TCR rearrangements before and after transplantation in children with high-risk ALL is an important predictor of outcome. The method and guidelines for its interpretation are very precise to avoid both false-negative and -positive results. In a group of 21 patients following transplantation, we observed detectable MRD positivities in Ig/TCR-based real-time quantitative PCR (RQ-PCR) leading to no further progression of the disease (11 of 100 (11%) total samples). We hypothesized that these positivities were mostly the result of nonspecific amplification despite the application of strict internationally agreed-upon measures. We applied two non-self-specific Ig heavy chain assays and received a similar number of positivities (20 and 15%). Nonspecific products amplified in these RQ-PCR systems differed from specific products in length and sequence. Statistical analysis proved that there was an excellent correlation of this phenomenon with B-cell regeneration in BM as measured by flow cytometry and Ig light chain-j excision circle quantification. We conclude that although Ig/TCR quantification is a reliable method for post transplant MRD detection, isolated positivities in Ig-based RQ-PCR systems at the time of intense B-cell regeneration must be viewed with caution to avoid the wrong indication of treatment.

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Donor lymphocyte infusions for the treatment of minimal residual disease in acute leukemia

Cited by 75 publications

References 9 publications

Prognostic and therapeutic implications of minimal residual disease at the time of transplantation in acute leukemia

Prognostic and therapeutic implications of minimal residual disease at the time of transplantation in acute leukemia

Full-intensity and reduced-intensity allogeneic stem cell transplantation in AML

B-cell reconstitution after allogeneic SCT impairs minimal residual disease monitoring in children with ALL

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