Interferon alpha for chronic myeloid leukemia relapsing after allogeneic bone marrow transplantation

Abstract

Summary:Interferon alpha (IFN alpha) induces cytogenetic responses in patients with chronic myeloid leukemia (CML) who relapse after allogeneic bone marrow transplantation (BMT). The purpose of this study was to analyze the therapeutic role of IFN alpha in this setting. The experience of a single institution and the published results on this topic were evaluated. We have included patients who received IFN alpha as a single agent, excluding those patients who received previous or simultaneous donor leukocyte infusions. The outcomes of 11 patients treated in our center and those of 108 previously reported patients have been analyzed. Five out of 11 patients treated in our institution obtained a complete cytogenetic response (CGR). Two patients continue in complete cytogenetic response 3.5 and 8.2 years later, and the qualitative RT-PCR is negative for bcrabl RNA. The CGR has been transient in one patient, and follow-up is short in the other two. Secondary effects have been acceptable, with myelosuppression as the main toxic effect. Graft-versus-host disease did not occur. The literature review identified 108 patients treated with IFN alpha as sole therapy for relapsed CML. Cytogenetic response and CGR seem to be better in patients with cytogenetic relapse, as compared to patients with hematologic relapse (61% vs 45% and 45% vs 28%, respectively). Several patients remained in CGR for more than 5 years. This overview also suggests that CGR is more frequent when IFN alpha is used in patients relapsing after non T-depleted BMT. IFN alpha induces complete cytogenetic response in nearly half of the patients with CML who relapse after allogeneic BMT, with acceptable toxicity. We believe that these results using IFN alpha as a front-line therapy for CML relapsing after BMT warrant a randomized comparison with donor lymphocyte infusions. Keywords: interferon alpha; chronic myeloid leukemia; allogeneic bone marrow transplantation; relapse The EBMT has estimated a 54% actuarial probability of survival at 8 years for CML patients receiving an unmanipulated allogeneic BMT in first chronic phase. Although the probability of relapse at 8 years is 19%, late relapses may be more frequent than previously assumed.

Relapse of chronic myeloid leukemia after allogeneic stem cell transplantation: outcome and prognostic factors. The Chronic Myeloid Leukemia Subcommittee of the GETH (Grupo Español de Trasplante Hemopoyético)

“…DLI and a-IFN have both demonstrated their efficacy in the treatment of CML relapse. [7][8][9][10][11]20,21 Although the aim of our study was not to assess the efficacy of the individual therapeutic options, we could not find differences between a-IFN and DLI. Features of both the patient and the disease, not specifically analyzed in our study, could have influenced these results.…”

Juvenile myelomonocytic leukemia relapsing after allogeneic bone marrow transplantation successfully treated with interferon-alpha

“…Analogous findings have been observed in patients with CML where IFN-␣, alone or combined with DLI, induced complete responses in a substantial number of patients who had relapsed after SCT. 1,2 DLI is another modality for the treatment of relapse after allo-SCT, and is especially effective for CML. However, there are no reports describing achievement of complete remission using DLI in relapsed JMML after SCT.…”

“…1,2 The activity of IFN-␣ in an SCT setting combines antiproliferative and immunomodulating effects. 3 Enhancement of the graft-versus-host-disease (GVHD) or graft-ver- sus-leukemia (GVL) effect was considered to be responsible for this immunomodulation.…”

Atypical chronic graft-versus-host disease following interferon therapy for chronic myeloid leukaemia relapsing after allogeneic BMT

“…Prolonged cytogenetic responses have been reported in a large number of patients. [1][2][3][4][5][6] Remissions after DLI therapy can be complicated by severe acute and chronic graft-versus-host disease (GVHD) contributing to poor performance status or increased mortality in high risk patients. [1][2][3] By contrast, treatment based on IFN alone results in less toxicity and induces durable cytogenetic responses but only occasional molecular remission.…”

“…[1][2][3] By contrast, treatment based on IFN alone results in less toxicity and induces durable cytogenetic responses but only occasional molecular remission. [4][5][6] Chronic GVHD is a pleiomorphic syndrome which varies in time of onset, organ systems involved and rate of progression, and its manifestations commonly resemble various autoimmune diseases. 7,8 It is a major cause of late morbidity and mortality following allogeneic BMT and DLI, but rarely documented outside these settings.…”