Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. The German CML Study Group [see comments]

Abstract

As curative bone marrow transplantation is available only to a minority of patients with chronic myelogenous leukemia (CML), drug therapy remains of central interest. Several nonrandomized studies have suggested that interferon-alpha (IFN) may prolong survival in CML. In a randomized multicenter study the influence of IFN versus busulfan or hydroxyurea (HU) on survival of Philadelphia-positive (Ph+) CML was examined. A total of 513 Ph+ patients were randomized for treatment as follows: 133 for IFN, 186 for busulfan, and 194 for HU. IFN-treated CML patients have a significant survival advantage over busulfan-treated (P = .008), but not over HU-treated patients (P = .44). The longer survival is due to slower progression to blast crisis. Median survival of IFN-treated patients is 5.5 years [5-year survival, 59%; 95% confidence interval (CI), 48%-70%], of busulfan-treated patients, 3.8 years (5-year survival, 32%; CI, 24%-40%), and of HU-treated patients, 4.7 years (5-year survival, 44%; CI, 36%-53%). Patients who continue on IFN survive longer than those in whom IFN is discontinued before blast crisis (P = .007). Complete hematologic IFN-responders have a survival advantage over partial responders or nonresponders (P = .02). Cytogenetic IFN-responders have no significant survival advantage over nonresponders (P = .2). Patients who attain white blood cell (WBC) counts of 10 x 10(9)/L or less have a survival advantage in the IFN (P = .007) and HU (P = .05) groups. Whereas toxicity in the IFN group was considerably higher than in the busulfan or HU groups, long-lasting cytopenias necessitating discontinuation of therapy as observed with busulfan have not been seen with IFN or HU. The problems of conventional prognostic scores (Sokal's score, Score 1) that we observed in IFN-treated patients support the idea that IFN changes the natural course of CML. We conclude that, with regard to survival of CML in the chronic phase, IFN is superior to busulfan and as effective as HU. Whether and to what extent IFN is superior to HU appears to depend, at least in part, on the degree of WBC suppression by HU-therapy and on the risk profile of the patients.

Mobilization of predominantly Philadelphia chromosome‐negative blood progenitors using cyclophosphamide and rHUG‐CSF in early chronic‐phase chronic myeloid leukaemia: correlation with Sokal prognostic index and haematological control

“…Only patients who had Ph-negative mobilization achieved a major cytogenetic response on aINF. The incidence of interferon intolerance, the median dose used, and the frequency of haematological and cytogenetic response are all similar to results from other studies where aINF has been used in early chronic phase (The Italian Cooperative Study on Chronic Myeloid Leukemia, 1994;Hehlmann et al, 1994;Allan et al, 1995).…”

“…The only other therapy which has been proved to prolong survival is alpha interferon (aINF). However, whether this agent produces a significant survival advantage for the majority of patients who do not achieve a major cytogenetic response is controversial Kloke et al, 1993; The Italian Cooperative Group on Chronic Myeloid Leukemia, 1994;Hehlmann et al, 1994;Allan et al, 1995).…”

Analysis of a Chronic Myelogenous Leukemia Patient Vaccinated with Leukemic Dendritic Cells Following Autologous Peripheral Blood Stem Cell Transplantation

“…A recent clinical study showed that the treatment of CML patients with interferon-α (IFN-α) was beneficial in some cases. 1) In particular, we demonstrated that in IFN-α-responsive patients, there is an enhancement of the accumulation of Vβ 9 + and Vβ 20 + T cells. 2) CML patients in the chronic phase who cannot undergo allo-BMT or who are unresponsive to IFN-α 3,4) may benefit from autografting.…”

Quantitative real‐time reverse‐transcription polymerase chain reaction for diagnosis of BCR‐ABL positive leukemias and molecular monitoring following allogeneic stem cell transplantation

“…Different results were found in four patients who received allogeneic peripheral blood stem cells from HLA-matched unrelated donors. These patients were followed for a median of 27.8 months (range 9.7-31 months) after transplantation, with a median sample number per patient of 12 (range [11][12][13][14][15][16][17][18][19][20][21]. In these patients, BCR-ABL transcripts were found at least once during the first 6 months after transplantation.…”