Treatment with interleukin-2 (IL-2) and interferon (IFNalpha 2b) after autologous bone marrow or peripheral blood stem cell transplantation in onco-hematological malignancies with a high risk of relapse

Abstract

Summary:Nine patients with onco-hematological malignancies with a poor prognosis due to high risk of relapse received immunotherapy with interleukin-2 (IL-2) and interferon (IFN alpha 2b ) s.c. as maintenance therapy after receiving autologous bone marrow or peripheral blood stem cell transplantation (ABMT/PBSCT). All the patients were considered at very high risk of relapse. We attempted to assess the efficiency, toxicity and clinical effects of these cytokines in these patients. Five patients were treated with high-dose of IL-2 and the other four patients with escalating doses every month. Side-effects in the first group of patients consisted of fever, chills, weakness, nausea, anorexia, loss of weight and local dermatitis in the injection site. Toxicity on the WHO scale was grade II in three patients and grade IV in the other two patients. In the second group of patients, the same clinical signs of toxicity appeared, but these were grade I on the WHO scale in all patients. None of the patients had infections or died in relation to administration of IL-2. Four patients died of relapse or progression of their hematological malignancies. The other five patients are alive, one in chronic phase of CML and the other four patients are in complete remission of their malignancies. Keywords: hematopoietic progenitor transplantation; immunotherapy; toxicity IL-2 is a cytokine secreted by T-helper lymphocytes and is able to stimulate proliferation of T-lymphocytes which carry IL-2 receptors. It also stimulates proliferation of Tlymphocytes with antitumoral activity. This characteristic was described in 1980. It was demonstrated that lymphocytes in the non-stimulated state were able to mediate lysis of tumoral cells but not lysis of normal cells 3 or 4 days later in presence of IL-2. 1,2 These lymphocytes were called LAK cells.These characteristics were studied in vitro in some animal tumours, 3-6 but it was not possible to obtain enough IL-2 of natural origin to study its use and efficiency in humans with disseminated cancer. In 1984 sufficient IL-2 was obtained to begin studies in human beings after identification of the DNA sequence of the gene that codifies synthesis of IL-2. It was possible to express this gene in E. coli. From then on it was used in human beings with disseminated cancer who had no possibilities of therapy. 7,8 Later some studies were undertaken using different dosages and different approaches to administration. [9][10][11][12][13][14][15][16] In 1990 the first results of the efficiency and toxicity of IL-2 s.c. and IFN alpha 2b i.m. in metastatic renal cancer were reported. 17,18 Later in 1991, Ackerstein et al 19 reported that immunotherapy with IL-2 in conjunction with bone marrow transplantation (BMT) in mice increased the graft-versusleukemia (GVL) effect and felt that it should be further investigated as a model for control of minimal residual disease and decreasing the relapse rate after BMT for hematologic malignancies.Rate of relapse in patients with poor prognostic malignancies after autolo...

Spinal injection of IL-2 or IL-15 alters mechanical and thermal withdrawal thresholds in rats

“…One set of evidence indicate that increased levels of IL-2 in and around sensory nerve endings or in the central nervous system promote nociceptive behaviors. Systemic administration of IL-2 in cancer patients induces pain at the site of injection, bone pain, and painful peripheral neuropathy [37][38][39]. Experimental studies in animals replicate many of these clinical observations.…”

Early recovery of aggressive cytotoxic cells and improved immune resurgence with post-transplant immunotherapy for multiple myeloma

“…The administration of post-transplant IL-2 has been evaluated in various malignancies, sometimes in combination with other cytokines or with adoptive cellular therapies. [31][32][33][34][35][36] The majority of these trials initiate IL-2 months following transplant, due to the potential for marrow suppression and the toxicities associated with IL-2. Our preliminary mouse models and early clinical trials, along with the recent publications focusing on the concept of lymphodepletion, emphasize the critical need to initiate IL-2 early posttransplant, in order to influence immune recovery during this period of immune recovery.…”

Severe persistent neuropsychiatric toxicity after a human leucocyte antigen‐non‐identical peripheral blood stem cell transplantation (total body irradiation, etoposide, thiotepa) and interleukin 2‐based experimental therapy for poor prognosis relapse acute lymphoblastic leukaemia

“…Here, donor T‐cell infusions are not feasible because of life‐threatening graft‐versus‐host disease (GvHD) (Aversa, 1996; Muller et al , 1999). However, NK cells may provide anti‐leukaemic activity without inducing GvHD (Asai et al , 1998) and this activity may be enhanced by immunotherapy using interleukin 2 (IL‐2) (Soiffer et al , 1994; Blaise & Maraninchi, 1998; Vivancos et al , 1999).…”