A Comparison of Long-Term Outcomes of Donor Lymphocyte Infusions and Tyrosine Kinase Inhibitors in Patients With Relapsed CML After Allogeneic Hematopoietic Cell Transplantation

Shanavas, Mohamed; Messner, Hans A.; Kamel‐Reid, Suzanne; Atenafu, Eshetu G.; Gupta, Vikas; Kuruvilla, John; Kim, Dennis Dong Hwan; Uhm, Jieun; Lambie, Anna; Ellis, Laura; Lipton, Jeffrey H.

doi:10.1016/j.clml.2013.09.010

Cited by 21 publications

(13 citation statements)

References 28 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although not statistically significant, the TKI-only group had the highest cumulative incidence of complete molecular response and lowest cumulative incidence of death compared Donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation REviEW future science group www.futuremedicine.com with DLI and TKI + DLI, again reinforcing that the combination of DLI with TKI, although is an attractive strategy, still need more studies to confirm its real benefit. The same result of superiority of TKI alone was also confirmed by others [54].…”

Section: • • Chronic Myelogenous Leukemiasupporting

confidence: 83%

Donor Lymphocyte Infusion After Allogeneic Hematopoietic Stem Cell Transplantation

Pereira

Danby

Rocha

2015

Int. J. Hematol. Oncol.

View full text Add to dashboard Cite

Donor lymphocyte infusion, a rescue therapy after hematopoietic stem cell transplantation, has been increasingly adopted, as modalities of stem cell transplantation have widened. First described as donor lymphocyte transfusion or cell therapy, it consists of infusion of donor lymphocytes, collected in steady state or after growth factor enhancement. As in literature the most used name is donor lymphocyte infusion, we'll adopt it here. Its most striking efficacy is observed in patients with chronic myelogenous leukemia, who relapsed after allogeneic stem cells transplantation. However, graft-versus-host disease, its main complication, may still hamper its feasibility. KEYWORDSAllogeneic hematopoietic stem cell transplantation (HSCT) has become an attractive approach for the treatment of many patients with hematological diseases, including malignant and nonmalignant disorders. Importantly, in the last 15 years, with the advent of reduced intensity conditioning (RIC) regimens, many older adult patients, initially excluded from this therapy approach, became eligible for HSCT. This approach decreased the transplant-related mortality, still maintaining T-cell immune response from the graft against the host tumor cells, also known as the graft-versus tumor or graft Practice points• Donor lymphocyte infusion (DLI) is an alternative strategy to reverse mixed chimerism, treat relapse and reconstitute immunity against infections after hematopoietic stem cell transplantation.• Responses to DLI are disease-dependent.• As main side effect, DLI can promote graft-versus-host disease (GVHD) in the range of 40-60% of patients.• The incidence of GVHD after unrelated DLI is similar to the incidence after related DLI, both presenting same pattern of presentation.• Although GVHD and graft versus leukemia (GVL) after DLI are highly correlated, some patients experience remission (GVL) without expressing GVHD.• Escalating doses for DLI is preferable, as it induces less GVHD. There is no clear association, yet confirmed, between T-cell dose and incidence of neither GVHD nor GVL after DLI.• The further DLI is made from transplantation, the better outcome.• Preadjuvant treatment before DLI is preferable as DLI effect is enhanced with low tumor burden.• Some strategies still under investigation are focused on separating GVHD and GVL, including graft engineering and gene therapy, to improve clinical outcome.For reprint orders, please contact: reprints@futuremedicine.com

show abstract

Section: • • Chronic Myelogenous Leukemiasupporting

confidence: 83%

Donor Lymphocyte Infusion After Allogeneic Hematopoietic Stem Cell Transplantation

Pereira

Danby

Rocha

2015

Int. J. Hematol. Oncol.

