Allogeneic cell therapy with donor peripheral blood cells and recombinant human interleukin-2 to treat leukemia relapse after allogeneic bone marrow transplantation

Abstract

Allogeneic bone marrow transplantation (BMT) is the only effective treatment for hematologic malignancies resistant to conventional chemotherapy. Until recently, no cure existed for patients who relapsed post-BMT. We present our long-term observations on remission induction, after relapse post-BMT, by allogeneic cell therapy (allo-CT) and the feasibility of remission induction in allo-CT-resistant patients by activation of antileukemia effector cells with recombinant human interleukin-2 (rhIL-2) in vitro and in vivo. The longest observation of successful allo-CT (event-free survival, greater than 8 years) was made in a patient with resistant pre-B lymphoblastic leukemia who received infusions with graded increments of donor (female) peripheral blood lymphocytes (PBL) as soon as bulky hematologic and extramedullary relapse was noticed early post-BMT. The patient is currently without evidence of residual host (male) cells as determined by polymerase chain reaction (PCR). Of 17 patients with acute and chronic leukemia in relapse after BMT, 10 were reinduced into complete remission. Four patients with cytogenetic relapse responded to allo-CT alone, while five of six patients with overt hematologic relapse responded only after additional activation of donor with rhIL-2. Allo-CT can, therefore, successfully reverse chemoradiotherapy-resistant relapse of both acute and chronic leukemia. Moreover, in patients resistant to donor lymphocyte infusion, remission can be accomplished by additionally activating donor PBL in vitro and/or in vivo with rhIL-2. Based on our observations, after BMT, allo-CT should be considered the treatment of choice for patients with hematologic malignancies resistant to conventional anticancer modalities. Allogeneic activated cell therapy (allo ACT) should be considered for patients with tumor cells resistant to allo-CT. Although allo-CT, followed if indicated by allo-ACT, can be effective for patients with overt hematologic relapse, reversal of persistent minimal residual disease or documented molecular/cytogenetic relapse early after BMT may also be considered as a possible indication for allo-CT.

Prevention of relapse using DLI can increase survival following HLA‐identical transplantation in patients with advanced‐stage acute leukemia: a multi‐center study

“…DLI following allogeneic HCT exhibits definite anti-leukemia effects in patients with advancedstage leukemia (17)(18)(19)(20)(21)(22)(23)(24)(25). Clinical application of prophylactic DLI to reduce the rate of relapse was published years earlier by several other transplant teams as was documented in several publications A B Fig.…”

Donor Leukocyte Transfusions for Treatment of Leukemic Relapse after Bone Marrow Transplantation

“…Again, this question cannot be answered by a retrospective analysis, since many patients were only treated with donor lymphocytes after interferon-a had failed. In some patients a response to donor lymphocytes was observed only after interferon-a had been added to the treatment plan while others only responded to the combination of donor lymphocytes with interferon-a and interleukin-2 [25] [26].…”

“…The use of interferon-a in the treatment of AML and ALL is less well documented than that in CML [24], but Kolb interferon-a may support immunotherapeutic approaches [ 151 .Interleukin-2 (IL-2) has been used more commonly in the treatment of acute leukemia [52], [53], [26], [54], [55]. It enhances antileukemic activity of natural killer (NK) cells and cytotoxic T-cells [56].…”

“…Activity of IL-2 as a single agent has been reported in a few patients only [59], [55], [48]. Its efficacy may be greater in conjunction with adoptive immunotherapy [26], [25]. Larger studies in leukemic relapses after allogeneic transplantation are required before its usefulness can be defined.…”

Red blood cell phenotyping is a sensitive technique for monitoring chronic myeloid leukaemia patients after T‐cell‐depleted bone marrow transplantation and after donor leucocyte infusion

“…After the ®rst encouraging results reported by Kolb et al (1990) and Slavin et al (1992Slavin et al ( , 1996, we started to administer DLI infusions to all patients relapsing from CML after BMT. Application of DLI to treat relapsed CML after BMT has been shown to induce a powerful antileukaemic effect, resulting in remission in 75±80% of patients (Gardiner et al, 1998).…”