Donor lymphocyte infusions (DLI) in patients with chronic myeloid leukemia following allogeneic bone marrow transplantation

Abstract

Summary:and discontinuation of infusions before life-threatening GVHD has developed. Donor lymphocyte infusions (DLI) were given between Keywords: chronic myeloid leukemia; graft-versusJune 1990 and March 1996 to 18 patients with chronic leukemia; donor lymphocyte infusions myeloid leukemia (CML) for the treatment of cytogenetic (n ‫؍‬ 6) or hematologic relapse (n ‫؍‬ 12) following an allogeneic bone marrow transplant (BMT). Patients were divided in two groups: patients in group A (n ‫؍‬ 8)Graft-versus-leukemia (GVL) is thought to play an received a large dose of donor lymphocytes important role in preventing relapse in patients undergoing (у1 ؋ 10 8 /kg), whereas patients in group B (n ‫؍‬ 10) allogeneic bone marrow transplants (BMT). 1,2 Although received escalating numbers of cells (2 ؋ 10 5 up to GVL was described in animals almost 20 years ago 3,4 little 2 ؋ 10 8 /kg). The median number of DLI in group A was is known about the magnitude of this effect on effector cells 2 (range 1-3); the median number of infusions in group and target antigens, at least in humans. 5 In the experimental B was 7 (range 3-9). Acute GVHD occurred in 12 animal, cells separately mediating GVL or graft-versus-host patients (grades I-III) and was a major cause of death disease (GVHD) have been described and can be identified in two. The risk of developing GVHD correlated with by surface markers. 3,6 In humans we have indirect evidence the number of cells infused: 37%, 14%, 5% and 0%for GVL: programs involving T cell depletion expose the for DLI with cells у1 ؋ 10 8 , 2 ؋ 10 7 /kg, 2 ؋ 10 6 /kg, and patients to a high risk of leukemic relapse, 2 and this has 2 ؋ 10 5 /kg, respectively (P ‫؍‬ 0.01). Median transaminnow been shown in very large numbers of patients.1,2 ase levels were found to be significantly increased in If mature donor T cells infused on the day of marrow patients with, as compared to patients without, acute transplant (an average of 6 × 10 7 /kg) have such an GVHD (GPT 412 vs 28 IU/l; P ‫؍‬ 0.03). Severe aplasia important role in preventing relapse, the use of large numoccurred in four and was a contributing cause of death bers of donor T cells which have undergone maturation in in two patients. Overall, four patients died as a consethe donor thymus, would possibly be helpful in treating quence of DLI and all received Ͼ1 ؋ 10 8 /kg cells: the relapse. Indeed this has been shown to be the case, actuarial risk was 38% in group A and 14% in group especially in patients with chronic myeloid leukemia B (P ‫؍‬ 0.1). There were 10 complete and three partial (CML), both for unfractionated 7-17 and CD8-depleted cytogenetic responses: the actuarial probability at 5 cells.18 years of being Ph negative was 69%: it was 46% for The exact mechanism by which the leukemic clone can group A and 85% for group B (P ‫؍‬ 0.1). The longest be reduced is unknown. GVHD has a deleterious effect on patient is now 6 years post-DLI, Ph negative, BCR-ABL hematopoietic cells 19,20 and it is quite possible that the sonegative. The actuarial 3 y...

Donor lymphocyte infusion induced molecular remission in relapse of acute myeloid leukaemia after allogeneic bone marrow transplantation

“…12 On the other hand, DLI has been effective against a wide range of haematological malignancies relapsing post BMT. [2][3][4] However, DLI might be associated with potentially life-threatening complications including severe GVHD and marrow aplasia. 2,13 Two prerequisites appear necessary for successful DLI.…”

“…2,13 Two prerequisites appear necessary for successful DLI. Firstly, it is more successful in minimal residual leukaemia than in gross haematological relapse, [2][3][4] as an initial cytoreduction might reduce the relapse clone to a level that can be effectively handled by GVL. 14 Secondly, the preservation of donor chimerism is important to avoid bone marrow aplasia post DLI.…”

“…1 Therefore, in leukaemia patients relapsing after BMT, donor lymphocyte infusion (DLI) to boost the GVL effect is a therapeutic option. [2][3][4] Although DLI has been shown to be highly effective for the treatment of post-BMT relapse of chronic myeloid leukaemia (CML), data on other haematological malignancies are scanty. Furthermore, DLI has been less effective in AML relapses, 2 with little data to show molecular eradication of leukaemia.…”

Serum cholinesterase is an early and sensitive marker of graft-versus host-disease (GVHD) and transplant-related mortality (TRM)

“…This is what we have observed by correlating serum CHE levels with acute GVHD grading at different time-points post transplant. Some years ago, we published that serum transaminase (GPT) could be used as a marker of GVHD in patients receiving donor lymphocyte infusions (DLI), 13 and we are now analyzing a larger number of infusions showing that gamma glutamyl transferase (ggT) is a marker of GVHD after DLI. 14 Taken altogether, these data would suggest that liver function tests, in addition to bilirubin, can be used to mark alloreactivity, and serum CHE is one of them.…”

Successful one antigen mismatched bone marrow transplant for chronic myeloid leukemia (CML) after two failed syngeneic transplants

“…2,3 The strongest evidence supporting the concept of GVL is the observation that patients with CML who relapse after allogeneic BMT can obtain a 2nd CR following infusion of donor lymphocytes. [5][6][7][8] …”