View full text Add to dashboard Cite

show abstract

“…In this high-risk group of patients, the use of DLI with re-introduction of TKI, may prevent the disease progression and improve the outcome. It is well known that patients with relapse detected on the molecular level respond to DLI with higher remission rate compared to any more advanced disease [ 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

Pretransplantation use of the second-generation tyrosine kinase inhibitors has no negative impact on the HCT outcome

et al. 2015

View full text Add to dashboard Cite

IntroductionAllogeneic hematopoietic cell transplantation (HCT) was a standard therapy in chronic phase (CP) chronic myeloid leukemia (CML). As a result of the effective therapy with tyrosine kinase inhibitors (TKI), HCT was shifted to defined clinical situations. We present the results of observational prospective analysis of 28 CML patients undergoing HCT after exposure to, at least, two lines of TKI (including dasatinib and/or nilotinib), with respect to response, overall survival (OS), treatment toxicity, graft versus host disease (GVHD), and progression/relapse incidence.ResultsAll the patients but one engrafted with median time 19 days. OS for patients in CP1 and CP2/accelerated phase (AcP) were 92.9 and 85.7 %, respectively. Six patients allotransplanted in blast crisis (BC) CML died early after HCT.Eighteen patients achieved deep molecular remission (MR4.5 or MR4.0). Relapse incidence was 29.6 %. Median time to progression (TTP) differs significantly depending on the CML phase prior to HCT, the best response achieved after HCT and development of chronic GvHD.NRM yielded the values 7.1, 12.5, and 50 % in CP1, CP2/AcP, and BC, respectively. Fatal outcome, due to veno-occlusive disease (VOD), was observed in two (7 %) patients. In five (17.9 %) patients, mild or moderate VOD was observed with no negative impact of preceding therapy with TKI2. Acute GvHD was diagnosed in 25.9 % of patients, while chronic GvHD developed in 42.9 % of individuals.ConclusionPretransplantation therapy with TKI2 in CP CML is safe and reasonable. In BC, the optimal approach before HCT is to reduce the leukemic burden and achieve subsequent CP.

show abstract

“…There are clear indications that no type of TKI given before or after the transplant has a deleterious effect on outcome after HSCT; in one study, results appeared even better for patients with TKI prior to HSCT. In contrast, type of response to TKI therapy will impact on post transplant outcome with a good outcome for patients intolerant to TKI but with a higher likelihood of worse outcome for those who failed TKI therapy before HSCT [34,[40][41][42][43][44][45].…”

Section: Impact Of Pretransplant Treatmentmentioning

confidence: 85%

“…There is no doubt about the astonishing graft-versusleukemia effects observed in CML as documented by the powerful effects of DLI [25,43]. Complete and lasting molecular remissions can be obtained with even one infusion of cells, some without any signs of graftversus-host disease.…”

Section: Graft-versus-host-graft-versus-leukemia Effectsmentioning

confidence: 99%

The role of hematopoietic stem cell transplantation in chronic myeloid leukemia

2015

View full text Add to dashboard Cite

Allogeneic hematopoietic stem cell transplantation (HSCT) is currently recommended as 2nd or 3rd line therapy for patients with chronic myeloid leukemia (CML) in first chronic phase or as salvage for patients with very advanced disease. As a consequence, numbers of HSCT in chronic phase have dropped significantly since the introduction of tyrosine kinase inhibitors (TKI), numbers of transplants in advanced disease to a lesser extent. These current recommendations consider primarily disease risk, defined as failure of TKI therapy; they might need to be adapted. We propose a more balanced appraisal of HSCT for individual patients which should include disease risk, transplant risk, and macroeconomic aspects. HSCT should be integrated into the treatment algorithms from diagnosis and be considered very early at first TKI failure for patients with high disease but low transplant risk. For patients with very advanced disease and high transplant risk in contrast, HSCT might only be recommended in a restricted research setting.

show abstract

A Comparison of Long-Term Outcomes of Donor Lymphocyte Infusions and Tyrosine Kinase Inhibitors in Patients With Relapsed CML After Allogeneic Hematopoietic Cell Transplantation

Cited by 21 publications

References 28 publications

Donor Lymphocyte Infusion After Allogeneic Hematopoietic Stem Cell Transplantation

Donor Lymphocyte Infusion After Allogeneic Hematopoietic Stem Cell Transplantation

Pretransplantation use of the second-generation tyrosine kinase inhibitors has no negative impact on the HCT outcome

The role of hematopoietic stem cell transplantation in chronic myeloid leukemia

Contact Info

Product

Resources

About