Treatment of Chronic Myeloid Leukemia with Interferon alpha (Roferon): Results of the Israeli Study Group on CML

Abstract

Thirty patients with chronic myeloid leukemia from 11 Israeli medical centers entered this study. Their ages ranged from 16-65 (median 41) and time from diagnosis to treatment was 1-16 months (median 4 months). After cytoreductive therapy with hydroxyurea (22 patients) or busulphan (8 patients), patients received 9 million units/day of recombinant interferon alpha-2 alpha (Roferon A) subcutaneously. Side effects included arthralgia or low back pain in 7 patients, thrombocytopenia in 9, weight loss in four, neurologic disturbances in 4 and leukopenia in 3 cases. Seventeen patients achieved complete hematologic remission (CHR) and 6 partial hematologic remission (PHR). Six patients achieved major cytogenetic response, 4 of them lost all Ph1 chromosome positive cells and 4 had minimal cytogenetic response. Frequency of relapse was high: 8 patients with CHR and 6 with PHR relapsed, but patients with major cytogenetic response did not relapse. Patients who had received prior therapy with busulphan had a higher remission rate but a lower quality of cytogenetic response. Escalation of Roferon to 12 million units per day in relapsing or nonresponding patients induced PHR in 2/7. Neutralizing anti-interferon antibodies occurred in 7 relapsing or nonresponding patients. The cytoreductive induction with hydroxyurea enhanced the hematologic remissions to a median of 6 weeks. Further studies should define the role of combination therapy in order to improve response and prevent relapses.

Serum Interferon (IFN)-Neutralizing Antibodies and Bioactivities of IFNs in Patients with Severe Type II Essential Mixed Cryoglobulinemia

“…The development of NABs against IFN-␣ has been correlated with a decline in therapeutic efficacy in patients with chronic myelogenous leukemia (39), hairy-cell leukemia (40), carcinoid tumors (33,36), and chronic hepatitis C (7,21,31) treated with IFN-␣ and, more recently, in patients with multiple sclerosis treated with IFN-␤ (26,27,37). It has also been observed in patients with severe type II essential mixed cryoglobulinemia (EMC), for whom IFN-␣ is a well-established and widely used therapy (9,10,12,32).…”

The effectiveness and cost-effectiveness of imatinib in chronic myeloid leukaemia: a systematic review

“…40,[66][67][68]72,73,82,[84][85][86] However, it is generally not clear whether the case series was retrospectively defined -in which follow-up is, almost by definition, complete -or prospectively defined. Six studies do not report on length of follow-up 68,72,76,79,82 and, while the majority of studies (24) do report some measure of length of follow-up, this varies considerably. Around half of the studies report on withdrawals, but in only a small proportion are figures for the number of withdrawals given.…”

“…Nine studies only included Ph+ CML patients, 40,46,73,75,76,78,79,82,84 but others did not specify this, so the denominator for calculating CR rates is not known.…”

“…No inclusion criteria are stated in seven studies. 19,[66][67][68][69][70][71] In addition, some of those that describe inclusion criteria are very broad, for example describing only a defined phase of CML, [72][73][74][75][76] while others are lengthy and include restrictions such as age and co-morbidity.…”

Interferon-α-2a

“…Rates of complete cytogenetic response in these studies ranged from 6 to 26%. [40][41][42][43][44] Dow et al [40] treated 15 children and young adults, aged 2.5 to 20 years at diagnosis, with Ph-positive CML with interferon-a-2a 5 to 10 MU/m2/day (intramuscularly) for approximately 2 years. Initial haematological responses were achieved in 10 patients (67%), and cytogenetic responses (4 complete and 5 partial or minor) in 9 patients.…”