Outcome of patients developing GVHD after DLI given to treat CML relapse: a study by the chronic leukemia working party of the EBMT

Abstract

We studied GVHD after donor lymphocyte infusion (DLI) in 328 patients with relapsed CML between 1991 and 2004 . A total of 122 patients (38%) developed some form of GVHD. We analyzed GVHD by clinical presentation (acute or chronic GVHD) and onset time after the first DLI (early (p45 days) or late (445 days)). There was a significant overlap between onset time and clinical presentation. Some form of GVHD occurred at a median of 104 days, acute GVHD at 45 days and chronic GVHD at 181 days after DLI. The clinical presentation was acute GVHD in 71 patients, of whom 31 subsequently developed chronic GVHD subsequently. De novo chronic GVHD was seen in 51 patients. OS for all patients was 69% (95% confidence interval (CI) 63-75) at 5 years, DLIrelated mortality was 11% (95% CI 8-15) and diseaserelated mortality was 20% (95% CI 16-25). Risk factors for developing GVHD after DLI were T-cell dose at first DLI, the time interval from transplant to DLI and donor type. In time-dependent multivariate analysis, GVHD after DLI was associated with a risk of death of 2.3-fold compared with patients without GVHD. Clinical presentation as acute GVHD and early onset GVHD were associated with increased mortality.

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

“…103 However, discrepancies exist among different studies. Chalendon et al 9 showed that GVHD was more frequent in patients with a higher cell dose for 410 7 CD3+ cells/kg than for o10 7 CD3+ cells/kg (47% vs 34%, Po 0.01) after DLI in patients with relapsed CML after allo-HSCT. Similarly, another study also showed that the dose of DLI (⩾1 × 10 7 ) was a predictive factor of acute GVHD.…”

“…As a prophylactic or therapeutic regimen, DLI has been widely employed to boost the graft-vs-tumor (GVT) or GVL effects. 3,6,7 Clinical data have shown that DLI is most effective for CML [7][8][9][10] and the response rate is 70-80% for hematological or cytogenetic relapse, 9 whereas the benefit of DLI for relapsed acute leukemia is often limited, 11 mainly because of the rapid growth of leukemic cell burden, poor response to the GVL reaction 9 and the development of GVHD 12 and aplasia. 8 To overcome these limitations, researchers have attempted to modify the DLI strategies depending on different clinical settings.…”

Low blood lymphocyte count at 30 days post transplant predicts worse acute GVHD and survival but not relapse in a large retrospective cohort

“…Although the use of DLI in some patients who relapse after AHSCT can result in disease remission, DLI may increase the risk of acute GVHD (aGVHD). [1][2][3][4][5] These findings have led to an interest in the kinetics of post-transplant lymphocyte recovery as a surrogate for effective immune reconstitution and as a predictor of transplant outcomes.…”

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

“…It seems that, although there is no clear time point that we could recommend, DLI could be postponed despite molecular evidence of relapse and be given no later than in hematologic chronic phase relapse, in line with previous reports that showed that DLI given at least two years after allogeneic HSCT had a lower risk of leading to GvHD. 14,19 This issue now becomes even more complicated in the era of TKI. Patients could receive TKI for posttransplant relapse 20,21 or DLI or both.…”