Allogeneic peripheral blood progenitor cells for treatment of relapse after bone marrow transplantation

Abstract

Summary:thrombocytopenia in spite of PBPC infusion, in one case followed by leukemic relapse. Repeated courses of chemotherapy and PBPC infusion were generally tolerDonor leukocyte infusions (DLI) are an effective therapy for patients who relapse with leukemia after bone ated well; no early deaths due to treatment-related toxicity or GVHD were observed. We conclude that the use marrow transplantation (BMT). Severe graft-versushost disease and prolonged periods of pancytopenia of allogeneic PBPC instead of DLI in patients with relapse after BMT is technically feasible and safe. The compromise the success of this treatment in a substantial number of patients. We used filgrastim-mobilized efficacy of PBPC infusions seems comparable to DLI in patients with CML. Patients with acute leukemias also peripheral blood progenitor cells (PBPCs), in some cases preceded by cytoreductive therapy, to circumvent achieved complete albeit transient remissions. Aggressive chemotherapy followed by PBPC infusions resulted some of the problems associated with DLI. Relapse of leukemia after allogeneic bone marrow transplete clinical and molecular remission for time periods plantation (BMT) is a serious event putting the patient at between 1 and 12 months. Six of six patients with acute an immediate risk of death. Due to patients' poor general leukemias achieved a complete remission. All of them condition, a second myeloblative therapy followed by transrelapsed after a median remission duration of 24 weeks plantation of hematopoietic cells is often not possible and (range 11-49 weeks). Three patients relapsed at extracannot generally be recommended because it is associated medullary sites (CNS, testes, skin). Four of six acute leuwith a high rate of life-threatening toxicity. 1,2 Other kemia patients received further cytoreductive therapy.approaches to treat relapse after BMT have also shown limAll patients responded again and are in complete ited benefit. 3,4 In contrast, the infusion of donor lymphoremission for time periods between 14 and 615 days.cytes as a novel way of adoptive immunotherapy proves to Two patients with acute leukemias have died due to disbe highly effective in a substantial number of patients. Up semination of the disease. The patient with MM did not to 70% of patients with chronic myeloid leukemia (CML) respond and is alive with disease. Severe (grade III) and approximately 30% of patients with acute myelocytic acute GVHD developed in two of 11 patients, three leukemia (AML) respond favorably to this treatment patients developed grade II disease, six patients did not modality and some of them sustain long-lasting second show any signs of GVHD. Extensive chronic GVHD has remissions. 5-11 However, the infusion of donor leukocytes developed in two cases to date. Patients with chemois not without problems. Profound and protracted periods therapy prior to PBPC infusion developed neutropenia of pancytopenia complicate the procedure in more than a and thrombocytopenia with a maximum duration of 20 third of patients so tr...

Graft-versus-myeloma

“…Kolb et al, 19 on behalf of the European Group for Blood and Marrow Transplantation (EBMT), reported two patients who received DLI for relapsed myeloma; one with 25 2 DLI, interleukin-2 1 1 (with GVHD) Bertz 28 1 Stop cyclosporine, DLI, interferon-␣ Yes Yes Collins 20 1 DLI, interferon-␣ Yes Yes Collins 27 4 DLI NS 2 Glass 30 1 DLI Yes No Kolb 19 2 DLI NS NS Lokhorst 22a 13 DLI 9 (acute) 8 (7 of 9 with and 1 of 4 without AGVHD; 6 7 (chronic) of 7 with and 0 of 5 without CGVHD) Orsini 29 4 CD8-depleted DLI 3 3 (all with GVHD) Pavord 18 1 20 reported a patient with primary refractory disease who did not respond to a T cell non-depleted allograft from an HLA-identical sibling. Four months after BMT, 1.63 × 10 8 donor mononuclear cells per kg were infused and interferon-␣ was started 4 weeks after DLI.…”

“…Glass et al 30 infused G-CSF-mobilized peripheral blood stem cells twice in a patient relapsing after BMT. No GVHD was seen after the first infusion.…”

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

“…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.…”

“…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.…”